Nice Haematological Csg Rep
Guidance on Cancer Services – Improving Outcomes in Haematological Cancers – The Manual
NHS
National Institute for
Clinical Excellence
Guidance on Cancer Services
Improving Outcomes in
Haematological Cancers
The Manual
Haematological cancers service guidance
Cancer service guidance supports the implementation of The NHS Cancer Plan for England,1 and the NHS Plan
for Wales Improving Health in Wales.2 The service guidance programme was initiated in 1995 to follow on from
the Calman and Hine Report, A Policy Framework for Commissioning Cancer Services.3 The focus of the cancer
service guidance is to guide the commissioning of services and is therefore different from clinical practice
guidelines. Health services in England and Wales have organisational arrangements in place for securing
improvements in cancer services and those responsible for their operation should take this guidance into account
when planning, commissioning and organising services for cancer patients. The recommendations in the guidance
concentrate on aspects of services that are likely to have significant impact on health outcomes. Both the
anticipated benefits and the resource implications of implementing the recommendations are considered. This
guidance can be used to identify gaps in local provision and to check the appropriateness of existing services.
References
1.
Department of Health (2001) The NHS Cancer Plan. Available from:
www.doh.gov.uk/cancer/cancerplan.htm
2.
National Assembly for Wales (2001) Improving Health in Wales: A Plan for the NHS and its Partners.
Available from: www.wales.gov.uk/healthplanonline/health_plan/content/nhsplan-e.pdf
3.
A Policy Framework for Commissioning Cancer Services: A Report by the Expert Advisory Group on
Cancer to the Chief Medical Officers of England and Wales (1995). Available from:
www.doh.gov.uk/cancer/pdfs/calman-hine.pdf
This guidance is written in the following context:
This guidance is a part of the Institute’s inherited work programme. It was commissioned by the Department
of Health before the Institute was formed in April 1999. The developers have worked with the Institute to
ensure that the guidance has been subjected to validation and consultation with stakeholders. The
recommendations are based on the research evidence that addresses clinical effectiveness and service
delivery. While cost impact has been calculated for the main recommendations, formal cost-effectiveness
studies have not been performed.
National Institute for
Clinical Excellence
MidCity Place
71 High Holborn
London
WC1V 6NA
Web: www.nice.org.uk
ISBN: 1-84257-398-5
Copies of this document can be obtained from the NHS Response Line by telephoning 0870 1555 455 and quoting
reference N0327. Bilingual information for the public has been published, reference N0328, and a CD with all
documentation including the research evidence on which the guidance is based is also available, reference N0329.
Published by the National Institute for Clinical Excellence
October 2003
© National Institute for Clinical Excellence October 2003. All rights reserved. This material may be freely reproduced
for educational and not-for-profit purposes within the NHS. No reproduction by or for commercial organisations is
permitted without the express written permission of the Institute.
Guidance on Cancer Services
Improving Outcomes in
Haematological Cancers
The Manual
Contents
Foreword .................................................................................................3
Key recommendations..............................................................................7
Background ...............................................................................................8
The topic areas
1.
Access to care ................................................................................26
2.
Patient-centred care .......................................................................32
3.
Diagnosis and evaluation ..............................................................44
4.
Organisation of specialist services................................................52
5.
Treatment (excluding high dose therapy) ...................................68
6.
High dose therapy .........................................................................84
7.
Continuing management ...............................................................95
8.
Palliative care ...............................................................................100
9.
Clinical trials and use of protocols.............................................106
Appendices
1.
Economic implications of the guidance .....................................109
2.
How this guidance manual was produced ................................115
3.
People and organisations involved in production of
the guidance.................................................................................117
4.
Glossary of terms.........................................................................137
5.
Abbreviations ...............................................................................149
1
Foreword
Professor R A Haward,
Chairman, National Cancer Guidance Steering Group
The haematological malignancies are a complex group of neoplastic
diseases, linked by their origin in bone marrow derived cells. The
growing understanding of how haematological malignancies arise
through disruption of the normal cellular processes in the bone
marrow and immune system by a variety of molecular and
cytogenetic abnormalities is challenging traditional approaches to
disease classification. These advances are transforming both
diagnosis and management of patients.
The characterisation of tumour cells by immunophenotypic and
molecular methods is now regarded as being as important as the
traditional morphological approach to diagnosis. This trend is being
accelerated by the introduction of monoclonal antibody therapy and
by novel drugs designed to specifically target the molecular
abnormalities responsible for the development of the tumour. Such
developments are of fundamental clinical importance as they
increasingly define not just the diseases themselves, but how an
individual patient should best be treated. Building these advances into
the routine care of patients represents a demanding agenda for the
clinicians and hospitals involved.
Just as the diseases are distinctive and show many differences from
solid tumours, so too is the organisation of services. There is a
degree of separation between the clinical services for haematological
malignancies and those for solid tumours, perhaps reflecting their
particular development pathways and the nature of the specialities
involved. This has traditionally extended to the organisation and
funding of research and many associated scientific activities.
Despite these differences, there are compelling reasons for regarding
all cancer services as a logical whole, in which the diagnosis and
treatment of the various disease types has an immense amount in
common. Operationally the reality is that local hospital services for
common solid tumours in cancer units rely in no small measure on
haematology services. The active support of haematology services
‘round the clock’ underpins the safe delivery of chemotherapy for all
tumour types, particularly the diagnosis and management of life-
threatening complications.
3
Services for patients with haematological malignancies do have
distinctive features. The generality of cancer patients are increasingly
managed by clinicians from different professions and medical
specialties, working together to combine their expertise and make
collective decisions on the management of their patients. Whilst the
management of haematological malignancies also involves a range of
clinical and laboratory skills, the processes of diagnosis and
subsequent clinical management are dominated by one medical
discipline, clinical haematology. Indeed it remains perfectly possible
for a patient’s diagnosis to be made by a single clinician who then
goes on to initiate treatment and subsequently determines further
treatment as the patient’s clinical course progresses. The same
individual may also determine the point at which active therapy may
no longer be appropriate for that patient. Thus for many patients,
particularly those with leukaemia, it is not unusual for decisions on
their management to involve only one or possibly two individual
consultants, probably colleagues in the same discipline and hospital.
It has been observed in some areas that less use is made of palliative
services in haemato-oncology than is the case for patients with many
solid tumours.
Other features of haemato-oncology services are equally characteristic.
The main form of therapy for these diseases is chemotherapy
(including immunotherapy). Other modalities such as radiotherapy
have their roles, but these are more limited. Chemotherapy is
particularly amenable to evaluation through randomised clinical trials.
An admirable feature of British clinical haematology has been the
widespread interest, and active participation of clinicians and
hospitals, in clinical trials. Indeed, many national trials in these
diseases have been extremely well supported by haematologists in all
types and sizes of hospital, with high rates of trial entry. This has led
to the widespread and routine adoption of evidence based protocols
to help guide care in the various malignancies.
Collaboration in research has frequently been extended in other ways.
In some places, but by no means all, there is professional networking
between clinicians in district hospitals and between them and
colleagues in more specialised units. In some places this
collaboration can be very close, in others relatively token.
It is a paradox that despite the mass of trial evidence about
chemotherapy regimens for the various clinical types and sub-types of
disease, there is no well-established Cochrane Group and less
research evidence than we would have wished to guide
recommendations in some areas. Limitations in the evidence should
always be acknowledged, but need not necessarily prevent important
recommendations where these are consistent with other knowledge or
experience in related areas. We have made some important
recommendations about service organisation and delivery.
4
The management of individual patients should, as always, be based
on sound and comprehensive diagnostic information. This is crucial in
these diseases as the precise diagnosis does, in many situations,
define the most appropriate treatment. Decisions on management
should involve a range of knowledgeable professionals in the disease
areas concerned, meeting together. They need to determine the
management of individual patients as well as agreeing more general
policies and operational procedures. Those managing patients with
these diseases face difficult diagnostic and clinical decisions - such as
defining the point at which further cycles of chemotherapy are not
appropriate and change to a more palliative approach may be
preferred. It is essential that this collective involvement in decision-
making is adopted for haematological malignancies, as for other
cancer types, even though for some disease-types most of those
involved will be from one discipline. These arrangements should
cover all patients and are likely to improve decisions about their care.
The number of patients with each discrete type of haematological
malignancy presenting each year to cancer units is, by the standards
of those who manage many solid tumours, often low. Whilst the use
of protocols derived from clinical trials evidence may be a partial
response to low throughput, issues remain about expertise and
specialisation which cannot be easily evaded. Working collaboratively
in teams, and hence being involved in decisions about the
management of larger numbers of new patients than arise in any one
clinician’s practice, or in a single institution, is therefore likely to be
beneficial. It will facilitate the development and sharing of expertise
as well as allowing a wider range of inputs into decision-making
about each patient.
Thus the challenge of preparing service guidance for haematological
malignancies is set against a very distinctive backcloth. Our
expectation is that a more systematic team-based approach will be an
important move forward. Our recommendations are designed to offer
considerable flexibility in implementation, which should enable local
influence over the preferred model in each place. We acknowledge
that much of what is described already exists in a number of
locations, and in some places these arrangements have existed for
many years. However, consistency in the quality of care is our
primary goal. It is evident that for some, what is being recommended
represents significant but necessary change.
5
Key recommendations
•
All patients with haematological cancer should be managed by
multi-disciplinary haemato-oncology teams which serve
populations of 500,000 or more.
•
In order to reduce errors, every diagnosis of possible
haematological malignancy should be reviewed by specialists in
diagnosis of haematological malignancy. Results of tests should
be integrated and interpreted by experts who work with local
haemato-oncology multi-disciplinary teams (MDTs) and provide
a specialised service at network level. This is most easily
achieved by locating all specialist haemato-pathology diagnostic
services in a single laboratory.
•
There should be rapid-access diagnostic services for patients
with lymphadenopathy (chronically swollen lymph nodes or
neck lumps).
•
Clinical nurse and palliative care specialists are to have central
roles in haemato-oncology teams, working closely with their
medical colleagues. Clinical nurse specialists will arrange for
patients and carers to receive multi-faceted support, co-
ordinated care, and all the information they want, throughout
the course of the illness.
•
MDTs which manage patients with acute leukaemia should
provide treatment intended to induce remission for sufficient
new patients for the units concerned to develop and maintain
expertise. Services are unlikely to be viable with five or fewer
new patients per year. This treatment should be provided at a
single facility within any one hospital site, in designated wards
with continuous access to specialist nurses and haematologists.
•
High dose therapy with progenitor cell transplantation is to be
carried out only in centres which meet JACIE accreditation
standards, including the minimum case-load criterion of 10
procedures per annum.
7
Background
Scope of this document
The purpose of this guidance is to describe key aspects of the service
required to achieve the best outcomes for adult patients with
haematological cancers. The guidance covers all aspects of care for
this group of patients, including medical diagnosis and management.
Guidance on paediatric and adolescent services is expected from the
newly-established National Institute for Clinical Excellence (NICE)
Collaborating Centre for Cancer. It will be for that guidance to
propose the definition of the interface between their service scope
and the work of adult services covered by this guidance.
This background section is intended to help non-expert users of the
manual to orientate themselves to this group of diseases and their
management.
Haematological cancers: nature and
numbers
Haematological cancers (cancer of blood cells) together represent the
fifth most common type of cancer in the UK, accounting for 7% of all
cancers. This is a uniquely diverse group which is sub-divided into
three main diseases: leukaemia, lymphoma and myeloma. Some
forms are highly aggressive, others so benign that they may only be
picked up by chance; the symptoms can include lumps (in a variety
of body sites), which are typical of lymphomas; bone fractures and
kidney problems, characteristic of myeloma; and fatigue and
vulnerability to infection, which can result from most types of
haematological cancer but are particularly severe in acute leukaemia.
Like the forms of disease, the treatments used vary widely. Some are
very demanding, both for patients and those who look after them.
Aggressive forms of haematological cancer such as acute leukaemia
may be curable, but only by repeated periods of intensive
chemotherapy which requires long periods of hospitalisation and
protection from infection, and sometimes, transplantation of blood
progenitor cells from bone marrow or other sources. A wider range
of treatments is needed for patients with lymphomas or myeloma,
8
including chemotherapy, radiotherapy and sometimes surgery; with
lymphomas as with acute leukaemias, intensive treatment may
continue over long periods of time. Less aggressive forms of
haematological cancer, which are more common among elderly
people, may only require monitoring or minimal palliative treatment,
often given on an out-patient basis.
Despite these variations, the underlying problem is basically the same
in all these diseases: a genetic change in a particular group (clone) of
blood cells (or its precursor) that leads these cells to develop
incorrectly and multiply in a disorganised and uncontrolled manner,
crowding out cells that are essential to normal function. The diversity
in the form of disease produced results from a combination of factors,
particularly the type of cell affected, the nature of the genetic change
that precipitates the malignancy, and the point in the cell’s maturation
process at which the malignant change occurs.
Blood cells begin their development in the bone marrow. When
genetic disruption occurs at this point, cancer replaces the cells which
would normally develop into oxygen-carrying red blood cells,
platelets which are essential for clotting, and white cells that fight
infection. This produces leukaemia, a disease characterised by
anaemia, fatigue, bleeding, and susceptibility to infection.
As they mature, white blood cells (lymphocytes) migrate from the
bone marrow and settle in lymph nodes or other parts of the immune
system – in particular, the lining of the intestine, the skin, or the lungs
– where their development continues. Malignant changes at this point
in the cell’s life cycle produce lymphomas. These tend to reveal
themselves as lumps but they also produce a variety of other
symptoms.
One particular type of blood cell (plasma cell) returns to the bone
marrow for the final period of its life. When malignant changes occur
here, excessive numbers of abnormal plasma cells destroy the
surrounding bone. This is myeloma, usually known as multiple
myeloma because it tends to happen in many parts of the skeleton
simultaneously.
9
Prevalence, incidence and survival rates
There are no precise and reliable figures for incidence and survival
rates for the different forms of haematological cancer in England and
Wales. Whilst the Office for National Statistics (ONS) and the Wales
Cancer Intelligence and Surveillance Unit do publish descriptive
statistics (Table 1), there are many problems with these figures. For
example, there is evidence that many cases are never reported to
cancer registries, so the actual number of patients could be
substantially higher than national figures suggest.1
With some of these diseases, it can be difficult to decide which
individuals should be defined as patients. Blood changes which
could be classified as chronic leukaemias are widespread among
older people and often produce no symptoms. Incidence rates for
these conditions therefore depend largely on whether anyone
happens to look at blood samples from such individuals, and on
clinicians’ criteria for deciding whether malignancy exists at all. Even
when it is clear that haematological malignancy is present, identifying
the particular form of cancer requires sophisticated methods which
are not available in many local hospitals, so a large number of
registrations do not include detailed information on the diagnosis.
This is especially true of non-Hodgkin’s lymphoma (NHL), a large and
varied group of conditions; indeed, the largest group of NHL
registrations in ONS statistics is described as “unspecified”. This issue
is discussed in more detail below.
1
The establishment of a new reporting system in the South Thames East Area was
associated with an increase of 43% in annual registrations. (South Thames Haematology
Specialist Committee and Thames Cancer Registry. Report of the South Thames
Haematology Register Cancer Sub-Committee on the Incidence of Haematological
Malignancies in 1999. London: King’s College, 2001.) This is consistent with anecdotal
evidence suggesting that many cases are not reported.
10
Table 1.
Haematological malignancies: incidence, survival
rates and deaths, England and Wales (ONS figures)2
Cancer
Disease Codes
No of Incidence: Deaths
Death:
Relative
cases a crude rate
2000
rate per
survival b
ICD 9
ICD 10
1999
per
100,000
100,000
2000
One
Five
1999
year
year
Acute
204.0
C91.0
593
1.1
252
0.5
53%
26%
lymphoblastic
leukaemia (ALL)
Acute myeloid
205.0
C92.0
1779
3.4
1604
3.0
24%
8%
leukaemia
(AML)
Chronic myeloid 205.1
C92.1
605
1.1
508
1.0
61%
22%
leukaemia
(CML)
Other &
204.2-204.9, C91.2,
751
1.4
392
0.7
no no
unspecified
205.2-205.9, C91.3,
data
data
leukaemias
206-208
C91.5-91.9,
C92.3-C95
Chronic
238.1
D47.1
643
1.2
173
0.3
no no
myeloproliferative
data
data
disorders (MPD)
Myelodysplastic 284.9, 285.0, D46
2047
3.9
110
0.2
no no
syndrome
288.8
data
data
(MDS)
Multiple
203
C90
2991
5.7
2024
3.8
55%
19%
myeloma
Hodgkin’s
201
C81
1218
2.3
241
0.5
88%
75%
lymphoma
Non-Hodgkin’s
200, 202
C82-85,
8075
15.3
4012
7.6
65%
45%
lymphoma
C91.4, C96
(NHL)
Chronic
204.1
C91.1
2071
3.9
778
1.5
77%
51%
lymphocytic
leukaemia (CLL)
a
The level of underreporting, particularly of non-malignant cancers (ICD10 D
codes), is not known.
b
Patients diagnosed in 1986-90. Source: Coleman MP, Babb PJ, Damiecki P,
Grosclaude P, Honjo S, Jones J, Knerer G, Pitard A, Quinn M, Sloggett A,
De Stavola B. Cancer survival trends in England and Wales, 1971-95:
deprivation and NHS Region. Studies in Medical and Population Subjects No.
61. London: The Stationary Office, 1999.
2
Data provided by the National Cancer Intelligence Centre, Office for National Statistics, on
request, October 2002.
11
Despite the problems with statistics, basic information is essential to
plan service provision. Registration figures suggest that 39 new cases
per 100,000 population are reported per annum, but those working in
the field believe that the numbers are considerably higher. It is also
crucial for service planning to know how many patients are likely to
require intensive or complex forms of treatment, so varied groups of
conditions like NHL must be split into aggressive, or ‘high grade’ and
less aggressive ‘low grade’ forms, sometimes described as indolent
lymphomas. Table 2 attempts to do this, although the figures are
acknowledged to be estimates, particularly since the distinctions
between some of these groups (such as high-grade and low-grade
lymphoma) are often unclear.
Table 2.
Haematological cancers: estimated annual incidence3
Disease
Incidence,
Per million
Per 500,000
Per 250,000
England and
population
Wales
Acute leukaemia
2400
48
24
12
CML
500
10
5
2-3
CLL
4000
80
40
20
NHL ‘high grade’
2000
40
20
10
NHL ‘low grade’
5000
100
50
25
Hodgkin’s lymphoma
1200
24
12
6
Myeloma
3000
60
30
15
MDS/MPD/other
2000
40
20
10
Incidence and mortality rates vary across England, with relatively high
rates in the South West – around 50% higher than in Yorkshire.4 The
reasons for these geographical variations are not known, but are
likely to include variations in diagnosis and reporting.
The overall prevalence of haematological cancer is rising, with the
greatest increase in the number of people with non-Hodgkin’s
lymphoma. The rate of diagnosis has increased by 3-5% per annum
between 1984 and 1993; ONS figures show that the age-standardised
3
Estimated figures based on expert opinion from the editorial board.
4
Cartwright, RA, McNally RJQ, Rowland J et al. The descriptive epidemiology of leukaemia
and related conditions in parts of the United Kingdom 1984-1993. London: Leukaemia
Research Fund, 1997.
12
incidence rose almost three-fold between 1971 and 1997. The
increased rate of diagnosis almost certainly reflects a real increase in
incidence.5
Prevalence is also increased by improved survival rates. Before the
1970s, non-Hodgkin’s lymphoma was usually fatal, but developments
in therapy between 1971 and 1986 led to a 14% increase in five-year
survival rates. Similar improvements are apparent for leukaemia: five-
year survival rates have doubled since the early 1970s. In multiple
myeloma, substantial improvements have been achieved in short-term
(one- to three-year) survival rates, although longer term survival rates
remain poor.5
Incidence and survival rates vary greatly with age. In people under
the age of 60, five-year relative survival rates for leukaemia are
around 40%; but in those over 70, only 20-25% survive this long after
diagnosis. Age-related differences in survival time are particularly
marked in acute myeloid leukaemia (AML). Leukaemia incidence and
mortality rates have risen sharply in the elderly but not so much in
younger people, which tends to depress overall survival rates.
Similar patterns can be seen for other forms of haematological cancer,
although aggressive lymphoma in older patients is unlike acute
leukaemia in that it can often be successfully treated.
Considered as a group, haematological cancers become more
common as populations age. The number of new cases among
adults almost doubles with each decade between 20 and 60, and
continues to rise until the eighth decade (Figure 1).
Figure 1. Number of new cases of haematological cancers (all
types, combined) by age group, 19975
3500
3000
2500
2000
1500
1000
Number of New Cases
500
0
20-29
30-39
40-49
50-59
60-69
70-79
80 plus
Age Group
Men
Women
5
Quinn M, Babb P, Brock A, et al. Cancer trends in England and Wales 1950-1999.
London: The Stationery Office, 2001.
13
It is not possible to judge whether outcomes for patients in Britain are
better or worse than elsewhere. Survival rates in England and Wales
are reported to be below the European average and lower than in the
USA, but these apparent differences may not accurately reflect reality.
For example, mortality statistics for haematological cancers are
particularly unreliable because many patients die from infections and
these, rather than the underlying cancer, may be recorded as the
cause of death; and when national descriptive statistics are unreliable,
international comparisons will be even more misleading.
Classification
One of the reasons for the lack of trustworthy statistics is that a
reliable classification system for haematological malignancies has only
recently been developed and agreed by oncologists and pathologists.
Accurate classification is important because each type of
haematological cancer has unique characteristics. To assess prognosis
and select the optimum form of therapy, it is essential to know
precisely what type of cancer the patient has.
There have been numerous attempts at classification, with 25 different
systems recorded for lymphoma alone over the last quarter-century.
The classification problem has recently been resolved by the
development of the REAL/WHO system, which has been adopted by
most pathologists in the UK. This allows the diagnosis of leukaemias
and lymphomas to be cross-checked and agreed by laboratory-based
pathologists and clinicians. Regrettably, the REAL/WHO system can
be difficult to relate to classification systems on which national
population statistics are based.
The REAL/WHO classification system is based on a combination of
features, which together define the type of cancer. These are:
•
Morphology of the tumour cells – their shape, size and general
appearance under a microscope;
•
Immunophenotype – specific proteins produced by tumour cells;
•
Genetic features – mutations or abnormal arrangements of
genes;
•
Clinical features, including symptoms.
Although the REAL/WHO system was developed for lymphomas, the
precise diagnosis of leukaemia is based on similar criteria. An initial
diagnosis of acute leukaemia may be made on the basis of the
patient’s symptoms and the microscopic appearance of a blood
sample, but, as with lymphoma, discrimination between sub-types
and treatment selection requires a wider range of diagnostic tests.
14
Symptoms and treatment
Leukaemias
Leukaemias tend to produce generalised symptoms, notably fatigue,
bruising, bleeding and reduced resistance to infection. The severity
of disease, rate of progression and treatment varies greatly between
leukaemias, so precise identification of the specific form of leukaemia
is crucial to optimum management.
Acute leukaemia
This is a group of rapidly-progressing diseases, which includes acute
myeloid leukaemia (AML) and acute lymphoblastic leukaemia (ALL).
Acute leukaemia can affect adults of any age, but the incidence of
AML rises sharply in middle age and is highest among elderly
patients, whilst most people with ALL are under 65.6 These diseases
cause severe anaemia which makes sufferers feel absolutely
exhausted; they are prone to repeated infections because they cannot
produce enough normal blood cells to mount an effective immune
response.
Acute leukaemia is treated with intensive chemotherapy, given on an
in-patient basis through intravenous catheters, over periods of about
four weeks at a time. Patients undergoing such treatment are
extremely vulnerable to life-threatening infections (neutropenic sepsis)
and great care has to be taken, both to minimise the risk of infection
and to treat it rapidly and effectively when it occurs. Specialist
nursing and 24-hour cover by appropriately trained medical staff are
required.
Stem cell rescue – infusion of tissue from which blood cells develop –
may be used in the hope of re-populating bone marrow destroyed by
chemotherapy with healthy cells. This may require a transplant of
donated bone marrow that closely matches the patient’s own
(allogeneic bone marrow transplant, or BMT) or re-infusion of cells
taken from the patient before high dose chemotherapy (autologous
stem cell rescue). Both methods carry specific risks: graft-versus-host
disease with allogeneic transplants, or re-seeding with tumour with
autologous transplantation.
Although acute leukaemia is sometimes cured, it frequently goes into
remission after treatment, only to recur some time later. When this
happens, the treatment may be repeated, perhaps intensified. It can
be very difficult to judge the point at which attempting to cure
leukaemia ceases to be in the best interest of the patient.
6
South Thames Haematology Specialist Committee and Thames Cancer Registry. Report of
the South Thames Haematology Register Cancer Sub-Committee on the Incidence of
Haematological Malignancies in 1999. London: King’s College, 2001.
15
Chronic leukaemia
Chronic lymphocytic leukaemia (CLL) is the most common form of
leukaemia, but it may also be classified as a form of lymphoma. It is
most often found in elderly people. The effects of CLL vary widely;
some people feel quite well and the condition is discovered
incidentally; others may experience gradually increasing fatigue,
repeated infections, sweats, bleeding problems, swollen lymph nodes
and a swollen spleen which can become painful. A wide range of
treatments may be used and there is considerable uncertainty about
optimum management.
The second major form of chronic leukaemia is chronic myeloid
leukaemia (CML). Younger people with CML can achieve long-term
freedom from the disease after high dose therapy and transplantation
of bone marrow from a matched donor (allogeneic BMT); although
risky, this is currently the only curative treatment. Palliative measures
may keep the symptoms under control for a few years, but the
progress of the disease cannot be halted except by BMT; without this,
CML is invariably fatal. Imatinib (Glivec) is a new form of treatment
for CML, the first of a range of drugs designed to target the specific
abnormal proteins produced by the cancer. This approach seems
very promising but its long-term effects are unknown.7
Myeloproliferative disorders (MPD)
These are chronic conditions caused by bone marrow abnormalities,
which usually affect older patients. People with myeloproliferative
disorders may experience few problems at first, but fatigue is
common as the condition progresses. Some develop night sweats,
enlarged and painful spleens, bleeding or circulation problems,
thromboses and other symptoms, depending on the condition. Out-
patient supportive treatment or single agent therapy is normally
sufficient, but some patients develop vascular complications and
require treatment from other clinical specialists.
Myelodysplastic syndrome (MDS)
Like myeloproliferative disorders, myelodysplastic syndrome is caused
by abnormal bone marrow and tends to affect older patients. It
causes progressive marrow failure, leading to anaemia, problems with
blood clotting and reduced resistance to infection. People with these
diseases are usually given supportive care and regular transfusions on
an out-patient basis. In about 30% of cases, myelodysplastic
syndrome turns into acute myeloid leukaemia; when this occurs in
younger patients, bone marrow transplantation may be offered.
7
National Institute for Clinical Excellence. Guidance on the use of imatinib for chronic
myeloid leukaemia. Technology Appraisal Guidance No. 50. London: NICE, 2002.
16
Lymphomas
Lymphoma, the most common type of haematological cancer,
includes a wide range of conditions. Lymphomas tend to produce
lumps in lymph nodes; some forms affect other tissues such as the
skin, lung or gut. Traditionally, lymphomas have been divided into
Hodgkin’s disease (now known as Hodgkin’s lymphoma) and non-
Hodgkin’s lymphoma (NHL), but NHL is a diverse group of conditions
which is often sub-divided into aggressive and indolent forms. This
distinction is, however, blurred, because some normally indolent
diseases are capable of progressing quite rapidly.
Hodgkin’s lymphoma
Hodgkin’s lymphoma is most common in relatively young people,
with maximum incidence rates between the ages of 20 and 30,
although it can affect adults of any age. It usually produces a
painless lump in the neck, but lumps can develop in other parts of
the body such as the chest. Other symptoms include recurring fevers
and night sweats, weight loss and itchy skin.
It is often possible to cure Hodgkin’s lymphoma with appropriate
treatment. Decision-making about treatment depends on accurate
staging, which requires specialist cross-sectional imaging facilities.
Hodgkin’s lymphoma is usually treated with multi-agent
chemotherapy, given on an out-patient basis for several months.
Radiotherapy may be given for localised or bulky disease or to treat
masses that persist after chemotherapy. High dose chemotherapy
with stem cell rescue can be offered to patients whose disease fails to
respond to initial treatment, or who relapse after treatment.
Many patients with Hodgkin’s lymphoma will want to have children
after treatment. They are particularly likely to need fertility services.
Aggressive non-Hodgkin’s lymphomas: diffuse large B-cell
lymphoma (DLBCL), peripheral T-cell lymphoma, Burkitt’s
lymphoma, mantle cell lymphoma and AIDS-related lymphoma
People with aggressive non-Hodgkin’s lymphomas usually develop
lumps, which may grow quite rapidly. Although these lumps most
often form in the neck, they can occur in other body sites, including
the groin, abdomen, or armpit; on the skin, in the brain, lung, or
bone marrow. By the time the condition is diagnosed, most patients
have widespread disease, with fever, fatigue, weight loss and night
sweats.
The most common aggressive lymphoma is DLBCL, which accounts
for about 30% of new cases of NHL. AIDS-related lymphoma is a
particularly aggressive condition. Burkitt’s lymphoma produces fast-
growing tumours in the abdomen.
17
Precise identification of the form of lymphoma and accurate staging
using cross-sectional imaging is crucial both for choosing the optimum
form of treatment and for monitoring progress. This requires specialist
diagnostic staff and facilities. Most patients are treated on an out-
patient basis with multi-agent chemotherapy over several months, but
those who have very aggressive conditions such as Burkitt’s lymphoma
require in-patient treatment. Radiotherapy may be used to reduce
bulky or localised tumours. About half of the total number of patients
with aggressive lymphomas will need second-line therapy, sometimes
high dose chemotherapy. Several trials are investigating the role of
monoclonal antibodies in the treatment of lymphoma.
Less aggressive (“low-grade” or “indolent”) lymphomas
Indolent, or low-grade, are misleading terms which should not be
taken to mean minor: these diseases are usually incurable and
eventually fatal. However, their rate of progression may be slow, with
median survival periods of up to 10 years for some follicular
lymphomas.8 Like chronic lymphocytic leukaemia (CLL), which can
be classified as a member of this group, these conditions tend to
affect older people. Follicular lymphoma, which accounts for 22% of
all cases of haematological cancer, is the most common form. Others
include Waldenstrom’s lymphoma and marginal zone lymphomas.
Some types of marginal zone lymphoma form in lymph nodes, whilst
others produce tumours outside lymph nodes – for example, on the
skin or in the stomach lining.
The clinical presentation, rate of disease progression and patterns of
treatment vary widely. The disease may continue for a decade or more
and treatment is not always required; watchful waiting, with appropriate
interventions when symptoms develop, is often the best option.
In a small minority of cases, the disease is localised and may be
curable, for example by radiotherapy to a single lymph node. Usually
(in probably 85-90% of cases), the disease has spread by the time of
diagnosis and these patients are not likely to be cured. Nevertheless,
there is much that can be done.
Selecting the most appropriate form of intervention is a complex
decision process that must be re-visited each time the patient relapses.
Once treatment becomes necessary, it is likely to be needed for the rest
of the patient’s life. Most patients are treated with single agent
chemotherapy on an out-patient basis, but some will require regular
supportive treatment such as blood transfusions and plasma exchange
to manage blood abnormalities. There may be multiple episodes of
remission and relapse, and the nature of the disease can change at
relapse – often to a more aggressive form.
8
National Institute for Clinical Excellence. Guidance on the use of rituximab for recurrent
or refractory Stage III or IV follicular non-Hodgkin’s lymphoma. Technology Appraisal
Guidance No. 37. London: NICE, 2002.
18
Patients with extra-nodal forms of NHL – that is, lymphomas that
develop outside lymph nodes, such as those which affect the skin or
intestine – may currently be treated by specialists who deal with that
particular body system, particularly dermatologists and
gastroenterologists. However, since these are systemic diseases, local
treatment is rarely sufficient.
Younger patients who relapse after initial treatment may be offered
high dose therapy, and there are several trials in progress to establish
whether the benefits of such aggressive treatment justify the
difficulties and risks. There are also several on-going trials of
1
monoclonal antibodies such as rituximab. This approach to treatment
is expected to become increasingly important in the future.
Myeloma and monoclonal gammopathy of uncertain
significance (MGUS)
Myeloma causes painful, crippling bone destruction. As the disease
progresses, the bones become very fragile and prone to fracture.
Most patients present with persistent bone pain (usually backache),
general malaise, and symptoms caused by blood abnormalities such
as headaches and bleeding. Destruction of the bones produces high
levels of calcium in the blood, which causes tiredness, thirst, nausea,
and kidney problems. Some patients develop neurological problems
such as spinal cord compression.
Many of these patients may be referred initially to hospital
departments other than haematology – in particular, rheumatology,
orthopaedics, and renal medicine. This may result in considerable
delay in diagnosis. Myeloma is diagnosed by blood tests, examination
of bone marrow, and imaging.
Myeloma is not curable but chemotherapy can often induce temporary
remission. Typically, patients experience repeated periods of relapse,
treatment and remission over the course of some years until the
disease can no longer be controlled. High dose therapy with stem
cell rescue is being increasingly used for those who can tolerate it, to
reduce symptoms and increase survival time.
Patients with myeloma require treatment by a range of specialists,
including haematologists, neurologists, oncologists, orthopaedic
surgeons, pain specialists and renal specialists.
MGUS – monoclonal gammopathy of uncertain significance – is an
abnormality which may be found on blood tests. Of itself, it
produces no symptoms, but it can turn into myeloma or other
haematological malignancies. In many people, MGUS remains stable
and no active treatment is required.
19
Long-term impact of treatment for
haematological cancer
Curative treatments for haematological cancer, particularly intensive or
high dose therapies, can have lasting effects. These include a
markedly increased risk of secondary primary cancers, particularly
among people treated for Hodgkin’s lymphoma. Secondary
leukaemias have been linked with chemotherapy, and solid tumours,
such as breast and lung cancers, with radiotherapy used to treat
leukaemia or lymphoma. All these forms of cancer tend to emerge at
a younger age in long-term survivors of haematological cancer than in
the general population.9
Long-term hormone-related problems are also relatively common.
Most patients will be rendered infertile by treatment for
haematological cancer, and fertility services are important to enable at
least some younger patients to have children.
Epidemiology, causes and trends
As stated earlier, the incidence of haematological malignancy,
particularly NHL, appears to be rising quite rapidly. If this rate of
increase continues, NHL will become one of the most common
cancers in the next few years.10 Although some of this apparent
increase could be due to better case-finding, it is likely that there has
been a real rise in the incidence of haematological cancers.
Environmental pollution – both chemical pollution and radiation – is
believed by many to be the underlying cause of a substantial part of
the rise in these forms of cancer, but there is not yet sufficient reliable
evidence to draw firm conclusions on this.11
Immune system depression, which has been linked with many forms
of haematological cancer, affects increasing numbers of people. This
can be due to diseases such as HIV, to drugs used to prevent rejection
of transplanted organs, or to cytotoxic treatment (chemotherapy or
radiotherapy), especially prolonged treatment with alkylating agents
such as cyclophosphamide. All are becoming more common.
9
This information is derived from studies summarised in Improving Outcomes in
Haematological Cancers, The Research Evidence. Available on the NICE website:
<www.nice.org.uk>
10 Cartwright RA. Non-Hodgkin’s Lymphoma. In Hancock BW, Selby PJ, MacLennon K,
Armitage JO. Malignant Lymphoma. London: Arnold, 2000.
11 Steingraber S. Living downstream: an ecologist looks at cancer and the environment.
London: Virago, 1999.
20
Immunosuppression can also be caused by agricultural and industrial
chemicals, and such chemicals could be responsible for at least some
of the rise in incidence of NHL. There are local excesses of NHL in
rural areas, relatively high incidence rates among farmers and
horticulturalists, and associations between exposure to agricultural
biocides and risk of NHL. However, whilst atrazine, lindane and
phenoxy herbicides such as 2,4D have all been implicated in some
studies, current evidence does not show a clear-cut association
between any specific agricultural chemical and lymphoma.12
Petrochemicals have been linked with various forms of
haematological cancer. Benzene is particularly hazardous; long-term
exposure is known to damage the bone marrow and to cause
myeloid leukaemia.13 These effects are dose-related but sensitivity
varies widely between individuals. Benzene is widespread in the
environment – it is found, for example, in cigarette smoke, engine
exhaust and petrol fumes – but it is not known whether low
concentrations precipitate leukaemia. The risk of acute myeloid
leukaemia is doubled in people who smoke 20 cigarettes daily; about
half of this excess risk can be attributed to the benzene content of
cigarette smoke.14
Exhaust from petrol and diesel engines contains several harmful
chemicals. Exposure to engine exhaust significantly increases the risk
of multiple myeloma, but recent analyses suggest that benzene is not
the causative agent, which remains unknown.15
Associations have also been found between exposure to
tetrachloroethylene, a solvent widely used for dry cleaning and
degreasing, and various forms of cancer including NHL. Although the
published evidence for increased risk of NHL among people working
with tetrachloroethylene is limited to three cohort studies, their results
are consistent. Tetrachloroethylene is known to cause leukaemia in
rats.16
12 Cartwright RA. Non-Hodgkin’s Lymphoma. In Hancock BW, Selby PJ, MacLennon K,
Armitage JO. Malignant Lymphoma. London: Arnold, 2000; pp171 and 173.
13 Rinsky RA, Smith AB, Hornung R, Filloon TG, Young RJ, Okun AH, Landrigan PJ. Benzene
and leukaemia: An epidemiologic risk assessment. New Engl J Med 1987;316:1044-1050.
14 UK Department of the Environment, The effects of benzene on human health. Available at:
<www.defra.gov.uk/environment/airquality/aqs/benzene/6.htm> International Association
for Research into Cancer (IARC) monograph vol. 83 on smoking, available on:
<http://monographs.iarc.fr>
15 Sonoda T, Nagata Y, Mori M, Ishida T, et al. Meta-analysis of multiple myeloma and
benzene exposure. J Epidemiol 2001;11:249-254.
16 International Association for Research into Cancer (IARC) monograph vol. 63 on
tetrachloroethylene, available on <http://monographs.iarc.fr>
21
NHS services for haematological cancers
A range of different levels of service, corresponding with the variety
of forms of disease, is required to manage patients with
haematological cancers. Patients with acute leukaemia may need
repeated periods of intensive in-patient treatment lasting over three or
four months; most will be re-admitted many times over a period of
years. Hospital episode statistics show that haematological cancers
account for about 17,000 in-patient bed days per million population
per year, but the actual figure could be substantially higher than this.
By contrast, patients with conditions at the opposite end of the
spectrum of aggressiveness may need little more than regular
monitoring.
The range of degrees of complexity of hospital treatment may be
summarised as follows; the levels correspond with those specified by
the British Committee for Standardisation in Haematology (BCSH).17
Level 1
Hospitals providing conventional chemotherapy and other
forms of out-patient treatment, using dose levels that
would not be expected to produce prolonged neutropenia.
This level may be subdivided into five types of service:
i.
Out-patient assessment and monitoring.
ii.
Out-patient chemotherapy and haematological
support (e.g. oral chemotherapy for CLL and palliative
interventions for myeloproliferative disorders).
iii.
Day case chemotherapy e.g. for NHL.
iv.
In-patient chemotherapy and palliative treatment, e.g.
for patients with NHL who cannot cope with day case
treatment.
v.
Facilities for management of neutropenic sepsis.
Level 2
Facilities for remission induction in patients with acute
leukaemia, using intensive chemotherapy regimes. This
level of facility is also required to treat patients with
aggressive lymphoma.
Level 3
Facilities for autologous transplantation, using the patient’s
own bone marrow or peripheral blood stem cells.
17 The four levels of care defined by BCSH are described in Guidelines on the provision of
facilities for the care of adult patients with haematological malignancies, available on the
BCSH website at: <www.bcshguidelines.com/pdf/CLH3.pdf>
22
Level 4
Centres with expertise in both autologous and allogeneic
transplantation, which provide bone marrow transplants
from matched donors.
It is believed that over a hundred hospitals in England and Wales
provide treatment at Levels 1 to 2; another 50 carry out autologous
transplantation (Level 3), of which about 30 also carry out allogeneic
transplants (Level 4). Accreditation standards for bone marrow
transplantation (available on www.ebmt.org) specify that any hospital
which offers stem cell rescue – whether autografts or allografts –
should carry out a minimum of 10 procedures of the type offered per
year. Returns to the European Group for Blood and Marrow
Transplantation (EBMT) suggest that this criterion is not met in all
Trusts.18
Complex chemotherapy for induction of remission in acute leukaemia
(Level 2) is just as clinically complex, demanding and risky as
autografting, with treatment-related death-rates of up to 25% in
patients over 60 years old and around 8% in younger patients. This
emphasises the importance of all units performing this work having
sufficient experience, staff, and facilities to deliver these treatments
safely and effectively.
At present, patients with leukaemias and most other forms of
haematological cancer are managed by haematologists. Although
Trusts vary widely, NHS services for patients with leukaemia have
some impressive features. The proportion of patients entered into
clinical trials is high; haematologists are particularly likely to work to
protocols; and follow-up systems are often good. There is a high
level of networking between haematologists, which may be seen as a
rational way of coping with individual lack of specialisation in
haematological malignancy. Pooling knowledge by involvement in
trials, extensive use of protocols and consultation with colleagues
tends to improve the probability that individual patients are offered
the most effective treatment.
Problems are more likely to occur with types of haematological
cancer other than acute leukaemia, where the cause of the symptoms
may be more difficult to identify. The symptom patterns within the
spectrum of haematological malignancy are very variable, so patients
who are not referred directly to a haematologist may take a range of
routes through the system, seeing a series of specialists before a
diagnosis is established.
18 Gratwohl A, Baldomero H, Horisberger B, et al. Current trends in hematopoietic stem cell
transplantation in Europe. Blood 2002;100:2374-2386.
23
Current services are, moreover, very heterogeneous. Although some
parts of England have established formal multi-disciplinary team
(MDT) working, with specified teams for each major form of
haematological cancer, many haematologists in other areas are
accustomed to working without such support; some, indeed, work
effectively single-handed. The level of integration between oncology
and haematology also varies widely and it may not be clear where
responsibility for some patients should lie.
Some specific aspects of NHS services give particular cause for
concern. For example, there is evidence showing an unacceptably
high rate of errors in diagnosis (see Topic 3, Diagnosis and
evaluation). Current diagnostic services fall into four broad
categories:
1.
Fully integrated specialist diagnostic laboratories.
2.
Services spread over different laboratories. Typically, pathology,
haematology and immunology departments share the workload.
With this way of working, the results have to be integrated into
a single interpretative report containing all the information
relevant to the management of the patient, to avoid duplication
and possible contradictions that may arise when key
investigations are carried out in separate laboratories.
3.
Access to some specialist technical services. Many district
general hospital laboratories can carry out a limited range of
diagnostic tests on site, with reports on tissue specimens (e.g.
lymph node biopsies) provided by general pathologists whilst
blood and bone marrow specimens are assessed by the
haematologist who also treats the patients. Some specimens
may be referred to larger centres for specialist investigations.
4.
No access to specialist diagnostic services (this is not believed to
be a common situation).
Even when specialist diagnostic review is available, treatment plans
are not always altered when expert review suggests that an alternative
treatment would be more appropriate. This suggests poor integration
between diagnostic and clinical services.
The level of expertise of clinical staff also varies widely from Trust to
Trust. Patients report excellent services in some hospitals, but
obvious inadequacies – lack of suitably trained nurses, for example –
in others. An adequate service requires high levels of staffing by
nurses and doctors who have sufficient expertise to respond
appropriately to medical crises which may occur at any time without
warning. A single-handed haematologist simply cannot provide this
level of care all the time.
24
Lack of integration between haematology and other clinical disciplines
means that people with haematological malignancies may not have
access to services from which they would benefit. Haematologists
who treat these patients need to be able to work closely with other
disciplines, particularly oncology (including adolescent oncology),
palliative care services and services for the elderly. Such integration
would benefit patients and reduce the load on haematologists.
Commissioning services for
haemato-oncology
All bodies which commission services for patients with
haematological cancers within each cancer network should work
together to ensure that these services function in a co-ordinated way.
Smaller networks may collaborate and pool resources to deliver a full
range of services. These issues are further discussed in Topic 4,
Organisation of specialist services.
25
Access to care
A. Recommendations
1
Urgent (two-week) referral guidelines
The following guidelines for urgent referral have been published by
the Department of Health:19
•
Blood count/film reported as suggestive of acute leukaemia or
chronic myeloid leukaemia;
•
Lymphadenopathy (>1cm) persisting for six weeks;
•
Hepatosplenomegaly;
•
Bone pain associated with anaemia and a raised ESR or plasma
viscosity;
•
Bone x-rays reported as being suggestive of myeloma;
•
Constellation of three or more of the following symptoms:
fatigue, night sweats, weight loss, itching, breathlessness,
bruising, recurrent infections, bone pain.
Patients with these symptoms should be referred to the haemato-
oncology multi-disciplinary team (MDT) without delay (see Topic 4,
Organisation of specialist services). Every hospital which receives
urgent referrals should establish a process to ensure that patients with
lymphadenopathy are seen by designated clinicians.
Routine referral
General practitioners (GPs) should work with specialist clinicians in
the cancer network to produce locally agreed referral guidelines for
haematological malignancies. These guidelines should be designed to
help GPs to identify possible sufferers, give contact details for the
haemato-oncology MDT to which patients with suspected
haematological cancer should be referred, and specify information
required from the referring doctor.
19 Department of Health. Referral Guidelines for Suspected Cancer. Available on:
<www.doh.gov.uk/cancer>.
26
Haematological malignancies tend to cause extreme forms of non-
specific symptoms that may seem common in general practice,
notably unusual tiredness. Patients describe the distressing and
destructive experience of feeling ill for long periods of time,
consulting GPs repeatedly, yet not being taken seriously. This
problem is an understandable consequence of the rarity of these
diseases: an individual GP may only see one new patient with one of
these conditions every two years; and although lymphadenopathy is
common, few patients with lymphadenopathy have cancer.
These conditions can cause a wide variety of symptoms. GPs should
1
consider the possibility of haematological cancer when patients
present with fatigue, night sweats, weight loss, itching in the absence
of a rash, breathlessness, bruising, recurrent infections or persistent
bone pain, and carry out a systematic assessment to check whether
they have other symptoms that might be consistent with such a
diagnosis.
Any patients with unexplained lymphadenopathy (a lump - usually in
the neck but sometimes in the axilla or groin - which persists for
more than six weeks in the absence of signs of infection) should have
a full blood count and should be referred either to a designated
clinician with specific responsibility for investigating lymph nodes, or
to a lump clinic (see below), for assessment within two weeks.
Patients who require biopsies should be referred to designated
surgeons who work with the lymphoma MDT (see Topic 3, Diagnosis
and evaluation). No patient should undergo surgical excision or
biopsy of an enlarged lymph node without preliminary discussion
with a haematologist or oncologist.
GPs should review their threshold for ordering blood counts to detect
haematological malignancy to check that it is in line with current
guidelines. A full blood count should always be carried out if the GP
is suspicious, but a normal blood count should not be taken as
definitive evidence that the patient does not have a haematological
malignancy.
In about three-quarters of cases, chronic lymphocytic leukaemia (CLL)
is diagnosed incidentally, by a blood test taken for reasons other than
suspected haematological malignancy. Such patients should be given
information and reassurance about their condition before referral to a
routine out-patient haematology clinic. Most will never require
treatment.
The range of time-scales over which haematological cancers develop
is wide, but probably fewer than 2% of patients present as
emergencies. These patients usually have acute infections and the
disease is likely to be diagnosed by a blood test at the time of
admission. A patient with acute leukaemia discovered by a blood test
would normally be admitted to hospital within 24 hours.
27
Patients with multiple myeloma may present in a variety of ways.
Early symptoms can include back pain, bone pain, fatigue, anaemia,
infections and kidney problems. Bone pain is the most common
presenting symptom and it is important that GPs should consider this
possibility and order appropriate blood tests and plain x-rays when
they see patients with bone pain and other symptoms that could be
due to myeloma, since non-steroidal anti-inflammatory drugs can
precipitate renal failure in these patients.
In about a third of patients with myeloma, the initial diagnosis is
made by a blood test and such patients come to the attention of
1
haematologists directly; the other two-thirds are referred through
various routes, such as rheumatology, orthopaedic or renal
departments. Any patient who is to have surgery for a lytic lesion
(hole in bone) should first have a test for paraprotein to check for
multiple myeloma.
Investigation of lymphadenopathy
Networks should ensure that adequate rapid access facilities are
available for investigation of lymphadenopathy, with a locally agreed,
specified process that ensures that appropriate investigations are
available quickly. GPs should refer all patients with persistent,
unexplained lymphadenopathy to designated clinicians with specific
responsibility for investigating this particular symptom. Formal lump
clinics may be established to investigate isolated lumps in the neck or
axilla; these would be broadly similar to one-stop breast diagnosis
clinics, but organised collaboratively by haematology, ENT, and
services for head and neck cancer.
Whatever form of organisational structure is used, it should be
designed to facilitate co-operation between designated haematologists,
radiologists, ENT specialists, head and neck surgeons and oncologists
(see lymphoma MDT, Topic 4, Organisation of specialist services),
who should work together to provide an appropriate diagnostic work-
up for patients with lymphadenopathy (see Topic 3, Diagnosis and
evaluation). Patients found to have cancer should be referred
without delay to the appropriate MDT. There should be pre-booking
systems for appointments at results clinics at which each patient with
a diagnosis of cancer would be seen by a senior member of the MDT
which deals with that type of cancer, and where support would be
available from a clinical nurse specialist.
Networks should agree local clinical guidelines designed to ensure
that patients who are seen initially in dermatology departments or
who present with gastro-intestinal or chest symptoms, but who are
found to have lymphomas, are referred without delay to the
haematological cancer team. Implementation of these guidelines
should be audited.
28
No definitive treatment should be given for haematological cancer,
with the exception of highly aggressive conditions such as Burkitt’s
lymphoma or acute leukaemia, without discussion by the appropriate
MDT. If such treatment is given, it should be discussed by the MDT
at the earliest opportunity.
B. Anticipated benefits
Implementation of these recommendations should lead to improved
detection of possible haematological cancer in primary care and more
1
appropriate referral of patients. This will reduce delays in diagnosis,
so that patients can be offered suitable treatment more quickly.
There is considerable anecdotal evidence that people who go through
ENT services but are found to have lymphomas may wait for long
periods before receiving appropriate treatment.
A significant proportion of patients with unexplained and persistent
lumps in the neck or axilla have malignant disease, often lymphoma.
Rapid-access lump clinics can offer an efficient route to treatment
both for patients with lymphomas and for those with head and neck
cancers.
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
Patient surveys suggest that a substantial proportion of people feel
unwell for long periods and consult their GPs repeatedly before
appropriate investigations are carried out to diagnose haematological
malignancy.(C) Delays in diagnosis do not seem to affect long-term
outcomes in lymphoma but the level of any potential risk posed by
delay is likely to depend on the nature of the disease. Shorter delays
appear to be associated with worse prognosis because more
aggressive disease is diagnosed more quickly; so evidence suggesting
no relationship between delay in diagnosis or treatment and clinical
outcomes may be misleading.
The NHS National Patient Survey reported that 68% of patients with
NHL were given a hospital appointment within a month of consulting
their GPs, and 43% were seen within two weeks. However, 6% had
to wait more than six months, and 41% said that their condition had
deteriorated while they waited for an appointment. The majority of
patients were told the diagnosis at, or before, their first hospital
appointment, but 25% had to wait another two weeks or more. The
29
delay before treatment began was also long for some patients – 13%
waited seven months or more after their first hospital appointment.20
A study of 89 patients with lymphomas from four UK centres between
1997 and 1999 found that the average delay between the onset of
symptoms and the beginning of treatment was 7.5 months. The largest
single component was delay by the patients themselves – on average,
nearly four months. The mean period between initial consultation
and diagnosis (diagnostic delay) was 2.8 months, the greatest part of
which occurred between the initial appointment and biopsy.(B)
1
Both patients and GPs report high levels of satisfaction with one-stop
diagnostic clinics. These allow initial investigations to be carried out
over a short time-period, thus reducing patient uncertainty and
diagnostic delay, and can help to rationalise referral patterns.(B)
Advantages of this arrangement include high levels of patient and GP
satisfaction and the capacity to screen out benign conditions and
epithelial cancers. Data from an established lymph node diagnostic
clinic at the Royal Marsden Hospital in London, to which patients are
directly referred by GPs, shows that median time from initial referral
to diagnosis of malignancy was three weeks. 12% of these patients
were found to have lymphomas. 46% of the patients referred by GPs
or hospital departments to a dedicated clinic for investigation of neck
masses at Wexham Park Hospital, Slough, had enlarged lymph nodes.
Of these, 7% had lymphoma and 22% had squamous cell
carcinoma.(B)
D. Measurement
Structure
•
Referral guidelines for GPs, agreed across the network, which
specify named clinicians to whom, or clinics to which, patients
with possible or suspected haematological cancer should be
referred.
•
Local clinical guidelines which specify that patients who present
with gastro-intestinal, chest or dermatological symptoms, but
who are found to have lymphomas, should be quickly referred
to an appropriate haematological cancer MDT when the
diagnosis is established.
20 Airey C, Becher H, Erens B, Fuller E. National Surveys of NHS Patients: Cancer, National
Overview 1999/2000. London: Department of Health, 2002.
30
•
Facilities for rapid investigation of lymphadenopathy. These
may be:
either: specific clinics for rapid investigation of lymphadenopathy
(rapid-access lump clinics at cancer units), staffed by designated
clinicians who work in haematology and/or oncology,
or: designated clinicians with close links with haematology
and/or oncology, who take responsibility for prompt and
appropriate investigation of lymphadenopathy.
1
•
Designated surgeons, who work with the clinicians or clinics
described above, who carry out lymph node biopsies within an
agreed time and refer patients with suspected haematological
cancer to the appropriate haemato-oncology MDT.
Process
•
Audit of time from first GP consultation with symptoms of
cancer to referral.
•
Audit of time from referral to diagnosis; this should be less than
four weeks.
•
Audit of patient pathways against guidelines which specify
referral patterns for patients with haematological cancer,
particularly those whose presenting symptoms affect the gastro-
intestinal tract, chest or skin.
Outcome
•
Patient satisfaction.
E. Resource implications
Improving access to appropriate diagnostic clinics for patients with
possible symptoms of haematological cancer is likely to involve
streamlining the current service. These patients are already in the
hospital system, so these resources will, to a large extent, already be
available. It should, therefore, be possible to implement the
recommendations in this topic area by re-organising the use of
existing resources.
31
Patient-centred care
It is planned that the National Institute for Clinical Excellence (NICE)
guidance on improving supportive and palliative care for adults with
cancer will be published early in 2004. This guidance is intended to
complement this manual, giving detailed and specific
recommendations on many of the issues introduced in this section as
2
they apply to cancer care generally, with supporting evidence. It will
cover the following topic areas:
•
Co-ordination of care;
•
Face-to-face communication;
•
Information;
•
Psychological support services;
•
Specialist palliative care services;
•
General palliative care services;
•
Social support services;
•
Rehabilitation services;
•
Complementary therapy services;
•
Spiritual support services;
•
Carer and bereavement support services;
•
User involvement.
32
A. Recommendations
Clinical nurse specialists
Clinical nurse specialists should be available to provide support for
patients with haematological cancer. These nurses should have
specific training in communication, counselling and ethics; they
should be full members of haematological cancer multi-disciplinary
teams (MDTs), with specific responsibility for facilitating the provision
of patient-centred care and the involvement, as necessary, of other
professionals. They will provide information and support for patients
and help other clinical staff to acknowledge and give full
consideration to individual patients’ perspectives. (See Topic 4,
Organisation of specialist services.)
2
From the time of diagnosis, each patient should have access to a
specific clinical nurse specialist who can offer psychosocial support
and continuity of care. Each patient and his/her carer should be
given a telephone number so that they can contact this nurse when
they feel they need information, help or support. Whilst most people
with cancer are primarily concerned that their chances of survival
should be maximised through appropriate treatment, it is important
that their other needs are also recognised and met. These include
emotional and practical needs, and may range from simple human
contact and reassurance to help and advice on practical issues such as
getting appropriate and acceptable food in hospital.
The counselling role of the clinical nurse specialist is likely to be
particularly important in haematological cancer. For some patients,
the balance between the potential survival benefits of treatment and
the risk and suffering that the process may entail is such that the
decision about whether to go through with it is very difficult. For
others, such as older patients with acute leukaemia, and those for
whom repeated efforts to control the disease have failed, the risks of
intensive treatment may make it inadvisable. In these cases, in
particular, counselling by a clinical nurse specialist who understands
both the nature of the disease and the dilemma faced by the patient,
and with whom patients and carers feel they can talk freely, can be
especially valuable.
Information for patients
A recurring theme in patients’ experiences of services for
haematological cancer is lack of information: first about their
diagnosis, and later about what may happen to them. Effective
systems should be established to ensure that clear, honest and
consistent information is given to patients from the outset.
33
Clinical nurse specialists can play crucial roles in ensuring that
patients and carers understand both what is happening to them and
what is likely to happen as they progress through the various phases
of their illness and treatment, but all those involved in caring for these
patients should adopt an attitude of openness and willingness to
share information.
The consultation at which patients learn that they have cancer is a
crucial event. Sensitive and compassionate communication is
essential. This is, literally, a life-changing experience for patients.21
Although factual details may be forgotten, the way the news that they
have cancer is broken is often remembered with great clarity; it
colours later relationships with health professionals, establishing either
trust or deep resentment. In haematological cancer, there is often
2
more than one “bad news” consultation during the course of the
disease.
Patients should be encouraged to bring a close friend or relative to
“bad news” consultations. The consultation should be held in a
private room by a senior clinician, preferably the individual who will
be responsible for the patient’s future care. Adequate time should be
allowed for explanation and there should be no interruptions.
The nurse specialist should be present during this consultation and
should remain with the patient afterwards to offer support and further
information tailored to individual needs. Other people, such as
students, should only be present with the patient’s explicit consent.
All clinicians, particularly those in senior positions, should have
specific training in communication skills. Such training should also be
available for other health professionals who have responsibility for
face-to-face care.
When there is a choice between different therapeutic approaches,
patients should be offered the opportunity to discuss the options in a
joint meeting with the clinicians who would be responsible for their
treatment and the specialist nurse. Providers should ask patients if
they want additional information and seek to discover how much they
wish to be involved in discussions about treatment. If there is
uncertainty about what treatment might be necessary, patients should
be given realistic information about the different possibilities.
Clinicians should tell patients as early as possible if they have reason
to believe that successive courses of treatment will be required, that
recovery could entail an extended period of time, or that the disease
is incurable.
21 National Cancer Alliance. Patients’ views of haematological cancer services and the draft
national haematological cancer guidance. April 2001, p 17.
34
It is important that patients’ views about treatment are respected.
Different individuals vary widely in their attitudes and in their
willingness to tolerate cancer treatment, and their views may change
from time to time. Some would choose the chance of extended
survival at almost any cost, some would rather die of their disease
than undergo intensive therapy, and others may choose to defer
radical treatment until after what they regard as a crucial life priority
such as having a baby.
Patients should be offered as much information about their disease
and its treatment as they wish to have, in forms they can use and
language they are likely to understand, and at a rate they can
assimilate. Doctors should ask patients what they want to know and
about their concerns, and check that they understand what they have
2
been told. Patients often find it difficult to take in information given
during the consultation, so they should be offered a record in writing
(which could take the form of a copy of a letter to their GP) or on
audiotape. Patients must be offered copies of letters written about
them to their GPs.
Patients should receive both individual support and guidance from
members of the MDT and well-produced information leaflets.22 They
should be encouraged to return to MDT members for additional
information and clarification when they want it. Written information
should be consistent across each network.
Patients should be given an outline of their overall treatment plan as
soon as the necessary clinical decisions have been made, and told of
the probable and potential time-scales. Clinicians should not seek to
minimise the impact of the treatments they offer, nor the length of
time required for recovery from treatment. They should do their best
to explain clearly what is happening at each point in the patient’s
journey, to be honest about uncertainty and the risk that treatment
might do more harm than good, and to make sure the patient
understands when treatment can only be expected to produce
temporary remission.
When English is not the patient’s first language, somebody who
speaks the patient’s language should be available to facilitate
communication. Providers should not normally expect members of
the patient’s family to act as interpreters.
22 Sources of information for patients with cancer can be found on the NHS Direct website
at: <www.nhsdirect.nhs.uk> telephone advice is available from NHS Direct on 0845 4647.
35
Information offered to patients should include:
•
Sufficient information about basic anatomy and pathology for
patients and their carers to understand the disease and how it
might affect them;
•
Realistic information about the disease and the range of
individual variation in its impact and rate of progression;
•
The aims, risks and likely effects of proposed diagnostic
procedures. Each procedure should be explained to the patient
before it is undertaken;
•
Balanced information with clear explanations about potential
2
treatment options, including the probability of improved survival
or symptom reduction (and uncertainties about benefits), known
risks and potential short- and long-term adverse effects;
•
Information about other potential effects of the illness and its
treatment on both patients and carers, such as anxiety and
depression;
•
The likelihood of long-term continuing contact with the
haematological cancer team;
•
Reasons for not offering interventions which patients might
anticipate.
Patients should also be given clear information about the hospital
service. This should include:
•
A description of the way the clinics and doctors function
together;
•
The way the appointments system operates;
•
The names of members of the MDT responsible for managing
the patient, and their different responsibilities;
•
Contact details for people with whom patients or carers can talk
if they feel concerned about any aspect of the illness, treatment,
or hospital service.
All health professionals involved with each patient should know what
information has been given to the patient. A record of this, along
with the patient’s preferences for information and involvement in
decision making and a comprehensive summary of the management
plan, should be included in the notes. This information should also
be given to the patient’s GP within 24 hours so that primary care staff
can provide additional support for patients and carers.
36
Fertility issues
Each network should agree policies on fertility issues.23 These should
include training for clinical nurse specialists in counselling patients
who could lose their fertility after treatment, and arrangements for
cryopreservation of sperm. Whenever possible, patients of
reproductive age should have specialist advice on the implications of
treatment for their fertility before treatment begins.
Practical and social support
Haematological malignancies often cause long periods of illness,
during which many patients are dependent on benefits. Nurse
specialists, primary care and palliative care teams all have important
roles in co-ordination with social services to ensure that the needs of
both patients and carers are identified and met. Patients and carers
2
should be given information about sources of help, such as local and
national services and support groups and disability and benefits
helplines, both verbally and in writing. Advice on benefits and help
with application forms should be available from someone who is
familiar with the benefits system.
Nutritional and dietetic support
Intensive treatment for haematological cancers causes problems with
nutrition. This issue is particularly important for patients who may
remain in hospital for weeks or months at a time. Providers should
ensure that patients receive specialist dietetic and nutritional support
and high-quality food that meets their individual needs and is
acceptable in the context of their ethical or religious beliefs. Dietetic
support should also be available after discharge, if required.
Physiotherapy and occupational therapy
Haematological cancer and its treatment can cause disability, fatigue,
weakness and loss of muscle, reduced exercise tolerance, pain and
respiratory disorders. Patients should have access to specialist
physiotherapists and occupational therapists who understand the disease
process and can provide appropriate and effective care, e.g. aids and
adaptations; advice on coping with the practical elements of disability.
B. Anticipated benefits
Provision of patient-centred, holistic care and clear and timely
information can help patients to cope with their disease, enhance
satisfaction with services, and reduce criticism and complaints.
Information has a variety of benefits for cancer patients, particularly
anxiety reduction, improved ability to cope with treatment and better
self-care.
23 Joint Council for Clinical Oncology. Management of gonadal toxicity resulting from the
treatment of adult cancer: Report of a working party for the Joint Council for Clinical
Oncology. London: Royal College of Physicians/Royal College of Radiologists, 1998.
37
Good communication – particularly sensitive delivery of bad news –
is appreciated by patients and leads to greater satisfaction with care.
But improving communication skills also benefits doctors, enhancing
job satisfaction and reducing stress. Effective communication tends to
heighten awareness of the various needs - whether medical, practical,
physical or psychological - of patients and carers, and increases the
probability that these needs can be met.
The application of Trust guidelines on obtaining and documenting
informed consent may facilitate the audit of process within networks.
C. Evidence
2
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
To inform this guidance manual, the National Cancer Alliance (NCA)
used focus group discussion and written submissions to explore the
feelings and experiences of patients who had been treated for
haematological cancers.24 The NCA report shows that health care
professionals often fail to provide the information that patients want
and that many are not honest about the likely effects of treatment on
patients’ lives.
Patients reported that they would have liked to know how long the
full course of treatment would take, and what it might involve, early
on in the process. Clinicians tended to minimise the impact of
treatment, using phrases like “a bit of radiotherapy” when referring to
daily treatment over a month. A patient who reported being told by
her consultant that, “ ‘We might do a bit of a transplant’,” said, “that
‘bit of a transplant’ has taken a year out of my life and I would like to
have known before.”25
In the focus group, patients explained that they needed information
about treatment effects, duration and potential consequences in order
to prepare themselves for the ordeal ahead, plan their lives, and
arrange for support for the whole course of their cancer journey. All
said that a copy of their treatment plan would have been helpful.
Several patients mentioned problems with hospital food and with
inadequately trained nurses on non-specialist wards.
24 National Cancer Alliance. Patients’ views of haematological cancer services and the draft
national haematological cancer guidance. April, 2001.
25 Ibid, p 26.
38
The National Patient Survey suggests that there may be particular
problems with information for patients with non-Hodgkin’s lymphoma
(NHL).26 These patients were more likely to report that they did not
completely understand the diagnosis than were patients with common
solid tumours (30% versus 17% for all patients), less likely to
understand the purpose of diagnostic tests (65% understood, versus
75% of all patients), and less likely to realise that different types of
treatment were available (59% versus 66%). 25% of patients did not
completely understand the purpose of their treatment and 32% did not
know how well their treatment had gone. 18% would have preferred
more information about the outcome of their treatment.(C) There
appear to be few high-quality research studies focusing specifically on
non-medical issues or psychosocial interventions for patients with
haematological cancers. Evidence reviews carried out for previous
2
documents in this series are, however, relevant. Summaries of studies
showing patients’ desire for clear information, the need for health
service professionals to have specific training in communication skills,
and patients’ continuing need for psychological, social and practical
support, are available in the Improving Outcomes series.27
The review did not assess studies describing the specific role of
clinical nurse specialists in haematological cancer. There are studies
of such nurses working with patients with other types of cancer,
notably breast; this role was, after all, developed in the context of
breast care services. It seems that care from specialist nurses is
generally valued by patients, and that contact with such nurses can
improve both physical and emotional well-being of patients.(A)
An analysis of the working practices of three cancer support nurses in
the UK describes their role and the types of problem with which they
assist. They report that psychological morbidity and social isolation
are particularly common among patients with cancer. Cancer support
nurses facilitate good communication amongst those responsible for
delivering care and ensure a prompt response to patients’ needs.(B)
A report of a small uncontrolled observational study of an emotional
support course (“Taking Control”) for patients with haematological
cancer suggests that the majority of participants responded very
positively. Although a minority (about 10%) reported some
discomfort – usually because they had to face information that they
had not wanted to acknowledge – most found that the course helped
them to cope emotionally with their situation and helped them to
think more positively. Meeting others with haematological cancer on
the course helped them to ‘feel normal’. Fifteen of the 26 participants
26 Airey C, Becher H, Erens B, Fuller E. National Surveys of NHS Patients: Cancer, National
Overview 1999/2000. London: Department of Health, 2002.
27 Improving outcomes in breast cancer and Improving outcomes in urological cancers are
available on the NICE website <www.nice.org.uk>; earlier documents dealing with other
common cancer sites can be found at: <www.doh.gov.uk/cancer>
39
who completed the post-course questionnaire said that what they had
learnt had been translated into behavioural changes.(B)
Where structured interventions such as this are not available, support
groups can facilitate interaction between patients with cancer. But
fewer than half of the NHS patients with NHL who took part in the
National Patient Survey were told about support or self-help groups.28
An older (1983) study reported on two small randomised controlled
trials (RCTs), run concurrently with patients with Hodgkin’s
lymphoma. One compared the effects of written educational material
about the disease (a booklet and newsletters) with no educational
material and found that patients’ knowledge was improved by the
intervention. This was associated with additional benefits including
2
significantly reduced anxiety and fewer treatment problems. The
other RCT assessed the effects of participation in eight meetings with a
peer support group designed to stimulate discussion, which was
attended by an oncologist, psychologist and social worker who took
non-directive roles. The peer support group did not appear to
produce any significant benefits.(A)
Telephone services that allow patients with cancer (or their carers) to
get help and advice with the problems they face at home are
appreciated and can be successfully run by trained oncology
nurses.(B) The majority of calls are for information and are fairly
short; only a minority require further action.
These studies suggest that information is beneficial for patients but that
talking about problems without being offered solutions is not helpful.
A longitudinal uncontrolled study, which included 22 leukaemia
patients who received psychotherapeutic interventions including
training in coping strategies and stress management, found significant
decreases in anxiety and depression.(B) However, it is not possible
to judge the effectiveness of the various components of what appears
to be a complex intervention.
An RCT from the US comparing “treatment as usual” with therapist
support, relaxation and imagery training and cognitive-behavioural
therapy for 94 patients with haematological cancers undergoing bone
marrow transplantation reported no significant differences in outcomes
between the interventions. No meaningful comparisons were made
between “treatment as usual” and the various psychotherapeutic
interventions so it is not possible to judge their effectiveness.(B)
28 Airey C, Becher, H, Erens B, Fuller E. National Surveys of NHS Patients: Cancer, National
Overview 1999/2000. London: Department of Health, 2002.
40
Various other authors describe psychotherapy services and
interventions for patients with haematological cancers, but none
provides reliable information on their effectiveness or
appropriateness.(B) They appear to assume that such interventions
are worthwhile.
There is a substantial body of research dealing with communication,
information, psychotherapeutic and other non-medical aspects of care
for patients with cancer. This literature does not focus specifically on
the needs of patients with haematological cancers but the findings
may be generalised to this group. Reviews of these aspects of
patient-centred care are summarised in other documents in the
Improving Outcomes series, available on the NICE and Department of
Health websites, and in Improving supportive and palliative care for
2
adults with cancer, planned to be published by NICE early in 2004. A
clear, evidence-based discussion of communication skills and how
they may be acquired has recently been published in the British
Medical Journal.29
D. Measurement
Structure
•
Availability of clear information for patients in appropriate forms
and languages, about their disease, proposed treatment and how
its effects might be managed, the hospital and MDT responsible
for their care, and any services and sources of support that are
likely to be appropriate.
•
Clinical nurse specialists who have had training in counselling
patients with haematological cancer.
•
Facilities and expertise for counselling patients about fertility
issues.
•
Facilities and support for patients’ mutual support groups.
Process
•
Attendance by clinicians (including consultants) at training
courses in communication skills.
•
Private rooms used for crucial meetings between health care staff
and patients (in particular, consultations at which patients are
given bad news).
29 Maguire P, Pitceathly C. Key communication skills and how to acquire them. BMJ
2002;325:697-700.
41
•
Audit of information offered when:
•
The patient is given bad news;
•
The patient is to undergo a potentially unpleasant
diagnostic procedure;
•
Decisions need to be made about treatment;
•
The patient is about to start a course of treatment.
•
Audit of patients’ and carers’ experience of psychological
support by suitably trained staff from the time of diagnosis and
at each subsequent stage of their journey through the illness.
2
•
Evidence that every patient has access to a named nurse
specialist who knows about his or her condition, who offers
advice and can arrange meetings with appropriate health or
social services staff when required.
•
Audit of the proportion of staff involved in direct patient care
who have had specific training in communication and
counselling skills.
•
Record of discussion with patients of information given and
patient’s involvement in decision-making about care.
•
Evidence of effective user involvement.
•
Audit of assessment for, and provision of, physical, practical and
social support.
Outcome
•
Providers should carry out surveys of patients’ experience to
assess the adequacy of each component of patient-centred care.
This should include the following:
•
Patients’ knowledge about resources relevant to them;
•
Their views on information they were given and the way it
was communicated;
•
Whether they felt able to participate (if they wished to do
so) in choosing between treatment options;
•
Whether patients felt that they had been offered sufficient
information to give informed consent to each intervention;
•
Quality of care and pain control;
42
•
Adequacy of nutritional support and food available,
especially for patients with eating problems;
•
Waiting times;
•
Adequacy of support for patients in their homes
(occupational therapy);
•
Transport arrangements.
E. Resource implications
2
Additional resources may be necessary for the provision of high-
quality information and educational material for patients and carers,
and to allow staff time and facilities for talking with patients and
carers.
Resources will be required for training, both for clinical nurse
specialists and to improve the communication skills of other health
professionals, including senior medical staff.
The main costs of improving patient-centred care in line with these
recommendations will be for training and employing more clinical
nurse specialists. It is estimated that about four new posts will be
required per typical cancer network serving 1.5 million people –
altogether, around 140 additional clinical nurse specialists for England
and Wales, at an estimated total cost of £4.6 million (see Appendix 1,
Economic implications of the guidance).
43
Diagnosis and
evaluation
The Department of Health is developing guidance on modernising
pathology services which supports the development of clinical
networks in pathology across a number of Trusts, to build capacity,
reduce fragmentation, and provide an enhanced level of equipment
and expertise.30 The recommendations below are consistent with this
strategy.
Improving the consistency and accuracy of diagnosis is probably the
3
single most important aspect of improving outcomes in
haematological cancer. Specialist pathology services should be
specifically designed to integrate with, and support, clinical haemato-
oncology. In order for this to work in practice, the following
structures and systems need to be established:
•
Haemato-oncology multi-disciplinary teams (MDTs), described in
the next chapter of this manual. These should include haemato-
pathologists, i.e. specialists in the diagnosis of haematological
malignancy who may come from a range of backgrounds;
•
All haemato-oncology MDTs should have adequate facilities for
rapid and accurate assessment of cellular morphology of blood
samples;
•
Effective systems for collecting suitable fresh tissue samples and
transporting them rapidly to specialist pathology facilities;
•
Access to accurate immunophenotyping, molecular biology, and
identification of genetic abnormalities. Immunophenotyping,
molecular biology and cytogenetics require specialist services;
•
Regularly updated computer software designed to support
precise identification of haematological malignancies. This
software should generate worksheets and instructions on an
appropriate sequence of diagnostic tests;31
30 The Department of Health has published its response to the consultation on its draft
guidance <www.doh.gov.uk/pathologymodernisation>, and the final guidance will be
published in 2003.
31 It is hoped that this software will shortly become available on the net.
44
•
Access to appropriate imaging facilities. Imaging requirements
for assessment of specific types of haematological cancer are
discussed below;
•
Arrangements to allow expert pathologists and radiologists to
share and discuss diagnostic information in meetings of MDTs
responsible for developing treatment plans for individual
patients. Teleconferencing systems may be established to
facilitate such discussion when geography makes it difficult for
crucial specialists to attend MDT meetings in person.
A. Recommendations
Haemato-pathology services should be organised at network level.
Smaller networks may collaborate to provide joint services and
3
achieve economies of scale.
Two levels of haemato-pathological service are required: a local
service, as exists at present in most district general hospitals and
cancer units, which provides initial assessment of specimens and
appropriate referral to a specialist service, which is likely to serve one
or more networks.
Involvement in external quality assurance (EQA) is necessary at both
levels. Haemato-pathologists should participate in EQA schemes,
which should normally be co-ordinated at national level, although
some may be best operated on a regional basis. All laboratories
should be covered by Clinical Pathology Accreditation (UK) Ltd (CPA)
accreditation.
Each diagnostic laboratory should serve as large a population base as
can be achieved without sacrificing personal involvement of specialist
laboratory-based haemato-pathologists in the haemato-oncology MDTs
with which they work.32 Trusts should identify clear pathways to
ensure that all samples are sent to specified laboratories which have
clearly defined arrangements for synthesis of laboratory and clinical
information at MDT meetings.
Tissue samples from all patients with possible or definite diagnoses of
haematological malignancy should be assessed by specialist haemato-
pathologists. A specified range of tests should be carried out on each
sample in a systematic way, following protocols which define both
the order and choice of tests.
32 Experience at Leeds demonstrates that this personal contact is possible even when the
specialist haematology pathology service serves a population base of over three million,
part urban and part rural.
45
Haemato-pathologists should keep records of all samples where
cancer is found and take responsibility for ensuring that each one of
these patients is discussed in an appropriate MDT meeting. An
accurate diagnosis should be established for every patient, according
to an appropriate clinical protocol.
Leukaemia
The initial diagnosis is likely to be made by examination of blood
films by a local haematologist. A member of a leukaemia MDT
should take immediate responsibility for managing any patient who
appears to have leukaemia and a blood specimen should be sent to
the specialist pathology laboratory for further assessment. Bone
marrow samples are likely to be required for precise assessment of
the disease.
Patients with acute leukaemia are likely to require treatment before a
precise diagnosis is available, but their management should be
3
discussed at the earliest possible meeting of the leukaemia MDT and
reviewed when a complete pathological assessment, including
molecular analysis, has been carried out.
Lymphoma
Achieving a precise diagnosis of lymphoma and making decisions
about appropriate treatment can be complex. It requires the same
level of haemato-pathological expertise as leukaemia, plus additional
input from other specialists. These are listed in the lymphoma MDT,
described in the next chapter of this manual.
Pathological diagnosis
Biopsy is required for pathological investigation of persistent lumps in
lymph nodes or abnormalities in other tissues that may be caused by
lymphoma. Specific ENT or head and neck surgeons should be
nominated to do lymph node biopsies within an agreed time and
send suitable specimens to be assessed by designated specialist
pathologists who work with lymphoma MDTs.
If clinical signs or the patient’s history (particularly smoking) suggest
that cancer originating outside the lymph node could be the cause of
the lump, this possibility should be investigated first, using endoscopy
of the upper aerodigestive tract and fine needle aspiration or core
biopsy of the lump. Only when this diagnosis has been excluded
should the affected node be removed. It should then be delivered
fresh to a specialised haemato-pathology laboratory.
46
Pathologists who assess lymphoma specimens should discuss their
findings with the MDT responsible for managing the patient, so that
clinical, laboratory and imaging information can be integrated in the
context of the MDT meeting. Treatment for lymphoma should ideally
be deferred until a definitive diagnosis is available. If treatment has
begun, it should be reviewed by the MDT in the light of detailed
diagnostic information.
Imaging
Imaging is essential to staging lymphoma. Clinical policies for the
co-ordinated use of appropriate imaging when required for patients
with lymphoma should be agreed at network level by all the
lymphoma MDTs in the network. Cross-sectional computed
tomography (CT) should be available without delay for planning
treatment, both initially to judge the extent of the disease, and after
treatment to assess residual disease. Magnetic resonance imaging
(MRI) is not routinely used in lymphoma, although it may be
3
required in specific clinical situations such as cranial disease.
Positron emission tomography (PET) scanning may be considered, if
available, for discriminating between residual lymphoma and fibrotic
tissue after chemotherapy, but further research is necessary to
determine its cost and utility in relation to other forms of imaging.
When carried out in centres with a high level of expertise, gallium
scanning can be a useful adjunct to CT.
Myeloma
Myeloma produces characteristic proteins which can be detected in
the serum and sometimes, the urine of patients. Staging and
decisions about treatment require information derived from the
clinical picture (including assessment of renal function), bone
marrow, and imaging.33 Plain x-rays should be used for all patients;
MRI should not be used routinely because its potential value for
informing decisions about management is unclear, but may be
appropriate in particular circumstances, for example to assess
possible spinal cord compression.
33 Guidelines developed by BCSH/UKMF on the diagnosis and management of multiple
myeloma are available on the net at: <www.ukmf.org.uk/guidelines.shtml>
47
B. Anticipated benefits
Expert review of pathology improves diagnostic accuracy. There is
evidence (see below) that up to 5% of people treated for lymphoma
in Wales actually have benign disease, and the situation is likely to be
much the same in England. This means that every year, 400 people
may suffer the distress and upheaval of a cancer diagnosis and
undergo risky treatment unnecessarily. Many more patients – at least
10% – receive sub-optimal treatment because their disease is classified
incorrectly. At a unit cost of £100-£150,34 the financial cost of a
precise diagnosis is a small fraction of the cost of treatment; and the
human cost of error can be enormous.
Once established, integrated diagnostic facilities for haematological
malignancies are likely to be highly cost-effective. Rational selection
of diagnostic tests, following precisely defined protocols, can
3
conserve resources by ensuring that only those tests that may yield
useful information about each particular patient are carried out.
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
Accuracy of diagnosis in lymphoma and leukaemia
There is consistent evidence from audit and similar studies, both of a
high level of inaccuracy in diagnosis, and that specialist pathological
review of diagnostic reports on haematological malignancies improves
accuracy. The level of major discrepancies between diagnoses made
by local clinicians and specialists – generally around a quarter of
lymphoma reports reviewed – is broadly similar in most studies.(B)
A report from the US suggests that similar problems arise in the
diagnosis of acute leukaemias.
Examples from the UK include the following:
•
In Wales, the first two years of central review of lymphoma
pathology (1998-2000) revealed major diagnostic discordance for
over 20% of 275 lymph nodes. In five cases judged by the
expert panel to be lymphoma, the district hospital diagnosed a
benign condition. Thirteen patients with benign conditions and
four with non-haematological cancers were given diagnoses of
lymphoma by local clinicians. Fifteen diagnoses were changed
from non-Hodgkin’s lymphoma (NHL) to Hodgkin’s lymphoma
34 Unit cost per specimen in Yorkshire, where the diagnostic facility serves a population of
3-4 million.
48
or vice versa. Sixteen patients with NHL were assigned to a
different prognostic group. In addition, in 21% of cases, the
submitted diagnosis was lymphoma but no REAL classification
was given. The central review group produced definitive
diagnoses in 95% of these cases.
A follow-up study using case notes from a random sample of 33
patients whose diagnosis had been changed revealed that the
management strategy should have been changed for half of this
group (17 cases). In practice, first-line treatment was altered for
12 patients;
•
There was diagnostic disagreement between a Lancashire
hospital and a regional oncology centre in nearly a quarter of
lymphoma pathology reports. 36% of the discrepancies were
considered to be major;
3
•
Audit by a specialist centre of 100 lymph node biopsies from
hospitals in north east England found diagnostic discrepancies
that would have changed management in 26% of cases;
•
In suspected Hodgkin’s lymphoma, 94% of diagnoses reviewed
by the Scottish and Newcastle Lymphoma Group were
confirmed but histological sub-typing was altered in 28% of 574
cases with initial sub-type information. This resulted in a
change of management for 10% of patients.
Problems have also been found in the interpretation of radiological
images by local clinicians. An audit of CT scans referred to a
regional oncology centre for a second opinion found fundamental
differences in the interpretation of CT findings for 34% of 124
patients. In most cases, more disease was found. Specialist review
had little impact on actual patient management, however; in 27% of
cases, treatment decisions had been made before the review was
requested.
Effectiveness of imaging
PET and gallium scanning for lymphoma
PET appears to be particularly effective for discriminating between
residual lymphoma and fibrotic tissue in patients who have been
treated with chemotherapy. It is more sensitive than gallium
scanning and is especially useful for showing when lymphoma has
not been successfully eradicated. Gallium scanning is more effective
than CT scanning for revealing residual lymphoma but can have a
moderate false negative rate, particularly in centres with less
expertise.(B)
49
MRI for detection of bone lesions in multiple myeloma
There is no evidence that routine use of MRI provides information
that is useful for decision-making about the treatment of patients with
myeloma. In asymptomatic stage I disease, MRI can reveal bone
marrow lesions that are not detected by other means, but it is not
clear how this information might affect patient management.
D. Measurement
Structure
•
Availability of specialist diagnostic laboratories.
•
Systems for rapid and efficient communication between
specialist pathologists, local haematologists and oncologists, and
3
haematological cancer MDTs.
•
Arrangements for rapid transfer of fresh biopsy specimens to
designated haemato-pathologists who assess the samples without
delay and arrange specialised pathological review.
Process
•
Time from GP referral to specialist diagnosis.
•
Time between lymph node biopsy and availability of detailed
pathology report (this should not be more than two weeks).
•
Time between initial clinic assessment of patients with suspected
lymphoma or myeloma and availability of imaging results.
Outcome
•
Audit of accuracy of diagnosis.
•
Audit of appropriateness of lymph node biopsy.
50
E. Resource implications
A minority of cancer networks in England already have centralised or
partly centralised specialist diagnostic services, but most will have to
create such services from scratch, at a cost of about £230,000 for an
average network (1.5 million people). Overall, the estimated setting
up costs for such services are around £5.8 million, with annual
running costs of about £7.5 million. There are substantial economies
of scale, so the actual costs will depend on the size of population
served. (See Appendix 1, Economic implications of the guidance.)
The situation in Wales differs from that in England, in that the All
Wales Lymphoma Pathology Review Service has secured funding for
specialist diagnostic review for all new cases of lymphoma. The All
Wales Lymphoma Panel audit found a diagnostic error rate of 17% in
lymphoma diagnosis without specialist review; it is believed that the
current cost of inappropriate treatment associated with misdiagnosis is
3
around £200,000 per year. In addition, there are huge potential
medico-legal costs.
Cost savings from avoided misdiagnosis in England are currently
unknown but could be substantial.
51
Organisation of
specialist services
A. Recommendations
Commissioning services for haemato-oncology
Service commissioning for each network should be carried out in a
co-ordinated way, using specific mechanisms which involve all
relevant commissioning bodies. Networks should establish explicit
organisational arrangements which identify those responsible for
overseeing the introduction and adoption of these recommendations.
Networks will need to conduct baseline assessments of current
provision and, using this guidance, set priorities and develop
proposals for local implementation.
4
Each network should carefully review the levels of service that it
provides, to ensure that its patients have access to each form of
treatment, either within that network or in another with which it
collaborates. All levels of service defined by the British Committee
for Standardisation in Haematology (BCSH) should be available:
Level 1
Hospitals providing conventional chemotherapy and
other forms of out-patient treatment, using dose levels
that would not be expected to produce prolonged
neutropenia.
Level 2
Facilities for remission induction in patients with acute
leukaemia, using standard intensive chemotherapy
regimes. This level of facility is also required to treat
patients with aggressive lymphoma.
Level 3
Facilities for autologous transplantation, using either
bone marrow or peripheral blood stem cells.
Level 4
Centres with expertise in both autologous and
allogeneic transplantation.
Networks which collaborate to provide specialist services or facilities
should have specific agreements defining the terms of such
collaboration.
52
Multi-disciplinary teams (MDTs)
Clinical services for patients with haematological cancers should be
delivered by multi-disciplinary haemato-oncology teams. A unitary
MDT, which could take responsibility for the management of patients
with any form of haematological cancer, is described below.
Trusts may, if desired, establish two or three haemato-oncology MDTs
based on this model, to treat specific forms of haematological cancer:
for example, a combined leukaemia/myeloma MDT and a separate
lymphoma MDT. Other arrangements can be envisaged; for example,
a Trust might form an MDT to provide local treatment for patients
with leukaemia, but refer those with lymphoma or myeloma to
specialist MDTs at other Trusts.
Networks should aim to develop these teams as rapidly as possible,
along with protocols describing how they function, to which Trusts
will be expected to adhere. The minimum population served by any
team should be 500,000, but networks should seek to concentrate
services so that teams deal with larger numbers of patients.
4
Every patient with any form of haematological cancer (including
myelodysplasias and chronic myeloproliferative disorders) should be
managed by a haemato-oncology MDT. Each network should ensure
that an appropriate range of MDTs is established for this to be
possible. All cases should be discussed in formal MDT meetings
attended by members involved in the diagnosis, treatment, or care of
that particular patient, and all the clinicians in the MDT should
regularly treat patients with the particular forms of haematological
cancer with which that MDT deals. These MDTs will be responsible
not only for initial recommendations about what treatment should be
offered, but also for delivery of treatment and long-term support for
patients. Individual clinicians will be responsible for discussing the
MDT’s recommendations with their patients, who should have the
opportunity to be informed of the outcome of MDT meetings.
When haemato-oncology MDTs have been established, clinicians who
are not members should refer any patient with suspected or
previously diagnosed haematological cancer to an appropriate MDT.
Written referral policies should be disseminated both within hospitals
(particularly to departments such as gastroenterology, dermatology,
rheumatology and medicine for the elderly) and to primary care
teams, to promote prompt and appropriate referral.
53
Core members of haemato-oncology MDTs
Each haemato-oncology MDT must include sufficient core members for
the following people to be present at every meeting:
•
Haemato-oncologists
At least two who specialise in each
(principally
tumour type being discussed at that
haematologists, some
meeting (e.g. leukaemia or lymphoma).
medical oncologists)
At least one from each hospital site
contributing to the MDT;
•
Haemato-pathologist At least one specialist in haemato-
pathology who liaises with pathologists
from other hospital sites;
•
Nurses
At least one clinical nurse specialist, also
ward sisters from hospitals which
provide services at BCSH Level 2 or
above;
4
•
Palliative care
At least one palliative care specialist
specialist
(doctor or nurse) who liaises with
specialists from other sites. If, because
of staff shortages, a palliative care
specialist cannot regularly attend MDT
meetings, the MDT must be able to
demonstrate that it reviews patients
regularly with such a specialist;
•
Support staff
Staff to organise team meetings and
provide secretarial support.
Teams established to manage patients with lymphoma should include
the following additional core members, who should be fully and
regularly involved in MDT discussions:
•
Clinical oncologist
At least one;
•
Radiologist
At least one, who liaises with radiologists
at other sites.
Teams responsible for managing patients with myeloma should include
at least one radiologist who liaises with radiologists at other sites and
is fully and regularly involved in MDT discussions. It is not necessary
for clinical oncologists to regularly attend team meetings for discussion
of myeloma patients, although teams which manage these patients
need rapid access to oncologists for palliative radiotherapy.
54
Extended team members
This group includes individuals whose expertise is frequently needed.
They do not have to be present at every MDT meeting, nor for the
whole of any meeting at which their contribution is required.
•
Clinical member of the transplant team to which patients could be
referred
•
Microbiologist (especially for patients with leukaemia)
•
Pharmacist
•
Vascular access specialist
•
State registered dietitian (SRD)
•
Orthopaedic surgeon (myeloma MDT)
•
Clinical oncologist (myeloma MDT and leukaemia MDT; provision
of cranial radiotherapy for patients with acute lymphoblastic
4
leukaemia (ALL) is an important role for a clinical oncologist)
Other specialists who may be required for specific cases:
•
Dermatologist
•
Gastroenterologist
•
ENT surgeon
•
Interventional radiologist
•
Renal physician (myeloma)
Support for patients and carers
All haemato-oncology MDTs should have access to designated staff who
can provide support for patients and carers when necessary (see Topic
2, Patient-centred care). These include the following:
•
Allied health professionals including rehabilitation specialists, as
described in the context of patient-centred care.
•
Liaison psychiatrist and/or clinical psychologist
•
Social worker
•
Bereavement counsellor
55
A clinical nurse specialist should normally be the initial point of
contact for patients who feel they need help in coping with their
disease, its treatment or consequences. This nurse should be able to
arrange re-admission, clinical review, or meetings between patients and
support staff such as those listed above. Networking between nurses
with different types of expertise should be encouraged, both to
provide mutual support and to deepen and broaden their perspective.
Achieving access to expertise
Patterns of MDT membership should be agreed and co-ordinated at
network level to achieve the best use of resources and to ensure that
each MDT has reliable access to the level of facilities and expertise it
needs to carry out its function effectively. When all the necessary
specialists are not available within a Trust, experts may contribute to the
MDT’s discussion through “in-reach” or “out-reach” arrangements.
In-reach arrangements are those where clinicians who work in
peripheral hospitals travel to the centre to attend MDT meetings,
bringing information about their patients with them. Everyone at the
meeting can then contribute to discussion about the management of
4
patients at each of the participating hospitals. Such arrangements
have to be set up and supported by specialists in the relevant disease
group at the cancer centre (or haematological equivalent) for the
network as a whole, and additional staff or facilities for
teleconferencing may be required. In large networks, two specialist
centres may work in this way.
In the out-reach model, MDT meetings are held in peripheral
hospitals, normally those that provide intensive in-patient treatment
(BCSH Level 2). Specialists take peripatetic roles; for example,
specialist haemato-pathologists, transplant specialists, oncologists and
radiologists may travel to several hospitals to meetings of various
MDTs. If this is not practicable, locally scarce specialists may
contribute to MDT meetings by teleconferencing. Where such
arrangements are established, they should be reviewed annually by
the network clinical lead.
Specialist input is particularly important for diagnosis and assessment
of lymphoma. If MDT members who do this work are not lymphoma
specialists, arrangements should be made either for visiting specialists
to join a substantial proportion of MDT meetings (out-reach), or for
MDT members to visit centres where they can discuss individual cases
with specialists (in-reach), using teleconferencing if necessary. The
aim of such meetings should be both to improve the accuracy of
assessment in these cases and to enhance the level of expertise of
MDT members.
56
When facilities or expertise are based outside the cancer network,
there should be arrangements to ensure smooth and efficient co-
operation across network boundaries.
Responsibilities of haemato-oncology MDTs
Haemato-oncology MDTs should, if possible, meet weekly, during
normal working hours. All core members must have a special interest
in haematological cancer and treat attendance at MDT meetings as a
clinical commitment. They should attend the majority of meetings
and allow adequate time to prepare for them.
MDT meetings have the following functions:
•
To establish, record and review diagnoses for all patients with
the forms of cancer that fit the team’s definition criteria;
•
To assess the extent of each patient’s disease and discuss its
probable course;
•
To work out treatment plans for all new patients and those with
4
newly-diagnosed relapses;
•
To review decisions about treatment, particularly those made in
the interval between MDT meetings. This review should cover
not only the clinical appropriateness of the treatment but also
the way patients’ views were elicited and incorporated in the
decision-making process;
•
To discuss patients’ responses to treatment, both during therapy
and when the course of treatment is complete. Lymphoma
MDTs should review each patient’s progress after three cycles of
chemotherapy and again at the end of the prescribed course.
The appropriateness of radiotherapy should be considered in the
light of the response to chemotherapy;
•
To consider patients’ other requirements such as palliative care
or referral to other services. MDTs must be able demonstrate
effective systems for collaboration with hospital and community
palliative care services;
•
To discuss discontinuing treatment. Each MDT should develop a
specific process for considering discontinuation of treatment
when its effectiveness has become so limited that adverse effects
might outweigh potential benefits;
•
To agree dates for reviewing patients’ progress;
•
To discuss clinical trials and audit results.
57
The MDT is also responsible for:
•
Identifying requirements for staff and facilities for any form of
treatment it provides (see Topic 5, Treatment (excluding high
dose therapy), and Topic 6, High dose therapy);
•
Liaison with primary care teams, palliative care teams, services
for the elderly and voluntary organisations such as hospices;
•
Ensuring that adequate information, advice and support is
provided for patients and their carers throughout the course of
the illness;
•
Ensuring that GPs are given prompt and full information about
the nature of their patients’ illness or treatment, any changes in
management, and the names of individual MDT members who
are primarily responsible for their patients’ management;
•
Recording, in conjunction with the cancer registry, the required
minimum dataset for all cases of haematological cancer within its
4
specified catchment area, including those cared for by clinicians
who are not haematological cancer MDT members;
•
Identifying training needs of MDT members and making sure
these needs are met;
•
Involvement in clinical trials and other research studies;
•
Collaboration in planning, and collecting data for, network-wide
audit.
One member of each team, usually the lead clinician, should act as
the administrative head of the team, taking overall responsibility for
the service it delivers. Lead clinicians from all haemato-oncology
teams in each network should collaborate to develop and document
evidence-based clinical and referral policies which should be
consistent over the network as a whole, and should agree process
and outcome measures for regular audit. All teams should be
involved in network-wide audit and clinical trials; these issues should
be discussed in MDT meetings, at network level by lead clinicians
from relevant MDTs, and with the research network.
58
There should be an operational policy meeting at least once a year at
which each MDT discusses its policies and reviews the way it
functions. This meeting should be organised around an open agenda
to which all members of the team are encouraged to contribute.
Maximising the effectiveness of MDT meetings
Suitable facilities should be provided to support effective and efficient
team working. In addition to basic physical facilities such as
adequate room and table space, there should be appropriate
equipment, for example to allow the group to review pathology slides
and imaging results.
Every MDT meeting should have a designated chairperson. Whilst
this may be the lead clinician, teams should consider rotating the role
of chairperson between members. Teams should aim for an
egalitarian mode of interaction, to facilitate open discussion to which
all members feel able to contribute. Formal training in effective
group working and team development may be helpful.
Each MDT should have named support staff who take the roles of
4
team secretary and co-ordinator. Since these roles overlap, one
person may be able to cover both functions in smaller teams. If a
team decides that a clinical nurse specialist should be responsible for
co-ordinating meetings, secretarial and administrative support must be
provided for this nurse. The team co-ordinator should arrange
meetings, inform all those who are expected to attend, and ensure
that all information necessary for effective team functioning and
clinical decision-making is available at each meeting. This will
include a list of patients to be discussed and copies of their case
notes, along with diagnostic, staging, and pathology information.
The secretary should take minutes at all meetings, and record and
circulate decisions made by the team within the casenotes and to
both MDT members and to those others identified as appropriate for
routine circulation by the MDT, such as GPs, who may require this
information. A designated member of the team’s support staff,
working with the administrative head of the team, should be
responsible for communication with primary care, palliative care, and
other MDTs in the network.
Local services should be developed around MDTs which include at
least three haematologists whose sole or main specialist interest is in
haemato-oncology.
59
All in-patients undergoing intensive forms of treatment such as
complex chemotherapy under the care of this team should be treated
either at one hospital, or, where there is a locally agreed case for
providing this service at more than one hospital, in hospitals which
each independently meet the full criteria for the safe delivery of these
treatments (summarised in Table 4, page 72). Members of the team
may provide palliative or out-patient care in other hospitals.
Each haemato-oncology MDT which provides treatment at BCSH
Level 2 or above must have facilities as specified by BCSH and must
be able to demonstrate adequate arrangements for 24-hour cover by
specialist medical and nursing staff. These arrangements must be
sufficiently robust to allow cover for holidays and other absences of
team members. Haemato-oncologists in such a team should work
together as a cohesive group, sharing management of patients. There
should be efficient systems for routine information-sharing and
frequent opportunities for informal discussion as well as formal
meetings.
Networks should review their arrangements for managing patients at
4
BCSH Level 2 (i.e. acute leukaemia, some intensive lymphoma
regimens, and other bone marrow failure patients) in conjunction
with their haematology MDTs, particularly those involved in acute
leukaemia. The aim should be to consolidate this work within a
stable system of service delivery, by ensuring that all hospitals
providing these services remain committed to supporting this work,
with the necessary staff, facilities and reliable arrangements for
specialist medical and nursing cover.
Networks should give priority to transferring BCSH Level 2 workloads
to those hospitals it identifies as most appropriate to undertake this
work on a long-term basis, giving particular consideration to the
future roles of those hospitals performing relatively little such work,
for example induction therapy to induce remission in acute leukaemia
in five or fewer new patients each year.
Clinicians working in such hospitals, who wish to continue to be
actively involved in this type of clinical responsibility, should consider
the feasibility of playing an active role in a haemato-oncology MDT
based in the hospital to which patients from their locality would be
referred.
60
Members of haemato-oncology MDTs will have other responsibilities
within their hospitals, and requirements for the management of
patients with haematological cancers should be considered in the
context of the wider role of haematology services. Haemato-
oncologists play essential roles in the care of patients with solid
tumours undergoing chemotherapy, in particular monitoring and
managing haematological adverse effects, and may provide services
such as placing central venous catheters. All hospitals which give
chemotherapy, or which are likely to admit patients undergoing
chemotherapy as medical emergencies, should have documented
clinical policies, agreed with haematology and oncology staff, which
clearly specify arrangements for the care of such patients.
B. Anticipated benefits
Since the publication of the Calman-Hine report,35 MDTs have become
central to services for cancer because they represent a way of working
that offers advantages for both clinicians and patients. MDT meetings
4
ensure that each patient is considered from a range of viewpoints by
people with different areas of specialisation, who can pool their
expertise and learn from one another.
Haematological cancer has many variants and both diagnosis and
management can be particularly complex; so the supportive
environment of an MDT meeting, which allows members to share
difficult problems, can be especially helpful for clinicians. Those who
have experience of working in MDTs report that they also provide
valuable, and often unanticipated, learning opportunities.
For patients, management by an MDT offers many potential benefits,
particularly a greater probability of timely and appropriate treatment
and better continuity of care.
The contributions made by clinical nurse specialists and palliative care
nurses to decision-making in the MDT can be particularly valuable
because patients are often more frank with nurses about their
symptoms, problems and desires. Such nurses can therefore help to
focus clinical decision-making on the needs, values and priorities of
individual patients. This is helpful to inform discussion about
supportive care, and becomes particularly important at the point in
the disease when continued active treatment may be doing more harm
than good – a point that can be difficult for clinicians to recognise.
Nurses and palliative care specialists can play important roles as
informed patient advocates in initiating the transition from active
treatment to palliative care.
35 Expert Advisory Group on Cancer, A policy framework for commissioning cancer services.
Department of Health/Welsh Office, 1995.
61
Regular discussion in the context of MDT meetings is likely to lead to
improved clinical policies, more effective delivery of care, and more
participation in clinical audit and research. Consolidation of services
for patients undergoing complex treatment in hospitals able to
consistently meet the required standards, and which have a sufficient
depth of clinical specialist cover, particularly in medicine and nursing,
will mean that all staff, including junior members, will be better able
to meet their needs. All of these factors will tend to improve
outcomes.
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
There is no research evidence demonstrating the superiority of any
specific model of MDT structure for the management of
4
haematological cancers, although there is now considerable anecdotal
evidence of benefits associated with team working in the
management of patients with solid tumours.
There are various strands of evidence to suggest that treatment in
low-volume hospitals, which tend to lack both specialist clinicians
and facilities, may be associated with poorer outcomes. There are
also data from cancer registries which, although not consistent
between regions, tend to suggest that specialised centres can achieve
better survival rates among some groups of patients; however, these
figures are not adjusted for severity of disease or co-morbidity, and
therefore could reflect differences in case-mix. The evidence
supporting specialised care, limited though it is, is stronger for
lymphomas than for other forms of haematological cancer.
Leukaemia
There is no definitive evidence to show that hospitals that treat more
patients with leukaemia achieve better outcomes, but some
suggestion that there may be problems with providing small numbers
of bone marrow transplants.
62
Two studies which sought relationships between acute leukaemia
outcomes and hospital volume were included in a systematic review.
One, a study of 879 adolescents and young adults in England and
Wales, found no specific benefit associated with treatment in a
national trial, care at a teaching hospital, or hospital case volume.
The second, which focused on bone marrow transplants for early
leukaemia, found a relationship of borderline significance between
centre throughput and outcome, but only when results from centres
which carried out fewer than five transplants per year were compared
with higher-volume centres. Above this level, there was no evidence
of any relationship between centre size and outcome.(B) Registry
data from Japan show higher survival rates after treatment in high
volume centres, but the effect is only significant for bone marrow
transplants from sibling donors, not for transplants from unrelated
donors.(B)
Limited data from cancer registries in various regions of the UK
suggest that some groups of patients with leukaemia treated in
specialist centres may survive longer, but this could be due to patient
selection. In the Northern and Yorkshire Region, 27% of patients are
4
alive five years after treatment in specialist centres, compared with
25% treated in non-specialist centres (p=0.04); this difference reflects
better outcomes in younger patients (below the age of 45) only.
Thames Cancer Registry figures show a highly significant survival
advantage for patients with acute myeloid leukaemia (AML) treated in
teaching hospitals, compared with those treated in non-teaching
hospitals. But there is no apparent relationship between specialisation
of treatment centre and survival rates in the South and West Region or
in Scotland.
Review of results by a specialist population-based registry for
lymphoid malignancy in the North West Region of England found that
significant factors affecting survival among patients with myeloid
leukaemia and ALL included treatment according to a recognised
protocol and treatment at a specialist oncology centre.
Audit evidence shows that patients with AML in the south-west of
England who were treated in a clinical trial did better than those of a
similar age who were not in a trial. Whilst this could be because
such patients are more likely to be treated according to an evidence-
based protocol, by clinicians with a special interest in this disease,
selection of patients may have contributed to the difference found.
This highlights the general difficulty of using evidence of outcomes
from patients entered into clinical trials to judge variations in
population outcomes. A separate trial – albeit including elderly
patients with aggressive lymphoma – reported that patients who were
not in the trial tended to have higher levels of co-morbidity and
therefore would not be expected to do so well.(B)
63
Multiple myeloma
There is conflicting evidence on whether treating higher numbers has
a beneficial effect. A study from Finland found no significant
differences in progression-free or overall survival between hospitals
which enrolled larger or smaller numbers in multi-centre trials, and
concluded that decentralisation of treatment was acceptable. As with
leukaemia, figures from some cancer registries suggest that specialist
centres achieve better survival rates than non-specialist centres, but
the pattern is not consistent between regions and any differences
could be due to patient selection. In Northern and Yorkshire, the
overall five-year survival rate for specialist centres is 21%, compared
with 14% for non-specialist centres, a highly significant difference; but
no such difference is apparent for the South and West.(B)
Lymphoma
Evidence of links between survival rates and hospital specialisation or
number of patients treated is generally more consistent for lymphoma
than for other forms of haematological cancer.
A US study described in a systematic review found that death-rates
4
were 50% higher among patients treated for lymphoma (type not
specified) in community hospitals than in specialist cancer centres
(relative risk of death 1.5, 95% CI: 1.3 to 1.7).(B) Another US study
reported better outcomes among patients with aggressive non-
Hodgkin’s lymphoma (NHL) who were treated in hospitals that
managed three or more such patients per year, compared with one or
two. 54% of patients were free from progression after two years at
the higher-volume centres, 32% where the numbers were small
(p=0.06); and overall survival rates were 71% versus 52%. All the
higher-volume hospitals, but only 27% of the others, were approved
transplant centres.(B)
Registry data from Northern and Yorkshire show significantly higher
five-year survival rates among patients treated for lymphoma in
specialist centres than in non-specialist hospitals. Overall, 47% of
those treated in specialist centres survived, compared with 35%
elsewhere, but the difference only becomes apparent in patients over
the age of 55. In Scotland, five-year survival rates achieved by
specialist centres are consistently higher, at 45% overall, than those at
non-specialist centres, with 39% (p<0.001). In the South and West,
however, no effect of specialisation is apparent.
Organisation
The Trent Region has demonstrated that it is possible, in practice, to
64
implement accreditation standards that include the establishment of
MDTs for the management of haematological malignancies. The
Trent standards require that lymphoma MDTs, which include
haematologists and/or oncologists, a specialist pathologist and a
radiologist, should meet at least monthly. The centre MDT designates
non-core members for additional roles in extended teams. Trent
lymphoma MDTs work out diagnoses, plan treatment, record
information about all patients on an agreed proforma, organise audit,
and agree clinical and referral guidelines with the network site-
specific group. Whilst MDTs based at cancer units can treat
lymphoma, patients with unusual forms of the disease, or for whom
intensive or combined modality treatment may be appropriate, are
discussed by the cancer centre MDT.
D. Measurement
Structure
4
•
MDTs established throughout each network for each major type
of haematological cancer.
•
Support staff in place for every MDT.
•
Rapid and effective communication systems between local
(peripheral) hospitals and specialist centres.
Process
•
Network baseline assessments should include the following
measures:
•
Numbers of haematologists and specialist haemato-
oncology nurses per Trust;
•
Current specialisation by Trust;
•
Current referral patterns for leukaemia, lymphoma and
myeloma;
•
Current information and audit of diagnosis and treatment;
•
Protocols in place, and whether they are agreed across the
network;
65
•
Relationship between different specialties involved in
diagnosis and/or management of patients with
haematological cancers, e.g. ENT, head and neck,
haematology;
•
Staffing and configuration of existing MDTs.
•
Evidence that every patient with a diagnosis of haematological
malignancy is discussed by an appropriate MDT.
•
Evidence that MDT members discussing patients at centre
meetings (in-reach arrangements) routinely bring all necessary
information with them.
•
Audit agreed and reviewed over whole network.
•
Patients with acute leukaemia treated in designated units which
meet the appropriate standards of staffing and facilities.
4
Outcome
•
Evidence that MDTs audit individual clinicians’ actions against
MDT decisions.
•
Record of each member’s attendance at MDT meetings.
•
Record of business carried out (including patients discussed and
decisions made) at MDT meetings.
E. Resource implications
MDTs for leukaemia and myeloma do not currently exist in the
majority of Trusts; and where lymphoma MDTs are established, many
lack the full range of members. The cost of additional staff time for
fortnightly MDT meetings to deal with all patients with haematological
cancers, and for ensuring that every MDT includes a co-ordinator, is
estimated to be £7.2 million per year for England and Wales as a
whole. The level of uncertainty is, however, high, because the
potential costs vary according to the model adopted (see Appendix 1,
Economic implications of the guidance).
66
In general, lower costs are associated with the following:
•
Less frequent MDT meetings: weekly meetings are likely to
increase costs by about 50%, compared with fortnightly
meetings;
•
Use of teleconferencing, with optimum charging packages;
•
A pragmatic mix of in-reach and out-reach arrangements for
access to specialist expertise;
•
Combining myeloma and leukaemia MDTs.
4
67
Treatment (excluding
high dose therapy)
A. Recommendations
Information about treatment in this section is intended to be used as
service guidance; the recommendations should not be taken as clinical
guidelines. Networks should agree detailed clinical guidelines and
update them regularly, using the best available evidence and any
specific guidance from the National Institute for Clinical Excellence
(NICE). Treatment provided should be audited against these guidelines.
Conventional dose therapy – that is, cytotoxic chemotherapy given in
doses that do not necessitate stem cell rescue – is appropriate for
most patients with haematological cancers. Often, this can be given
on an out-patient basis, but treatment may continue over long periods
of time. Other types of treatment are appropriate for specific
5
conditions. Some patients, particularly those with acute leukaemia,
chronic myeloid leukaemia, myeloma and some forms of lymphoma,
can only achieve remission with more intensive treatment, and the use
of high dose therapy and stem cell rescue is increasing. This is
discussed in the next chapter of this manual (Topic 6, High dose
therapy).
Chemotherapy for induction of remission in acute leukaemia is
particularly demanding (see Treatment requirements, Acute leukaemia,
below). These patients require in-patient treatment lasting for weeks
or months together; and, because both the disease and the therapy
reduce immunity to infection, they are very vulnerable throughout this
period. This form of treatment should therefore be offered only by
hospitals which can provide adequate levels of staffing and facilities
(see previous chapter – Topic 4, Organisation of specialist services).
National standards have been developed for chemotherapy services
generally.36 These call for:
•
Clearly defined leadership and organisational arrangements;
•
Provision of suitably equipped areas for the administration of
chemotherapy;
36 See Accreditation Standards for Chemotherapy in the Manual of Cancer Services
Assessment Standards. NHS, 2000.
68
•
Co-ordination and control over the use of specified
chemotherapy regimens within networks;
•
Supervision of chemotherapy prescribing by appropriate
specialists, who may be consultant or specialist registrar level
oncologists or clinical haematologists;
•
Administration of chemotherapy by appropriately trained staff;
•
Use of guidelines for the prevention and treatment of side effects
of chemotherapy;
•
Provision of facilities for aseptic reconstitution of cytotoxic
agents;
•
Clear and comprehensive documentation of chemotherapy.
Specific treatments vary widely. Table 3, below, shows the main
types of treatment currently used for the various forms of
haematological cancer, and Table 4 summarises facilities required for
their delivery. The choice of agents and the way they are used
depends both on the type of cancer and on the individual features of
the case. For some patients, no treatment is necessary at the time of
5
diagnosis; for the majority, conventional dose therapy is appropriate,
but some of these may be offered high dose therapy if the disease
does not respond or if they relapse. Patients whose disease
progresses despite continued or intensified treatment may reach a
point at which anti-cancer therapy does more harm than good, and
palliative therapy becomes more appropriate. Systems for decision-
making and delivery of treatment must therefore be flexible and
responsive to changing patient needs.
69
Table 3. Illustrations of types of systemic anti-cancer treatment
and the settings in which they are usually
administered*
Treatment, disease groups
Examples
Setting
High dose therapy + progenitor BEAM
In-patient, intravenous
cell rescue (allogeneic or
therapy on dedicated
autologous)
Total body irradiation
ward with specialised
nursing/support team.
AML, ALL, CML, Hodgkin’s
busulphan/
Isolation facilities and
lymphoma, NHL, myeloma.
cyclophosphamide
specialised rooms
normally used.
• Induction chemotherapy
3+7, UKALL protocol
In-patient, intravenous
for acute leukaemia
therapy on dedicated
ward with specialised
• Induction treatment for
CODOX-M
nursing/support team.
Burkitt’s & lymphoblastic
lymphoma
• Treatment of recurrent high ESHAP, ICE
grade NHL
Initial treatment of:
Normally day-case,
intravenous therapy in
5
• High grade NHL
CHOP
dedicated out-patient
unit with specialised
• Hodgkin’s lymphoma
ABVD
chemotherapy team.
• Myeloma
C-VAMP
Monoclonal antibody therapy
Rituximab,
Normally day-case,
Alemtuzumab
intravenous therapy in
NHL, AML, CLL
dedicated out-patient unit
with specialised
chemotherapy team.
Radioimmunotherapy
Ibritumomab,
In-patient suite with
Tositumomab
radioprotection facilities
NHL
and specialist nuclear
medicine team.
Cytokine treatment
Interferon
Out-patient treatment;
usually subcutaneous
CML, NHL, Myeloma
injection, self-
administered by the
patient.
Oral chemotherapy
Chlorambucil,
Out-patient oral
Fludarabine, treatment,
self-
Myeloma, CML, CLL, NHL,
Hydroxyurea
administered by the
palliation for ALL/AML
patient.
Kinase inhibitor
Imatinib
Out-patient oral
treatment, self-
CML
administered by the
patient.
* Inclusion in this table of any treatment should not be taken as a recommendation
on its use.
70
Treatments for haematological malignancies are being continuously
developed and there are several clinical trials in progress. Each
network should agree and adopt guidelines for involvement in such
trials. Network-wide formularies and policies for the adoption of new
drugs should be agreed by commissioning bodies, chemotherapy lead
clinicians, and haematologists, oncologists and pharmacists involved
in treating patients with haematological malignancies.
Treatment requirements
Facilities necessary for provision of intensive chemotherapy
The standards necessary for units which manage remission induction
for patients with acute leukaemia using current standard intensive
chemotherapy regimens (together with equivalent treatments for some
lymphomas and bone marrow failure) are summarised in Table 4.
These patients must be treated on specialist haematology/oncology
wards, where they are likely to remain for several months.
Indwelling venous catheters are used to deliver intensive
chemotherapy. These should only be handled by designated staff
members, since scrupulous hygiene and expertise are essential.
Insertion should be carried out in dedicated areas (special procedure
room or operating room) and real-time imaging should be available.
5
Trainees must be closely supervised by personnel with documented
competence in such supervision.
Patients undergoing treatment for acute haematological malignancies
are highly susceptible to infection. There should be a written policy
which specifies responses to life-threatening problems, which should
be readily accessible in a ward book which explains precisely what
should be done for each eventuality. There should be strict policies
on hand washing, adherence to which should be regularly audited.
This should be part of a wider education programme to reduce levels
of hospital-acquired infection.
71
Table 4.
Summary of standards necessary for all units
providing induction therapy for acute leukaemia or
aggressive lymphoma, and other patients likely to
have prolonged neutropenia
Table 4a
Facilities
•
Provision for direct admission to the ward or unit.
•
Specific beds in a single dedicated ward within the hospital
with the capacity to treat the planned volumes of work.
•
In-patient unit that minimises airborne microbial contamination.
•
For isolation: a number of single rooms with en-suite facilities.
All patients receiving induction therapy or other high-dose
chemotherapy should be housed in single rooms with en-suite
facilities.
•
Designated area for out-patient care that reasonably protects the
patient from transmission of infectious agents, and can provide,
as necessary, for patient isolation, long duration intravenous
5
infusions, multiple medications, and/or blood component
transfusions.
•
Full haematology and blood transfusion laboratories on site.
Rapid availability of blood counts and blood products including
products such as CMV seronegative and gamma-irradiated
blood components.
•
Central venous or Portacath catheter insertion must be available
by a committed and experienced specialist.
•
Central venous catheters and pumps (portable and static).
•
On-site facilities for emergency computed tomography (CT)
scanning.
•
Cytotoxic drug reconstitution centralised at the pharmacy.
72
Table 4b
Staffing
•
Consultant-level specialist medical staff should be available at
any time of the day or night. This level of cover demands at
least three consultants, all full members of a single haematology
multi-disciplinary team (MDT) and providing in-patient care at a
single site. Levels of staffing must comply with the EU working
time directive.
•
Specialist registrars and staff grade doctors providing cover
should be working in haematology/oncology and part of the
unit. They should be involved in looking after these patients
during the normal working day. They should be familiar with,
and have received formal instruction in, the unit protocols.
•
A nurse/patient ratio satisfactory to cover the severity of the
patients’ clinical status. The level of staffing required for
neutropenic patients is equivalent to that in a high dependency
unit.
•
At least one trained specialist nurse* on the ward at all times,
able to deal with indwelling venous catheters, recognise early
symptoms of infection, and respond appropriately to potential
5
crisis situations.
•
Consultant microbiological advice must be available at all times.
There must be ready access to specialist laboratory facilities for
the diagnosis of fungal or other opportunistic pathogens.
•
A consultant clinical oncologist must be available for
consultation, although radiotherapy facilities need not be on
site.
•
On-site advice from a specialist oncology pharmacist.
•
Access to staff (e.g. data manager) to support entry of patients
into the local portfolio of National Cancer Research Network
(NCRN) clinical trials.
* There is no universally agreed definition of specialist nurse in this context.
However the term is understood to cover nurses with sufficient experience (i.e. at
least a year of experience as a qualified nurse in haematology and/or oncology),
and usually formal academic qualifications including ENB 237, diploma courses
with specialist modules in oncology or haematology, or locally organised
university validated courses or specialist degree courses in
haeamatology/oncology and palliative care.
73
Table 4c
Clinical support
•
On-site access to bronchoscopy, intensive care and support for
patients with renal failure.
•
Written policies for all procedures, including infection
prevention and control,37 insertion of indwelling venous
catheters,38 high dose therapy and/or immunosuppressive
agent administration (including intrathecal chemotherapy39),
and blood component transfusion.
•
Participation in network based audit of process and outcome.
Treatment for specific forms of haematological cancer
Acute leukaemia
Combination chemotherapy, normally using two or three drugs
including an anthracycline, is appropriate for patients with acute
leukaemia who are sufficiently fit to withstand it. Remission
induction should be considered for fitter older patients, but careful
judgements need to be made about the appropriateness of treatment
5
because of the risk of treatment-related death and of impairing the
quality of the patient’s remaining life. About 70% of patients with
acute myeloid leukaemia (AML) (the most common form of acute
leukaemia) are over 60 years of age and outcomes in this group are
poor, with early treatment-related death-rates of around 25%.
Patients with acute lymphoblastic leukaemia (ALL) require intrathecal
as well as intravenous treatment. Cranial radiotherapy should also be
available when required, and should be given by a member of the
extended leukaemia MDT.
37 Standard Principles for Preventing Hospital Acquired Infections. Department of Health,
2001; available on: <www.doh.gov.uk/hai/standardprinciples.pdf>
38 These are available on the HICPAC website at:
<www.cdc.gov/ncidod/hip/guide/guide.htm>.
39 National Guidance on the Safe Administration of Intrathecal Chemotherapy. HSC
2001/022. See also A Spoonful of Sugar - Medicines Management in NHS Hospitals. Audit
Commission, 2001.
74
B-cell chronic lymphocytic leukaemia (CLL)
Treatment is not necessary for all patients when CLL is first
diagnosed, but about half of those known to have CLL will require
treatment at some stage. When treatment is required to control
symptoms such as anaemia, oral out-patient therapy is usually
appropriate. The most commonly used drug is oral chlorambucil, but
a Medical Research Council (MRC) trial (CLL-4), comparing different
drugs (including fludarabine) for such patients is currently in
progress. Recruitment to this trial should be supported.
Recurrence is inevitable and many patients will need second-line
treatment. A variety of drugs may be used, either as single agents or
in combination. Fludarabine, which can usually be taken by mouth,
is specifically recommended by NICE for patients for whom first-line
chemotherapy has failed or who cannot tolerate it, and who would
otherwise receive combination chemotherapy.40
Chronic leukaemias, myeloproliferative disorders and
myelodysplastic syndrome
In most of these conditions, the emphasis should be on symptom
control. Supportive treatments ranging from single-agent
chemotherapy to regular transfusion, given on an out-patient basis,
are appropriate for most patients. Vascular complications of
5
myeloproliferative disorders may require input from other specialists
who should be members of the extended leukaemia MDT.
Treatment for chronic myeloid leukaemia (CML) varies according to
the phase of the illness and other prognostic factors, in particular,
presence or absence of the “Philadelphia chromosome” and the
patient’s age. Interferon-α and/or conventional chemotherapy –
usually hydroxyurea – either of which can be given on an out-patient
basis, can often control the disease during the chronic phase but the
benefits may be short-lived and a substantial proportion of patients
develop intolerable side-effects. Supportive treatment to normalise
the balance of blood constituents is required as the disease
progresses.
NICE has recommended that imatinib should be offered to patients
with chronic-phase Philadelphia-positive CML if treatment with
interferon fails to control the disease or produces unacceptable side-
effects. NICE has also recommended imatinib as an option for the
treatment of adults with Philadelphia-positive CML in accelerated
phase or blast crisis, provided they have not received imatinib at an
earlier stage. This is an area of rapid change; the role of imatinib
earlier in therapy is currently being considered.
40 National Institute for Clinical Excellence. Guidance on the use of fludarabine for B-cell
chronic lymphocytic leukaemia. Technology Appraisal Guidance No. 29. London: NICE,
2001.
75
Allogeneic bone marrow transplantation should be discussed with
younger patients (see Topic 6, High dose therapy).
Lymphomas
All patients with lymphomas should be discussed at, and managed
by, lymphoma MDTs.
Hodgkin’s lymphoma
Out-patient treatment with multi-agent chemotherapy (usually ABVD)
over a period of months is normally required. Radiotherapy should
be available for patients with localised disease, bulky masses or an
incomplete response to chemotherapy. High dose therapy (Topic 6,
High dose therapy) should be discussed with younger patients who
are potentially able to benefit from it, in particular those who have
relapsed or whose disease fails to respond to standard dose
treatment.
Non-Hodgkin’s lymphoma (NHL)
The disease groups described below include a variety of conditions
which require very different management strategies (see
Background). Even within diagnostic categories, there is great
diversity between patients. A range of medical specialists may be
involved in caring for these patients, for example dermatologists and
5
gastroenterologists. These should be members of the extended
lymphoma MDT.
The forms of clinical management regarded as optimal are changing
continuously and will not be described in detail here.
Aggressive NHL, including diffuse large B-cell lymphoma,
peripheral T-cell lymphoma and Burkitt’s lymphoma
Haematologists and oncologists may be involved in the treatment of
patients with aggressive (high-grade) forms of lymphoma.
Chemotherapy followed by limited field radiotherapy is likely to be
appropriate for patients with localised aggressive NHL. CHOP-based
chemotherapy is used for patients with disseminated aggressive
disease who are fit enough to tolerate it; this can cure about one-third
of these patients.
Evidence is emerging to suggest that rituximab may have a role in
selected patients with diffuse large B-cell lymphoma since survival
appears to be lengthened by its co-administration with CHOP in one
trial. NICE will be producing guidance on this.
Combination chemotherapy using a different group of drugs from that
initially used may induce remission if the disease recurs. High dose
therapy (see Topic 6, High dose therapy) may be appropriate for
selected younger patients if standard chemotherapy fails.
76
Patients who need other forms of treatment, such as surgery, should
be treated by designated clinicians who are members of the extended
lymphoma MDT.
Other forms of NHL
Single-agent out-patient therapy is appropriate for initial treatment for
most patients; a wide variety of types of treatment may be used. In
the majority of cases, disseminated low grade lymphomas are not
cured by any of the treatments currently in use. Repeated courses of
treatment, sometimes using combination chemotherapy or
radiotherapy, are likely to be required over many years. Patients
should be discussed by the lymphoma MDT each time symptoms
recur, since decision-making about the most appropriate form of
management can be complex.
Asymptomatic patients are often managed by observation alone
initially, although most require treatment at some stage. Single
alkylating agents are widely used in initial therapy, and at recurrence
or for those requiring alternative treatment there is a range of options
including combination chemotherapy, purine analogues, rituximab,
radioimmunotherapy, and high dose chemotherapy with progenitor
cell rescue. Which of these is appropriate will depend upon the
condition of the patient and their prior treatment, and many trials
5
evaluating these approaches are in progress. Wherever possible,
patients should be offered the opportunity to take part in these.
NICE has issued guidance on the use of the monoclonal antibody,
rituximab, for follicular lymphomas. Currently, rituximab is
recommended only in the context of a prospective case series, for
last-line treatment when alternative therapeutic options have been
exhausted.
Multiple myeloma
Out-patient combination chemotherapy is appropriate for most
patients, but high dose treatment with autologous stem cell rescue
should be discussed with those who are sufficiently fit to withstand it
(see Topic 6, High dose therapy). Orthopaedic and renal
complications require involvement of other specialists, who should be
members of the extended myeloma MDT. Long-term treatment with
bisphosphonates should be considered from the time of diagnosis.
Rapid access to palliative radiotherapy is essential for these patients,
both to control pain and to reduce the risk of fractures and spinal
cord compression.
77
Management of complications of chemotherapy
Networks should agree, document and disseminate guidelines for
both prophylaxis and management of neutropenic sepsis. Patients,
their carers, primary care teams, accident and emergency departments,
and others who may encounter this type of problem should be given
precise information about whom they should contact and where
patients should be taken in the event of treatment complications.
These patients should be managed by a specialist haemato-oncology
MDT (see Topic 4, Organisation of specialist services).
B. Anticipated benefits
Many patients are already being treated in ways outlined here, but for
those who are not, a range of benefits may be anticipated. Crucially,
patients would be looked after by staff who know about their condition,
in appropriate facilities. This will both ensure that patients receive the
most appropriate forms of treatment and enhance safety. For example,
it will allow complications of treatment to be recognised quickly and
managed efficiently, thus reducing iatrogenic morbidity and death.
5
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
Most of the evidence on the effectiveness of treatment for
haematological malignancies has been systematically reviewed by the
Swedish Council on Technology Assessment in Health Care (SBU).
The text below summarises information from these reviews.
Acute leukaemia
The review includes nearly 70 publications (n=17,009), including one
meta-analysis (n=1897) and 31 randomised controlled trials (RCTs)
(n=10,516). This shows that initial therapy with an anthracycline
(usually daunorubicin or idarubicin and ara-C) can produce lasting
remission in some patients; the total doses of both drugs are
important to maximise time in remission.(A) Response rates,
remission duration and survival are better with idarubicin than
daunorubicin.(A)
The inclusion of other agents, such as mitoxantrone and etoposide,
has been found to improve outcomes in some studies, but the
evidence is not conclusive. Post-remission intensive chemotherapy
may improve the duration of remission in younger patients but it is
not clear whether it increases long-term survival rates.(A)
78
Standard dose chemotherapy can prolong survival in elderly patients
with good performance status, but it is too toxic for the majority.(A)
For those with poor performance status, palliative treatment with
lower doses of chemotherapeutic agents may be helpful, but the
optimum treatment has not been identified.
Chronic myeloid leukaemia (CML)
Evidence from RCTs carried out before imatinib became available has
been reviewed by the American Society of Haematology. This
suggests that newly diagnosed patients with good prognostic factors in
the early stage of chronic-phase CML are most likely to survive if they
receive interferon with added chemotherapy. Observational studies
suggest that complete remission is likely to require four to six months
of treatment. For patients who prefer conventional chemotherapy to
interferon, hydroxyurea appears to be the agent more likely to
improve survival without producing serious toxicity.(A) Uncontrolled
studies suggest that high dose therapy with allogeneic transplantation
can be effective for some patients (see Topic 6, High dose therapy).
Early results from an ongoing major RCT41 that includes patients in
the chronic phase of CML treated with imatinib (the IRIS trial,
n=1106), confirms that it represents an important advance in
treatment. Patients were randomised to treatment with imatinib or
5
interferon-α plus cytarabine. After a median follow-up period of 19
months, 76.2% of patients in the imatinib group had a complete
cytogenetic response, compared with 14.5% of those taking the
alternative treatment; differences between groups in other outcome
measures are similarly dramatic. Although imatinib was associated
with higher rates of some adverse effects (such as superficial oedema,
muscle cramps and rash), it was generally much better tolerated and
few patients discontinued treatment because of adverse effects.(A)
Additional research evidence on imatinib has been summarised by
NICE.42 Whilst it is clear that imatinib can control the symptoms of
CML, there is as yet no information on its long-term effects.
41 O’Brien SG, Guilhot F, Larson RA, Gathmann I, et al. Imatinib compared with interferon
and low-dose cytarabine for newly diagnosed chronic-phase chronic myeloid leukemia.
New Engl J Med 2003;348:994-1004.
42 National Institute for Clinical Excellence. Guidance on the use of imatinib for chronic
myeloid leukaemia. Technology Appraisal Guidance No. 50. London: NICE, 2002.
79
Chronic lymphocytic leukaemia (CLL)
A meta-analysis of studies of chemotherapy for CLL found no
advantage in treating the condition before symptoms develop. Initial
treatment with combination chemotherapy does not produce
significantly better survival rates than single-agent chlorambucil, but
drug combinations often induce remission when the disease has
progressed despite single-drug treatment.(A) Fludarabine, which can
usually be taken by mouth, can be effective for patients for whom
first-line chemotherapy has failed or who cannot tolerate it, and
appears to produce less nausea, vomiting and hair loss than
combination chemotherapy.(A)43
Two national (MRC) trials, CLL-4 and CLL-5, which are currently in
progress, will provide more evidence on optimum treatment strategies
for patients with CLL.
Multiple myeloma
High dose treatment is being used increasingly frequently for patients
with myeloma. The evidence supporting this approach is summarised
in Topic 6, High dose therapy. For those who cannot tolerate high
dose treatment, combination chemotherapy or melphalan plus
prednisolone seem equally effective. Time to disease progression can
be prolonged by six months with interferon maintenance therapy
5
(p<0.01), but this is a costly form of treatment with unpleasant side-
effects. Interferon appears to increase overall survival time by about
four months.(A)
The British Society for Haematology has recommended that all
patients with multiple myeloma should be treated with
bisphosphonates, whether or not bone lesions are present.(A) Meta-
analysis of data from 11 RCTs shows that a vertebral fracture can be
prevented in one in 10 patients (OR 0.59, 95% CI: 0.45 to 0.78,
P=0.0001) and the absolute risk of bone pain is reduced by 9% (95%
CI: 3.5% to 14.4%). There is consistent evidence of benefits from a
variety of studies, including reductions in pain, hypercalcaemia and
pathological fractures.(A) Zoledronic acid, a new, more potent
bisphosphonate, is at least as effective as pamidronate.(A)
43 National Institute for Clinical Excellence. Guidance on the use of fludarabine for B-cell
chronic lymphocytic leukaemia. Technology Appraisal Guidance No. 29. London: NICE,
2001.
80
Aggressive non-Hodgkin’s lymphoma (NHL)
The SBU review reports that chemotherapy followed by radiotherapy
is usually effective for patients with localised disease, but the
optimum dose of radiotherapy is uncertain. CHOP chemotherapy is
effective for most patients (including the elderly) with aggressive
disseminated NHL. No chemotherapy regimen has been shown to be
superior overall, nor is there clear evidence that adding other drugs
improves the effectiveness of CHOP. For second-line therapy after
relapse, combinations of agents not used for initial treatment can
produce complete remission in 20-40% of patients but fewer than 10%
will have prolonged remission.(A)
Hodgkin’s lymphoma
Chemotherapy and radiotherapy have been used alone and in
combination for patients with Hodgkin’s lymphoma. Several
combination chemotherapy regimens, for example ABVD or
MOPP/ABVD hybrid or alternating schemes, are similarly effective but
have different patterns of acute and late adverse effects (see
Improving Outcomes in Haematological Cancers, The Research
Evidence for details). Extended field radiotherapy is more likely to
produce long-term adverse effects such as breast and lung cancer,
and for this reason, is less often used than previously. The addition
of radiotherapy does not improve survival rates, but limited field
5
radiotherapy is appropriate for selected patients to reduce the risk of
relapse and need for further intensive treatment.(A)
Management of complications
Preventing infection in neutropenic patients
The evidence does not allow any definitive conclusions to be made
on the necessity of isolating neutropenic patients and the role of air
filtration. The apparently simple measure of hand washing is
important and should be part of a wider education programme to
prevent hospital-acquired infection. The role of barrier nursing as a
routine procedure in the management of neutropenic patients and
transplantation is unclear.(B)
A study of infection control interventions in a US teaching hospital
highlighted the poor rate of compliance with hand washing protocols,
particularly among physicians (56% compliance, compared with 86%
among nurses).
81
Indwelling venous catheters (central lines)
The use of specialist teams to insert central lines and the care of such
lines by designated, trained personnel can reduce infection rates and
complications.(B) Suitably trained clinical nurse specialists can
provide this type of service. Ultrasound guidance can significantly
improve the success rate and may reduce complications.(B) Line
insertion outside a special procedure room or operating room has
been identified as a risk factor for blood stream infection associated
with central lines in patients treated in intensive care units.(B)
Colony-stimulating factors (CSF)
The evidence suggests that CSF should not be used routinely in
patients with neutropenia who are not febrile. The collective results
of eight trials provide strong evidence for not using CSF routinely as
adjunct therapy for uncomplicated fever and neutropenia.(A) There
was a decrease in the duration of neutropenia of less than 500/µL,
but no consistent clinical benefit. There is no reliable evidence that
CSF is beneficial for patients with fever and neutropenia who are at
higher risk of infection-associated complications, and who have
prognostic factors that are predictive of poor clinical outcome.
Epoetin for prevention and treatment of anaemia
Epoetin (commonly known as epo) is a synthetic form of the natural
5
hormone erythropoietin, which regulates production of red blood
cells. It is used to treat or prevent anaemia caused by cancer or
cancer treatment, reducing patients’ need for transfusions.
In patients with haematological cancers, the response to epoetin
varies according to the type of disease and treatment. It is
particularly effective for patients with multiple myeloma and may be
valuable for those with NHL and CLL who are treated with
chemotherapy, but is less effective for those with myelodysplastic
syndrome.(A) It does not appear to be useful for patients receiving
autologous stem cell transplants, nor for those with mild anaemia
(haemoglobin levels above 10g/dL).
82
D. Measurement
Structure
•
See Table 4.
Process
•
Audit of adherence to guidelines for hand washing and
prevention of infection.
•
Audit of management of patients with neutropenic sepsis.
•
Number of patients treated per annum for induction of remission
of acute leukaemia.
Outcome
•
Iatrogenic deaths and deaths due to infection.
•
One, five and 10-year survival rates.
•
Long-term adverse effects of treatment.
5
•
Outcomes registers should be linked with research.
E. Resource implications
Concentration of services for provision of intensive chemotherapy in
hospitals and wards which have appropriate levels of qualified staff
and adequate facilities will require significant resources in some areas.
The short-term cost of transferring patients from hospitals which
currently treat fewer than five patients per year for induction of
remission of acute leukaemia to higher-volume units is estimated to
be about £1.9 million for England and Wales as a whole (see
Appendix 1, Economic implications of the guidance). This figure is
based on the assumption that 115 new patients per annum are
currently treated in hospitals which deal with small numbers.
83
High dose therapy
A. Recommendations
Whenever possible, high dose therapy with stem (progenitor) cell
rescue should be given in the context of well-designed randomised
controlled trials (RCTs), so that the value of this form of treatment can
be more clearly established.
High dose therapy is potentially toxic and must be fully discussed
with patients and their carers before the decision to begin treatment is
made (see Topic 2, Patient-centred care). This is particularly true of
allogeneic bone marrow transplantation. The intention of high dose
therapy is normally to eliminate malignant cells by myeloablation –
destruction of rapidly-dividing tissue in the bone marrow. This is
described as “conditioning” and it may be achieved either by high
dose chemotherapy or radiotherapy (total body irradiation, or TBI).
Patients and their families should be fully aware of how this form of
treatment could affect them, and that the possibility of long-term
6
remission and good quality of life is balanced by significant risks of
treatment-related death or chronic illness in some survivors.
Psychological factors should be taken into account in decision-making
about the appropriateness of transplantation, and psychosocial
support should be available for patients and their close family
members throughout the period of treatment and isolation.
Continuing psychosocial support and rehabilitation may be necessary
for an extended period after transplantation.
Facilities and expertise
High dose therapy and stem cell rescue should be provided only in
specialised centres which meet JACIE accreditation standards for bone
marrow transplantation. These are described in full on the European
Group for Blood and Marrow Transplantation (EBMT) website
(www.ebmt.org), the main points of which are summarised below.
TBI is appropriate before allogeneic transplantation. This is a
specialised technique that should only be given in radiotherapy
centres which perform such treatments regularly and have the
requisite scientific and physics support. Careful attention should be
given to the clinical management and commissioning arrangements
for the radiotherapy component of the service to ensure the efficient
operation of the transplant service as a whole.
84
JACIE accreditation requirements44
Each clinical haemopoietic progenitor cell transplantation programme
must meet the following criteria:
•
It must consist of an integrated medical team housed in
geographically contiguous space with a single programme
director, common staff training programmes, protocols and
quality assessment systems;
•
It must work with cell collection facilities and processing
laboratories which also meet JACIE standards;
•
It must carry out a minimum of 10 autologous and/or 10
allogeneic stem cell transplant procedures per year;
•
The medical team must include the programme director and
attending physicians who are haematologists or medical
oncologists. All members of the medical team should have had
specialist training in stem cell transplantation, which includes
training in patient selection, stem cell harvesting, administration
of high dose therapy, and management of the various problems
that may develop in patients undergoing transplantation;
•
There must be access to named consulting physicians from
other key disciplines, including surgery, pulmonary medicine,
intensive care, gastroenterology, nephrology, infectious disease,
6
cardiology, pathology, psychiatry, and, if large-field or total
body irradiation is used, clinical oncology;
•
There must be sufficient nurses experienced in the care of
transplant patients to produce a nurse/patient ratio adequate for
the care of severely ill patients;
•
There must be support staff including pharmacists, dietitians,
social workers, physical therapy and data management;
•
There must be a designated in-patient unit that minimises
airborne microbial contamination, and a designated out-patient
area that protects patients from transmission of infection, where
medication and blood product transfusion can be provided;
•
There must be written policies for all clinical procedures.
44 Criteria derived from JACIE standards described in the Haematopoietic progenitor cell
collection, processing & transplantation accreditation manual, on <www.ebmt.org>
(downloaded October 2002).
85
It is essential to minimise the risk of infection in patients who have
undergone high dose therapy (see Table 4). Strict isolation facilities
are important for patients undergoing allogeneic transplantation.
However, standard single rooms with en-suite facilities, as
recommended for patients undergoing intensive chemotherapy (see
Table 4), may be sufficient for patients undergoing autologous stem
cell rescue. Rooms with laminar airflow and high-efficiency
particulate air (HEPA) filtration should be available for all patients
undergoing high dose therapy, particularly when there is risk of
contamination by environmental organisms such as Aspergillus, for
example during periods of building renovation.
Colony-stimulating factors should be considered to enhance recovery
after high dose therapy.
High dose therapy with autologous stem cell rescue
High dose therapy with autologous stem cell rescue should be
available for patients who have multiple myeloma or recurrent or
treatment-resistant Hodgkin’s lymphoma or aggressive lymphomas and
who are fit enough to undergo this form of treatment. It should only
be offered to those with other types of haematological cancer in the
context of multi-centre RCTs.
High dose therapy with allogeneic stem cell
transplantation
Allogeneic stem cell (normally bone marrow) transplantation should
6
be considered for younger patients with leukaemia whose disease
cannot be controlled with chemotherapy alone. Allogeneic
transplantation has a particularly high treatment-related mortality rate
but appears to offer the only hope of cure for some forms of
haematological cancer (notably chronic myeloid leukaemia (CML)). It
should be carried out only by specialist MDTs working in major
centres which meet JACIE accreditation standards. Well-designed
multi-centre RCTs are essential to assess the effectiveness of
allogeneic bone marrow transplantation.
Some allogeneic transplants are now carried out using treatment that
is strongly immunosuppresive but not myeloablative, in order to
create a state of recipient-donor mixture (chimerism). The
chemotherapy is of relatively low intensity so its acute side effects are
less severe, but the risk of graft-versus-host disease remains and these
patients require intensive follow-up with monitoring for opportunistic
infections. This approach – often described as “mini-allo” – has
allowed allogeneic transplantation to be used for patients who would
have otherwise been excluded because of age or co-existing medical
conditions, but no prospective trials have yet been performed to
determine its usefulness.
86
B. Anticipated benefits
Delivering high dose therapy in specialised centres which deal with
larger numbers of patients is likely to create a more cost-effective
service with better staffing levels, facilities and expertise. This should
reduce the incidence of life-threatening complications, improve
management of patients, and thus reduce the frequency of treatment-
related deaths.
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
Effectiveness of high dose therapy and stem cell
rescue
Autologous stem cell rescue
RCTs have been carried out comparing high dose therapy and
autologous stem cell rescue with conventional chemotherapy or no
treatment in patients with a variety of forms of haematological cancer.
High dose treatment, being more toxic than conventional
chemotherapy, is more likely to lead to treatment-related death or
6
death in remission.(A) However, there is good evidence for benefit in
patients with multiple myeloma or recurrent aggressive lymphoma or
Hodgkin’s lymphoma.(A)
It is not clear whether high dose therapy is beneficial for initial
treatment of patients with aggressive lymphoma, and this should still
be regarded as experimental. High dose therapy does not appear to
convey benefit when used after a short course of induction treatment;
two studies suggest a benefit from the completion of conventional
therapy. In patients with poor prognostic features it may be
appropriate to test the place of high dose therapy after a full course
of induction. There is better evidence for high dose therapy in
second remission and this is now routine practice.
In Hodgkin’s lymphoma, the only randomised trials of high dose
therapy show improved progression-free survival but not overall
survival.(A) Nevertheless, this approach is now routine in second or
subsequent remission.
In acute leukaemias, there is no clear evidence that autologous
transplantation produces higher survival rates than chemotherapy
without transplantation.(A)
87
Larger randomised studies, stratified by age and with long follow-up
periods, are urgently required to clarify the role of high dose therapy
with autologous transplantation, particularly for patients with
lymphoma.
Allogeneic bone marrow transplantation (BMT) for leukaemia
Allogeneic BMT is a high-risk treatment strategy, with significant rates
of treatment-related death and morbidity, especially in older patients.
Despite these risks, there have been very few controlled trials
comparing allogeneic BMT with conventional chemotherapy.
Two RCTs have assessed the effectiveness of high dose therapy and
allogeneic stem cell rescue during first remission of acute myeloid
leukaemia (AML). In both, patients randomised to the high dose
therapy arm underwent allogeneic BMT if suitable donors were
available, but when no donor could be found, autologous stem cell
rescue was used. These trials found that allogeneic BMT was
significantly more risky than intensive chemotherapy with or without
autologous stem cell rescue, and did not lead to better survival
rates.(A)
There do not appear to be any other RCTs comparing allogeneic bone
marrow or peripheral stem cell transplantation with standard
chemotherapy for any form of haematological cancer.
Information from six controlled (non-randomised) trials (CCTs)
6
suggests that allogeneic transplantation may be associated with
improved survival rates among selected patients with acute
lymphoblastic leukaemia (ALL). Meta-analysis of data from three CCTs
(n=261) gives a combined two-year OR of 0.38 (95% CI: 0.22 to 0.65)
for progression-free survival - an absolute survival benefit of about
23% (95% CI: 11 to 35%) in favour of high dose therapy with
allogeneic transplantation. Pooled three- and four-year progression-
free survival data from two CCTs (n=123) showed an absolute survival
benefit of about 35% (95% CI: 15 to 51%) (OR 0.23, 95% CI: 0.10 to
0.51).(B)
Allogeneic bone marrow transplantation may offer the only hope of
long-term remission for patients with CML. The best outcomes are
achieved with human leucocyte antigen (HLA)-matched sibling
allografts, with survival rates in most published reports of around 60%
among relatively young patients (median age 37 years or less) in the
chronic stage of the disease. It is considered significant that survival
rates after allogeneic transplantation reach a plateau, whilst those for
patients treated with conventional chemotherapy show an inexorable
decline. Among older patients, those given poorly matched grafts or
transplants from unrelated donors, outcomes are considerably worse,
with higher rates of death, relapse, and graft-versus-host disease.
Where rates of chronic graft-versus-host disease are reported, they
range from 18% to 67%.(B)
88
One report of dose-reduced conditioning in 44 older patients (median
age 52 years) was included in the review. The median overall
survival time was 37 months, but 41% of patients were still
leukaemia-free at 47 months.(B)
Conditioning regimens
Several comparative trials have demonstrated that survival rates are
slightly higher after total body irradiation (TBI) than after busulphan-
cyclophosphamide conditioning (BUCY).(A) Less toxic regimens,
known as “mini-allografts”, are beginning to be used for older or less
fit patients. In 2001, 231 mini-allografts were reported in England and
Wales.45 No trials have been identified which compare mini-allografts
with other treatments.
Granulocyte-colony-stimulating factor (G-CSF)
Recovery after transplantation seems to be quicker after the
administration of granulocyte-colony-stimulating factor (G-CSF),
whether used to improve the harvest of stem cells or after
transplantation. There is no advantage in using doses over
5µg/kg/day, and treatment may be delayed until up to 10 days after
transplant.(A)
Minimising risk of infection
There is conflicting information on the value of isolation and air
filtration for patients undergoing allogeneic transplantation, and there
have been no randomised studies addressing these issues. Registry
6
analysis of large numbers of patients nursed in isolation suggest that
HEPA filtration and laminar airflow are beneficial, but other non-
randomised studies have found that similar outcomes (in terms of
infection rates) could be achieved using standard single rooms.(B)
There is evidence that patients undergoing autologous transplantation
do not need strict isolation; indeed, carefully selected patients can be
treated as out-patients. Many of those given out-patient treatment will
require hospital admission for treatment-related illness, but are likely
to spend less time in hospital (median, 7 nights versus 14,
p<0.001).(B)
Strong associations have been found between environmental
contamination with Aspergillus and building renovation. HEPA
filtration alone is not sufficient to protect against this, but HEPA
filtration plus laminar airflow is effective against Aspergillus.(B)
45 Data provided on request by British Society for Bone Marrow Transplantation (BSBMT)
Registry, October 2002.
89
Psychological issues
Patients’ ability to cope with transplantation
A prospective study of patients with acute leukaemia found that
distraction coping techniques and fighting spirit had highly significant
impacts on the probability of survival five years after allogeneic
transplantation. The only clinical factor that had a significant
influence on survival was stage of disease at transplant.(B)
Quality of life after high dose treatment and transplantation
High dose treatment is both physically and emotionally stressful and
people who go through it continue to feel exhausted and depressed
for a long period – several months, perhaps years – afterwards.
Sexual function may be particularly slow to recover. Patients who
undergo high dose treatment experience poorer quality of life than
those who had conventional chemotherapy for about a year, but these
differences diminish with increasing time. High dose therapy can
produce long-term adverse effects such as fatigue, which affect day-
to-day functioning; this may still be reported a decade later.(B)
Chronic graft-versus-host disease, a relatively common consequence of
allogeneic transplantation, can cause persistent malaise and poor
quality of life. Patients may require long-term treatment with steroids.
This problem appears to be particularly common when peripheral
blood stem cells are used for allogeneic transplantation.(B)
6
Use of transplants for adults with haematological
cancers in England and Wales
The British Society for Bone Marrow Transplantation (BSBMT) registry
maintains a database of the use of stem cell transplantation in
England and Wales. Table 5 shows the number of transplants carried
out for each type of haematological cancer in adults in 39 centres in
2001, along with the change in the use of this form of treatment in
the five-year period since 1996.
90
Table 5.
Number of stem cell transplants in adults with
haematological cancers, England and Wales, 200146
Disease
Type of transplant
Total number,
% change
2001
since 1996
Autologous
Allogeneic
AML
53
162
215
+23
ALL
20
125
145
+21
CML
10
93
103
-18
MDS
5
45
50
+56
CLL
8
20
28
+65
Myeloma
499
35
534
+124
Hodgkin’s
lymphoma 132
16
148
-25
NHL
402
73
475
+47
Totals
1129
569
1698
+38
BSBMT figures show that the annual number of stem cell transplants
6
given for these forms of cancer as a group increased by 38% over this
period, from 1228 to 1698. The largest single component of this
increase is due to greater use of autologous stem cell rescue for
patients with myeloma.
Number of transplants undertaken by individual teams
A recent report gives figures for the number of patients treated with
high dose treatment and stem cell rescue in hospitals in the UK.47
This reveals that 10 or more procedures were carried out by 26 teams
in 2000; these are listed below, with the number of allografts and
autografts reported by each. It appears that some of these teams
worked in two hospitals, some distance apart (e.g. Cambridge and
Norwich). (Children’s hospitals are excluded where separate figures
are given.)
46 Data provided on request by BSBMT Registry, October 2002.
47 Gratwohl A, Baldomero H, Horisberger B, et al. Current trends in hematopoietic stem cell
transplantation in Europe. Blood 2002;100:2374-2386.
91
Table 6.
Teams in England and Wales which carried out 10 or
more allografts and/or autografts in 2000
Hospital
Number of
Number of
allografts
autografts
Birmingham, Heartlands Hospital
14
20
Birmingham, Queen Elizabeth Hospital
42
49
Bournemouth, Royal Bournemouth Hospital
0
11
Bristol, Royal Hospital for Sick Children and
Southmead Hospital
65
19
Cambridge, Addenbrooke’s Hospital and
Norwich Hospital
11
34
Cardiff, University Hospital of Wales
11
29
Exeter, Royal Devon and Exeter Hospital
0
13
Leeds, St James’s University Hospital and
Leeds General Infirmary
26
76
Leicester, Royal Infirmary
13
38
Liverpool, University Hospital
13
35
London, Guy’s Hospital
8
17
London, Hammersmith and Charing Cross Hospital
45
75
London, King’s College Hospital
41
24
6
London, Royal Free Hospital
44
17
London, St Bartholomew’s and the Royal
London Hospital
19
34
London, University College Hospital
54
89
Manchester, Christie Hospital
20
66
Manchester, Royal Infirmary
32
21
Newcastle upon Tyne, Royal Victoria Infirmary
41
43
Nottingham, City Hospital
43
42
Oxford, John Radcliffe Hospital
14
26
Plymouth, Derriford Hospital
11
22
Poole, Dorset Cancer Centre
0
20
Sheffield, Royal Hallamshire, Weston Park and
the Children’s Hospitals
19
26
Southampton General Hospital, CRC Wessex
0
20
Stoke-on-Trent, North Staffordshire Royal Infirmary
0
12
92
Teams at the following hospitals carried out fewer than 10 of one or
both of these procedures (number of allografts/autografts in 2000):
Bangor, Ysbyty Gwynedd (0/8); Coventry, Walsgrave Hospital (0/6);
London, Oncology Marrow Transplantation Group (1/6); London, St
George’s Hospital (7/5); Manchester, Hope Hospital (0/2); Manchester,
Trafford General Hospital (0/1); Rotherham, General Hospital (0/1);
Sunderland, Royal Hospital (0/4); Swansea, Ysbyty Singleton (0/7);
Swindon, Princess Margaret Hospital (0/4); Taunton, Somerset and
Taunton Hospital (1/7); Wakefield, Pinderfield and Pontefract
Hospitals (0/9).
D. Measurement
Structure
•
Appropriate facilities for high dose therapy at specified centres.
•
Availability of rooms with filtered air.
Process
•
Evidence that patients are fully informed about what high dose
treatment involves, its potential consequences and the
6
uncertainty about benefit, before they agree to it.
•
Implementation of accreditation systems for transplant centres.
•
Number of patients undergoing each type of procedure per
annum.
Outcome
•
Mortality rates at one and five years.
•
Submission of results from accredited centres to the national
registry (BSBMT).
•
Rates of graft-versus-host disease requiring long-term treatment.
•
Quality of life measures from long-term monitoring and audits of
care.
93
E. Resource implications
The main resource implications for high dose therapy arise from a
continuing increase in the number of transplants (based not on
recommendations in this guidance, but on extrapolation from current
trends), and the need for adequate staff levels and bed numbers in
units providing this form of treatment. The expected growth in the
volume of activity is discussed in Appendix 1, Economic implications
of the guidance.
It is believed that there will be a particularly large rise in the number
of “mini-allografts”, which are at least as expensive as standard
allogeneic transplants (£40,269), and may cost up to 30% more.
Overall, the cost of increasing transplant activity in England and Wales
is likely to be around £7.3 million per year, but there is considerable
uncertainty about both the rate of increase and its potential cost; huge
variations in the reported costs of transplants in individual centres add
to this uncertainty.
The costs of engaging more staff have not been calculated, but about
half of the centres which carry out both autologous and allogeneic
transplants report shortages of trained nurses and many also lack data
managers. It is believed that only minor service reconfiguration will
be required to achieve the minimum patient numbers recommended
by JACIE, so this has not been included in the economic analysis.
6
Although not a direct consequence of this guidance, resources are
required to develop and sustain existing commitments to JACIE
accreditation systems and to cover the running costs of the BSBMT
transplant registry. Both activities are important to quality assurance.
94
Continuing
management
A. Recommendations
Most forms of haematological cancer follow a chronic relapsing
course, so patients need regular monitoring. There is no reliable
evidence on what form of monitoring is most appropriate, or what
the optimum intervals between clinic visits might be. Local clinical
policies should be agreed by all the haemato-oncology multi-
disciplinary teams (MDTs) within each network.
The progress of haematological cancer is generally assessed by blood
tests, often including ongoing cytogenetic testing. Molecular follow-
up is increasingly used for chronic myeloid leukaemia (CML) and
acute leukaemia. In lymphoma, CT scans may also be required.
Long-term follow-up
This document does not deal with follow-up for people treated for
haematological cancer as children or adolescents; this issue should be
covered in forthcoming National Institute for Clinical Excellence
(NICE) guidance on child and adolescent cancers.
7
Patients should be informed that routine long-term follow-up does
not offer any clinical advantage to them. Those whose disease is
believed to be cured should normally be discharged, but long-term
follow-up by telephone or written questionnaire should be
considered. The primary aim of such long-term follow-up should be
to identify and collect information on delayed effects of treatment.
Since it is not possible to be certain whether a permanent cure has
been achieved, patients should be given clear written instructions on
whom they should contact if they are concerned about any new
symptoms. They should be given information about the level of risk
of recurrence of their disease and reassured that relapse is rare after
five years’ freedom from signs of disease. Patients and their GPs
should also be given information about the risk of delayed adverse
effects of treatment, and symptoms that should prompt contact with
the haematological cancer MDT.
95
Long-term problems are particularly common after high dose
treatment and allogeneic bone marrow transplantation (BMT).
Providers may therefore consider establishing long-term follow-up
systems for patients who have undergone this procedure. Follow-up
may also be valuable for collection of information on long-term
outcomes of treatment in people who participated in clinical trials.
A database should be maintained to record information about all
patients who have undergone treatment for haematological cancer,
whether or not they are being actively followed up. There is an
increased risk of a variety of cancers after intensive treatment for
haematological malignancies, especially among those who were
treated as children or adolescents. One particular cause for concern
after extended field radiotherapy for Hodgkin’s lymphoma is the high
rate of breast cancer in relatively young women. Patients who have
had radiotherapy to the neck should have regular thyroid function
tests.
B. Anticipated benefits
Since follow-up offers no clinical benefit for asymptomatic patients
who appear to be cured, discharging such people allows clinic time to
be used for others whose need is greater. A database of information
about patients who have undergone treatment for haematological
cancer will both improve knowledge of long-term epidemiology and
permit patients to be recalled if new evidence emerges on delayed
effects of treatment; such a database could be efficiently maintained
7
through postal or telephone contact.
C. Evidence
Note: the reliability and quality of evidence supporting the recommendations
is graded as A, B and C, where A is the strongest evidence. The grading
taxonomy is explained in Appendix 2.
Effectiveness of follow-up
There is no reliable evidence showing that intensive follow-up of
patients who have completed treatment for any form of
haematological cancer is beneficial.
The risk of recurrence of Hodgkin’s lymphoma is highest in the first
two years after initial treatment. Recurrence can be identified through
regular physical examination, blood counts, x-rays for those who had
disease in the chest, but there have been no comparative studies to
show whether this improves long-term outcomes. Retrospective
studies suggest that educating and informing patients so that they
96
recognise sinister symptoms and seek prompt attention may be more
useful than routine follow-up, since most recurrences are detected by
patients themselves.(B)
In leukaemia, relapse is usually signalled by changes in the blood; the
evidence does not support routine use of more invasive procedures
such as bone marrow aspiration or lumbar puncture for detecting
recurrent disease.(B)
In patients who have been treated for non-Hodgkin’s lymphoma
(NHL), physical examination and measurement of serum lactate
dehydrogenase (LDH) can be helpful for diagnosing relapse. Imaging
may detect a higher proportion of recurrences in low-grade
lymphoma but there is no evidence to suggest that this affects
survival.(B)
Long-term effects of treatment
Quality of life
A review of studies suggests that quality of life and health status
improves with increasing time since treatment. 80% of long-term
survivors of BMT experience good to excellent health. People treated
for Hodgkin’s lymphoma may experience persistent side-effects of
treatment, with generally poorer physical functioning and more
health-related unemployment than age-matched controls; nevertheless,
75-85% of former patients are able to continue in work.(B)
Secondary malignancies
Secondary malignancies are recognised long-term adverse effects of
7
treatment for haematological cancers. The incidence of both
haematological malignancies and solid tumours is greatly increased
among patients who were treated when young; and those who
develop secondary cancers are more likely to die from their disease
than other cancer patients of the same age.(B)
Risk estimates for secondary haematological malignancies vary widely
between patient populations. In general, the risk of leukaemia is
more strongly associated with chemotherapy, especially in patients
who had six or more cycles of chemotherapy, who received MOPP, or
who were treated for relapse of their primary cancer. Solid tumours
are more common after radiotherapy, and usually develop within the
treatment field. The excess risk of secondary leukaemia peaks
between five and nine years after treatment, but the risk of a
secondary solid tumour continues to rise.(B)
Large studies reveal that patients treated for Hodgkin’s lymphoma face
about three to seven times the population risk of developing cancer
(of any type). The absolute risk for these patients is about 5-7% 10
years after the initial diagnosis, rising to 14% after 20 years. One
97
study reported that 28% of a group of 1253 patients who underwent
initial treatment aged 40 or less, had developed a secondary cancer
after 25 years of follow-up.(B) However, these patients would have
undergone more risky treatment than is normally used today.
The risk of breast cancer among women treated for Hodgkin’s
lymphoma depends on their age at the time of their primary disease.
Retrospective studies reveal that women treated at 21-30 years old are
about six times more likely to develop breast cancer than normal, but
among those treated aged 31-40, the risk is 2.4 times normal. A
cumulative risk of breast cancer of 16% has been reported at 25 years
after treatment.(B)
High dose therapy with allogeneic transplantation for any form of
haematological cancer appears to be associated with a similar level of
long-term hazard to treatment for Hodgkin’s lymphoma - around four
to five times the population risk for any form of cancer. About 12-
15% of these patients will develop a secondary cancer within 15 years
of initial treatment.(B)
D. Measurement
Structure
•
Local clinical policies on continuing management of
asymptomatic patients with haematological cancer, agreed by all
haemato-oncology MDTs in the network.
7
•
Local clinical policies on long-term follow-up of patients whose
haematological cancer is believed to be cured.
•
Database for recording secondary cancers among people treated
for haematological malignancies.
Process
•
Audit of local follow-up practice against policy guidelines.
Outcome
•
Rates of secondary malignancy after intensive treatment for
haematological cancer.
•
Patients’ satisfaction with, and comprehension of, information on
symptoms that should lead them to contact the haematological
cancer MDT.
98
E. Resource implications
These recommendations are not expected to have significant
additional resource implications. Resources will be required to
establish and maintain a long-term follow-up database, but no
analysis has been carried out of the potential cost.
7
99
Palliative care
The National Institute for Clinical Excellence (NICE) guidance on
improving supportive and palliative care for adults with cancer48 is
planned to be published early in 2004. It is intended to complement
the site-specific guidance, giving detailed recommendations on many
issues relevant to this section as they apply to cancer care generally,
with supporting evidence. The areas it covers are listed in Topic 2,
Patient-centred care.
A. Recommendations
Palliative care services and haemato-oncology should work together
to provide integrated care for patients with haematological cancers.
These patients need ongoing management by the haemato-oncology
multi-disciplinary team (MDT) throughout the course of their disease.
Adequate palliative care is nevertheless important to maximise quality
of life and there should be effective integration between palliative
care and haemato-oncology services throughout the patient’s illness,
not just when it is acknowledged that the terminal phase has been
reached.
Palliative care specialists should be members of haematological cancer
8
MDTs (see Topic 4, Organisation of specialist services). They should
take active roles, both as advisors for those who provide direct care
for patients on palliation of symptoms such as pain, and working
directly with those patients who might benefit from their expertise.
Patients and their carers often need multi-faceted support, including
information on managing symptoms and help with accessing social
care and benefits. This can be provided by palliative care teams,
both in the community and in hospitals.
Palliative care specialists should be involved in discussing the
management of patients, especially those for whom the possible
survival benefits of treatment might be outweighed by its
disadvantages. There should be agreed guidelines for managing the
transition from aggressive treatment to palliative care which ensure
that it is handled sensitively and appropriately, and that it takes
account of individual patients’ emotional and physical needs.
48 National Institute for Clinical Excellence. Improving supportive and palliative care for
adults with cancer.
100
This transition should be regarded as a change in treatment goals and
emphasis, not a complete handover from haemato-oncology to
palliative care services.
Palliative treatment in haemato-oncology
Long-term support for patients is part of normal haematology practice
and most of the long-term treatment provided for patients with
haematological cancers is actually palliative in nature. Blood product
support may be necessary at many points in the disease process and
it becomes essential to continued survival in the later stages of
leukaemia and myeloma. Haemato-oncology MDTs should make
arrangements to enable blood product support to be provided to
patients in places other than acute hospitals or haematology units.
Some symptom control issues for haemato-oncology patients are the
same as for many other malignancies. Pain can be a major problem
for some patients. Effective pain control is particularly important for
those who undergo intensive treatment and for those with inherently
painful diseases such as myeloma. Each haemato-oncology MDT
should have access to a pain specialist (who may be the palliative
care specialist member of the MDT) who has specific expertise in the
management of the types of problem that patients with
haematological cancer may experience. Palliative radiotherapy should
be available for patients with bone pain and for those with low-grade
lymphomas.
The specialist palliative care team
Palliative care is essentially a local service and specialist palliative care
teams should be based both in local hospitals and in the community.
The role of the specialist palliative care team includes both direct care
for patients and families with complex problems, and the provision of
advice, support and education for other health professionals. One
8
member of the team should be responsible for ensuring efficient co-
ordination of palliative care services and rapid communication
between professionals and with patients and their families.
The specialist palliative care team should include, as a minimum, the
following members:
•
Palliative care physician;
•
Palliative care nurse specialists.
The team should have close links with the following:
•
Pain management team;
•
Clinical psychologist/liaison psychiatrist;
•
Social worker;
101
•
Chaplain/pastoral care worker who can offer counselling and
spiritual guidance for patients with advanced incurable illness
and their carers;
•
Bereavement care worker;
•
The primary care team.
Those who care for these patients should be able to get advice by
telephone from appropriately trained nurses at any time of the day or
night. A named member of the palliative care team should be
responsible for ensuring effective co-ordination of services to support
patients, facilitating both continuity of care and rapid communication
between professionals, with patients, and with carers.
The team should endeavour to make it possible for patients to spend
their remaining life in the place they prefer, whether this is home,
hospital or hospice; but team members should be alert to the
possibility that patients’ views about where they would prefer to die
may change as death approaches.
Bereavement counselling should be available for carers and close
family members, who may become very distressed by an extended
period of aggressive treatment which ends with the patient’s death.
Some patients and carers may need counselling at the point of
transition from attempted cure to purely palliative measures, to help
them accept that further aggressive treatment is pointless.
Palliative care in the community
Palliative care teams should be available to arrange the provision both
of relief from symptoms and social and psychological support for
8
patients living at home whose needs cannot be adequately met by
primary care teams. Community palliative care services should work
closely with primary care teams and hospital-based services; rapid
and effective communication and information-sharing between teams
is essential.
Criteria for referral for specialist care should be agreed and
documented for the whole cancer network by palliative care
specialists and representatives from primary care and haemato-
oncology teams. Primary care teams should assess patients’ needs
regularly and accurately, to ensure that patients who require specialist
palliative care or treatment are quickly referred to the appropriate
MDT.
102
B. Anticipated benefits
Better integration of palliative care with treatment services throughout
the course of the illness can be expected to enhance quality of life for
both patients and their carers. Integrated care is particularly essential
at the end of life, and the contribution of palliative care specialists
can help to create a more appropriate balance between efforts to
preserve life and the need for comfort, peace and the support of
close family members when it becomes clear that death is inevitable.
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
There is weak but consistent evidence that palliative care is used less
in haematological cancers than in patients with solid tumours, and
that access to specialised palliative care support may have been less
available to haematologists than solid tumour oncologists, particularly
for patients in the final phase of illness. Much of this evidence
originates outside the UK, but whilst it is not clear how similar
attitudes here may be to those in the US and Australia (where most
studies have been carried out), information from the UK does point to
the same conclusions.
The National Cancer Alliance survey carried out to inform this
guidance found that few patients had had contact with palliative care
teams, but those who had received support from palliative care teams
for pain management reported that it had been valuable. This survey
8
did not, however, focus on patients in the terminal phase.
One particular problem with haematological cancer is judging when
to stop using intensive forms of treatment; clinicians, patients and
their families often find it difficult to acknowledge when remission
induction is no longer possible. The decision to change to a
palliative approach may be taken too late or not at all, and
persistence with aggressive treatment can cause great distress.(B)
A survey based on accounts from carers in the UK bereaved in 1990,
found that patients who died of haematological cancer were
considerably less likely to receive care from community specialist
palliative care nurses in the last months of life than those with other
forms of cancer (OR 0.37, p<0.001).(B) These patients are more
likely to die in hospital than at home or in a hospice.(B)
103
A study from the US, based on case-notes of patients who had died
of haematological cancer, reported that there was significant variation
between doctors in the probability of providing palliative therapy.(B)
There are a few reports of more satisfactory management of the dying
process of patients with haematological cancers, but each is based
only on one or two cases. Factors that appear to produce better
emotional outcomes include early involvement of the palliative care
team, whose members may be able to assist the transition from
curative to palliative care; reducing use of medical technology and
invasive treatment, concentrating instead on the patient’s physical and
psychological comfort; and facilitating dying at home whenever
possible. The research suggests that the emotional and spiritual
needs of patients and their families are often not recognised and
addressed.(C)
A randomised controlled trial (RCT) assessing the effects of improved
co-ordination of services for patients dying from a variety of forms of
cancer show that this is cost-effective and can improve outcomes for
patients. Patients who could contact a co-ordinator who could
facilitate access to appropriate services spent significantly less time in
hospital or hospice, required significantly fewer home visits by
nursing services, and were more likely to receive effective treatment
for vomiting.(A)
D. Measurement
Structure
•
Availability of palliative care teams to support patients at home
8
or in hospices.
•
Availability of telephone support, advice and information
services for patients and their carers.
•
Availability of bereavement counselling for close family members
and carers.
Process
•
Audit of involvement of palliative care teams in the management
of patients with haematological cancers.
•
Evidence that providers elicit information about patients’
preferences about place of death and their views about medical
intervention in the terminal phase of illness.
104
Outcome
•
Audit of patients’ experience of pain and satisfaction with pain
control during intensive treatment.
•
Audit of myeloma patients’ experience of pain and satisfaction
with pain control.
•
Audit of patients’ and carers’ preferences about place of death.
•
Carers’ comments on services provided during the patient’s final
month of life.
E. Resource implications
The use of palliative radiotherapy and services for the provision of
blood product support are not expected to change significantly under
the new guidance. Improving service provision, including the
availability of palliative care teams to support patients at home and in
hospices and providing bereavement counselling, is likely to have the
greatest cost impact. These services provide support to patients with
all types of cancer, and is being considered in the context of the
NICE guidance on improving supportive and palliative care for adults
with cancer, planned to be published early in 2004.
8
105
Clinical trials and use
of protocols
A. Recommendations
Improvements in the management of haematological cancers (as for
solid tumours) require reliable evidence that interventions are effective
and that they improve outcomes for patients. It is therefore important
that health service commissioners should support the well-designed
clinical trials within the National Cancer Research Network (NCRN)
portfolio. There should be network-wide co-ordination of local
participation in NCRN clinical trials in haematology through each
cancer research network. Haemato-oncologists should regularly
review the national portfolio of recognised studies and identify those
they wish to support at local research network level.
During the period between trials and publication of any National
Institute for Clinical Excellence (NICE) appraisal of the interventions
assessed, there should be continued support to provide ongoing
treatment for patients who took part in the trials.
Multi-disciplinary teams (MDTs) should aim to maximise entry into
trials by considering this issue, discussing on-going trials, and
reporting on problems and progress at their regular meetings. The
possibility of entry into an appropriate trial should be discussed with
every patient who fits the inclusion criteria. Such patients should be
given accurate and accessible information to inform their decision
about whether to participate in the trial (see Topic 2, Patient-centred
9
care).
Trials of treatment for haematological cancer should be designed with
outcome measures that reflect quality of life (assessed by patients, not
just clinicians) as well as survival time and clinical measures with
prognostic significance (surrogate endpoints).
Patients who are not involved in a clinical trial should be treated
according to local clinical guidelines based on research evidence.
106
B. Anticipated benefits
Reliable information on the effectiveness of clinical interventions can
only be obtained from large, well-designed trials. Thus, the more
patients included in such trials, the better the knowledge base for
optimum treatment. Management in the context of trials also tends to
be associated with longer survival times for patients with cancer.
In acute leukaemia in particular, survival rates have increased
dramatically over the past few decades, especially among young
people. This improvement may be directly attributable to knowledge
gained from clinical trials.
C. Evidence
Note: the reliability and quality of evidence supporting the
recommendations is graded as A, B and C, where A is the strongest
evidence. The grading taxonomy is explained in Appendix 2.
In acute leukaemia, the level of participation in multi-centre research
studies is high; a majority of eligible patients are currently entered
into trials. The same is not true, however, of other forms of
haematological cancer; in lymphoma, it is estimated that only about
10% of those who fit the entry criteria for major clinical trials are
actually in them. Overall, perhaps as few as 5% of patients with
haematological cancer are treated in the context of a clinical trial.(C)
A systematic review of cancer trials provides some evidence that
participation in clinical trials can benefit patients, but it is difficult to
distinguish between a real protocol effect from bias due to clinician
selection.(A) Audit data from the UK shows that among patients with
either acute myeloid leukaemia (AML) or aggressive lymphoma,
participation in a trial is associated with a significantly higher chance
9
of complete remission and improved survival.(B) However, patient
selection could again account for much of the apparently better
outcome. In one of the few studies identified that described outcomes
in eligible patients who were not randomised for entry into a trial (of
treatment for non-Hodgkin’s lymphoma (NHL)), there was no
significant difference in disease-free survival between the groups.(A)
Outcome measures of trials of treatments for haematological cancers
are, in almost every case, confined to survival rates and clinical
measures that have prognostic value but may not clearly reflect the
way patients feel. Since evidence-based decision-making about
treatment relies heavily on the results of these trials, it is important
that patients’ views of their experience of treatment and its after-
effects should be considered. Reliable and reproducible quality of life
measures are available for use in trials of cancer treatment and can
have important implications, both for the appropriate use of
107
interventions and so that patients can give truly informed consent to
treatment. See Improving Outcomes in Lung Cancer49 for a discussion
of this issue.
Although the evidence in haematology is far from definitive, treatment in
accordance with local clinical guidelines (protocols) is generally
associated with better outcomes (see Improving Outcomes in Breast
Cancer50). The development of local protocols demands a critical
attitude towards best practice which is likely to have a beneficial effect
on those involved. However, further research is required which looks at
treatment protocols and outcome in all patients, not just those in trials.
D. Measurement
Structure
•
Network-wide information systems that allow clinicians to identify
trials for which specific patients might be eligible.
•
Availability of support for clinical trials.
•
Availability of continued support for patients who have been
successfully treated with products used in clinical trials.
Process
•
Evidence of regular discussion of participation in clinical trials at
MDT meetings.
Outcome
•
Proportion of patients with each type of haematological cancer
entered into trials.
9
E. Resource implications
Treatment in the context of a clinical trial tends to cost more than
standard treatment. Adequate resources need to be made available,
both to support research and to provide appropriate and effective
continuing management for patients who have participated in clinical
trials. The potential cost impact of these recommendations has not
been calculated.
49 Available on the Department of Health website <www.doh.gov.uk/cancer> under the
heading Guidance for NHS.
50 Available on the NICE website <www.nice.org.uk>, where it is described as “Breast cancer
service guidance”.
108
Appendix 1
Economic
implications of the
guidance
A1
An economic modelling exercise was carried out to estimate the cost
implications for England and Wales of implementation of the main
recommendations of this guidance.
The major impacts on costs fall in five broad areas:
•
Specialist diagnostic services
•
Multi-disciplinary teams (MDTs)
•
Patient-centred care (clinical nurse specialists)
•
High dose therapy and transplant services
•
Induction chemotherapy for remission of acute leukaemia
Specialist diagnostic services
Improving the consistency and accuracy of diagnosis for
haematological malignancies is a key objective of the guidance. Two
levels of haemato-pathological service are recommended: a local
service, as exists at present in most district general hospitals and
cancer units, and a specialist service providing molecular biology and
identification of genetic abnormalities, which is likely to serve one or
more cancer networks.
In England a number of networks are already operating with
centralised or partly-centralised diagnostic services. In other
networks, centralised specialist services will need to be developed
more or less from scratch. Initial one-off payments needed to set up
the system in England are estimated to be around £5.8 million, with
annual running costs of approximately £7.5 million per annum. Costs
will vary according to the size of centralised services and the type of
equipment purchased. In the low scenario set up costs are estimated
at £4.7 million with annual running costs of £6.7 million (assuming a
high proportion of services cover a large population of 3 million and
no services purchase a gene sequencer and quantitative PCR
machine). In the high scenario set up costs are estimated to be £7.5
million with annual running costs of £8.1 million (assuming a high
109
proportion of services cover a population of 1.5 million, with all
services purchasing a gene sequencer and quantitative PCR machine).
In Wales the All Wales Lymphoma Pathology Review Service has
recently secured funding to allow 100% of cases of new lymphoma to
be reviewed using a wide spectrum of diagnostic techniques
including immunocytochemistry, flow cytometry, conventional
cytogenetics, interphase cytogenetics together with molecular genetic
studies and, in the near future, gene expression profiling.
Cost savings from avoided misdiagnosis are not known but may be
A1
substantial.
Multi-disciplinary teams
Multi-disciplinary team (MDT) working allows patients to benefit from
the expertise of a range of specialists for their diagnosis and
treatment, and helps ensure that care is given according to recognised
guidelines. Lymphoma MDTs are already well-established in many
Trusts. However, MDTs for leukaemia and myeloma do not currently
exist in a significant proportion of Trusts and therefore new MDTs
will need to be created.
A wider range of staff will need to be involved, with additional time
required for attending meetings and travelling, in order that MDTs can
function in accordance with the guidance. Many Trusts, particularly
units, currently suffer from lack of administrative support. Other
staffing issues include shortages of radiologists, pathologists and
oncologists.
The cost of additional staff time for MDT meetings and for ensuring
that all MDTs have a co-ordinator is estimated to be an additional
£7.2 million per year. The level of uncertainty is high, with a range of
£4.2 million to £10.0 million. The cost of service re-configuration for
an individual cancer network will vary according to the existing MDT
configuration and staffing levels, as well as the future MDT
configuration model adopted. The base case assumes that meetings
are held fortnightly. Moving to weekly meetings would almost double
the cost of running MDTs. Factors such as the number of teams
serving the cancer, which team members travel and the distances
travelled (or the price package for line charges) will impact on the
annual cost of running MDTs and should be investigated
independently by each cancer network.
Staffing issues will be significant and the development of MDTs will
need to evolve gradually over a number of years. Additional staff
may need to be recruited to allow existing staff the time to attend
meetings. Shortages of radiologists, pathologists and oncologists will
hamper development of full MDTs in the short term.
110
The use of teleconferencing facilities offers potential cost savings in
networks where geographical dispersion of hospitals results in long
travel times. Costs for purchasing and running teleconferencing
facilities will vary according to the type of system required and the
number of sites involved. Assuming that all networks will need to
purchase new equipment, the initial investment for England and
Wales is estimated to be £3.5 million for the basic system, increasing
to £6.3 million if remote diagnosis is required at each site. It is
however anticipated that other MDTs will utilise the equipment once
purchased and therefore the initial cost would be shared across a
wide range of specialities and is not included in the cost summary.
A1
Patient-centred care (clinical nurse specialists)
The guidance emphasises the need for improved information and
support for patients with haematological malignancies, and the central
role that clinical nurse specialists (CNS) should play in delivering
more patient–centred care. CNSs should also play an active role in
MDT meetings.
Data on current numbers of nurse specialists are limited. The
CHI/Audit Commission report indicated that at the time of their
survey (winter 2000/2001) around 55% of Trusts had no CNS posts
and that around 80% of those working with patients with
haematological cancers reported severe time constraints on the service
that they could provide.
An order of magnitude estimate of the additional number of nurses
required was made, based on the CHI report and discussions with a
number of CNSs. This was cross-checked against local estimates of
future posts required in a number of areas. It is estimated that
around 140 additional CNS posts are required nationally,
approximately four new posts per typical cancer network of 1.5
million population. The total cost of providing additional CNSs for
haematological malignancies in England and Wales is estimated to be
£4.6 million.
High dose therapy and transplant services
The guidance recommends that high dose therapy and stem cell
rescue should be provided only in specialist centres which meet
JACIE accreditation standards for bone marrow transplantation (BMT).
These standards include a minimum activity level of 10 autologous
and/or 10 allogeneic stem cell transplants per year. Data from the
British Society for Bone Marrow Transplantation (BSBMT) registry
database for 2001 suggest that there is already considerable
centralisation of these services, with only a small number of centres
in England and Wales undertaking fewer than 10 transplants per year.
111
Data from the BSBMT registry database show that the annual number
of stem cell transplants for haematological malignancies in England
and Wales increased by 38% between 1996 and 2001, from 1,228 to
1,698. The largest single component of this increase was the volume
of autologous stem cell rescue for patients with myeloma. Other
recent trends include the increasing use of “mini” or “reduced
intensity” allografts. Discussions with a number of leading clinicians
suggest that the most significant trend over the next four to five years
is likely to be a continuation of the rise in mini-allografts. The volume
of autologous and standard allogeneic transplants is also expected to
rise slowly. The cost implication of the rise in the volume of
A1
transplants is estimated to be £7.3 million.
In addition, there are expected to be significant economic implications
in relation to facilities and staffing requirements to meet JACIE
standards. A recent survey of UK BMT centres, facilities and staffing
on behalf of the Executive Committee of the BSBMT identified a
number of areas where resources were inadequate. The scale of the
cost consequences of these shortfalls is currently unknown, but will be
significant. Further detailed work is recommended to identify the likely
resource implications of tackling current shortages and the future
consequences of meeting JACIE standards.
Induction chemotherapy for remission of acute
leukaemia
It is assumed that resource implications of recommendations on services
for treatment of patients with acute myeloid leukaemia (AML) and acute
lymphoblastic leukaemia (ALL) are similar. These patients require high
levels of facilities, staff cover and expertise, and it is unlikely that these
requirements can be met without some concentration of services.
Three scenarios are presented, each illustrating a different pattern of
hospital provision. The first is based on a slight increase in
concentration of this work, the second a radical increase, and the third
sets out an intermediate position. It is not suggested that greater
changes are to be preferred, but that the potential cost implications are
best illustrated by showing a wide range of possibilities.
In scenario 1, the cost of achieving a minimum of five new patients in
all treating hospitals is estimated.
Scenario 2 estimates the potential cost impact of radical restructuring,
such that all hospitals which offer this form of treatment deal with at
least 10 new patients per annum.
In scenario 3, it is assumed that all units treating fewer than five new
patients per annum will give up this work. Of those treating between
five and 10 new patients per annum, an arbitrary proportion of 50%
will re-structure their services so that all units deal with 10 or more,
whilst the remaining 50% will continue to provide this form of
treatment for between five and 10.
112
Data on current local patterns of presentation and treatment suggest
that about 115 patients receive chemotherapy for remission induction
in units treating fewer than five new patients per annum, whilst
between 300 and 800 are treated in hospitals with fewer than 10 such
patients per year. The cost impact of re-structuring services will vary
according to current treatment patterns and the extent of
consolidation or centralisation. The costs of implementing the three
levels of concentration of services described above are estimated to
be £1.9 million for scenario 1, £9.0 million for scenario 2, and £4.3
million for scenario 3.
Other potential cost implications
A1
Assessment
Lymphoma patients need access to computed tomography (CT)
scanning for initial diagnosis to judge the extent of the disease and
after treatment to assess residual disease. The guidance recommends
that cross-sectional CT should be available without delay. This may
require additional CT scanning capacity in some Trusts. Investment in
new CT equipment is ongoing, as part of existing Department of
Health funding programmes. By 2003/4 there will be 182 new CT
scanners (110 replacements and 72 additional). It is assumed that no
additional investment in CT scanners will be required to
accommodate any growth in haematological malignancies. Running
costs (staffing and consumables) will need to be funded to ensure
scanners can be fully utilised.
Rapid investigation of lymphadenopathy
The guidance recommends either the use of designated clinicians with
close links with haematology and/or oncology, who take responsibility
for prompt investigation of lymphadenopathy or alternatively, the
development of specific clinics for rapid investigation of
lymphadenopathy (rapid-access lump clinics) at cancer units. A single
access point will streamline service for patients. Given that these
patients are already in the hospital system it is assumed that these
resources will, to a large extent, already be available and this should
be achievable with some re-organisation of existing resources.
Palliative care
The use of palliative radiotherapy and services for the provision of
blood product support are not expected to change significantly under
the new guidance. Recommendations relating to service provision
issues including the availability of palliative care teams to support
patients at home and in hospice and availability of bereavement
counselling are likely to have the most significant cost impact. These
types of services provide support to patients with all types of cancer
and the cost impact of such service re-configuration is being
considered separately as part of the Guidance for Improving
supportive and palliative care for adults with cancer, planned to be
published in 2004.
113
Cost summary
(All costs in £ million per year)
Specialist diagnostic services
Annual running costs
£ 7.5
Low scenario
£ 6.7
High scenario
£ 8.1
One-off set up costs
£ 5.8
Low scenario
£ 4.7
A1
High scenario
£ 7.5
Multi-disciplinary teams
Additional costs of staff time for MDT meetings
£ 6.2
Low scenario
£ 3.2
High scenario
£ 9.0
MDT co-ordinator for all hospitals
£ 1.0
Patient–centred care
£ 4.6
(clinical nurse specialists)
Induction chemotherapy for
remission of acute leukaemia
Intermediate scenario
£ 4.3
Minimal consolidation
£ 1.9
Radical re-structuring of services
£ 9.0
Transplant services
£ 7.3
Low scenario
£ 3.0
High scenario
£12.4
Total
£36.7
Range
£25.2-£51.5
114
Appendix 2
How this guidance
manual was produced
The manuals in this series are intended to guide health organisations
(strategic health authorities, primary care trusts, cancer networks and
trusts), their managers and lead clinicians in improving the
effectiveness and efficiency of services for patients with cancer. The
information and recommendations in the manual are based on
A2
systematic reviews of the best available evidence on diagnosis,
treatment and service delivery. This evidence is assessed by experts
and the recommendations are the product of extensive discussion
with leading clinical specialists. The production process is described
briefly below; more detail is available in earlier guidance manuals in
the series.
The production process begins with a two-day residential event
where proposals for improving services for patients with cancer of a
specific site (or sites) are generated. A large group of relevant health
care professionals, people with personal experience of the particular
type of cancer being considered, health care commissioners and
academics from around the country, meet to put forward structured
proposals based on their experience and knowledge of the research
literature. All proposals share a common structure and are intended to
improve outcomes for patients. These proposals are then sent to
referees, including clinicians, academics, representatives of health
authorities, the Department of Health, patient organisations, and
relevant charities, many of whom make detailed comments and
suggestions. They are also reviewed as part of the process of the
National Institute for Clinical Excellence (NICE) and form the basis of
the scope of the guidance. Systematic reviews of the research
literature, designed to evaluate the proposals, are then carried out or
commissioned by the NHS Centre for Reviews and Dissemination
(CRD) at the University of York.
This process culminates in the production of two large sources of
information, one with a practical or operational focus, and the other
containing detailed research evidence on effectiveness. The guidance
draws on both these sources, with added input from commissioners,
patients, and experts in the particular fields. The writing of the
guidance manual is overseen by an editorial group chaired by
Professor Bob Haward, accountable to the National Cancer Guidance
Steering Group. The writing is undertaken by Dr Arabella Melville, in
conjunction with CRD.
115
Complementary research, designed to quantify the potential cost of
major changes in services, is carried out by the School of Health and
Related Research at the University of Sheffield. This work involves
literature searching, interviews with clinicians and managers, and
analyses of costs.
The production of this guidance was funded by NICE, and it has been
subject to the full NICE consultation process.
Evidence grading
The reliability and quality of evidence which supports the
recommendations in the guidance manual is graded throughout the
A2
document. The grades are as follows:
A.
Evidence derived from randomised controlled trials or systematic
reviews of randomised trials.
B.
Evidence from non-randomised controlled trials or observational
studies.
C. Professional
consensus.
The quality of research evidence forms a continuum and there is
overlap between these categories. Most of the published research on
cancer focuses on clinical evaluations of treatment; little direct
research has been carried out on the organisation and delivery of
services, issues on which randomised controlled trials (categorised
here as the highest quality evidence) may not be feasible. Research
designs which might be regarded as of relatively poor quality for
evaluating a clinical intervention may therefore be the most reliable
available for assessing the organisational issues.
The systematic reviews used to inform the manual are summarised in
the document Improving Outcomes in Haematological Cancers: The
Research Evidence. This document includes details of all the studies
to which the manual refers. It is available on the CD-ROM provided
with this manual, and is also available in printed format as a CRD
report (email: crdpub@york.ac.uk, Tel: 01904-433648).
2
116
Appendix 3
People and organisations
involved in production
of the guidance
3.1
National Cancer Guidance Steering Group
3.2
Participants in the proposal generating event
3.3
People/organisations invited to comment on original
A3
proposals
3.4
Researchers carrying out literature reviews and
complementary work
3.5
Members of focus groups
Guidance synthesis and writing
Ms A Eastwood
Senior Research Fellow, NHS Centre for
Reviews and Dissemination, University of York
Professor J Kleijnen
Director, NHS Centre for Reviews and
Dissemination, University of York
Dr A Melville
Independent Consultant
assisted by members of the National Cancer Guidance Steering Group,
together with:
Dr R E Clark, Consultant Haematologist, Royal Liverpool Hospital
Dr M H Cullen, Consultant Medical Oncologist, Queen Elizabeth
Hospital, Birmingham
Dr A Frater, Director of Public Health, North Hampshire Primary Care
Trust
Dr A Jack, Consultant Histopathologist, The General Infirmary at Leeds
Professor P Johnson, Professor of Medical Oncology, Southampton
General Hospital
Dr R Johnson, Consultant in Diagnostic Radiology, Christie Hospital,
Manchester
Dr S A N Johnson, Consultant Haematologist, Taunton and Somerset
Hospital
Professor N H Russell, Professor of Haematology, Nottingham City
Hospital
117
Dr D Swirsky, Consultant Haematologist, The General Infirmary at
Leeds
Dr M V Williams, Consultant Clinical Oncologist, Addenbrooke’s
Hospital, Cambridge
People/organisations invited to comment on drafts of the
guidance
National Cancer Guidance Steering Group
Focus groups
Various professional organisations
Department of Health
NICE Stakeholders; the drafts were subject to the full NICE
consultation process
Economic reviews
School of Health and Related Research, University of Sheffield
A3
Project support
The Northern and Yorkshire Cancer Registry and Information Service
118
Appendix 3.1
Membership of the
National Cancer Guidance
Steering Group
(This Group, originally established to oversee production of the
‘Improving Outcomes’ programme, also managed its transition to the
NICE programme)
Chairman
Professor R A Haward
Professor of Cancer Studies, University of
A3
Leeds
Vice Chairman
Professor M A Richards
Sainsbury Professor of Palliative Medicine,
St Thomas’ Hospital, London and National
Cancer Director
Members
Dr J Barrett
Consultant Clinical Oncologist and Clinical
Director, Four Counties Cancer Network
Mrs G Batt
Section Head, Cancer Policy Team,
Department of Health, Wellington House
Mr A Brennan
Director of Operational Research, School
of Health and Related Research, University
of Sheffield
Ms A Eastwood
Senior Research Fellow, NHS Centre for
Reviews and Dissemination, York
Dr J Hanson
Cancer Services Project Co-ordinator,
Welsh Office
Dr G Harding
GP and Medical Director, St John’s
Hospice, Doncaster
Professor J Kleijnen
Director, NHS Centre for Reviews and
Dissemination, York
Professor P Littlejohns
Clinical Director, National Institute for
Clinical Excellence
Professor R E Mansel
Chairman, Division of Surgery, University
of Wales College of Medicine, Cardiff
Dame G Oliver
Director of Service Development,
Macmillan Cancer Relief
Mrs V Saunders
Manager, Northern and Yorkshire Cancer
Registry and Information Service
Dr J Verne
Director, South West Public Health
Observatory
119
Appendix 3.2
Participants in the
haematological
cancers proposal
generating event
Dr J Apperley
Consultant Haematologist, Hammersmith
Hospital, London
A3
Professor M R Baker
Director/Lead Clinician, Yorkshire Cancer
Network
Ms C Beardmore
Radiotherapy Services Manager, Royal
Berkshire Hospital, Reading
Dr S F Beardsworth
Consultant Physician, Castle Hill Hospital,
Cottingham
Dr E M Bessell
Consultant Clinical Oncologist, Nottingham
City Hospital
Ms R Bratt-Wyton
Clinical Nurse Specialist, Russells Hall
Hospital, Dudley
Mrs C Brown
Patient
Mrs M Brown
Nurse Lecturer in Haematology, Thames
Valley University
Ms T Burgoyne
Nurse Lecturer/Practitioner in
Haematology/Oncology, University of
Central England, Birmingham
Dr S Closs
Consultant in Palliative Medicine, Ty
Olwen Palliative Care Service, Morriston
Hospital
Dr R Cowan
Consultant Clinical Oncologist, Christie
Hospital, Manchester
Mrs L Czyzewska
Patient
Dr J Davies
Consultant Haematologist, Western General
Hospital, Edinburgh
Ms J Downing
Lecturer in Cancer Care, The Centre for
Cancer & Palliative Care Studies, The Royal
Marsden Hospital, London
Professor A Faulkner
Professor of Communication in Health
Care, Great Barrow, Cheshire
Dr J Ferguson
Clinical Director, South East London
Strategic Health Authority
120
Mr M Geering
Patient
Dr S George
Senior Lecturer in Public Health Medicine,
Health Care Research Unit, Southampton
General Hospital
Miss V Goode
Nurse Clinician, Christie Hospital,
Manchester
Professor B Hancock
Professor of Clinical Oncology, Weston
Park Hospital, Sheffield
Dr A Haynes
Consultant Haematologist, Nottingham City
Hospital
Dr J Healey
Consultant Radiologist, Chelsea &
Westminster Hospital, London
Dr F Hicks
Consultant in Palliative Medicine, St
James’s University Hospital, Leeds
Dr P Hoskin
Consultant Clinical Oncologist, Mount
Vernon Hospital, Middlesex
Dr M Howard
Consultant Haematologist, York District
A3
Hospital
Ms S Hunton
Director, Bradford Cancer Support Centre
Dr T Illidge
Consultant Clinical Oncologist, Royal South
Hants Hospital, Southampton
Dr A Jack
Consultant Histopathologist, The General
Infirmary at Leeds
Professor P Johnson
Professor of Medical Oncology,
Southampton General Hospital
Dr C C Kibbler
Consultant Medical Microbiologist, Royal
Free Hospital, London
Professor K MacLennan
Professor of Cytopathology &
Histopathology, St James’s University
Hospital, Leeds
Dr A McMillan
Consultant Haematologist, Mount Vernon
Hospital, Middlesex
Dr R Marcus
Consultant Haematologist, Addenbrooke’s
Hospital, Cambridge
Dr P Norris
GP, Kingston upon Thames
Dr R Pettengell
Consultant Medical Oncologist, St George’s
Hospital Medical School, London
Mr C Pilmoor
Patient
Professor R Powles
Professor of Haematological Oncology,
The Royal Marsden Hospital, Surrey
Dr A Prentice
Consultant Haematologist, Derriford
Hospital, Plymouth
Ms A Ridehalgh
Haematology Clinical Nurse Specialist, The
Ipswich Hospital
Mrs J Sale
Patient
Dr S Schey
Consultant Haematologist, Guy’s Hospital,
London
Dr C Singer
Consultant Haematologist, Royal United
Hospital, Bath
121
Dr J Spencer
Consultant Radiologist, St James’s
University Hospital, Leeds
Mr M Summerhayes
Pharmacist, Guy’s Hospital, London
Dr G Tanner
GP, Bridgwater
Dr B Walker
GP, Seascale
Mr D Watson
Clinical Nurse Manager, Clinical Apheresis
Unit, Glasgow Royal Infirmary
Professor J Wilkinson
Professor of Public Health, North East
Public Health Observatory
Facilitated by:
Dr J Barrett
Consultant Clinical Oncologist and Clinical
Director, Four Counties Cancer Network
Professor R A Haward
Professor of Cancer Studies, University of
Leeds
Professor J Kleijnen
Director, NHS Centre for Reviews and
Dissemination
A3
Professor M A Richards
Sainsbury Professor of Palliative Medicine,
St Thomas’ Hospital, London and National
Cancer Director
122
Appendix 3.3
Referees of the
haematological
cancers proposals
The guidance was subject to the NICE consultation process (see
website www.nice.org.uk for details)
The individuals listed below were also invited by the Developer to act
as referees of whom 43% responded.
A3
Dr S Allard
Consultant Haematologist, Northwick Park
Hospital, Middlesex
Mr R Anderson
Economic Adviser, Department of Health
Dr B Angus
Senior Lecturer in Pathology, Royal Victoria
Infirmary, Newcastle upon Tyne
Dr D Armstrong
Consultant in Public Health Medicine,
Guy’s, King’s and St Thomas’ School of
Medicine, London
Professor P Armstrong
Professor of Radiology, St Bartholomew’s
Hospital, London
Dr D Ash
President of the Royal College of
Radiologists and Consultant Clinical
Oncologist, Cookridge Hospital, Leeds
Dr R Attanoos
Consultant Histopathologist, Llandough
Hospital, Penarth
Ms L Baker
Senior Haematology Nurse,
Birmingham Heartlands Hospital
Dr M Baker
GP, Lincoln
Mr J J Bannister
Consultant Surgeon, Barnsley District
General Hospital
Dr J Barrett
Consultant Clinical Oncologist and Clinical
Director, Four Counties Cancer Network
Dr M Bhavnani
Consultant Haematologist, Royal Albert
Edward Infirmary, Wigan
Dr N Bienz
Consultant Haematologist, Wexham Park
Hospital, Slough
Dr D Black
GP and Chair, Nottingham Clinical
Haematology Project
Dr P Blain
Member of the National Cancer
Implementation Group
Ms R Bradley
Clinical Nurse Specialist, St Bartholomew’s
Hospital, London
123
Ms R Bratt-Wyton
Clinical Nurse Specialist, Russells Hall
Hospital, Dudley
Mr A Brennan
Director of Operational Research, School
of Health and Related Research, University
of Sheffield
Ms J Buckham
Oncology Services Pharmacist, Sheffield
Children’s Hospital
Dr C Bunch
Medical Director, John Radcliffe Hospital,
Oxford
Mr S Burgess
Consultant Obstetrician & Gynaecologist,
King George Hospital, Essex
Ms T Burgoyne
Nurse Lecturer/Practitioner in
Haematology/Oncology, University of
Central England, Birmingham
Professor A K Burnett
Professor of Haematology, University of
Wales College of Medicine, Cardiff
Dr A Byrne
Consultant in Palliative Medicine, Holme
A3
Tower Marie Curie Centre, Penarth
Ms L Bywater
Clinical Nurse Specialist, John Radcliffe
Hospital, Oxford
Ms C Cafferty
Radiographer, Weston Park Hospital,
Sheffield
Dr G Carroll
Clinical Director, Eastern Region
Specialised Services Commissioning Group,
Cambridge
Professor J A Child
Consultant Haematologist, The General
Infirmary at Leeds
Dr D Clark
Consultant Cellular Pathologist, Grantham
and District Hospital
Ms H Clements
Radiographer, The Churchill Hospital,
Oxford
Ms D Coats
Senior Cancer Information Nurse Specialist,
CancerBACUP
Dr R Coltart
Consultant Clinical Oncologist, Kent and
Canterbury Hospital
Ms J Connelly
Director, Cancer Action Team, St Thomas’
Hospital, London
Dr B Cottier
Head of Cancer Services Analysis, National
Cancer Services Analysis Team
Dr I Cox
GP, Birmingham
Ms S Crofts
Haematology & Myeloma Research Nurse,
Royal South Hants Hospital, Southampton
Ms D Crowther
Chief Executive, Wirral Holistic Care
Services
Dr M H Cullen
Consultant Medical Oncologist, Queen
Elizabeth Hospital, Birmingham
Dr J Cullis
Consultant Haematologist, Salisbury District
Hospital
Dr P Cumber
Consultant Haematologist, West Wales
General Hospital
124
Dr D Cunningham
Consultant Medical Oncologist, The Royal
Marsden Hospital, Surrey
Ms E Dannie
Clinical Nurse Specialist, Hammersmith
Hospital, London
Dr P Darragh
Deputy Chief Medical Officer, Department
of Health, Social Services and Public
Safety, Northern Ireland
Ms J Davie
Sister, Ninewells Hospital, Dundee
Dr T W Davies
Director, East Anglian Cancer Registry,
Cambridge
Dr D Deakin
Consultant Clinical Oncologist, Christie
Hospital, Manchester
Dr S Devereux
Consultant Haematologist, King’s College
Hospital, London
Professor A K Dixon
Professor of Radiology, Addenbrooke’s
Hospital, Cambridge
Professor L Donaldson
Chief Medical Officer, Department of
A3
Health
Ms S Eagle
Radiographer, The Royal Marsden Hospital
Surrey
Ms A Eastwood
Senior Research Fellow, NHS Centre for
Reviews & Dissemination, University of
York
Dr J Ellershaw
Medical Director, Liverpool Marie Curie
Centre
Ms M Ellis
Bone Marrow Transplant Co-ordinator,
John Radcliffe Hospital, Oxford
Dr D Empey
Medical Director, The Royal London
Hospital
Mr S Evans
Chief Executive, The Society of
Radiographers
Ms J Fenelon
Member of the National Cancer
Implementation Group
Dr J Ferguson
Clinical Director, South East London
Strategic Health Authority
Professor I Finlay
Medical Director, Holme Tower Marie
Curie Centre, Penarth
Ms A Flory
Haematology Sister, Royal Berkshire
Hospital, Reading
Dr A Ford
GP, Nottingham
Dr A Frater
Director of Public Health, North Hampshire
Primary Care Trust
Dr J Galloway
GP, Kings Lynn
Professor K Gatter
Professor of Pathology, John Radcliffe
Hospital, Oxford
Professor D George
President, British Association of Surgical
Oncology
Dr D Gilson
Consultant Clinical Oncologist, Cookridge
Hospital, Leeds
125
Dr J Goepel
Consultant Histopathologist, Royal
Hallamshire Hospital, Sheffield
Professor J Goldman
Professor of Leukaemia Biology and
Chairman, Department of Haematology,
Hammersmith Hospital, London
Professor A H Goldstone
Professor of Haematology, University
College Hospital, London
Professor E C
Professor of Haematology, St George’s
Gordon-Smith
Hospital Medical School
Dr H W Habboush
Consultant Haematologist, Nevill Hall
Hospital, Abergavenny
Dr R Hall
Chief Medical Officer, Welsh Office
Dr J Halpin
Lead Clinician, Mount Vernon Cancer
Network
Professor G W Hanks
Professor of Palliative Medicine, University
of Bristol
Dr J Hanson
Cancer Services Project Co-ordinator, Welsh
A3
Office
Professor J D Hardcastle
Network Lead Clinician, Mid Trent Cancer
Services Network
Dr M Harding
Consultant in Public Health Medicine,
Sutton and Merton Primary Care Trust
Mr T Harris
Director, Association of Community Health
Councils for England and Wales
Dr C Harrison
Medical Director, Greater Manchester
Strategic Health Authority
Dr P Harvey
Consultant Clinical Psychologist, Queen
Elizabeth Hospital, Birmingham
Dr C Hatton
Consultant Haematologist, John Radcliffe
Hospital, Oxford
Dr V Hempsall
Cancer Lead, Dorset and Somerset Strategic
Health Authority
Dr A Hibble
GP, Stamford
Dr N Hicks
Consultant in Public Health Medicine, East
Hampshire Primary Care Trust
Professor I Higginson
Professor of Palliative Care and Policy,
Guy’s, King’s and St Thomas’ School of
Medicine, London
Dr R Hillier
Consultant Physician in Palliative Medicine,
Countess Mountbatten House, Southampton
Ms H Hollis
Clinical Nurse Specialist, Royal Berkshire
Hospital, Reading
Professor A Horwich
Professor of Clinical Oncology, The Royal
Marsden Hospital, Surrey
Dr G Houghton
GP, Birmingham
Dr M Howard
Consultant Haematologist, York District
Hospital
Dr P A Hulse
Consultant Radiologist, Christie Hospital,
Manchester
Ms S Hunton
Director, Bradford Cancer Support Centre
126
Professor P G Isaacson
Professor of Histopathology, Royal Free
and University College Medical School,
London
Sir B Jackson
Former President, Royal College of
Surgeons of England
Dr P James
GP, Birmingham
Dr M Jefferson
Consultant in Palliative Medicine,
University of Wales College of Medicine
Dr R Johnson
Consultant in Diagnostic Radiology,
Christie Hospital, Manchester
Dr S A N Johnson
Consultant Haematologist, Taunton and
Somerset Hospital, Taunton
Dr I D A Johnston
Medical Director, University Hospital,
Nottingham
Dr A C Jones
Consultant Clinical Oncologist, The
Churchill Hospital, Oxford
Dr E Jorge
Former Director of Public Health,
A3
Portsmouth and South East Hampshire
Health Authority
Ms H Kelly
Radiographer, Royal South Hants Hospital,
Southampton
Dr S Kelly
GP, Chichester, West Sussex
Dr P R Kelsey
Consultant Haematologist, Victoria
Hospital, Blackpool
Ms V Kelsey
Haematology Clinical Nurse Specialist,
Guy’s Hospital, London
Professor D Kerr
Professor of Clinical Oncology, University
of Birmingham
Dr N Ketley
Consultant Haematologist, Greenwich
District Hospital, London
Dr C C Kibbler
Consultant Medical Microbiologist, Royal
Free Hospital, London
Mrs D Knupfer
Executive Director of Nursing, Christie
Hospital, Manchester
Dr A Kyle
Consultant Haematologist, Antrim Area
Hospital, Belfast
Dr A K Lakhani
Consultant Haematologist, Farnborough
Hospital, Orpington
Dr R Lane
Consultant in Palliative Medicine,
Dewsbury & District Hospital
Ms E Lardner
Clinical Nurse Specialist, Singleton
Hospital, Swansea
Dr A W Lee
GP, Scunthorpe
Dr S Levy
GP, Stockport
Ms C Lewis
Research Nurse, Royal Berkshire Hospital,
Reading
Professor D C Linch
Professor of Haematology, Royal Free and
University College Medical School, London
Professor T A Lister
Professor of Medical Oncology, St
Bartholomew’s Hospital, London
127
Professor P Littlejohns
Clinical Director, National Institute for
Clinical Excellence
Dr P Lorigan
Consultant Medical Oncologist, Weston
Park Hospital, Sheffield
Mr G McGhee
Senior Staff Nurse, Western General
Hospital, Edinburgh
Dr M McGovern
Senior Policy/Medical Adviser, Department
of Health
Dr I MacLellan-Smith
GP, Cheadle, Cheshire
Dr A D L MacVicar
Consultant Radiologist, The Royal Marsden
Hospital, London
Professor G McVie
Director General, Cancer Research
Campaign
Dr J Maher
Consultant Clinical Oncologist, Mount
Vernon Hospital, Middlesex
Dr A R Manhire
Consultant Radiologist, Nottingham City
Hospital
A3
Dr I Manifold
Medical Director, Weston Park Hospital,
Sheffield
Professor R E Mansel
Chairman, Division of Surgery, University
of Wales College of Medicine, Cardiff
Dr R Marcus
Clinical Director, British Committee for
Standards in Haematology
Mr I Mark
Consultant Urologist, Lincoln County
Hospital
Dr T S Maughan
Consultant Clinical Oncologist, Velindre
Hospital, Cardiff
Dr G M Mead
Consultant Medical Oncologist, Royal
South Hants Hospital, Southampton
Dr A B Mehta
Consultant Haematologist, Royal Free
Hospital, London
Mrs R Miles
Chair, National Cancer Alliance
Dr D W Milligan
Consultant Haematologist, Birmingham
Heartlands Hospital
Professor G Morgan
Professor of Haematology, University of
Leeds
Ms C Morris
Sister, Haematology Day Care Unit, Royal
Cornwall Hospital, Truro
Dr T C M Morris
Consultant Haematologist, Belfast City
Hospital
Professor G J Mufti
Professor of Haemato-oncology, Guy’s,
King’s and St Thomas’ School of Medicine,
London
Dr S Munday
Director of Public Health, South
Warwickshire Primary Care Trust
Ms M Nendick
Nursing Officer, Department of Health
Dr G Newman
Consultant Clinical Oncologist, Royal
Sussex County Hospital
Dr P Norris
GP, Kingston upon Thames
128
Dr A J Norton
Senior Lecturer in Histopathology, St
Bartholomew’s Hospital, London
Dame G Oliver
Director of Service Development,
Macmillan Cancer Relief
Dr B A Oppenheim
Consultant Microbiologist, Withington
Hospital, Manchester
Ms H Outhwaite
Clinical Nurse Specialist, Guy’s Hospital,
London
Mrs S Pacey
Pharmacist, Nottingham City Hospital
Dr A Pagliuca
Consultant Haematologist, King’s College
Hospital, London
Ms J Palin
Project Manager, Cancer Action Team, St
Thomas’ Hospital, London
Dr G Park
GP, Stokesley
Dr M Parmar
Head, Cancer Division, MRC Clinical Trials
Unit, Cambridge
Dr H Parry
Consultant Haematologist, Ysbyty
A3
Gwynedd, Bangor
Dr J Pawade
Consultant Histopathologist, Bristol Royal
Infirmary
Professor M Pearson
Deputy Director of Human Resources,
Department of Health
Dr S Pearson
Director of Clinical Strategy,
Gloucestershire Hospitals NHS Trust
Ms S Perrett
Macmillan Clinical Nurse Specialist for
Haematology, University Hospital of Wales,
Cardiff
Dr F Pitt
Consultant in Public Health Medicine,
North Sheffield Primary Care Trust
Mrs E Porterfield
Member of the National Cancer
Implementation Group
Dr M Potter
Consultant Haematologist, Royal Free
Hospital, London
Dr C Poynton
Consultant Haematologist, University
Hospital of Wales, Cardiff
Dr A Prentice
Consultant Haematologist, Derriford
Hospital, Plymouth
Dr T Priestman
Consultant Clinical Oncologist, New Cross
Hospital, Wolverhampton
Dr J Pritchard
Scientific Adviser, Welsh Office
Professor S J Proctor
Professor of Haematological Medicine,
Royal Victoria Infirmary, Newcastle upon
Tyne
Dr E Pugh
Medical Director, Butterwick Hospice,
Stockton-on-Tees
Dr J Radford
Consultant Physician, Christie Hospital,
Manchester
Dr S Ramakrishnan
Lead Clinician, Weston Park Hospital,
Sheffield
129
Dr A D Ramsay
Secretary, British Lymphoma Pathology
Group, Great Ormond Street Hospital for
Children, London
Mr B Rees
Consultant General Surgeon, University
Hospital of Wales, Cardiff
Dr P Revell
Consultant Haematologist, Staffordshire
General Hospital, Stafford
Professor R H Reznek
Professor of Diagnostic Imaging, St
Bartholomew’s Hospital, London
Professor M A Richards
Sainsbury Professor of Palliative Medicine,
St Thomas’ Hospital, London
Ms A Ridehalgh
Haematology Clinical Nurse Specialist,
Ipswich General Hospital
Ms M Rigge
Director, College of Health
Dr M H Robinson
Senior Lecturer in Clinical Oncology,
Weston Park Hospital, Sheffield
Professor P Robinson
Professor of Clinical Radiology, St James’s
A3
University Hospital, Leeds
Dr P Roderick
Senior Lecturer in Public Health Medicine,
Health Care Research Unit, Southampton
Professor T Rogers
Imperial College Medical School, London
Professor A Z S Rohatiner Professor of Haemato-oncology, St
Bartholomew’s Hospital, London
Dr N Rooney
Consultant Pathologist, Royal United
Hospital, Bath
Dr A W W Roques
Consultant Haematologist, Worthing
Hospital, West Sussex
Mr R D Rosin
Consultant Surgeon, St Mary’s Hospital,
London
Dr J R Y Ross
Consultant Haematologist, Northampton
General Hospital
Professor G Rubin
GP, Yarm
Professor N H Russell
Professor of Haematology, Nottingham City
Hospital
Dr R D Russell-Jones
Consultant Dermatologist, St Thomas’
Hospital, London
Dr S Schey
Director of Clinical Haematology, Guy’s
Hospital, London
Dr E A Scott
Implementation Director, NHS
Modernisation Agency
Dr M Sekhar
Consultant Haematologist, West Middlesex
University Hospital,
Professor P Selby
Professor of Cancer Medicine, St James’s
University Hospital, Leeds
Professor K Sikora
Professor of Clinical Oncology,
Hammersmith Hospital, London
Dr C Sinnott
Consultant and Senior Lecturer in Palliative
Medicine, St Thomas’ Hospital, London
130
Dr D N Slater
Consultant Histopathologist/
Dermatopathologist, Royal Hallamshire
Hospital, Sheffield
Mr J Smallwood
Lead Cancer Clinician, Southampton
General Hospital
Mr C Smee
Chief Economic Adviser, Department of
Health
Dr A G Smith
Consultant Haematologist, Southampton
General Hospital
Dr M J Smith
Consultant Physician, Heatherwood
Hospital, Ascot
Dr S R Smith
Consultant Haematologist, Torbay Hospital,
Torquay
Dr J Spiby
Consultant in Environmental Public Health,
Chemical Incident Response Service,
London
Mr M Stone
Director, The Patient’s Association
A3
Mrs R Stone
Manager, Hogarth Haematology and Bone
Marrow Transplant Unit, Nottingham City
Hospital
Dr N Stuart
Consultant Medical Oncologist, Ysbyty
Gwynedd, Bangor
Mr M Summerhayes
Principal Oncology Pharmacist, Guy’s
Hospital, London
Dr N Summerton
Clinical Senior Lecturer in Primary Care
Medicine, University of Hull
Dr P Sutton
GP, Brigg, North Lincolnshire
Dr N Sykes
Consultant in Palliative Medicine, St
Christopher’s Hospice, London
Dr G Tanner
GP, Bridgwater, Somerset
Dr T Tate
Medical Adviser, Marie Curie Cancer Care
Dr J Thomas
Director of Public Health, Sunderland
Teaching Primary Care Trust
Mrs H Thornton
Chairman, Consumers’ Advisory Group for
Clinical Trials
Mr A Turner
Member of the National Cancer
Implementation Group
Dr P Twentyman
Secretary, United Kingdom Co-ordinating
Committee on Cancer Research
Dr E A Vandenberghe
Consultant Haematologist, Royal
Hallamshire Hospital, Sheffield
Dr J van der Walt
Consultant Histopathologist, St Thomas’
Hospital, London
Dr J Verne
Director, South West Public Health
Observatory
Dr S Vinnicombe
Consultant Radiologist, St Bartholomew’s
Hospital, London
131
Dr C Waine
Former Director of Health Programmes and
Primary Care Development, Sunderland
Health Authority
Mr D Watson
Clinical Nurse Manager, Clinical Apheresis
Unit, Glasgow Royal Infirmary
Dr P Watson
Medical Director, Essex Strategic Health
Authority
Dr B Wee
Consultant in Palliative Medicine, Countess
Mountbatten House, Southampton
Dr N C West
Consultant Haematologist, West
Cumberland Hospital, Whitehaven
Mrs K Westbrook
Radiographer, Bristol Royal Infirmary
Dr B S Wilkins
Senior Lecturer in Pathology, University of
Southampton
Dr M V Williams
Consultant Clinical Oncologist,
Addenbrooke’s Hospital, Cambridge
Dr J Z Wimperis
Consultant Haematologist, Norfolk and
A3
Norwich Hospital
Dr H Winter
Senior Lecturer in Public Health Medicine,
University of Birmingham
Dr C Wolfe
Reader in Public Health Medicine, Guy’s,
King’s & St Thomas’ School of Medicine
Dr A Wotherspoon
Consultant Histopathologist, The Royal
Marsden Hospital, London
Mr N Young
Chief Executive, Macmillan Cancer Relief
132
Appendix 3.4
Researchers carrying
out literature reviews
and complementary
work
Overall co-ordinators
Ms A Eastwood
NHS Centre for Reviews and Dissemination,
Professor J Kleijnen
University of York
A3
and Dr H McIntosh
i) Literature reviews
Professor P Johnson and Cancer Research UK Oncology Unit,
Ms B Bennett-Lloyd
Cancer Sciences Division, University of
Southampton School of Medicine
Dr S Agrawal
Barts and the London School of Medicine
and Dentistry
Dr S George
Health Services Research Unit, Community
Clinical Sciences Research Division,
University of Southampton School of
Medicine.
Contributed reviews which were used to inform guidance on Topics 1,
3, 4, 5, 6, and 7.
Miss R Collins
NHS Centre for Reviews and Dissemination,
and Miss M Womphrey
University of York
Contributed reviews which were used to inform guidance on Topics 2
and 8.
Ms K Misso and
NHS Centre for Reviews and Dissemination,
Ms G Ritchie
University of York
Undertook the literature searches for the review work.
133
ii) Patient views of haematological cancer services
Ms R Miles and
National Cancer Alliance, Oxford
Ms C Smith
iii) Economic review
V Abbott
School of Health and Related Research,
R Ara
University of Sheffield
M Holmes
C Knight
M Stephenson
S Ward
A3
134
Appendix 3.5
Focus groups:
membership
Ms E Andelin
Assistant Director of Patient Services,
Bradford City Primary Care Trust
Professor M R Baker
Director/Lead Clinician, Yorkshire Cancer
Network
Mr M Bellamy
Former Chief Executive, Ealing,
Hammersmith and Hounslow Health
Authority
Dr A Benghiat
Cancer Lead Clinician, Leicester Royal
A3
Infirmary
Dr P Bevan
Deputy Director of Public Health,
Directorate of Health and Social Care for
London
Mr D Campbell
Chief Executive, Liverpool Central Primary
Care Trust
Dr A Champion
Assistant Cancer Services Project Co-
ordinator, Welsh Office
Dr I G Cox
Macmillan GP Adviser in Cancer and
Palliative Care, Birmingham
Miss C Edwards
Chief Executive, North Trent
Commissioning Network, Barnsley Primary
Care Trust
Mrs S Ellis
Partnership Director, West Yorkshire
Primary Care Organisations, Wakefield
West Primary Care Trust
Mr J Grimes
Director of Finance, North & East
Yorkshire and Northern Lincolnshire
Strategic Health Authority
Dr J Halpin
Lead Clinician, Mount Vernon Cancer
Network
Dr V Hempsall
Cancer Lead, Dorset and Somerset Strategic
Health Authority
Dr J Kearney
Director of Public Health, Dacorum
Primary Care Trust
Dr A W Lee
GP, Scunthorpe
Dr M Marshall
Cancer Lead, Middlesbrough Primary Care
Trust
Dr S Munday
Director of Public Health, South
Warwickshire Primary Care Trust
Dame G Oliver
Director of Service Development,
Macmillan Cancer Relief
135
Dr S Pearson
Director of Clinical Strategy,
Gloucestershire Hospitals NHS Trust
Dr F A Pitt
Consultant in Public Health Medicine,
North Sheffield Primary Care Trust
Mr R J Priestley
Former Chief Executive, North Staffordshire
Health Authority
Dr E A Scott
Implementation Director, NHS
Modernisation Agency
Dr J Spiby
Consultant in Environmental Public Health,
Chemical Incident Response Service,
London
Dr J Thomas
Director of Public Health, Sunderland
Teaching Primary Care Trust
Dr J Verne
Director, South West Public Health
observatory
Dr P Watson
Medical Director, Essex Strategic Health
Authority
A3
Facilitated by:
Ms S O’Toole
Consultant in Health Policy and
Management
Supported by:
Mrs V Saunders
Manager, Northern and Yorkshire Cancer
Registry and Information Service
136
Appendix 4
Glossary of terms
Acute
Sudden or severe, in onset.
Acute leukaemia
A rapidly progressive cancer of the blood forming system of sudden
onset where immature white blood cells proliferate uncontrollably.
Acute lymphoblastic leukaemia (ALL)
A type of acute leukaemia in which the white blood cells produced in
excess are immature lymphocytes (white blood cells formed from
lymphoid stem cells).
A4
Acute myeloid leukaemia (AML)
A type of acute leukaemia in which the white blood cells produced in
excess are immature granulocytes or monocytes (types of white blood
cells formed from myeloid stem cells).
Age-standardised incidence
A method of more accurately comparing incidence rates between
populations by removing differences in the age distributions of those
populations.
Agricultural biocides
Chemicals that kill organisms e.g. herbicides and pesticides.
Alkylating agents
A family of drugs that prevent the division of cancer cells by
damaging DNA.
Allogeneic transplantation/allograft
A procedure in which a patient receives bone marrow or blood stem
cells from a genetically matched donor following high dose therapy to
destroy their own bone marrow.
Anaemia
A condition in which the number of red blood cells in the blood is
below normal.
Antibodies
Proteins made by plasma cells in response to a foreign substance
(antigen) in the body.
137
Antigen
Any molecule recognised by the immune system as being foreign and
therefore provoking the production of antibodies.
Audit
A method by which those involved in providing services assess the
quality of care. Results of a process or intervention are assessed,
compared with a pre-existing standard, changed where necessary,
then reassessed.
Autologous transplantation/autograft
A procedure in which a patient receives their own bone marrow or
stem cells which were collected prior to a course of high dose therapy
to destroy their remaining bone marrow. Also see stem cell harvesting.
Axilla
The armpit.
Biopsy
Removal of a sample of tissue or cells from the body to assist in
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diagnosis of a disease.
Bisphosphonates
Drugs used to slow bone damage caused by myeloma cells, reduce
the risk of fractures and reduce bone pain.
Blast crisis
A phase of CML in which the disease progression becomes more
rapid and aggressive and the number of immature, abnormal white
blood cells (blasts) in the bone marrow and blood is extremely high.
Also called the blast or acute phase.
Blood products
Whole blood or components of the blood including red blood cells,
platelets and plasma.
Blood stem cells
Progenitor cells which give rise to red blood cells and immune system
blood cells.
Bone marrow
The soft inner part of the bone. Bone marrow produces the stem cells
which develop into the three different types of blood cells: red blood
cells, white blood cells and platelets.
138
Bone marrow transplantation (BMT)
A procedure to replace bone marrow that has been destroyed by high
dose therapy. There are two types of transplant – allogeneic where
healthy bone marrow is taken from a donor who has a similar tissue
type to the patient and autologous, where the patient’s own bone
marrow is used.
Cardiology
A branch of medicine concerned with the diagnosis and treatment of
diseases affecting the heart and blood vessels.
Central venous catheter/central line
A thin plastic tube which is inserted through the skin into a vein in
the chest through which blood tests can be taken and intravenous
chemotherapy and blood transfusions can be given. Once in place it
can remain in the vein for many months.
Chemotherapy
The use of drugs that kill cancer cells, or prevent or slow their
growth.
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Chronic
Long-lasting or slowly progressing.
Chronic leukaemia
Generally a slowly progressing cancer of the blood, usually of gradual
onset, where the white blood cells present in excess are more mature
than those in acute leukaemia. In some types of chronic leukaemia
the blood cells are not over-produced but fail to die when they
should do.
Chronic lymphocytic leukaemia (CLL)
A type of chronic leukaemia in which the white blood cells present in
excess are lymphocytes (white blood cells formed from lymphoid stem
cells).
Chronic myeloid leukaemia (CML)
A type of chronic leukaemia in which the white blood cells present in
excess are granulocytes (white blood cells formed from myeloid stem
cells).
Clinical oncologist
A doctor who specialises in the treatment of cancer patients,
particularly through the use of radiotherapy, but may also use
chemotherapy.
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Cognitive and behavioural therapy
Types of therapy, often delivered by psychologists, usually based on
talking and practising specific types of voluntary activity. This group
of interventions can include, for example, relaxation training,
counselling, and psychological approaches to pain control.
Colony-stimulating factors (CSF)
Substances which stimulate the production of certain blood cells e.g.
G-CSF stimulates granulocytes. They may be used to produce extra
stem cells prior to a stem cell harvest, or to promote the recovery of
white blood cells following chemotherapy.
Combination chemotherapy
The use of more than one drug to kill cancer cells.
Computed tomography (CT)
An x-ray imaging technique.
Conditioning
The elimination of malignant cells by the use of high dose therapy
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prior to bone marrow or stem cell transplantation.
Core biopsy
The removal of a tissue sample with a needle for laboratory
examination. This test uses a slightly larger needle than the one used
for fine needle aspiration (FNA) and is usually done under local
anaesthetic.
Cranial
Of or relating to the skull.
Cryopreservation
Preservation by freezing.
Cytogenetic abnormalities
Abnormalities of chromosomes.
Cytogenetics
The study of chromosomes and chromosomal abnormalities.
Cytokines
Proteins that are released by cells of the immune system which have
specific effects on other cells. Some cytokines help the body to
destroy abnormal cells. Examples of cytokine treatment include
interferon and interleukins.
Cytotoxic
Toxic to cells. This term is used to describe drugs which kill cancer
cells or slow their growth.
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Dermatologist
A doctor who specialises in disorders of the skin.
Epidemiology
The study of populations in order to determine the frequency and
distribution of disease and measure risks.
Epithelial cancers
Cancers originating in epithelial tissue. This is a membrane-like tissue
that lines internal and external surfaces of the body including organs,
vessels and other small cavities.
Erythrocyte sedimentation rate (ESR)
A test that measures the rate at which red blood cells settle out of
suspension in blood plasma. The amount of protein in the plasma
may increase as a result of infection or cancer which causes the red
cells (erythrocytes) to settle out more quickly than normal.
Febrile
Feverish.
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Fibrotic tissue
Fibrous tissue that replaces normal tissue e.g. scars or tissue that is
left after the cancer has been killed by treatment.
Fine needle aspiration (FNA)
The removal of cells using a fine needle for examination in the
laboratory.
Gallium scanning
An imaging technique sometimes used to provide further information
about abnormalities identified on plain x-ray or CT scan images.
Gastroenterologist
A doctor who specialises in disorders of the digestive system
including the liver.
Graft-versus-host disease
A serious complication of bone marrow transplantation where the
donated bone marrow reacts against the patient’s own tissue.
Granulocyte
A white blood cell that is an essential component of the immune
system.
Granulocyte-colony-stimulating factor (G-CSF)
See colony-stimulating factors.
Haematological cancers
Cancers of the blood and blood-forming tissues.
141
Haematologist
A doctor who specialises in disorders of the blood and blood-forming
tissues.
Haematology
A branch of medicine concerned with the study and treatment of
disorders of the blood and blood-forming tissues.
Haemato-oncology
A branch of medicine concerned with the study and treatment of
cancers of the blood and blood-forming tissues.
Haemopoietic or haematopoietic
The process by which blood cells are produced in the bone marrow.
Hepatosplenomegaly
Abnormal enlargement of both the liver and the spleen.
High dose therapy
Intensive treatment with chemotherapy and/or radiotherapy to kill
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malignant cells in the bone marrow. As the treatment also kills
healthy bone marrow cells, it must be followed by bone marrow or
stem cell transplantation.
High grade lymphomas
Faster growing, clinically aggressive lymphomas.
Hodgkin’s lymphoma
A type of cancer in which the cells of the lymph tissue are produced
in excess and result in the progressive, painless enlargement of lymph
nodes, the spleen and general lymph tissue. A particular abnormal cell,
known as the Reed-Sternberg cell is found in Hodgkin’s lymphoma.
Human Leukocyte Antigen (HLA)
Comparing the tissue type of patients and potential donors.
Hypercalcaemia
Abnormally high levels of calcium in the blood.
Iatrogenic
As a consequence of treatment.
Immunophenotype
Pattern of specific proteins (antigens) present on the surface
membrane of blood cells.
Immunosupression
Suppression of the immune system.
142
Immunotherapy
Treatment by stimulating or restoring the body’s own immune system.
Indolent lymphomas
Lymphomas that grow and spread slowly (also called low grade
lymphomas).
Induction chemotherapy
The first phase of chemotherapy treatment designed to induce
remission.
Indwelling venous catheters
See central venous catheters.
Intrathecal
Into the fluid around the spine.
Intravenous (IV)
Into a vein.
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Kinase inhibitors
Drugs that interfere with the growth of some cancer cells by blocking
the signals that prompt the cancer cells to divide.
Leukaemia
Cancer of the blood forming system in the bone marrow, usually
characterised by the production of abnormal white blood cells which
may be present in the bone marrow and blood.
Lymphadenopathy
Disease or swelling of the lymph nodes.
Lymphocytes
A class of white blood cell that fights infection and disease by
producing antibodies and other protective substances. There are two
categories – B cells and T cells.
Lymphoid cell
Pertaining to cells involved in lymph or lymphatic tissue.
Lymphoma
Cancer of the lymphatic system. There are two main types of
lymphoma - Hodgkin’s lymphoma and non-Hodgkin’s lymphoma.
Magnetic resonance imaging (MRI)
A non-invasive method of imaging which allows the form and
metabolism of tissues and organs to be visualised (also known as
nuclear magnetic resonance).
143
Medical oncologist
A doctor who specialises in the treatment of cancer through the use
of chemotherapy.
Meta-analysis
The statistical analysis of the results of a collection of individual
studies to synthesise their findings.
Microbiologist
A person who specialises in the study of micro-organisms such as
bacteria, viruses and yeasts, who may also be involved in the
development of treatment plans for such infections.
Monoclonal antibody therapy
Antibodies produced in the laboratory from a single copy of a human
antibody that can target specific cancer cells wherever they may be in
the body.
Monoclonal gammopathy of uncertain significance (MGUS)
A condition in which increased numbers of abnormal plasma cells
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produce identical (monoclonal) antibodies. The condition is of little
significance in itself and does not require treatment. However, 20-30%
of people with MGUS go on to develop myeloma.
Morphology
The shape, size and general appearance of cells under a microscope.
Multiple myeloma
See myeloma.
Myelodysplasia
Abnormal formation of blood cells in the bone marrow.
Myelodysplastic syndrome (MDS)
A group of diseases in which the bone marrow functions abnormally
and fails to produce enough normal blood cells. It may progress to
acute myeloid leukaemia.
Myeloid leukaemia
A type of leukaemia in which the white blood cells produced in
excess are those produced by myeloid stem cells. Also see acute
myeloid leukaemia and chronic myeloid leukaemia.
Myeloma/multiple myeloma
A type of cancer characterised by the uncontrolled production of
plasma cells in the bone marrow (myeloma cells). As it can develop
in many places simultaneously, it is also known as multiple myeloma.
144
Myeloproliferative disorders (MPD)
Disorders in which too many blood cells are made by the bone
marrow with increased numbers of red cells, white cells or platelets in
the blood.
Neoplastic disease
Disease characterised by new and abnormal growth of tissue (cancer).
Nephrology
A branch of medicine concerned with the diagnosis and treatment of
diseases of the kidneys.
Neutropenia
A condition in which the number of granulocytes (neutrophils) in the
blood is below normal.
Neutropenic sepsis
Life-threatening infection made more severe by the reduced
neutrophils.
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Neutrophils
A specific sub-type of granulocyte.
Non-Hodgkin’s lymphoma (NHL)
Any cancer of the lymphatic system other than Hodgkin’s lymphoma.
There are two main groups – high grade which are aggressive and
fast growing and low grade which are slow growing (also known as
indolent lymphomas). High grade lymphomas include: diffuse large B-
cell lymphoma (DLBCL), peripheral T-cell lymphoma, Burkitt’s
lymphoma, mantle cell lymphoma and AIDS-related lymphoma. Low
grade or indolent lymphomas include: follicular lymphomas,
Waldenstrom’s lymphoma and marginal zone lymphomas. Extra-nodal
lymphomas are those that develop outside lymph nodes such as those
affecting the skin or intestine.
Oncologist
A doctor who specialises in treating cancer.
Oncology
The study of the biology and physical and chemical features of
cancers. Also the study of the causes and treatment of cancers.
Palliative
Anything which serves to alleviate symptoms due to the underlying
cancer but is not expected to cure it. Hence palliative care.
Paraprotein
An abnormal antibody produced by myeloma cells.
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Pathologist
A person who specialises in the diagnosis of disease through study of
the microscopic structure of cells and tissues.
Peripheral blood stem cells
Stem cells in the bloodstream (as opposed to the bone marrow).
Philadelphia chromosome
A chromosomal abnormality found in the blood cells of all people
with chronic myeloid leukaemia.
Plasma cells
Plasma cells are a type of lymphoid cell. They produce antibodies
(also called immunoglobulins) in response to infection.
Positron emission tomography (PET)
A highly specialised imaging technique used to produce a
computerised image of metabolic activity of body tissues.
Precursor
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A substance from which another substance is formed.
Progenitor cells
Parent cells that give rise to progeny that serve more specialised
functions e.g. stem cells.
Prophylaxis
An intervention used to prevent an unwanted outcome.
Protocol
A policy or strategy which defines appropriate action.
Psychosocial
Concerned with psychological influence on social behaviour.
Pulmonary
Having to do with the lungs.
Quality of life
The individual’s overall appraisal of his/her situation and subjective
sense of well-being.
Radioimmunotherapy
Treatment with a radioactive substance linked to antibodies in order
to specifically target tumour cells.
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Radiologist
A doctor who specialises in creating and interpreting pictures of areas
inside the body. An interventional radiologist specialises in the use of
imaging techniques to assist treatment e.g. the insertion of
intravenous catheters.
Radiotherapy
The use of radiation, usually x-rays or gamma rays, to kill cancer
cells.
Randomised controlled trial (RCT)
A type of experiment which is used to compare the effectiveness of
different treatments. The crucial feature of this form of trial is that
patients are assigned at random to groups which receive the
interventions being assessed or control treatments. RCTs offer the
most reliable (i.e. least biased) form of evidence of effectiveness.
Recurrence
The return of cancer.
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Remission
A period when cancer has responded to treatment and there are no
signs of cancer or cancer-related symptoms.
Renal
Having to do with the kidneys.
Serum
The clear liquid that separates from blood on clotting.
Spleen
An organ which is part of the lymphatic system. It produces
lymphocytes, stores blood cells, filters the blood and removes and
destroys worn-out red blood cells.
Squamous cell carcinoma
Cancer originating in squamous cells – thin, flat cells resembling fish
scales – found in the tissue that forms the surface of the skin, the
lining of the hollow organs of the body, and the respiratory and
digestive tracts.
Staging
The extent (stage) of disease defined by internationally agreed
criteria. Staging helps determine treatment and indicates prognosis.
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Stem cell harvesting
Collection of stem cells either from the bone marrow (for bone
marrow transplantation) or the bloodstream (for stem cell
transplantation). Stem cells are normally found in the bone marrow.
However, the bone marrow can be stimulated to produce lots of stem
cells by the administration of growth factors (see colony-stimulating
factors) causing the stem cells to spill into the bloodstream for easier
collection. If the stem cells are being collected for autologous
transplantation, they may be purged to destroy any remaining
malignant cells before being preserved until required.
Stem cell rescue
See stem cell transplantation.
Stem cells
Blood cells at their very earliest stage of development; they may
become red cells, white cells or platelets.
Stem cell transplantation
A procedure similar to a bone marrow transplant, but using stem cells
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obtained from the blood rather than from the bone marrow.
Steroids
Steroids are hormonal substances naturally produced in the body.
They can also be made artificially and used as drugs. Some types of
steroid have been found to destroy some types of cancer cells and
can make chemotherapy more effective.
Thrombosis
Formation or presence of a blood clot within a blood vessel.
Total body irradiation (TBI)
Radiation to the whole body.
Ultrasound
High-frequency sound waves used to create images of structures and
organs within the body.
Vascular
Having to do with blood vessels.
White blood cells
Blood cells that do not contain haemoglobin. They are part of the
immune system and are present in the blood and lymphatic system,
including the lymph glands and spleen. The bone marrow produces a
number of different types of white blood cells which work together to
fight infection.
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Appendix 5
Abbreviations
ABVD
Adriamycin (doxorubicin), bleomycin,
vinblastine and dacarbazine
AIDS
Acquired immune deficiency syndrome
ALL
Acute lymphoblastic leukaemia
AML
Acute myeloid leukaemia
BCSH
British Committee for Standardisation in
Haematology
BEAM
Carmustine (BCNU), etoposide, cytosine
arabinoside and melphalan
BMT
Bone marrow transplantation
BSBMT
British Society for Bone Marrow Transplantation
BUCY
Busulphan-cyclophosphamide (conditioning for
BMT)
CCT
Controlled (non-randomised) trials
A5
CHI
Commission for Health Improvement
CHOP
Cyclophosphamide, doxorubicin, vincristine and
prednisolone
CI
Confidence interval
CLL
Chronic lymphocytic leukaemia
CML
Chronic myeloid leukaemia
CMV
Cytomegalovirus
CNS
Clinical Nurse Specialist
CODOX-M
Cyclophosphamide, vincristine, doxorubicin and
high-dose methotrexate
CPA
Clinical Pathology Accreditation (UK) Ltd
CSF
Colony-stimulating factors
CT
Computed tomography
C-VAMP
Cyclophosphamide, vincristine, adriamycin
(doxorubicin) and methyl prednisolone
DLBCL
Diffuse large B-cell lymphoma
EBMT
European Group for Blood and Marrow
Transplantation
ENT
Ear, nose and throat
EQA
External quality assurance
ESHAP
Etoposide, methyl prednisolone, cytarabine and
cisplatin
ESR
Erythrocyte sedimentation rate
G-CSF
Granulocyte-colony-stimulating factor
HEPA
High efficiency particulate air
HICPAC
Healthcare Infection Control Practices Advisory
Committee
149
HIV
Human immunodeficiency virus
HLA
Human leukocyte antigens
ICE
Ifosfamide, carboplatin and etoposide
JACIE
Joint Accreditation Committee EBMT-
EurolSHAGE
JCCO
Joint Council for Clinical Oncology
MDS
Myelodysplastic syndrome
MDT
Multi-disciplinary team
MGUS
Monoclonal gammopathy of uncertain
significance
MOPP
Mechlorethamine, vincristine, procarbazine and
prednisone
MPD
Myeloproliferative disorders
MRC
Medical Research Council
MRI
Magnetic resonance imaging
NCA
National Cancer Alliance
NCRN
National Cancer Research Network
NHL
Non-Hodgkin’s lymphoma
NICE
National Institute for Clinical Excellence
ONS
Office for National Statistics
OR
Odds ratio
PCR
Polymerase chain reaction
PET
Positron emission tomography
A5
RCT
Randomised controlled trial
REAL
Revised European-American Classification of
Lymphomas
SBU
Swedish Council on Technology Assessment in
Health Care
SRD
State registered dietitian
TBI
Total body irradiation
UKALL
United Kingdom Acute Lymphoblastic
Leukaemia trials
UKMF
United Kingdom Myeloma Forum
WHO
World Health Organisation
150
