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Guidance on Cancer Services Guidance on Cancer Services

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Guidance on Cancer ServicesImproving Outcomes inHaematological Cancers National Institute forClinical Excellence NHS Haematological cancers service guidance for Wales Improving Health in Waleshe serv ID: 287128

Guidance Cancer ServicesImproving Outcomes

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Guidance on Cancer Services Ð Improving Outcomes in Haematological Cancers Ð The Manual Guidance on Cancer ServicesImproving Outcomes inHaematological Cancers National Institute forClinical Excellence NHS Haematological cancers service guidance for Wales Improving Health in Wales.he service guidance programme was initiated in 1995 to follow on fromguidelines.Health services in England and Wales have organisational arrangements in place for securingimprovements in cancer services and those responsible for their operation should take this guidance into accountwhen planning,commissioning and organising services for cancer patients.The recommendations in the guidanceconcentrate on aspects of services that are likely to have significant impact on health outcomes.Both theanticipated benefits and the resource implications of implementing the recommendations are considered.Thisguidance can be used to identify gaps in local provision and to check the appropriateness of existing services.References1.Department of Health (2001) Available from: .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 Cancer to the Chief Medical Officers of England and Wales(1995).Available from: .doh.gov .uk/cancer/pdfs/calman-hine .pdf National Institute forClinical ExcellenceMidCity Place 71 High HolbornWeb:www .nice .org.uk ISBN:1-84257-398-5documentation including the research evidence on which the guidance is based is also available,reference N0329.© National Institute for Clinical Excellence October 2003.All rights reserved.This material may be freely reproducedfor educational and not-for-profit purposes within the NHS.No reproduction by or for commercial organisations ispermitted without the express written permission of the Institute. his guidance is a part of the InstituteÕs inherited work programme.It was commissioned by the Departmentof Health before the Institute was formed in April 1999.The developers have worked with the Institute toensure that the guidance has been subjected to validation and consultation with stakeholders.Thedelivery.While cost impact has been calculated for the main recommendations,formal cost-effectiveness Guidance on Cancer ServicesImproving Outcomes inHaematological Cancers Foreword.................................................................................................3Key recommendations..............................................................................7Background...............................................................................................8The topic areas1.Access to care................................................................................262.Patient-centred care.......................................................................323.Diagnosis and evaluation..............................................................444.Organisation of specialist services................................................525.Treatment (excluding high dose therapy)...................................686.High dose therapy.........................................................................847.Continuing management...............................................................958.Palliative care...............................................................................1009.Clinical trials and use of protocols.............................................1061.Economic implications of the guidance.....................................1092.How this guidance manual was produced................................1153.People and organisations involved in production of the guidance.................................................................................1174.Glossary of terms.........................................................................1375.Abbreviations...............................................................................149 Professor R A Haward, Chairman, National Cancer Guidance Steering Groupdiseases, linked by their origin in bone marrow derived cells. Thethrough disruption of the normal cellular processes in the bonecytogenetic abnormalities is challenging traditional approaches todisease classification. These advances are transforming bothThe characterisation of tumour cells by immunophenotypic andtraditional morphological approach to diagnosis. This trend is beingby novel drugs designed to specifically target the molecularabnormalities responsible for the development of the tumour. SuchJust as the diseases are distinctive and show many differences fromsolid tumours, so too is the organisation of services. There is amalignancies and those for solid tumours, perhaps reflecting theirinvolved. This has traditionally extended to the organisation andDespite these differences, there are compelling reasons for regardingcommon. Operationally the reality is that local hospital services forcommon solid tumours in cancer units rely in no small measure onhaematology services. The active support of haematology servicestumour types, particularly the diagnosis and management of life- distinctive features. The generality of cancer patients are increasinglymanaged by clinicians from different professions and medicalspecialties, working together to combine their expertise and makecollective decisions on the management of their patients. Whilst thediscipline, clinical haematology. Indeed it remains perfectly possiblegoes on to initiate treatment and subsequently determines furthertreatment as the patientÕs clinical course progresses. The sameindividual may also determine the point at which active therapy mayno longer be appropriate for that patient. Thus for many patients,consultants, probably colleagues in the same discipline and hospital.The main form of therapy for these diseases is chemotherapy(including immunotherapy). Other modalities such as radiotherapyhave their roles, but these are more limited. Chemotherapy iswidespread interest, and active participation of clinicians andhospitals, in clinical trials. Indeed, many national trials in thesediseases have been extremely well supported by haematologists in alltypes and sizes of hospital, with high rates of trial entry. This has ledto the widespread and routine adoption of evidence based protocolsto help guide care in the various malignancies. In some places, but by no means all, there is professional networkingcolleagues in more specialised units. In some places thisresearch evidence than we would have wished to guiderecommendations in some areas. Limitations in the evidence shouldalways be acknowledged, but need not necessarily prevent importantexperience in related areas. We have made some importantrecommendations about service organisation and delivery. 4 on sound and comprehensive diagnostic information. This is crucial indefine the most appropriate treatment. Decisions on managementshould involve a range of knowledgeable professionals in the diseaseareas concerned, meeting together. They need to determine themanagement of individual patients as well as agreeing more generalthese diseases face difficult diagnostic and clinical decisions - such asdefining the point at which further cycles of chemotherapy are notappropriate and change to a more palliative approach may bepreferred. It is essential that this collective involvement in decision-making is adopted for haematological malignancies, as for otherinvolved will be from one discipline. These arrangements shouldThe number of patients with each discrete type of haematologicalof those who manage many solid tumours, often low. Whilst the usespecialisation which cannot be easily evaded. Working collaborativelyin teams, and hence being involved in decisions about themanagement of larger numbers of new patients than arise in any onebeneficial. It will facilitate the development and sharing of expertiseabout each patient. malignancies is set against a very distinctive backcloth. Ourimportant move forward. Our recommendations are designed to offerinfluence over the preferred model in each place. We acknowledgemany years. However, consistency in the quality of care is ourprimary goal. It is evident that for some, what is being recommended 5 diagnosis of haematological malignancy. Results of tests shouldhaemato-oncology multi-disciplinary teams (MDTs) and providea specialised service at network level. This is most easilywith lymphadenopathy (chronically swollen lymph nodes ormedical colleagues. Clinical nurse specialists will arrange forordinated care, and all the information they want, throughoutMDTs which manage patients with acute leukaemia shouldprovide treatment intended to induce remission for sufficientnew patients for the units concerned to develop and maintainexpertise. Services are unlikely to be viable with five or fewernew patients per year. This treatment should be provided at awith continuous access to specialist nurses and haematologists. 7 required to achieve the best outcomes for adult patients withhaematological cancers. The guidance covers all aspects of care forthis group of patients, including medical diagnosis and management. newly-established National Institute for Clinical Excellence (NICE)Collaborating Centre for Cancer. It will be for that guidance topropose the definition of the interface between their service scopeand the work of adult services covered by this guidance.manual to orientate themselves to this group of diseases and theircancers. This is a uniquely diverse group which is sub-divided intothree main diseases: leukaemia, lymphoma and myeloma. Someforms are highly aggressive, others so benign that they may only beof body sites), which are typical of lymphomas; bone fractures andhaematological cancer but are particularly severe in acute leukaemia. Like the forms of disease, the treatments used vary widely. Some areAggressive forms of haematological cancer such as acute leukaemiaprogenitor cells from bone marrow or other sources. A wider range 8 including chemotherapy, radiotherapy and sometimes surgery; withcontinue over long periods of time. Less aggressive forms ofhaematological cancer, which are more common among elderlyincorrectly and multiply in a disorganised and uncontrolled manner,crowding out cells that are essential to normal function. The diversityin the form of disease produced results from a combination of factors,particularly the type of cell affected, the nature of the genetic changethat precipitates the malignancy, and the point in the cellÕs maturationBlood cells begin their development in the bone marrow. Whenwould normally develop into oxygen-carrying red blood cells,infection. This produces leukaemia, a disease characterised byAs they mature, white blood cells (lymphocytes) migrate from thesystem Ð in particular, the lining of the intestine, the skin, or the lungsÐ where their development continues. Malignant changes at this pointin the cellÕs life cycle produce lymphomas. These tend to revealOne particular type of blood cell (plasma cell) returns to the bonemarrow for the final period of its life. When malignant changes occurhere, excessive numbers of abnormal plasma cells destroy thesurrounding bone. This is myeloma, usually known as multiple 9 rates for the different forms of haematological cancer in England andales. Whilst the Office for National Statistics (ONS) and the Walesstatistics (Table 1), there are many problems with these figures. Forcancer registries, so the actual number of patients could beith some of these diseases, it can be difficult to decide whichindividuals should be defined as patients. Blood changes whicholder people and often produce no symptoms. Incidence rates forthese conditions therefore depend largely on whether anyonecliniciansÕ criteria for deciding whether malignancy exists at all. Evenwhen it is clear that haematological malignancy is present, identifyingthe particular form of cancer requires sophisticated methods whichare not available in many local hospitals, so a large number ofregistrations do not include detailed information on the diagnosis.This is especially true of non-HodgkinÕs lymphoma (NHL), a large andvaried group of conditions; indeed, the largest group of NHLregistrations in ONS statistics is described as ÒunspecifiedÓ. This issue The establishment of a new reporting system in the South Thames East Area wasassociated with an increase of 43% in annual registrations. (South Thames HaematologyLondon: KingÕs College, 2001.) This is consistent with anecdotal able 1.Haematological malignancies: incidence, survival rates and deaths, England and Wales (ONS figures)The level of underreporting, particularly of non-malignant cancers (ICD10 DPatients 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, Cancer survival trends in England and Wales, 1971-95:Studies in Medical and Population Subjects No.61. London: The Stationary Office, 1999. Data provided by the National Cancer Intelligence Centre, Office for National Statistics, on Cancer Disease CodesNo of Incidence:DeathsDeath:Relativecrude rate2000rate persurvival ICD 9ICD 101999per 100,000100,0002000OneFive1999yearyear204.0C91.05931.12520.553%26%205.0C92.017793.416043.024%8%205.1C92.16051.15081.061%22%7511.43920.7no no 205.2-205.9,C91.3,datadata206-208C91.5-91.9,238.1D47.16431.21730.3no no datadata284.9,285.0,D4620473.91100.2no no datadata203C9029915.720243.855%19%201C8112182.32410.588%75%200, 202C82-85, 807515.340127.665%45%204.1C91.120713.97781.577%51% Despite the problems with statistics, basic information is essential toplan service provision. Registration figures suggest that 39 new casesthe field believe that the numbers are considerably higher. It is alsocrucial for service planning to know how many patients are likely torequire intensive or complex forms of treatment, so varied groups ofless aggressive Ôlow gradeÕ forms, sometimes described as indolentlymphomas. Table 2 attempts to do this, although the figures areacknowledged to be estimates, particularly since the distinctionslymphoma) are often unclear.able 2.Haematological cancers: estimated annual incidencerates in the South West Ð around 50% higher than in Yorkshire.greatest increase in the number of people with non-HodgkinÕslymphoma. The rate of diagnosis has increased by 3-5% per annumbetween 1984 and 1993; ONS figures show that the age-standardised et al. The descriptive epidemiology of leukaemiaand related conditions in parts of the United Kingdom 1984-1993. DiseaseIncidence, Per million Per 500,000Per 250,000England and populationAcute leukaemia2400482412CML5001052-3CLL4000804020NHL Ôhigh gradeÕ2000402010NHL Ôlow gradeÕ50001005025120024126Myeloma3000603015MDS/MPD/other2000402010 incidence rose almost three-fold between 1971 and 1997. ThePrevalence is also increased by improved survival rates. Before thesurvival rates. Similar improvements are apparent for leukaemia: five-year survival rates have doubled since the early 1970s. In multiplemyeloma, substantial improvements have been achieved in short-term(one- to three-year) survival rates, although longer term survival ratesremain poor.Incidence and survival rates vary greatly with age. In people underdiagnosis. Age-related differences in survival time are particularlymarked in acute myeloid leukaemia (AML). Leukaemia incidence andmortality rates have risen sharply in the elderly but not so much inSimilar patterns can be seen for other forms of haematological cancer,common as populations age. The number of new cases amongcontinues to rise until the eighth decade (Figure 1). Figure 1.Number of new cases of haematological cancers (alltypes, combined) by age group, 1997Quinn M, Babb P, Brock A, et al. Cancer trends in England and Wales 1950-1999.London: The Stationery Office, 2001. 3500 Age Group 60-69 80 plus Number of New Cases better or worse than elsewhere. Survival rates in England and WalesUSA, but these apparent differences may not accurately reflect reality.these, rather than the underlying cancer, may be recorded as theinternational comparisons will be even more misleading. One of the reasons for the lack of trustworthy statistics is that ahaematological cancer has unique characteristics. To assess prognosisand select the optimum form of therapy, it is essential to knowThere have been numerous attempts at classification, with 25 differentsystems recorded for lymphoma alone over the last quarter-century.most pathologists in the UK. This allows the diagnosis of leukaemiaspathologists and clinicians. Regrettably, the REAL/WHO system canbe difficult to relate to classification systems on which nationalThe REAL/WHO classification system is based on a combination offeatures, which together define the type of cancer. These are: Genetic features Ð mutations or abnormal arrangements ofprecise diagnosis of leukaemia is based on similar criteria. An initialand treatment selection requires a wider range of diagnostic tests. Leukaemias tend to produce generalised symptoms, notably fatigue,bruising, bleeding and reduced resistance to infection. The severityleukaemias, so precise identification of the specific form of leukaemiaAcute leukaemia can affect adults of any age, but the incidence ofAML rises sharply in middle age and is highest among elderlycause severe anaemia which makes sufferers feel absolutelyproduce enough normal blood cells to mount an effective immunefour weeks at a time. Patients undergoing such treatment areand to treat it rapidly and effectively when it occurs. Specialistnursing and 24-hour cover by appropriately trained medical staff aremay be used in the hope of re-populating bone marrow destroyed bychemotherapy with healthy cells. This may require a transplant ofdonated bone marrow that closely matches the patientÕs owntaken from the patient before high dose chemotherapy (autologousstem cell rescue). Both methods carry specific risks: graft-versus-hostdisease with allogeneic transplants, or re-seeding with tumour withremission after treatment, only to recur some time later. When thishappens, the treatment may be repeated, perhaps intensified. It canbe very difficult to judge the point at which attempting to cure Chronic leukaemiaChronic lymphocytic leukaemia (CLL) is the most common form ofleukaemia, but it may also be classified as a form of lymphoma. It ismost often found in elderly people. The effects of CLL vary widely;some people feel quite well and the condition is discoveredand a swollen spleen which can become painful. A wide range ofThe second major form of chronic leukaemia is chronic myeloidleukaemia (CML). Younger people with CML can achieve long-termof bone marrow from a matched donor (allogeneic BMT); althoughrisky, this is currently the only curative treatment. Palliative measuresmay keep the symptoms under control for a few years, but theprogress of the disease cannot be halted except by BMT; without this,CML is invariably fatal. Imatinib (Glivec) is a new form of treatmentfor CML, the first of a range of drugs designed to target the specificabnormal proteins produced by the cancer. This approach seemsvery promising but its long-term effects are unknown.Myeloproliferative disorders (MPD)These are chronic conditions caused by bone marrow abnormalities,which usually affect older patients. People with myeloproliferativecommon 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 normallysufficient, but some patients develop vascular complications andMyelodysplastic syndrome (MDS)by abnormal bone marrow and tends to affect older patients. Itcauses progressive marrow failure, leading to anaemia, problems withblood clotting and reduced resistance to infection. People with thesediseases are usually given supportive care and regular transfusions onan out-patient basis. In about 30% of cases, myelodysplasticsyndrome turns into acute myeloid leukaemia; when this occurs inyounger patients, bone marrow transplantation may be offered. National Institute for Clinical Excellence. Guidance on the use of imatinib for chronic ymphoma, the most common type of haematological cancer,includes a wide range of conditions. Lymphomas tend to producelumps in lymph nodes; some forms affect other tissues such as theskin, lung or gut. Traditionally, lymphomas have been divided intoHodgkinÕs disease (now known as HodgkinÕs lymphoma) and non-which is often sub-divided into aggressive and indolent forms. Thisdistinction is, however, blurred, because some normally indolentalthough it can affect adults of any age. It usually produces athe body such as the chest. Other symptoms include recurring feverstreatment. Decision-making about treatment depends on accuratemasses that persist after chemotherapy. High dose chemotherapywith stem cell rescue can be offered to patients whose disease fails toafter treatment. They are particularly likely to need fertility services.Aggressive non-HodgkinÕs lymphomas: diffuse large B-celllymphoma (DLBCL), peripheral T-cell lymphoma, BurkittÕslymphoma, mantle cell lymphoma and AIDS-related lymphomalumps, which may grow quite rapidly. Although these lumps mostoften form in the neck, they can occur in other body sites, includingthe groin, abdomen, or armpit; on the skin, in the brain, lung, orbone marrow. By the time the condition is diagnosed, most patientshave widespread disease, with fever, fatigue, weight loss and nightfor about 30% of new cases of NHL. AIDS-related lymphoma is aparticularly aggressive condition. BurkittÕs lymphoma produces fast- 17 Precise identification of the form of lymphoma and accurate stagingform of treatment and for monitoring progress. This requires specialistdiagnostic staff and facilities. Most patients are treated on an out-require in-patient treatment. Radiotherapy may be used to reducebulky or localised tumours. About half of the total number of patientshigh dose chemotherapy. Several trials are investigating the role ofmonoclonal antibodies in the treatment of lymphoma.Less aggressive (Òlow-gradeÓ or ÒindolentÓ) lymphomasIndolent, or low-grade, are misleading terms which should not beeventually fatal. However, their rate of progression may be slow, withaffect older people. Follicular lymphoma, which accounts for 22% ofall cases of haematological cancer, is the most common form. Othersinclude WaldenstromÕs lymphoma and marginal zone lymphomas.Some types of marginal zone lymphoma form in lymph nodes, whilstothers produce tumours outside lymph nodes Ð for example, on theThe clinical presentation, rate of disease progression and patterns oftreatment vary widely. The disease may continue for a decade or moreinterventions when symptoms develop, is often the best option. curable, for example by radiotherapy to a single lymph node. Usuallydiagnosis and these patients are not likely to be cured. Nevertheless,Selecting the most appropriate form of intervention is a complexof the patientÕs life. Most patients are treated with single agentto manage blood abnormalities. There may be multiple episodes ofrelapse Ð often to a more aggressive form. National Institute for Clinical Excellence. Guidance on the use of rituximab for recurrentor refractory Stage III or IV follicular non-HodgkinÕs lymphoma. Patients with extra-nodal forms of NHL Ð that is, lymphomas thatdevelop outside lymph nodes, such as those which affect the skin orparticular body system, particularly dermatologists andgastroenterologists. However, since these are systemic diseases, localtreatment is rarely sufficient.ounger patients who relapse after initial treatment may be offeredhigh dose therapy, and there are several trials in progress to establishwhether the benefits of such aggressive treatment justify thedifficulties and risks. There are also several on-going trials ofmonoclonal antibodies such as rituximab. This approach to treatmentis expected to become increasingly important in the future. Myeloma causes painful, crippling bone destruction. As the diseasegeneral malaise, and symptoms caused by blood abnormalities suchas headaches and bleeding. Destruction of the bones produces highlevels of calcium in the blood, which causes tiredness, thirst, nausea,and kidney problems. Some patients develop neurological problemssuch as spinal cord compression.departments other than haematology Ð in particular, rheumatology,remission. Typically, patients experience repeated periods of relapse,disease can no longer be controlled. High dose therapy with stemsurgeons, pain specialists and renal specialists.abnormality which may be found on blood tests. Of itself, itproduces no symptoms, but it can turn into myeloma or otherhaematological malignancies. In many people, MGUS remains stable 19 Long-term impact of treatment forCurative treatments for haematological cancer, particularly intensive orhigh dose therapies, can have lasting effects. These include aamong people treated for HodgkinÕs lymphoma. Secondaryleukaemias have been linked with chemotherapy, and solid tumours,such as breast and lung cancers, with radiotherapy used to treatleukaemia or lymphoma. All these forms of cancer tend to emerge ata younger age in long-term survivors of haematological cancer than inLong-term hormone-related problems are also relatively common.Most patients will be rendered infertile by treatment forhaematological cancer, and fertility services are important to enable atAs stated earlier, the incidence of haematological malignancy,particularly NHL, appears to be rising quite rapidly. If this rate ofincrease could be due to better case-finding, it is likely that there hasthe rise in these forms of cancer, but there is not yet sufficient reliableevidence to draw firm conclusions on this.Immune system depression, which has been linked with many formsof haematological cancer, affects increasing numbers of people. Thiscan be due to diseases such as HIV, to drugs used to prevent rejectionof transplanted organs, or to cytotoxic treatment (chemotherapy orsuch as cyclophosphamide. All are becoming more common. This information is derived from studies summarised in Improving Outcomes inHaematological Cancers, The Research Evidence.&#xwww.;&#xnice;&#x.or1;.70;g.ukCartwright RA. Non-HodgkinÕs Lymphoma. In Hancock BW, Selby PJ, MacLennon K,Armitage JO. Malignant Lymphoma. London: Arnold, 2000.Living downstream: an ecologist looks at cancer and the environment.London: Virago, 1999. of the rise in incidence of NHL. There are local excesses of NHL inrural areas, relatively high incidence rates among farmers andbiocides and risk of NHL. However, whilst atrazine, lindane andstudies, current evidence does not show a clear-cut associationPetrochemicals have been linked with various forms ofhaematological cancer. Benzene is particularly hazardous; long-termexposure is known to damage the bone marrow and to causeThese effects are dose-related but sensitivityvaries widely between individuals. Benzene is widespread in theenvironment Ð it is found, for example, in cigarette smoke, engineconcentrations precipitate leukaemia. The risk of acute myeloidleukaemia is doubled in people who smoke 20 cigarettes daily; abouthalf of this excess risk can be attributed to the benzene content ofcigarette smoke.Exhaust from petrol and diesel engines contains several harmfulchemicals. Exposure to engine exhaust significantly increases the riskdegreasing, and various forms of cancer including NHL. Although thepublished evidence for increased risk of NHL among people workingare consistent. Tetrachloroethylene is known to cause leukaemia in Cartwright RA. Non-HodgkinÕs Lymphoma. In Hancock BW, Selby PJ, MacLennon K,Armitage JO. Malignant Lymphoma. London: Arnold, 2000; pp171 and 173. Rinsky RA, Smith AB, Hornung R, Filloon TG, Young RJ, Okun AH, Landrigan PJ. Benzeneand leukaemia: An epidemiologic risk assessment. UK Department of the Environment, The effects of benzene on human health. Available at:&#xwww.;෯r; .go;&#xv.uk;&#x/env;&#xiron;&#xment;&#x/air;&#xqual;&#xity/; qs/;¾nz;ne/;.ht;&#xm000;national Associationfor Research into Cancer (IARC) monograph vol. 83 on smoking, available on:Sonoda T, Nagata Y, Mori M, Ishida T, . Meta-analysis of multiple myeloma andInternational Association for Research into Cancer (IARC) monograph vol. 63 on A range of different levels of service, corresponding with the varietyof forms of disease, is required to manage patients withhaematological cancers. Patients with acute leukaemia may needrepeated periods of intensive in-patient treatment lasting over three oryears. Hospital episode statistics show that haematological cancersaccount for about 17,000 in-patient bed days per million populationper year, but the actual figure could be substantially higher than this.The range of degrees of complexity of hospital treatment may besummarised as follows; the levels correspond with those specified bythe British Committee for Standardisation in Haematology (BCSH).Level 1Hospitals providing conventional chemotherapy and otherforms of out-patient treatment, using dose levels thati.Out-patient assessment and monitoring.ii.Out-patient chemotherapy and haematologicaliii.Day case chemotherapy e.g. for NHL.iv.In-patient chemotherapy and palliative treatment, e.g.v.Facilities for management of neutropenic sepsis.Level 2Facilities for remission induction in patients with acuteleukaemia, using intensive chemotherapy regimes. Thislevel of facility is also required to treat patients withLevel 3Facilities for autologous transplantation, using the patientÕsown bone marrow or peripheral blood stem cells. Guidelines on the provision offacilities for the care of adult patients with haematological malignancies Level 4Centres with expertise in both autologous and allogeneicIt is believed that over a hundred hospitals in England and Walestransplants (Level 4). Accreditation standards for bone marrowtransplantation (available on www.ebmt.org) specify that any hospitalwhich offers stem cell rescue Ð whether autografts or allografts Ðshould carry out a minimum of 10 procedures of the type offered peryear. Returns to the European Group for Blood and Marrowautografting, with treatment-related death-rates of up to 25% inpatients over 60 years old and around 8% in younger patients. Thisemphasises the importance of all units performing this work havingsufficient experience, staff, and facilities to deliver these treatmentssafely and effectively.At present, patients with leukaemias and most other forms ofhaematological cancer are managed by haematologists. Althoughsome impressive features. The proportion of patients entered intoprotocols; and follow-up systems are often good. There is a highhaematological malignancy. Pooling knowledge by involvement intrials, extensive use of protocols and consultation with colleaguestends to improve the probability that individual patients are offeredthe most effective treatment.Problems are more likely to occur with types of haematologicalmay be more difficult to identify. The symptom patterns within the Gratwohl A, Baldomero H, Horisberger B, . Current trends in hematopoietic stem cell Current services are, moreover, very heterogeneous. Although someparts of England have established formal multi-disciplinary team(MDT) working, with specified teams for each major form ofhaematological cancer, many haematologists in other areas areeffectively single-handed. The level of integration between oncologyconcern. For example, there is evidence showing an unacceptablyhigh rate of errors in diagnosis (see Topic 3, ). Current diagnostic services fall into four broad1.Fully integrated specialist diagnostic laboratories. 2.Services spread over different laboratories. Typically, pathology,haematology and immunology departments share the workload.ith this way of working, the results have to be integrated intoa single interpretative report containing all the informationrelevant to the management of the patient, to avoid duplication3.Access to some specialist technical services. Many districtgeneral hospital laboratories can carry out a limited range ofhaematologist who also treats the patients. Some specimensmay be referred to larger centres for specialist investigations.4.No access to specialist diagnostic services (this is not believed toare not always altered when expert review suggests that an alternativetreatment would be more appropriate. This suggests poor integrationThe level of expertise of clinical staff also varies widely from Trust torust. Patients report excellent services in some hospitals, butin others. An adequate service requires high levels of staffing bynurses and doctors who have sufficient expertise to respondwarning. A single-handed haematologist simply cannot provide this 24 Lack of integration between haematology and other clinical disciplinesaccess to services from which they would benefit. Haematologistswho treat these patients need to be able to work closely with otherpalliative care services and services for the elderly. Such integrationrange of services. These issues are further discussed in Topic 4,Organisation of specialist services. 25 A.RecommendationsUrgent (two-week) referral guidelinesThe following guidelines for urgent referral have been published byConstellation of three or more of the following symptoms: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 receivesurgent referrals should establish a process to ensure that patients withRoutine referral the cancer network to produce locally agreed referral guidelines forhaematological malignancies. These guidelines should be designed tohelp GPs to identify possible sufferers, give contact details for thehaemato-oncology MDT to which patients with suspectedhaematological cancer should be referred, and specify informationrequired from the referring doctor. 26 . Available on: Haematological malignancies tend to cause extreme forms of non-notably unusual tiredness. Patients describe the distressing andconsulting GPs repeatedly, yet not being taken seriously. Thiscommon, few patients with lymphadenopathy have cancer.These conditions can cause a wide variety of symptoms. GPs shouldconsider the possibility of haematological cancer when patientsthey have other symptoms that might be consistent with such adiagnosis. Any patients with unexplained lymphadenopathy (a lump - usually insurgeons who work with the lymphoma MDT (see Topic 3, ). No patient should undergo surgical excision orbiopsy of an enlarged lymph node without preliminary discussionguidelines. A full blood count should always be carried out if the GPis suspicious, but a normal blood count should not be taken assuspected haematological malignancy. Such patients should be giveninformation and reassurance about their condition before referral to aroutine out-patient haematology clinic. Most will never requireis wide, but probably fewer than 2% of patients present asemergencies. These patients usually have acute infections and thedisease is likely to be diagnosed by a blood test at the time ofadmission. A patient with acute leukaemia discovered by a blood testwould normally be admitted to hospital within 24 hours. 27 infections and kidney problems. Bone pain is the most commonprecipitate renal failure in these patients.made by a blood test and such patients come to the attention ofvarious routes, such as rheumatology, orthopaedic or renaldepartments. Any patient who is to have surgery for a lytic lesion(hole in bone) should first have a test for paraprotein to check foravailable for investigation of lymphadenopathy, with a locally agreed,specified process that ensures that appropriate investigations areavailable quickly. GPs should refer all patients with persistent,unexplained lymphadenopathy to designated clinicians with specificresponsibility for investigating this particular symptom. Formal lumpclinics may be established to investigate isolated lumps in the neck orclinics, but organised collaboratively by haematology, ENT, andservices for head and neck cancer. Whatever form of organisational structure is used, it should bedesigned to facilitate co-operation between designated haematologists,radiologists, ENT specialists, head and neck surgeons and oncologists(see lymphoma MDT, Topic 4, Organisation of specialist servicesup for patients with lymphadenopathy (see Topic 3, ). Patients found to have cancer should be referredwithout delay to the appropriate MDT. There should be pre-bookingsystems for appointments at results clinics at which each patient withwhich deals with that type of cancer, and where support would beavailable from a clinical nurse specialist. Networks should agree local clinical guidelines designed to ensurethat patients who are seen initially in dermatology departments orfound to have lymphomas, are referred without delay to thehaematological cancer team. Implementation of these guidelines 28 No definitive treatment should be given for haematological cancer,lymphoma or acute leukaemia, without discussion by the appropriateMDT. If such treatment is given, it should be discussed by the MDTB.Anticipated benefitsappropriate referral of patients. This will reduce delays in diagnosis,so that patients can be offered suitable treatment more quickly.lumps in the neck or axilla have malignant disease, often lymphoma.Rapid-access lump clinics can offer an efficient route to treatmentC.Evidenceevidence. The grading taxonomy is explained in Appendix 2.appropriate investigations are carried out to diagnose haematologicalmalignancy.(C) Delays in diagnosis do not seem to affect long-termoutcomes in lymphoma but the level of any potential risk posed bydelay is likely to depend on the nature of the disease. Shorter delaystheir GPs, and 43% were seen within two weeks. However, 6% haddeteriorated while they waited for an appointment. The majority ofappointment, but 25% had to wait another two weeks or more. The 29 waited seven months or more after their first hospital appointment.A study of 89 patients with lymphomas from four UK centres betweensymptoms and the beginning of treatment was 7.5 months. The largestnearly four months. The mean period between initial consultationand diagnosis (diagnostic delay) was 2.8 months, the greatest part ofdiagnostic clinics. These allow initial investigations to be carried outover a short time-period, thus reducing patient uncertainty anddiagnostic delay, and can help to rationalise referral patterns.(B)epithelial cancers. Data from an established lymph node diagnosticclinic at the Royal Marsden Hospital in London, to which patients aredirectly referred by GPs, shows that median time from initial referralto diagnosis of malignancy was three weeks. 12% of these patientswere found to have lymphomas. 46% of the patients referred by GPsor hospital departments to a dedicated clinic for investigation of neckmasses at Wexham Park Hospital, Slough, had enlarged lymph nodes.D.MeasurementStructureReferral guidelines for GPs, agreed across the network, whichLocal clinical guidelines which specify that patients who presentwith gastro-intestinal, chest or dermatological symptoms, butwho are found to have lymphomas, should be quickly referred 30 National Surveys of NHS Patients: Cancer, National Facilities for rapid investigation of lymphadenopathy. Thesespecific clinics for rapid investigation of lymphadenopathy(rapid-access lump clinics at cancer units), staffed by designatedappropriate investigation of lymphadenopathy.Designated surgeons, who work with the clinicians or clinicsdescribed above, who carry out lymph node biopsies within ancancer to the appropriate haemato-oncology MDT.ProcessAudit of patient pathways against guidelines which specifyreferral patterns for patients with haematological cancer,particularly those whose presenting symptoms affect the gastro-E.Resource implicationsstreamlining the current service. These patients are already in thehospital system, so these resources will, to a large extent, already beavailable. It should, therefore, be possible to implement therecommendations in this topic area by re-organising the use of 31 It is planned that the National Institute for Clinical Excellence (NICE)cancer will be published early in 2004. This guidance is intended tocomplement this manual, giving detailed and specificrecommendations on many of the issues introduced in this section asthey apply to cancer care generally, with supporting evidence. It willInformation; 32 A.RecommendationsClinical nurse specialists should be available to provide support forpatients with haematological cancer. These nurses should haveshould be full members of haematological cancer multi-disciplinaryteams (MDTs), with specific responsibility for facilitating the provisionprofessionals. They will provide information and support for patientsand help other clinical staff to acknowledge and give fullconsideration to individual patientsÕ perspectives. (See Topic 4,Organisation of specialist servicesspecific clinical nurse specialist who can offer psychosocial supportand continuity of care. Each patient and his/her carer should bethey feel they need information, help or support. Whilst most peoplewith cancer are primarily concerned that their chances of survivalthat their other needs are also recognised and met. These includegetting appropriate and acceptable food in hospital. The counselling role of the clinical nurse specialist is likely to beparticularly important in haematological cancer. For some patients,the risk and suffering that the process may entail is such that thedecision about whether to go through with it is very difficult. Forothers, such as older patients with acute leukaemia, and those forwhom repeated efforts to control the disease have failed, the risks ofintensive treatment may make it inadvisable. In these cases, inparticular, counselling by a clinical nurse specialist who understandsInformation for patients haematological cancer is lack of information: first about theirdiagnosis, and later about what may happen to them. Effectivesystems should be established to ensure that clear, honest andconsistent information is given to patients from the outset. 33 what is likely to happen as they progress through the various phasesof their illness and treatment, but all those involved in caring for theseshare information.The consultation at which patients learn that they have cancer is acrucial event. Sensitive and compassionate communication isessential. This is, literally, a life-changing experience for patients.Although factual details may be forgotten, the way the news that theytrust or deep resentment. In haematological cancer, there is oftenmore than one Òbad newsÓ consultation during the course of theÒbad newsÓ consultations. The consultation should be held in abe responsible for the patientÕs future care. Adequate time should beThe nurse specialist should be present during this consultation andshould remain with the patient afterwards to offer support and furtherinformation tailored to individual needs. Other people, such asstudents, should only be present with the patientÕs explicit consent.specific training in communication skills. Such training should also beWhen there is a choice between different therapeutic approaches,patients should be offered the opportunity to discuss the options in atreatment and the specialist nurse. Providers should ask patients ifthey want additional information and seek to discover how much theywish to be involved in discussions about treatment. If there isbe given realistic information about the different possibilities. 34 National Cancer Alliance. PatientsÕ views of haematological cancer services and the draftnational haematological cancer guidance. April 2001, p 17. Different individuals vary widely in their attitudes and in theirwillingness to tolerate cancer treatment, and their views may changefrom time to time. Some would choose the chance of extendedthan undergo intensive therapy, and others may choose to deferradical treatment until after what they regard as a crucial life priorityPatients should be offered as much information about their diseaseand its treatment as they wish to have, in forms they can use andassimilate. Doctors should ask patients what they want to know andabout their concerns, and check that they understand what they havebeen told. Patients often find it difficult to take in information givenduring 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 onaudiotape. Patients must be offered copies of letters written aboutPatients should receive both individual support and guidance frommembers of the MDT and well-produced information leaflets.should be encouraged to return to MDT members for additionalinformation and clarification when they want it. Written informationshould be consistent across each network.the probable and potential time-scales. Clinicians should not seek tominimise the impact of the treatments they offer, nor the length oftime required for recovery from treatment. They should do their bestto explain clearly what is happening at each point in the patientÕsjourney, to be honest about uncertainty and the risk that treatmentmight do more harm than good, and to make sure the patientcommunication. Providers should not normally expect members of 35 Sources of information for patients with cancer can be found on the NHS Direct website Information offered to patients should include:Sufficient information about basic anatomy and pathology forpatients and their carers to understand the disease and how itmight affect them;Realistic information about the disease and the range ofThe aims, risks and likely effects of proposed diagnosticprocedures. Each procedure should be explained to the patientBalanced information with clear explanations about potentialor symptom reduction (and uncertainties about benefits), knownrisks and potential short- and long-term adverse effects; Information about other potential effects of the illness and itstreatment on both patients and carers, such as anxiety andThe likelihood of long-term continuing contact with theReasons for not offering interventions which patients mightPatients should also be given clear information about the hospitalservice. This should include: the patient, and their different responsibilities; if they feel concerned about any aspect of the illness, treatment,or hospital service. information has been given to the patient. A record of this, alongwith the patientÕs preferences for information and involvement inplan, should be included in the notes. This information should alsobe given to the patientÕs GP within 24 hours so that primary care staffcan provide additional support for patients and carers. 36 cryopreservation of sperm. Whenever possible, patients oftreatment for their fertility before treatment begins. Haematological malignancies often cause long periods of illness,during which many patients are dependent on benefits. Nurseroles in co-ordination with social services to ensure that the needs ofboth patients and carers are identified and met. Patients and carersshould be given information about sources of help, such as local andhelplines, both verbally and in writing. Advice on benefits and helpwith application forms should be available from someone who isNutritional and dietetic supportnutrition. This issue is particularly important for patients who mayremain in hospital for weeks or months at a time. Providers shouldensure that patients receive specialist dietetic and nutritional supportacceptable in the context of their ethical or religious beliefs. Dieteticsupport should also be available after discharge, if required.respiratory disorders. Patients should have access to specialistprocess and can provide appropriate and effective care, e.g. aids andB.Anticipated benefitsinformation can help patients to cope with their disease, enhancesatisfaction with services, and reduce criticism and complaints.Information has a variety of benefits for cancer patients, particularly 37 Management of gonadal toxicity resulting from thetreatment of adult cancer: Report of a working party for the Joint Council for ClinicalLondon: Royal College of Physicians/Royal College of Radiologists, 1998. job satisfaction and reducing stress. Effective communication tends toThe application of Trust guidelines on obtaining and documentinginformed consent may facilitate the audit of process within networks.C.Evidenceinform this guidance manual, the National Cancer Alliance (NCA)professionals often fail to provide the information that patients wantand that many are not honest about the likely effects of treatment onIn the focus group, patients explained that they needed informationabout treatment effects, duration and potential consequences in orderarrange for support for the whole course of their cancer journey. All 38 224National Cancer Alliance. PatientsÕ views of haematological cancer services and the draftnational haematological cancer guidance. April, 2001.25Ibid, p 26. problems with information for patients with non-HodgkinÕs lymphomacompletely understand the diagnosis than were patients with commonsolid tumours (30% versus 17% for all patients), less likely tounderstand the purpose of diagnostic tests (65% understood, versus75% of all patients), and less likely to realise that different types oftreatment were available (59% versus 66%). 25% of patients did notcompletely understand the purpose of their treatment and 32% did notknow how well their treatment had gone. 18% would have preferredmore information about the outcome of their treatment.(C) Thereappear to be few high-quality research studies focusing specifically onnon-medical issues or psychosocial interventions for patients withhaematological cancers. Evidence reviews carried out for previousdocuments in this series are, however, relevant. Summaries of studiesshowing patientsÕ desire for clear information, the need for healthand patientsÕ continuing need for psychological, social and practicalImproving Outcomes clinical nurse specialists in haematological cancer. There are studiesof such nurses working with patients with other types of cancer,notably breast; this role was, after all, developed in the context ofbreast care services. It seems that care from specialist nurses isassist. They report that psychological morbidity and social isolationare particularly common among patients with cancer. Cancer supportsupport course (ÒTaking ControlÓ) for patients with haematologicalpositively. Although a minority (about 10%) reported somediscomfort Ð usually because they had to face information that theyhad not wanted to acknowledge Ð most found that the course helpedthink more positively. Meeting others with haematological cancer onthe course helped them to Ôfeel normalÕ. Fifteen of the 26 participants 39 National Surveys of NHS Patients: Cancer, NationalImproving outcomes in breast cancerImproving outcomes in urological cancersavailable on the NICE website &#xwww.;&#xnice;&#x.or1;.70;g.uk; earlier documents dealing with other&#xwww.; oh.;&#xgov.;&#xuk/c; nce;&#xr000;common cancer sites can be found at: who completed the post-course questionnaire said that what they hadlearnt had been translated into behavioural changes.(B)Where structured interventions such as this are not available, supportgroups can facilitate interaction between patients with cancer. Butfewer than half of the NHS patients with NHL who took part in thetrials (RCTs), run concurrently with patients with HodgkinÕslymphoma. One compared the effects of written educational materialabout the disease (a booklet and newsletters) with no educationalintervention. This was associated with additional benefits includingsignificantly reduced anxiety and fewer treatment problems. Theother RCT assessed the effects of participation in eight meetings with anon-directive roles. The peer support group did not appear toproduce any significant benefits.(A)get help and advice with the problems they face at home arenurses.(B) The majority of calls are for information and are fairlyThese studies suggest that information is beneficial for patients but thattalking about problems without being offered solutions is not helpful.decreases in anxiety and depression.(B) However, it is not possibleto judge the effectiveness of the various components of what appearsAn RCT from the US comparing Òtreatment as usualÓ with therapistsupport, relaxation and imagery training and cognitive-behaviouraltherapy for 94 patients with haematological cancers undergoing bonemarrow transplantation reported no significant differences in outcomesbetween the interventions. No meaningful comparisons were madeinterventions so it is not possible to judge their effectiveness.(B) 40 Airey C, Becher, H, Erens B, Fuller E. National Surveys of NHS Patients: Cancer, National provides reliable information on their effectiveness orappropriateness.(B) They appear to assume that such interventionsinformation, psychotherapeutic and other non-medical aspects of carefor patients with cancer. This literature does not focus specifically onthe needs of patients with haematological cancers but the findingsmay be generalised to this group. Reviews of these aspects ofImproving Outcomes Health websites, and in Improving supportive and palliative care foradults with cancer,planned to be published by NICE early in 2004. Aclear, evidence-based discussion of communication skills and howMedical JournalD.MeasurementStructurevailability of clear information for patients in appropriate formsand languages, about their disease, proposed treatment and howits effects might be managed, the hospital and MDT responsiblefor their care, and any services and sources of support that arepatients with haematological cancer. ProcessPrivate rooms used for crucial meetings between health care staffand patients (in particular, consultations at which patients are 41 Maguire P, Pitceathly C. Key communication skills and how to acquire them. Audit of information offered when:The patient is given bad news;The patient is to undergo a potentially unpleasantAudit of patientsÕ and carersÕ experience of psychologicalsupport by suitably trained staff from the time of diagnosis andat each subsequent stage of their journey through the illness.specialist who knows about his or her condition, who offerssocial services staff when required.Audit of the proportion of staff involved in direct patient careRecord of discussion with patients of information given andpatientÕs involvement in decision-making about care.Evidence of effective user involvement.Audit of assessment for, and provision of, physical, practical andPatientsÕ knowledge about resources relevant to them;Their views on information they were given and the way itWhether they felt able to participate (if they wished to doWhether patients felt that they had been offered sufficientinformation to give informed consent to each intervention; 42 especially for patients with eating problems;Adequacy of support for patients in their homesE.Resource implicationsquality information and educational material for patients and carers,and to allow staff time and facilities for talking with patients andprofessionals, including senior medical staff. nurse specialists. It is estimated that about four new posts will bealtogether, around 140 additional clinical nurse specialists for Englandand Wales, at an estimated total cost of £4.6 million (see Appendix 1, The Department of Health is developing guidance on modernisingnetworks in pathology across a number of Trusts, to build capacity,reduce fragmentation, and provide an enhanced level of equipmenthaematological cancer. Specialist pathology services should beoncology. In order for this to work in practice, the followingHaemato-oncology multi-disciplinary teams (MDTs), described inthe next chapter of this manual. These should include haemato-malignancy who may come from a range of backgrounds;All haemato-oncology MDTs should have adequate facilities forEffective systems for collecting suitable fresh tissue samples andidentification of genetic abnormalities. Immunophenotyping,molecular biology and cytogenetics require specialist services;Regularly updated computer software designed to supportprecise identification of haematological malignancies. Thissoftware should generate worksheets and instructions on an The Department of Health has published its response to the consultation on its draftguidance &#xwww.; oh.;&#xgov.;&#xuk/p; tho;&#xlogy;&#xmode;&#xr-15;&#x.100;nisation, and the final guidance will bepublished in 2003.It is hoped that this software will shortly become available on the net. Access to appropriate imaging facilities. Imaging requirementsshare and discuss diagnostic information in meetings of MDTspatients. Teleconferencing systems may be established tofacilitate such discussion when geography makes it difficult forcrucial specialists to attend MDT meetings in person.A.RecommendationsHaemato-pathology services should be organised at network level.wo levels of haemato-pathological service are required: a localInvolvement in external quality assurance (EQA) is necessary at bothlevels. Haemato-pathologists should participate in EQA schemes,which should normally be co-ordinated at national level, althoughsome may be best operated on a regional basis. All laboratoriesshould be covered by Clinical Pathology Accreditation (UK) Ltd (CPA)Each diagnostic laboratory should serve as large a population base aslaboratory-based haemato-pathologists in the haemato-oncology MDTsusts should identify clear pathways toinformation at MDT meetings. pathologists. A specified range of tests should be carried out on eachsample in a systematic way, following protocols which define both 45 part urban and part rural. these patients is discussed in an appropriate MDT meeting. Anfilms by a local haematologist. A member of a leukaemia MDTthe specialist pathology laboratory for further assessment. BoneAchieving a precise diagnosis of lymphoma and making decisionsabout appropriate treatment can be complex. It requires the sameinput from other specialists. These are listed in the lymphoma MDT,described in the next chapter of this manual.lymph nodes or abnormalities in other tissues that may be caused bylymphoma. Specific ENT or head and neck surgeons should bepathologists who work with lymphoma MDTs. that cancer originating outside the lymph node could be the cause ofbiopsy of the lump. Only when this diagnosis has been excludedshould the affected node be removed. It should then be delivered 46 Pathologists who assess lymphoma specimens should discuss theirclinical, laboratory and imaging information can be integrated in thecontext of the MDT meeting. Treatment for lymphoma should ideallybe deferred until a definitive diagnosis is available. If treatment hasbegun, it should be reviewed by the MDT in the light of detaileddiagnostic information.Imaging is essential to staging lymphoma. Clinical policies for theco-ordinated use of appropriate imaging when required for patientslymphoma MDTs in the network. Cross-sectional computedtreatment, both initially to judge the extent of the disease, and aftertreatment to assess residual disease. Magnetic resonance imagingPositron emission tomography (PET) scanning may be considered, ifavailable, for discriminating between residual lymphoma and fibroticdetermine its cost and utility in relation to other forms of imaging.When carried out in centres with a high level of expertise, galliumscanning can be a useful adjunct to CT.the serum and sometimes, the urine of patients. Staging anddecisions about treatment require information derived from theclinical picture (including assessment of renal function), boneinforming decisions about management is unclear, but may be 47 myeloma are available on the net at: &#xwww.;&#xukmf;&#x.or1;.80;g.uk/guidelines.shtml B.Anticipated benefitsExpert review of pathology improves diagnostic accuracy. There isin Wales actually have benign disease, and the situation is likely to bemuch the same in England. This means that every year, 400 peoplemay suffer the distress and upheaval of a cancer diagnosis andundergo risky treatment unnecessarily. Many more patients Ð at leastincorrectly. At a unit cost of £100-£150,precise diagnosis is a small fraction of the cost of treatment; and thehuman cost of error can be enormous. Once established, integrated diagnostic facilities for haematologicalmalignancies are likely to be highly cost-effective. Rational selectionuseful information about each particular patient are carried out.C.Evidenceevidence. The grading taxonomy is explained in Appendix 2.Accuracy of diagnosis in lymphoma and leukaemiahigh level of inaccuracy in diagnosis, and that specialist pathologicalaccuracy. The level of major discrepancies between diagnoses madeA report from the US suggests that similar problems arise in theIn Wales, the first two years of central review of lymphomaover 20% of 275 lymph nodes. In five cases judged by theexpert panel to be lymphoma, the district hospital diagnosed abenign condition. Thirteen patients with benign conditions andfour with non-haematological cancers were given diagnoses oflymphoma by local clinicians. Fifteen diagnoses were changedfrom non-HodgkinÕs lymphoma (NHL) to HodgkinÕs lymphoma 48 Unit cost per specimen in Yorkshire, where the diagnostic facility serves a population of different prognostic group. In addition, in 21% of cases, thewas given. The central review group produced definitivegroup (17 cases). In practice, first-line treatment was altered forlymphoma pathology reports. 36% of the discrepancies wereconsidered to be major;In suspected HodgkinÕs lymphoma, 94% of diagnoses reviewedby the Scottish and Newcastle Lymphoma Group wereconfirmed but histological sub-typing was altered in 28% of 574cases with initial sub-type information. This resulted in aProblems have also been found in the interpretation of radiologicalimages by local clinicians. An audit of CT scans referred to adifferences in the interpretation of CT findings for 34% of 124patients. In most cases, more disease was found. Specialist reviewhad little impact on actual patient management, however; in 27% ofEffectiveness of imagingPET appears to be particularly effective for discriminating betweentreated with chemotherapy. It is more sensitive than galliumscanning and is especially useful for showing when lymphoma hasnot been successfully eradicated. Gallium scanning is more effective There is no evidence that routine use of MRI provides informationmyeloma. In asymptomatic stage I disease, MRI can reveal bonemarrow lesions that are not detected by other means, but it is notclear how this information might affect patient management.D.MeasurementStructureSystems for rapid and efficient communication betweenhaematological cancer MDTs.Arrangements for rapid transfer of fresh biopsy specimens todesignated haemato-pathologists who assess the samples withoutProcessTime from GP referral to specialist diagnosis.Time between lymph node biopsy and availability of detailedTime between initial clinic assessment of patients with suspectedlymphoma or myeloma and availability of imaging results.Audit of accuracy of diagnosis.Audit of appropriateness of lymph node biopsy. 50 E.Resource implicationsaverage network (1.5 million people). Overall, the estimated settingrunning costs of about £7.5 million. There are substantial economiesof scale, so the actual costs will depend on the size of populationserved.(See Appendix 1, The situation in Wales differs from that in England, in that the Allales Lymphoma Pathology Review Service has secured funding forspecialist diagnostic review for all new cases of lymphoma. The Allales Lymphoma Panel audit found a diagnostic error rate of 17% incurrent cost of inappropriate treatment associated with misdiagnosis isaround £200,000 per year. In addition, there are huge potential 51 Organisation ofA.RecommendationsService commissioning for each network should be carried out in arelevant commissioning bodies. Networks should establish explicitorganisational arrangements which identify those responsible forprovides, to ensure that its patients have access to each form ofcollaborates. All levels of service defined by the British CommitteeLevel 1Hospitals providing conventional chemotherapy andother forms of out-patient treatment, using dose levelsLevel 2Facilities for remission induction in patients with acuteregimes. This level of facility is also required to treatLevel 3Facilities for autologous transplantation, using eitherLevel 4Centres with expertise in both autologous andshould have specific agreements defining the terms of such 52 Multi-disciplinary teams (MDTs)delivered by multi-disciplinary haemato-oncology teams. A unitaryMDT, which could take responsibility for the management of patientswith any form of haematological cancer, is described below. rusts may, if desired, establish two or three haemato-oncology MDTsbased on this model, to treat specific forms of haematological cancer:lymphoma MDT. Other arrangements can be envisaged; for example,a Trust might form an MDT to provide local treatment for patientsspecialist MDTs at other Trusts. along with protocols describing how they function, to which Trustswill be expected to adhere. The minimum population served by anyservices so that teams deal with larger numbers of patients.Every patient with any form of haematological cancer (includingmyelodysplasias and chronic myeloproliferative disorders) should bemanaged by a haemato-oncology MDT. Each network should ensurethat an appropriate range of MDTs is established for this to bepossible. All cases should be discussed in formal MDT meetingsattended by members involved in the diagnosis, treatment, or care ofregularly treat patients with the particular forms of haematologicalcancer with which that MDT deals. These MDTs will be responsibleoffered, but also for delivery of treatment and long-term support foropportunity to be informed of the outcome of MDT meetings.When haemato-oncology MDTs have been established, clinicians whopreviously diagnosed haematological cancer to an appropriate MDT.(particularly to departments such as gastroenterology, dermatology, 53 Core members of haemato-oncology MDTsEach haemato-oncology MDT must include sufficient core members forHaemato-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-Nurses At least one clinical nurse specialist, alsoPalliative care At least one palliative care specialist specialist(doctor or nurse) who liaises withspecialists from other sites. If, becauseof staff shortages, a palliative carespecialist cannot regularly attend MDTmeetings, the MDT must be able toregularly with such a specialist; Support staff Staff to organise team meetings andeams established to manage patients with lymphoma should includeregularly involved in MDT discussions: Clinical oncologistAt least one; RadiologistAt least one, who liaises with radiologistsis fully and regularly involved in MDT discussions. It is not necessaryfor clinical oncologists to regularly attend team meetings for discussion 54 PharmacistState registered dietitian (SRD)Orthopaedic surgeon (myeloma MDT)Clinical oncologist (myeloma MDT and leukaemia MDT; provisionof cranial radiotherapy for patients with acute lymphoblasticOther specialists who may be required for specific cases:DermatologistENT surgeonSupport for patients and carersAll haemato-oncology MDTs should have access to designated staff whocan provide support for patients and carers when necessary (see TopicPatient-centred care). These include the following:Allied health professionals including rehabilitation specialists, asdescribed in the context of patient-centred care.Liaison psychiatrist and/or clinical psychologistSocial worker 55 A clinical nurse specialist should normally be the initial point ofcontact for patients who feel they need help in coping with theirdisease, its treatment or consequences. This nurse should be able tosupport staff such as those listed above. Networking between nurseswith different types of expertise should be encouraged, both toprovide mutual support and to deepen and broaden their perspective. Patterns of MDT membership should be agreed and co-ordinated atneeds to carry out its function effectively. When all the necessaryspecialists are not available within a Trust, experts may contribute to theperipheral hospitals travel to the centre to attend MDT meetings,bringing information about their patients with them. Everyone at themeeting can then contribute to discussion about the management ofpatients at each of the participating hospitals. Such arrangementsnetwork as a whole, and additional staff or facilities forteleconferencing may be required. In large networks, two specialistIn the out-reach model, MDT meetings are held in peripheralhospitals, normally those that provide intensive in-patient treatment(BCSH Level 2). Specialists take peripatetic roles; for example,radiologists may travel to several hospitals to meetings of variousMDTs. If this is not practicable, locally scarce specialists maycontribute to MDT meetings by teleconferencing. Where sucharrangements are established, they should be reviewed annually bySpecialist input is particularly important for diagnosis and assessmentof lymphoma. If MDT members who do this work are not lymphomato join a substantial proportion of MDT meetings (out-reach), or forwith specialists (in-reach), using teleconferencing if necessary. TheMDT members. 56 there should be arrangements to ensure smooth and efficient co-Responsibilities of haemato-oncology MDTsHaemato-oncology MDTs should, if possible, meet weekly, duringnormal working hours. All core members must have a special interestclinical commitment. They should attend the majority of meetingsthe forms of cancer that fit the teamÕs definition criteria; review decisions about treatment, particularly those made inthe interval between MDT meetings. This review should covernot only the clinical appropriateness of the treatment but alsothe way patientsÕ views were elicited and incorporated in thediscuss patientsÕ responses to treatment, both during therapyand when the course of treatment is complete. LymphomaMDTs should review each patientÕs progress after three cycles ofconsider patientsÕ other requirements such as palliative careor referral to other services. MDTs must be able demonstrateeffective systems for collaboration with hospital and communityspecific process for considering discontinuation of treatmentwhen its effectiveness has become so limited that adverse effects 57 Identifying requirements for staff and facilities for any form oftreatment it provides (see Topic 5, Treatment (excluding high, and Topic 6, Liaison with primary care teams, palliative care teams, servicesfor the elderly and voluntary organisations such as hospices;Ensuring that adequate information, advice and support isprovided for patients and their carers throughout the course ofEnsuring that GPs are given prompt and full information aboutminimum dataset for all cases of haematological cancer within itsCollaboration in planning, and collecting data for, network-widethe service it delivers. Lead clinicians from all haemato-oncologyconsistent over the network as a whole, and should agree processand outcome measures for regular audit. All teams should beinvolved in network-wide audit and clinical trials; these issues shouldfrom relevant MDTs, and with the research network. 58 functions. This meeting should be organised around an open agendato 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 efficientteam working. In addition to basic physical facilities such asequipment, for example to allow the group to review pathology slidesEvery MDT meeting should have a designated chairperson. Whilstthis may be the lead clinician, teams should consider rotating the roleof chairperson between members. Teams should aim for anall members feel able to contribute. Formal training in effectivegroup working and team development may be helpful. Each MDT should have named support staff who take the roles ofteam secretary and co-ordinator. Since these roles overlap, oneperson may be able to cover both functions in smaller teams. If aco-ordinating meetings, secretarial and administrative support must beprovided for this nurse. The team co-ordinator should arrangemeetings, inform all those who are expected to attend, and ensurethat all information necessary for effective team functioning andclinical decision-making is available at each meeting. This willinclude a list of patients to be discussed and copies of their casenotes, along with diagnostic, staging, and pathology information. The secretary should take minutes at all meetings, and record andboth MDT members and to those others identified as appropriate forroutine circulation by the MDT, such as GPs, who may require thisinformation. A designated member of the teamÕs support staff,other MDTs in the network. Local services should be developed around MDTs which include atleast three haematologists whose sole or main specialist interest is inhaemato-oncology. 59 All in-patients undergoing intensive forms of treatment such aseither at one hospital, or, where there is a locally agreed case forproviding this service at more than one hospital, in hospitals whichtreatments (summarised in Table 4, page 72). Members of the teammay provide palliative or out-patient care in other hospitals.Each haemato-oncology MDT which provides treatment at BCSHspecialist medical and nursing staff. These arrangements must besufficiently robust to allow cover for holidays and other absences ofteam members. Haemato-oncologists in such a team should worktogether as a cohesive group, sharing management of patients. Thereshould be efficient systems for routine information-sharing andfrequent opportunities for informal discussion as well as formalregimens, and other bone marrow failure patients) in conjunctionwith their haematology MDTs, particularly those involved in acuteleukaemia. The aim should be to consolidate this work within awith the necessary staff, facilities and reliable arrangements forspecialist medical and nursing cover. Networks should give priority to transferring BCSH Level 2 workloadswork on a long-term basis, giving particular consideration to thefuture roles of those hospitals performing relatively little such work,in five or fewer new patients each year. actively involved in this type of clinical responsibility, should considerthe feasibility of playing an active role in a haemato-oncology MDT Members of haemato-oncology MDTs will have other responsibilitiescontext of the wider role of haematology services. Haemato-oncologists play essential roles in the care of patients with solidtumours undergoing chemotherapy, in particular monitoring andmanaging haematological adverse effects, and may provide servicessuch as placing central venous catheters. All hospitals which givechemotherapy, or which are likely to admit patients undergoingchemotherapy as medical emergencies, should have documentedclinical policies, agreed with haematology and oncology staff, whichB.Anticipated benefitsSince the publication of the Calman-Hine report,MDTs have becomethat offers advantages for both clinicians and patients. MDT meetingsensure that each patient is considered from a range of viewpoints bypeople with different areas of specialisation, who can pool theirexpertise and learn from one another. difficult problems, can be especially helpful for clinicians. Those whohave experience of working in MDTs report that they also providevaluable, and often unanticipated, learning opportunities.For patients, management by an MDT offers many potential benefits,particularly a greater probability of timely and appropriate treatmentsymptoms, problems and desires. Such nurses can therefore help tofocus clinical decision-making on the needs, values and priorities ofindividual patients. This is helpful to inform discussion aboutsupportive care, and becomes particularly important at the point inthe disease when continued active treatment may be doing more harmthan good Ð a point that can be difficult for clinicians to recognise.informed patient advocates in initiating the transition from active 61 Expert Advisory Group on Cancer, Department of Health/Welsh Office, 1995. improved clinical policies, more effective delivery of care, and moreparticipation in clinical audit and research. Consolidation of servicesfor patients undergoing complex treatment in hospitals able toconsistently meet the required standards, and which have a sufficientdepth of clinical specialist cover, particularly in medicine and nursing,will mean that all staff, including junior members, will be better ableto meet their needs. All of these factors will tend to improveC.Evidenceevidence. The grading taxonomy is explained in Appendix 2.evidence of benefits associated with team working in theand facilities, may be associated with poorer outcomes. There arebetween regions, tend to suggest that specialised centres can achievebetter survival rates among some groups of patients; however, thesetherefore could reflect differences in case-mix. The evidencelymphomas than for other forms of haematological cancer. There is no definitive evidence to show that hospitals that treat more 62 outcomes and hospital volume were included in a systematic review.One, a study of 879 adolescents and young adults in England andales, found no specific benefit associated with treatment in aThe second, which focused on bone marrow transplants for earlywith higher-volume centres. Above this level, there was no evidenceof any relationship between centre size and outcome.(B) Registryvolume centres, but the effect is only significant for bone marrowspecialist centres may survive longer, but this could be due to patientselection. In the Northern and Yorkshire Region, 27% of patients are25% treated in non-specialist centres (p=0.04); this difference reflectsbetter outcomes in younger patients (below the age of 45) only.teaching hospitals, compared with those treated in non-teachinghospitals.But there is no apparent relationship between specialisationof treatment centre and survival rates in the South and West Region orReview of results by a specialist population-based registry forlymphoid malignancy in the North West Region of England found thatsignificant factors affecting survival among patients with myeloidEngland who were treated in a clinical trial did better than those of asimilar age who were not in a trial. Whilst this could be becausebased 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 outcomespopulation outcomes. A separate trial Ð albeit including elderly 63 There is conflicting evidence on whether treating higher numbers hasa beneficial effect. A study from Finland found no significantdifferences in progression-free or overall survival between hospitalswhich enrolled larger or smaller numbers in multi-centre trials, andconcluded that decentralisation of treatment was acceptable. As withleukaemia, figures from some cancer registries suggest that specialistthe pattern is not consistent between regions and any differencescould be due to patient selection. In Northern and Yorkshire, thewith 14% for non-specialist centres, a highly significant difference; butno such difference is apparent for the South and West.(B)number of patients treated is generally more consistent for lymphomathan for other forms of haematological cancer. were 50% higher among patients treated for lymphoma (type not(relative risk of death 1.5, 95% CI: 1.3 to 1.7).(B) Another US studymanaged three or more such patients per year, compared with one ortwo. 54% of patients were free from progression after two years atthe higher-volume centres, 32% where the numbers were small(p=0.06); and overall survival rates were 71% versus 52%. All thehigher-volume hospitals, but only 27% of the others, were approvedtransplant centres.(B)Registry data from Northern and Yorkshire show significantly higherfive-year survival rates among patients treated for lymphoma inspecialist centres than in non-specialist hospitals. Overall, 47% ofelsewhere, but the difference only becomes apparent in patients overthe age of 55. In Scotland, five-year survival rates achieved byspecialist centres are consistently higher, at 45% overall, than those atnon-specialist centres, with 39% (p)est,however, no effect of specialisation is apparent.OrganisationThe Trent Region has demonstrated that it is possible, in practice, to 64 MDTs for the management of haematological malignancies. Theent standards require that lymphoma MDTs, which includeradiologist, should meet at least monthly. The centre MDT designatesnon-core members for additional roles in extended teams. Trentlymphoma MDTs work out diagnoses, plan treatment, recordinformation about all patients on an agreed proforma, organise audit,specific group. Whilst MDTs based at cancer units can treatlymphoma, patients with unusual forms of the disease, or for whomdiscussed by the cancer centre MDT. D.MeasurementStructureMDTs established throughout each network for each major typeof haematological cancer.Support staff in place for every MDT.Rapid and effective communication systems between localProcessoncology nurses per Trust;Current specialisation by Trust;Current referral patterns for leukaemia, lymphoma andCurrent information and audit of diagnosis and treatment; Relationship between different specialties involved inhaematological cancers, e.g. ENT, head and neck,Staffing and configuration of existing MDTs.malignancy is discussed by an appropriate MDT. information with them.Patients with acute leukaemia treated in designated units whichmeet the appropriate standards of staffing and facilities.Evidence that MDTs audit individual cliniciansÕ actions againstRecord of business carried out (including patients discussed andE.Resource implicationsMDTs for leukaemia and myeloma do not currently exist in themajority of Trusts; and where lymphoma MDTs are established, manylack the full range of members. The cost of additional staff time forcancers, and for ensuring that every MDT includes a co-ordinator, isestimated to be £7.2 million per year for England and Wales as awhole. The level of uncertainty is, however, high, because the 66 In general, lower costs are associated with the following:Use of teleconferencing, with optimum charging packages; Combining myeloma and leukaemia MDTs. 67 A.RecommendationsInformation about treatment in this section is intended to be used asguidelines. Networks should agree detailed clinical guidelines andupdate them regularly, using the best available evidence and anyspecific guidance from the National Institute for Clinical Excellence(NICE). Treatment provided should be audited against these guidelines. most patients with haematological cancers. Often, this can be givenof time. Other types of treatment are appropriate for specificconditions. Some patients, particularly those with acute leukaemia,chronic myeloid leukaemia, myeloma and some forms of lymphoma,of high dose therapy and stem cell rescue is increasing. This isdiscussed in the next chapter of this manual (Topic 6particularly demanding (see Treatment requirements, Acute leukaemia,below). These patients require in-patient treatment lasting for weeksperiod. This form of treatment should therefore be offered only byhospitals which can provide adequate levels of staffing and facilities(see previous chapter Ð Topic 4, Organisation of specialist servicesThese call for:Clearly defined leadership and organisational arrangements; See Accreditation Standards for Chemotherapy in the Assessment Standards. specialists, who may be consultant or specialist registrar levelAdministration of chemotherapy by appropriately trained staff;Use of guidelines for the prevention and treatment of side effectsSpecific treatments vary widely. Table 3, below, shows the maintypes of treatment currently used for the various forms ofhaematological cancer, and Table 4 summarises facilities required fortheir delivery. The choice of agents and the way they are useddepends both on the type of cancer and on the individual features ofthe case. For some patients, no treatment is necessary at the time ofdiagnosis; for the majority, conventional dose therapy is appropriate,but some of these may be offered high dose therapy if the diseasedoes not respond or if they relapse. Patients whose diseaseprogresses despite continued or intensified treatment may reach apoint at which anti-cancer therapy does more harm than good, andpalliative therapy becomes more appropriate. Systems for decision- 69 able 3. Illustrations of types of systemic anti-cancer treatmentand the settings in which they are usuallyadministered** Inclusion in this table of any treatment should not be taken as a recommendation 70 eatment, disease groupsExamplesSettingHigh dose therapy + progenitor BEAMIn-patient, intravenous cell rescue (allogeneic or therapy on dedicated autologous)Total body irradiationward with specialised AML, ALL, CML, HodgkinÕs busulphan/ Isolation facilities and lymphoma, NHL, myeloma. cyclophosphamidespecialised rooms normally used.Induction chemotherapy 3+7, UKALL protocolIn-patient, intravenous for acute leukaemia therapy on dedicated ward with specialised Induction treatment for CODOX-Mnursing/support team.eatment of recurrent high ESHAP, ICEInitial treatment of:Normally day-case,High grade NHLCHOPdedicated out-patient HodgkinÕs lymphomaABVDchemotherapy team.MyelomaC-VAMPMonoclonal antibody therapy Rituximab, Normally day-case, Alemtuzumabintravenous therapy in NHL, AML, CLLdedicated out-patient unit RadioimmunotherapyIbritumomab, In-patient suite with ositumomabradioprotection facilities NHLand specialist nuclear Cytokine treatmentInterferonOut-patient treatment;CML, NHL, Myelomainjection, self-Oral chemotherapyChlorambucil, Out-patient oral Fludarabine, treatment, self-Myeloma, CML, CLL, NHL, Hydroxyureaadministered by the palliation for ALL/AMLpatient.Kinase inhibitorImatinibOut-patient oral CMLadministered by the developed and there are several clinical trials in progress. Eachnetwork should agree and adopt guidelines for involvement in suchtrials. Network-wide formularies and policies for the adoption of newclinicians, and haematologists, oncologists and pharmacists involvedin treating patients with haematological malignancies. eatment requirementsFacilities necessary for provision of intensive chemotherapylymphomas and bone marrow failure) are summarised in Table 4.chemotherapy. These should only be handled by designated staffInsertion should be carried out in dedicated areas (special procedurePatients undergoing treatment for acute haematological malignanciesare highly susceptible to infection. There should be a written policyshould be done for each eventuality. There should be strict policies 71 able 4.Summary of standards necessary for all unitsproviding induction therapy for acute leukaemia oraggressive lymphoma, and other patients likely tohave prolonged neutropeniaable 4aFacilities 72 Specific beds in a single dedicated ward within the hospitalIn-patient unit that minimises airborne microbial contamination.chemotherapy should be housed in single rooms with en-suitepatient from transmission of infectious agents, and can provide,as necessary, for patient isolation, long duration intravenousOn-site facilities for emergency computed tomography (CT)Cytotoxic drug reconstitution centralised at the pharmacy. able 4bStaffingHowever the term is understood to cover nurses with sufficient experience (i.e. atand usually formal academic qualifications including ENB 237, diploma courseswith specialist modules in oncology or haematology, or locally organised 73 Consultant-level specialist medical staff should be available atany time of the day or night. This level of cover demands atleast three consultants, all full members of a single haematologysingle site. Levels of staffing must comply with the EU workingSpecialist registrars and staff grade doctors providing coverduring the normal working day. They should be familiar with,and have received formal instruction in, the unit protocols.patientsÕ clinical status. The level of staffing required forAt least one trained specialist nurse* on the ward at all times,On-site advice from a specialist oncology pharmacist.Access to staff (e.g. data manager) to support entry of patientsinto the local portfolio of National Cancer Research Network able 4cClinical supporteatment for specific forms of haematological cancerCombination chemotherapy, normally using two or three drugsleukaemia who are sufficiently fit to withstand it. Remissionbecause of the risk of treatment-related death and of impairing thequality of the patientÕs remaining life. About 70% of patients withacute myeloid leukaemia (AML) (the most common form of acutepoor, with early treatment-related death-rates of around 25%. as well as intravenous treatment. Cranial radiotherapy should also beextended leukaemia MDT. 74 prevention and control,agent administration (including intrathecal chemotherapy Standard Principles for Preventing Hospital Acquired Infections. Department of Health,&#xwww.; oh.;&#xgov.;&#xuk/h; i/s;&#xtand; rdp;&#xrinc;&#xiple;&#xs.pd;2001; available on: These are available on the HICPAC website at:2001/022. See also B-cell chronic lymphocytic leukaemia (CLL)treatment at some stage. When treatment is required to controlappropriate. The most commonly used drug is oral chlorambucil, buta Medical Research Council (MRC) trial (CLL-4), comparing differentprogress. Recruitment to this trial should be supported.treatment. A variety of drugs may be used, either as single agents orin combination. Fludarabine, which can usually be taken by mouth,Chronic leukaemias, myeloproliferative disorders andmyelodysplastic syndromecontrol. Supportive treatments ranging from single-agentare appropriate for most patients. Vascular complications ofwho should be members of the extended leukaemia MDT.the phase of the illness and other prognostic factors, in particular,presence or absence of the ÒPhiladelphia chromosomeÓ and thepatientÕs age. Interferon-usually hydroxyurea Ð either of which can be given on an out-patientbasis, can often control the disease during the chronic phase but thedevelop intolerable side-effects. Supportive treatment to normaliseNICE has recommended that imatinib should be offered to patientsinterferon fails to control the disease or produces unacceptable side-effects. NICE has also recommended imatinib as an option for theearlier stage. This is an area of rapid change; the role of imatinib National Institute for Clinical Excellence. chronic lymphocytic leukaemia. Technology Appraisal Guidance No. 29. London: NICE, Allogeneic bone marrow transplantation should be discussed withyounger patients (see Topic 6, All patients with lymphomas should be discussed at, and managedby, lymphoma MDTs. over a period of months is normally required. Radiotherapy shouldincomplete response to chemotherapy. High dose therapy (Topic 6,relapsed or whose disease fails to respond to standard doseThe disease groups described below include a variety of conditionswhich require very different management strategies (seeBackground). Even within diagnostic categories, there is greatdiversity between patients. A range of medical specialists may beinvolved in caring for these patients, for example dermatologists andgastroenterologists. These should be members of the extendedlymphoma MDT. The forms of clinical management regarded as optimal are changingAggressive NHL, including diffuse large B-cell lymphoma,peripheral T-cell lymphoma and BurkittÕs lymphomaHaematologists and oncologists may be involved in the treatment ofpatients with aggressive (high-grade) forms of lymphoma.Chemotherapy followed by limited field radiotherapy is likely to beappropriate for patients with localised aggressive NHL. CHOP-basedchemotherapy is used for patients with disseminated aggressiveof these patients. Evidence is emerging to suggest that rituximab may have a role inselected patients with diffuse large B-cell lymphoma since survivaltrial. NICE will be producing guidance on this.Combination chemotherapy using a different group of drugs from thatinitially used may induce remission if the disease recurs. High dosetherapy (see Topic 6, 76 77 Patients who need other forms of treatment, such as surgery, shouldlymphoma MDT. Other forms of NHLSingle-agent out-patient therapy is appropriate for initial treatment formost patients; a wide variety of types of treatment may be used. Incured by any of the treatments currently in use. Repeated courses ofradiotherapy, are likely to be required over many years. Patientsrecur, since decision-making about the most appropriate form ofinitially, although most require treatment at some stage. Singlealkylating agents are widely used in initial therapy, and at recurrenceor for those requiring alternative treatment there is a range of optionsradioimmunotherapy, and high dose chemotherapy with progenitorcell rescue. Which of these is appropriate will depend upon theevaluating 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 isrecommended only in the context of a prospective case series, forlast-line treatment when alternative therapeutic options have beenexhausted. Out-patient combination chemotherapy is appropriate for mostshould be discussed with those who are sufficiently fit to withstand it(see Topic 6, ). Orthopaedic and renalcomplications require involvement of other specialists, who should bemembers of the extended myeloma MDT. Long-term treatment withboth to control pain and to reduce the risk of fractures and spinal 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 givenprecise information about whom they should contact and wherepatients should be taken in the event of treatment complications.MDT (see Topic 4, Organisation of specialist services)B.Anticipated benefitsMany patients are already being treated in ways outlined here, but forthose 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 themost appropriate forms of treatment and enhance safety. For example,it will allow complications of treatment to be recognised quickly andmanaged efficiently, thus reducing iatrogenic morbidity and death.C.Evidenceevidence. The grading taxonomy is explained in Appendix 2.Most of the evidence on the effectiveness of treatment forSwedish Council on Technology Assessment in Health Care (SBU).The text below summarises information from these reviews. meta-analysis (n=1897) and 31 randomised controlled trials (RCTs)(n=10,516). This shows that initial therapy with an anthracyclineimportant to maximise time in remission.(A) Response rates,remission duration and survival are better with idarubicin thanhas been found to improve outcomes in some studies, but theevidence is not conclusive. Post-remission intensive chemotherapynot clear whether it increases long-term survival rates.(A) 78 79 Standard dose chemotherapy can prolong survival in elderly patientswith good performance status, but it is too toxic for the majority.(A)For those with poor performance status, palliative treatment withoptimum treatment has not been identified. Chronic myeloid leukaemia (CML)Evidence from RCTs carried out before imatinib became available hasbeen reviewed by the American Society of Haematology. Thisreceive interferon with added chemotherapy. Observational studiesof treatment. For patients who prefer conventional chemotherapy tointerferon, hydroxyurea appears to be the agent more likely toimprove survival without producing serious toxicity.(A) Uncontrolledcan be effective for some patients (see Topic 6, the chronic phase of CML treated with imatinib (the IRIS trial,n=1106), confirms that it represents an important advance intreatment. Patients were randomised to treatment with imatinib orinterferon-plus cytarabine. After a median follow-up period of 19alternative treatment; differences between groups in other outcomemeasures are similarly dramatic. Although imatinib was associatedwith higher rates of some adverse effects (such as superficial oedema,few patients discontinued treatment because of adverse effects.(A) CML, there is as yet no information on its long-term effects. OÕBrien SG, Guilhot F, Larson RA, Gathmann I, . Imatinib compared with interferonGuidance on the use of imatinib for chronic. Technology Appraisal Guidance No. 50. London: NICE, 2002. Chronic lymphocytic leukaemia (CLL)advantage in treating the condition before symptoms develop. Initialtreatment with combination chemotherapy does not producesignificantly better survival rates than single-agent chlorambucil, butprogressed despite single-drug treatment.(A) Fludarabine, which canusually be taken by mouth, can be effective for patients for whomfirst-line chemotherapy has failed or who cannot tolerate it, andappears to produce less nausea, vomiting and hair loss thanwo national (MRC) trials, CLL-4 and CLL-5, which are currently inprogress, will provide more evidence on optimum treatment strategiesHigh dose treatment is being used increasingly frequently for patientswith myeloma. The evidence supporting this approach is summarisedin Topic 6, . For those who cannot tolerate highprednisolone seem equally effective. Time to disease progression canbe prolonged by six months with interferon maintenance therapy(p)m of treatment with unpleasant side-effects. Interferon appears to increase overall survival time by aboutbisphosphonates, whether or not bone lesions are present.(A) Meta-analysis of data from 11 RCTs shows that a vertebral fracture can beP=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 apathological fractures.(A) Zoledronic acid, a new, more potentbisphosphonate, is at least as effective as pamidronate.(A) 80 National Institute for Clinical Excellence. chronic lymphocytic leukaemia. Technology Appraisal Guidance No. 29. London: NICE, 81 Aggressive non-HodgkinÕs lymphoma (NHL)is usually effective for patients with localised disease, but theoptimum dose of radiotherapy is uncertain. CHOP chemotherapy iseffective for most patients (including the elderly) with aggressivedisseminated NHL. No chemotherapy regimen has been shown to beimproves the effectiveness of CHOP. For second-line therapy afterwill have prolonged remission.(A) combination for patients with HodgkinÕs lymphoma. SeveralMOPP/ABVD hybrid or alternating schemes, are similarly effective buthave different patterns of acute and late adverse effects (seeImproving Outcomes in Haematological Cancers, The Researchfor details). Extended field radiotherapy is more likely toproduce long-term adverse effects such as breast and lung cancer,and for this reason, is less often used than previously. The additionof radiotherapy does not improve survival rates, but limited fieldradiotherapy is appropriate for selected patients to reduce the risk ofManagement of complications Preventing infection in neutropenic patientsfiltration. The apparently simple measure of hand washing isprevent hospital-acquired infection. The role of barrier nursing as aroutine procedure in the management of neutropenic patients andtransplantation is unclear.(B) The use of specialist teams to insert central lines and the care of suchcomplications.(B) Suitably trained clinical nurse specialists canprovide this type of service. Ultrasound guidance can significantlyimprove the success rate and may reduce complications.(B) Linebut no consistent clinical benefit. There is no reliable evidence thatCSF is beneficial for patients with fever and neutropenia who are athigher risk of infection-associated complications, and who haveprognostic factors that are predictive of poor clinical outcome.Epoetin for prevention and treatment of anaemiaEpoetin (commonly known as epo) is a synthetic form of the naturalhormone erythropoietin, which regulates production of red bloodcells. It is used to treat or prevent anaemia caused by cancer orIn patients with haematological cancers, the response to epoetinvaries according to the type of disease and treatment. It isparticularly effective for patients with multiple myeloma and may bechemotherapy, but is less effective for those with myelodysplasticsyndrome.(A) It does not appear to be useful for patients receiving(haemoglobin levels above 10g/dL). 82 83 D.MeasurementStructureSee Table 4.ProcessIatrogenic deaths and deaths due to infection.Long-term adverse effects of treatment.E.Resource implicationshospitals and wards which have appropriate levels of qualified staffThe short-term cost of transferring patients from hospitals whichremission of acute leukaemia to higher-volume units is estimated tobe about £1.9 million for England and Wales as a whole (see). This figure is A.Recommendationsrescue should be given in the context of well-designed randomisedcontrolled trials (RCTs), so that the value of this form of treatment canHigh dose therapy is potentially toxic and must be fully discussedmade (see Topic 2, Patient-centred care). This is particularly true ofallogeneic bone marrow transplantation. The intention of high dosetherapy is normally to eliminate malignant cells by myeloablation Ðdestruction of rapidly-dividing tissue in the bone marrow. This isdose chemotherapy or radiotherapy (total body irradiation, or TBI).Patients and their families should be fully aware of how this form oftreatment could affect them, and that the possibility of long-termPsychological factors should be taken into account in decision-makingsupport should be available for patients and their close familyfor an extended period after transplantation.marrow transplantation. These are described in full on the EuropeanGroup 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 acentres which perform such treatments regularly and have therequisite scientific and physics support. Careful attention should befor the radiotherapy component of the service to ensure the efficient 84 85 JACIE accreditation requirementsdirector, common staff training programmes, protocols andlaboratories which also meet JACIE standards; It must carry out a minimum of 10 autologous and/or 10allogeneic stem cell transplant procedures per year; The medical team must include the programme director andoncologists. All members of the medical team should have hadof high dose therapy, and management of the various problemsthat may develop in patients undergoing transplantation;other key disciplines, including surgery, pulmonary medicine,cardiology, pathology, psychiatry, and, if large-field or totalThere must be sufficient nurses experienced in the care ofThere must be support staff including pharmacists, dietitians,airborne microbial contamination, and a designated out-patientCriteria derived from JACIE standards described in the Haematopoietic progenitor cellcollection, processing & transplantation accreditation manual, on &#xwww.;ëmt;&#x.or1;.70;g undergone high dose therapy (see Table 4). Strict isolation facilitiesare important for patients undergoing allogeneic transplantation.However, standard single rooms with en-suite facilities, asrecommended for patients undergoing intensive chemotherapy (seeable 4), may be sufficient for patients undergoing autologous stemcell rescue. Rooms with laminar airflow and high-efficiencyparticulate air (HEPA) filtration should be available for all patientsundergoing high dose therapy, particularly when there is risk ofcontamination by environmental organisms such as Aspergillus,example during periods of building renovation. High dose therapy with autologous stem cell rescuewho are fit enough to undergo this form of treatment. It should onlybe offered to those with other types of haematological cancer in thecontext of multi-centre RCTs. Allogeneic stem cell (normally bone marrow) transplantation shouldcannot be controlled with chemotherapy alone. Allogeneicbut appears to offer the only hope of cure for some forms ofhaematological cancer (notably chronic myeloid leukaemia (CML)). Itshould be carried out only by specialist MDTs working in majorcentres which meet JACIE accreditation standards. Well-designedmulti-centre RCTs are essential to assess the effectiveness ofis strongly immunosuppresive but not myeloablative, in order tocreate a state of recipient-donor mixture (chimerism). Thechemotherapy is of relatively low intensity so its acute side effects areless severe, but the risk of graft-versus-host disease remains and theseconditions, but no prospective trials have yet been performed todetermine its usefulness. 86 87 B.Anticipated benefitslarger numbers of patients is likely to create a more cost-effectiveservice with better staffing levels, facilities and expertise. This shouldmanagement of patients, and thus reduce the frequency of treatment-C.Evidenceevidence. The grading taxonomy is explained in Appendix 2.Effectiveness of high dose therapy and stem cellAutologous stem cell rescueRCTs have been carried out comparing high dose therapy andtreatment in patients with a variety of forms of haematological cancer.death in remission.(A) However, there is good evidence for benefit inbe regarded as experimental. High dose therapy does not appear totherapy. In patients with poor prognostic features it may beof induction. There is better evidence for high dose therapy insurvival.(A) Nevertheless, this approach is now routine in second orsubsequent remission. Larger randomised studies, stratified by age and with long follow-upperiods, are urgently required to clarify the role of high dose therapyAllogeneic bone marrow transplantation (BMT) for leukaemiaAllogeneic BMT is a high-risk treatment strategy, with significant ratesof treatment-related death and morbidity, especially in older patients.comparing allogeneic BMT with conventional chemotherapy. wo RCTs have assessed the effectiveness of high dose therapy andallogeneic stem cell rescue during first remission of acute myeloidleukaemia (AML). In both, patients randomised to the high dosetherapy arm underwent allogeneic BMT if suitable donors wererescue was used. These trials found that allogeneic BMT wasThere do not appear to be any other RCTs comparing allogeneic bonechemotherapy for any form of haematological cancer. Information from six controlled (non-randomised) trials (CCTs)suggests that allogeneic transplantation may be associated withlymphoblastic leukaemia (ALL). Meta-analysis of data from three CCTs23% (95% CI: 11 to 35%) in favour of high dose therapy withallogeneic transplantation. Pooled three- and four-year progression-free survival data from two CCTs (n=123) showed an absolute survivalAllogeneic bone marrow transplantation may offer the only hope oflong-term remission for patients with CML. The best outcomes areallografts, with survival rates in most published reports of around 60%chronic stage of the disease. It is considered significant that survivalrates after allogeneic transplantation reach a plateau, whilst those fordecline. Among older patients, those given poorly matched grafts orrange from 18% to 67%.(B) 88 89 age 52 years) was included in the review. The median overallsurvival time was 37 months, but 41% of patients were stillConditioning regimenscyclophosphamide conditioning (BUCY).(A) Less toxic regimens,fit patients. In 2001, 231 mini-allografts were reported in England andtransplantation. There is no advantage in using doses overThere is conflicting information on the value of isolation and airfiltration for patients undergoing allogeneic transplantation, and therehave been no randomised studies addressing these issues. Registryanalysis of large numbers of patients nursed in isolation suggest thatHEPA filtration and laminar airflow are beneficial, but other non-randomised studies have found that similar outcomes (in terms ofThere is evidence that patients undergoing autologous transplantationtreated as out-patients. Many of those given out-patient treatment willto spend less time in hospital (median, 7 nights versus 14,Aspergillusand building renovation. HEPAfiltration alone is not sufficient to protect against this, but HEPAfiltration plus laminar airflow is effective against Aspergillus.Data provided on request by British Society for Bone Marrow Transplantation (BSBMT) A prospective study of patients with acute leukaemia found thattransplantation. The only clinical factor that had a significantQuality of life after high dose treatment and transplantationHigh dose treatment is both physically and emotionally stressful andfor a long period Ð several months, perhaps years Ð afterwards.Sexual function may be particularly slow to recover. Patients whoundergo high dose treatment experience poorer quality of life thanthose who had conventional chemotherapy for about a year, but thesedifferences diminish with increasing time. High dose therapy canproduce long-term adverse effects such as fatigue, which affect day-to-day functioning; this may still be reported a decade later.(B)quality of life. Patients may require long-term treatment with steroids.Use of transplants for adults with haematologicalcancers in England and WalesThe British Society for Bone Marrow Transplantation (BSBMT) registrymaintains a database of the use of stem cell transplantation inEngland and Wales. Table 5 shows the number of transplants carried2001, along with the change in the use of this form of treatment in 90 91 able 5.Number of stem cell transplants in adults withhaematological cancers, England and Wales, 2001BSBMT figures show that the annual number of stem cell transplantsgiven for these forms of cancer as a group increased by 38% over thisperiod, from 1228 to 1698. The largest single component of thisincrease is due to greater use of autologous stem cell rescue forNumber of transplants undertaken by individual teamshigh dose treatment and stem cell rescue in hospitals in the UK.autografts reported by each. It appears that some of these teamsNorwich). (ChildrenÕs hospitals are excluded where separate figures DiseaseType of transplantTotal number, % change 2001since 1996 AutologousAllogeneicAML53162215+23ALL20125145+21CML1093103-18MDS54550+56CLL82028+65Myeloma49935534+124lymphoma 13216148-25NHL40273475+47otals11295691698+38 Gratwohl A, Baldomero H, Horisberger B, . Current trends in hematopoietic stem cell able 6.Teams in England and Wales which carried out 10 ormore allografts and/or autografts in 2000 92 HospitalNumber of Number of allograftsautograftsBirmingham, Heartlands Hospital1420Birmingham, Queen Elizabeth Hospital 4249Bournemouth, Royal Bournemouth Hospital011Southmead Hospital6519Norwich Hospital1134Cardiff, University Hospital of Wales1129Exeter, Royal Devon and Exeter Hospital013Leeds General Infirmary2676Leicester, Royal Infirmary1338Liverpool, University Hospital1335London, GuyÕs Hospital817London, Hammersmith and Charing Cross Hospital4575London, KingÕs College Hospital4124London, Royal Free Hospital4417London, St BartholomewÕs and the Royal London Hospital1934London, University College Hospital5489Manchester, Christie Hospital2066Manchester, Royal Infirmary3221Newcastle upon Tyne, Royal Victoria Infirmary4143Nottingham, City Hospital4342Oxford, John Radcliffe Hospital1426Plymouth, Derriford Hospital1122Poole, Dorset Cancer Centre020Sheffield, Royal Hallamshire, Weston Park and the ChildrenÕs Hospitals1926Southampton General Hospital, CRC Wessex020Stoke-on-Trent, North Staffordshire Royal Infirmary012 eams at the following hospitals carried out fewer than 10 of one orBangor, Ysbyty Gwynedd (0/8); Coventry, Walsgrave Hospital (0/6);London, Oncology Marrow Transplantation Group (1/6); London, StGeorgeÕs Hospital (7/5); Manchester, Hope Hospital (0/2); Manchester,rafford General Hospital (0/1); Rotherham, General Hospital (0/1);Swindon, Princess Margaret Hospital (0/4); Taunton, Somerset andaunton Hospital (1/7); Wakefield, Pinderfield and PontefractD.MeasurementStructurevailability of rooms with filtered air.ProcessEvidence that patients are fully informed about what high doseuncertainty about benefit, before they agree to it.Implementation of accreditation systems for transplant centres.Number of patients undergoing each type of procedure perRates of graft-versus-host disease requiring long-term treatment.Quality of life measures from long-term monitoring and audits of E.Resource implicationsThe main resource implications for high dose therapy arise from acontinuing increase in the number of transplants (based not ontrends), and the need for adequate staff levels and bed numbers inunits providing this form of treatment. The expected growth in thevolume of activity is discussed in Appendix 1, It is believed that there will be a particularly large rise in the numberOverall, the cost of increasing transplant activity in England and Walesis likely to be around £7.3 million per year, but there is considerableuncertainty about both the rate of increase and its potential cost; hugeThe costs of engaging more staff have not been calculated, but aboutmanagers. It is believed that only minor service reconfiguration willbe required to achieve the minimum patient numbers recommendedby JACIE, so this has not been included in the economic analysis.accreditation systems and to cover the running costs of the BSBMTtransplant registry. Both activities are important to quality assurance. 94 A.RecommendationsMost forms of haematological cancer follow a chronic relapsingcourse, so patients need regular monitoring. There is no reliableevidence on what form of monitoring is most appropriate, or whatthe optimum intervals between clinic visits might be. Local clinicaldisciplinary teams (MDTs) within each network.tests, often including ongoing cytogenetic testing. Molecular follow-acute leukaemia. In lymphoma, CT scans may also be required. Long-term follow-uphaematological cancer as children or adolescents; this issue should bePatients should be informed that routine long-term follow-up doesnot offer any clinical advantage to them. Those whose disease isbelieved to be cured should normally be discharged, but long-termconsidered. The primary aim of such long-term follow-up should beto identify and collect information on delayed effects of treatment.Since it is not possible to be certain whether a permanent cure haswhom they should contact if they are concerned about any newsymptoms. They should be given information about the level of riskfive yearsÕ freedom from signs of disease. Patients and their GPsshould also be given information about the risk of delayed adverseeffects of treatment, and symptoms that should prompt contact withthe haematological cancer MDT. 95 Long-term problems are particularly common after high doseProviders may therefore consider establishing long-term follow-upsystems for patients who have undergone this procedure. Follow-upmay also be valuable for collection of information on long-termA database should be maintained to record information about allpatients who have undergone treatment for haematological cancer,whether or not they are being actively followed up. There is anincreased risk of a variety of cancers after intensive treatment fortreated as children or adolescents. One particular cause for concernafter extended field radiotherapy for HodgkinÕs lymphoma is the highrate of breast cancer in relatively young women. Patients who haveB.Anticipated benefitsSince follow-up offers no clinical benefit for asymptomatic patientswho appear to be cured, discharging such people allows clinic time tobe used for others whose need is greater. A database of informationabout patients who have undergone treatment for haematologicalcancer will both improve knowledge of long-term epidemiology andpermit patients to be recalled if new evidence emerges on delayedeffects of treatment; such a database could be efficiently maintainedC.Evidenceis graded as A, B and C, where A is the strongest evidence. The gradingEffectiveness of follow-upThere is no reliable evidence showing that intensive follow-up ofpatients who have completed treatment for any form oftwo years after initial treatment. Recurrence can be identified throughshow whether this improves long-term outcomes. Retrospectivestudies suggest that educating and informing patients so that they 96 In leukaemia, relapse is usually signalled by changes in the blood; thedehydrogenase (LDH) can be helpful for diagnosing relapse. Imaginglymphoma but there is no evidence to suggest that this affectsLong-term effects of treatmentA review of studies suggests that quality of life and health statusimproves with increasing time since treatment. 80% of long-termsurvivors of BMT experience good to excellent health. People treatedfor HodgkinÕs lymphoma may experience persistent side-effects of75-85% of former patients are able to continue in work.(B)Secondary malignancies are recognised long-term adverse effects oftreatment for haematological cancers. The incidence of bothamong patients who were treated when young; and those whobetween patient populations. In general, the risk of leukaemia iswho had six or more cycles of chemotherapy, who received MOPP, orwho were treated for relapse of their primary cancer. Solid tumoursare more common after radiotherapy, and usually develop within thetreatment field. The excess risk of secondary leukaemia peaksLarge studies reveal that patients treated for HodgkinÕs lymphoma face(of any type). The absolute risk for these patients is about 5-7% 10years after the initial diagnosis, rising to 14% after 20 years. One 97 study reported that 28% of a group of 1253 patients who underwentafter 25 years of follow-up.(B) However, these patients would haveundergone more risky treatment than is normally used today. about six times more likely to develop breast cancer than normal, butamong those treated aged 31-40, the risk is 2.4 times normal. AHigh dose therapy with allogeneic transplantation for any form oflong-term hazard to treatment for HodgkinÕs lymphoma - around fourto five times the population risk for any form of cancer. About 12-D.MeasurementStructureasymptomatic patients with haematological cancer, agreed by allhaemato-oncology MDTs in the network.Local clinical policies on long-term follow-up of patients whoseProcessRates of secondary malignancy after intensive treatment forhaematological cancer.PatientsÕ satisfaction with, and comprehension of, information onsymptoms that should lead them to contact the haematologicalcancer MDT. 98 E.Resource implicationsadditional resource implications. Resources will be required toestablish and maintain a long-term follow-up database, but no 99 The National Institute for Clinical Excellence (NICE) guidance onimproving supportive and palliative care for adults with cancerplanned to be published early in 2004. It is intended to complementthe site-specific guidance, giving detailed recommendations on manywith supporting evidence. The areas it covers are listed in Topic 2,Patient-centred careA.Recommendationsmulti-disciplinary team (MDT) throughout the course of their disease.Adequate palliative care is nevertheless important to maximise qualityof life and there should be effective integration between palliativenot just when it is acknowledged that the terminal phase has beenreached. MDTs (see Topic 4, Organisation of specialist services). They shouldPatients and their carers often need multi-faceted support, includinginformation on managing symptoms and help with accessing socialcare and benefits. This can be provided by palliative care teams,Palliative care specialists should be involved in discussing themanagement of patients, especially those for whom the possiblesurvival benefits of treatment might be outweighed by itsdisadvantages. There should be agreed guidelines for managing thetransition from aggressive treatment to palliative care which ensurethat it is handled sensitively and appropriately, and that it takesaccount of individual patientsÕ emotional and physical needs. National Institute for Clinical Excellence. Improving supportive and palliative care foradults with cancer. 8 Palliative treatment in haemato-oncologyLong-term support for patients is part of normal haematology practiceand most of the long-term treatment provided for patients withhaematological cancers is actually palliative in nature. Blood productleukaemia and myeloma. Haemato-oncology MDTs should makearrangements to enable blood product support to be provided topatients in places other than acute hospitals or haematology units. Some symptom control issues for haemato-oncology patients are thesame as for many other malignancies. Pain can be a major problemfor some patients. Effective pain control is particularly important forthose who undergo intensive treatment and for those with inherentlypainful diseases such as myeloma. Each haemato-oncology MDThaematological cancer may experience. Palliative radiotherapy shouldThe specialist palliative care teamadvice, support and education for other health professionals. Onemember of the team should be responsible for ensuring efficient co- 101 Chaplain/pastoral care worker who can offer counselling andspiritual guidance for patients with advanced incurable illnessnight. A named member of the palliative care team should beresponsible for ensuring effective co-ordination of services to supportThe team should endeavour to make it possible for patients to spendtheir remaining life in the place they prefer, whether this is home,possibility that patientsÕ views about where they would prefer to dieperiod of aggressive treatment which ends with the patientÕs death.Some patients and carers may need counselling at the point oftransition from attempted cure to purely palliative measures, to helpthem accept that further aggressive treatment is pointless.Palliative care in the communityof relief from symptoms and social and psychological support forprimary care teams. Community palliative care services should workand effective communication and information-sharing between teamsis essential.oncology teams. Primary care teams should assess patientsÕ needsMDT. B.Anticipated benefitsBetter integration of palliative care with treatment services throughoutboth patients and their carers. Integrated care is particularly essentialcan help to create a more appropriate balance between efforts toC.Evidenceevidence. The grading taxonomy is explained in Appendix 2.for patients in the final phase of illness. Much of this evidencestudies have been carried out), information from the UK does point toThe National Cancer Alliance survey carried out to inform thisguidance found that few patients had had contact with palliative carefor pain management reported that it had been valuable. This surveydid not, however, focus on patients in the terminal phase.to stop using intensive forms of treatment; clinicians, patients andtheir families often find it difficult to acknowledge when remissioninduction is no longer possible. The decision to change to apalliative approach may be taken too late or not at all, andpersistence with aggressive treatment can cause great distress.(B)found that patients who died of haematological cancer wereconsiderably less likely to receive care from community specialistforms of cancer (OR 0.37, p)() 103 of haematological cancer, reported that there was significant variationonly on one or two cases. Factors that appear to produce bettercurative to palliative care; reducing use of medical technology andpsychological comfort; and facilitating dying at home wheneverpossible. The research suggests that the emotional and spiritualA randomised controlled trial (RCT) assessing the effects of improvedco-ordination of services for patients dying from a variety of forms ofcancer show that this is cost-effective and can improve outcomes forpatients. Patients who could contact a co-ordinator who couldhospital or hospice, required significantly fewer home visits bynursing services, and were more likely to receive effective treatmentD.MeasurementStructurevailability of palliative care teams to support patients at homevailability of telephone support, advice and informationProcessAudit of involvement of palliative care teams in the managementof patients with haematological cancers. Evidence that providers elicit information about patientsÕintervention in the terminal phase of illness. 104 Audit of patientsÕ experience of pain and satisfaction with painAudit of patientsÕ and carersÕ preferences about place of death.E.Resource implicationsblood product support are not expected to change significantly underavailability of palliative care teams to support patients at home and inall types of cancer, and is being considered in the context of thewith cancer, planned to be published early in 2004. 8 A.Recommendationssolid tumours) require reliable evidence that interventions are effectiveand that they improve outcomes for patients. It is therefore importantthat health service commissioners should support the well-designedclinical trials within the National Cancer Research Network (NCRN)portfolio. There should be network-wide co-ordination of localparticipation in NCRN clinical trials in haematology through eachcancer research network. Haemato-oncologists should regularlyreview the national portfolio of recognised studies and identify thosethey wish to support at local research network level.During the period between trials and publication of any NationalInstitute for Clinical Excellence (NICE) appraisal of the interventionsMulti-disciplinary teams (MDTs) should aim to maximise entry intoreporting on problems and progress at their regular meetings. Theevery patient who fits the inclusion criteria. Such patients should begiven accurate and accessible information to inform their decisionabout whether to participate in the trial (see Topic 2, Patient-centredcare 106 B.Anticipated benefitsReliable information on the effectiveness of clinical interventions canonly be obtained from large, well-designed trials. Thus, the moreoptimum treatment. Management in the context of trials also tends tobe associated with longer survival times for patients with cancer.In acute leukaemia in particular, survival rates have increasedpeople. This improvement may be directly attributable to knowledgeC.Evidenceevidence. The grading taxonomy is explained in Appendix 2.In acute leukaemia, the level of participation in multi-centre researchinto trials. The same is not true, however, of other forms ofhaematological cancer; in lymphoma, it is estimated that only about10% of those who fit the entry criteria for major clinical trials areactually in them. Overall, perhaps as few as 5% of patients withparticipation in clinical trials can benefit patients, but it is difficult todistinguish between a real protocol effect from bias due to clinicianselection.(A) Audit data from the UK shows that among patients withparticipation in a trial is associated with a significantly higher chanceof complete remission and improved survival.(B) However, patientoutcome. In one of the few studies identified that described outcomessignificant difference in disease-free survival between the groups.(A) way patients feel. Since evidence-based decision-making aboutthat patientsÕ views of their experience of treatment and its after-effects should be considered. Reliable and reproducible quality of life 107 interventions and so that patients can give truly informed consent totreatment. See Improving Outcomes in Lung CancerAlthough the evidence in haematology is far from definitive, treatment inImproving Outcomes in Breast). The development of local protocols demands a criticalattitude towards best practice which is likely to have a beneficial effecton those involved. However, further research is required which looks atD.MeasurementStructureNetwork-wide information systems that allow clinicians to identifyvailability of continued support for patients who have beenProcessProportion of patients with each type of haematological cancerE.Resource implicationseatment in the context of a clinical trial tends to cost more thanstandard treatment. Adequate resources need to be made available,both to support research and to provide appropriate and effectivecontinuing management for patients who have participated in clinicaltrials. The potential cost impact of these recommendations has not &#xwww.; oh.;&#xgov.;&#xuk/c; nce;&#xr000;vailable on the Department of Health website vailable on the NICE website &#xwww.;&#xnice;&#x.or1;.80;g.uk, where it is described as ÒBreast cancer 9 implications for England and Wales of implementation of the mainThe major impacts on costs fall in five broad areas:Multi-disciplinary teams (MDTs)haematological malignancies is a key objective of the guidance. Twoidentification of genetic abnormalities, which is likely to serve one orcentralised or partly-centralised diagnostic services. In othermore or less from scratch. Initial one-off payments needed to set uphigh proportion of services cover a large population of 3 million and 109 In Wales the All Wales Lymphoma Pathology Review Service hasrecently secured funding to allow 100% of cases of new lymphoma tobe reviewed using a wide spectrum of diagnostic techniquesthe expertise of a range of specialists for their diagnosis andtreatment, and helps ensure that care is given according to recognisedguidelines. Lymphoma MDTs are already well-established in manyrusts. However, MDTs for leukaemia and myeloma do not currentlyexist in a significant proportion of Trusts and therefore new MDTsA wider range of staff will need to be involved, with additional timerequired for attending meetings and travelling, in order that MDTs canfunction in accordance with the guidance. Many Trusts, particularlyunits, currently suffer from lack of administrative support. Otherstaffing issues include shortages of radiologists, pathologists andThe cost of additional staff time for MDT meetings and for ensuringthat 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 foran individual cancer network will vary according to the existing MDTconfiguration and staffing levels, as well as the future MDTthe cost of running MDTs. Factors such as the number of teamsserving the cancer, which team members travel and the distancestravelled (or the price package for line charges) will impact on theannual cost of running MDTs and should be investigatedStaffing issues will be significant and the development of MDTs willneed to evolve gradually over a number of years. Additional staffmay need to be recruited to allow existing staff the time to attendmeetings. Shortages of radiologists, pathologists and oncologists willhamper development of full MDTs in the short term. 110 The use of teleconferencing facilities offers potential cost savings intravel times. Costs for purchasing and running teleconferencingfacilities will vary according to the type of system required and thenumber of sites involved. Assuming that all networks will need tohowever anticipated that other MDTs will utilise the equipment oncewide range of specialities and is not included in the cost summary.Patient-centred care (clinical nurse specialists)The guidance emphasises the need for improved information andData on current numbers of nurse specialists are limited. Thesurvey (winter 2000/2001) around 55% of Trusts had no CNS postsnumber of CNSs. This was cross-checked against local estimates offuture posts required in a number of areas. It is estimated thathaematological malignancies in England and Wales is estimated to beHigh dose therapy and transplant servicesrescue should be provided only in specialist centres which meetand/or 10 allogeneic stem cell transplants per year. Data from theBritish Society for Bone Marrow Transplantation (BSBMT) registrycentralisation of these services, with only a small number of centresin England and Wales undertaking fewer than 10 transplants per year. 111 of stem cell transplants for haematological malignancies in Englandand Wales increased by 38% between 1996 and 2001, from 1,228 to1,698. The largest single component of this increase was the volumeof autologous stem cell rescue for patients with myeloma. OtherintensityÓ allografts. Discussions with a number of leading cliniciansis likely to be a continuation of the rise in mini-allografts. The volumeof autologous and standard allogeneic transplants is also expected torise slowly. The cost implication of the rise in the volume ofIn addition, there are expected to be significant economic implicationsin relation to facilities and staffing requirements to meet JACIEstandards. A recent survey of UK BMT centres, facilities and staffingon behalf of the Executive Committee of the BSBMT identified anumber of areas where resources were inadequate. The scale of thesignificant. Further detailed work is recommended to identify the likelyInduction chemotherapy for remission of acuteIt is assumed that resource implications of recommendations on serviceslymphoblastic leukaemia (ALL) are similar. These patients require highlevels of facilities, staff cover and expertise, and it is unlikely that theseThree scenarios are presented, each illustrating a different pattern ofhospital provision. The first is based on a slight increase insets out an intermediate position. It is not suggested that greaterIn scenario 1, the cost of achieving a minimum of five new patients insuch that all hospitals which offer this form of treatment deal with atpatients per annum will give up this work. Of those treating betweenwill re-structure their services so that all units deal with 10 or more,whilst the remaining 50% will continue to provide this form of 112 Data on current local patterns of presentation and treatment suggestin units treating fewer than five new patients per annum, whilstbetween 300 and 800 are treated in hospitals with fewer than 10 suchpatients per year. The cost impact of re-structuring services will varyaccording to current treatment patterns and the extent ofconsolidation or centralisation. The costs of implementing the threeafter treatment to assess residual disease. The guidance recommendsthat cross-sectional CT should be available without delay. This mayrequire additional CT scanning capacity in some Trusts. Investment inHealth funding programmes. By 2003/4 there will be 182 new CTscanners (110 replacements and 72 additional). It is assumed that noaccommodate any growth in haematological malignancies. Runningcosts (staffing and consumables) will need to be funded to ensurefor prompt investigation of lymphadenopathy or alternatively, thelymphadenopathy (rapid-access lump clinics) at cancer units. A singleaccess point will streamline service for patients. Given that theseresources will, to a large extent, already be available and this shouldbe achievable with some re-organisation of existing resources. Palliative careblood product support are not expected to change significantly underthe new guidance. Recommendations relating to service provisionissues including the availability of palliative care teams to supportpatients at home and in hospice and availability of bereavementcounselling are likely to have the most significant cost impact. Thesetypes of services provide support to patients with all types of cancerGuidance for Improvingsupportive and palliative care for adults with cancer 113 Low scenario£ 6.7High scenario£ 8.1One-off set up costsLow scenario£ 4.7High scenario£ 7.5Additional costs of staff time for MDT meetingsLow scenario£ 3.2High scenario£ 9.0PatientÐcentred care Intermediate scenarioMinimal consolidation£ 1.9Radical re-structuring of services£ 9.0Low scenario£ 3.0High scenario£12.4 The manuals in this series are intended to guide health organisationseffectiveness and efficiency of services for patients with cancer. Theinformation and recommendations in the manual are based onand the recommendations are the product of extensive discussionspecific site (or sites) are generated. A large group of relevant healthimprove outcomes for patients. These proposals are then sent toauthorities, the Department of Health, patient organisations, andsuggestions. They are also reviewed as part of the process of theNational Institute for Clinical Excellence (NICE) and form the basis ofliterature, designed to evaluate the proposals, are then carried out or(CRD) at the University of York.This process culminates in the production of two large sources ofinformation, one with a practical or operational focus, and the othercontaining detailed research evidence on effectiveness. The guidance 115 Related Research at the University of Sheffield. This work involvesliterature searching, interviews with clinicians and managers, andThe reliability and quality of evidence which supports theA. Evidence derived from randomised controlled trials or systematicreviews of randomised trials.B. Evidence from non-randomised controlled trials or observationalC. Professional consensus.The quality of research evidence forms a continuum and there isresearch has been carried out on the organisation and delivery ofservices, issues on which randomised controlled trials (categoriseddesigns which might be regarded as of relatively poor quality forevaluating a clinical intervention may therefore be the most reliableavailable for assessing the organisational issues.The systematic reviews used to inform the manual are summarised inImproving Outcomes in Haematological Cancers: TheResearch Evidence. This document includes details of all the studiesto which the manual refers. It is available on the CD-ROM providedwith this manual, and is also available in printed format as a CRDreport (email: crdpub@york.ac.uk, Tel: 01904-433648). 3.1 National Cancer Guidance Steering Group3.2 Participants in the proposal generating event3.3 People/organisations invited to comment on originalproposals3.4 Researchers carrying out literature reviews and 3.5 Members of focus groupsMs A EastwoodSenior Research Fellow, NHS Centre for Reviews and Dissemination, University of YorkProfessor J KleijnenDirector, NHS Centre for Reviews and Dissemination, University of YorkDr A MelvilleIndependent ConsultantDr R E Clark, Consultant Haematologist, Royal Liverpool HospitalHospital, BirminghamDr A Frater, Director of Public Health, North Hampshire Primary CareDr A Jack, Consultant Histopathologist, The General Infirmary at LeedsDr S A N Johnson, Consultant Haematologist, Taunton and SomersetProfessor N H Russell, Professor of Haematology, Nottingham City People and organisations Dr D Swirsky, Consultant Haematologist, The General Infirmary atDr M V Williams, Consultant Clinical Oncologist, AddenbrookeÕsPeople/organisations invited to comment on drafts of thearious professional organisationsNICE Stakeholders; the drafts were subject to the full NICEEconomic reviewsSchool of Health and Related Research, University of SheffieldProject supportThe Northern and Yorkshire Cancer Registry and Information Service 118 (This Group, originally established to oversee production of theChairmanProfessor R A HawardProfessor of Cancer Studies, University ofice ChairmanProfessor M A RichardsSainsbury Professor of Palliative Medicine,St ThomasÕ Hospital, London and NationalDr J BarrettConsultant Clinical Oncologist and ClinicalDirector, Four Counties Cancer NetworkMrs G BattSection Head, Cancer Policy Team,Department of Health, Wellington HouseMr A BrennanDirector of Operational Research, Schoolof SheffieldMs A EastwoodSenior Research Fellow, NHS Centre forReviews and Dissemination, YorkDr J HansonCancer Services Project Co-ordinator,elsh OfficeDr G HardingGP and Medical Director, St JohnÕsProfessor J KleijnenDirector, NHS Centre for Reviews andDissemination, YorkProfessor P LittlejohnsClinical Director, National Institute forProfessor R E ManselChairman, Division of Surgery, Universityof Wales College of Medicine, CardiffDame G OliverDirector of Service Development,Mrs V SaundersManager, Northern and Yorkshire CancerRegistry and Information ServiceDr J VerneDirector, South West Public Health Appendix 3.1Membership of theSteering Group Dr J Apperley Consultant Haematologist, HammersmithProfessor M R BakerDirector/Lead Clinician, Yorkshire CancerMs C BeardmoreRadiotherapy Services Manager, RoyalDr S F BeardsworthConsultant Physician, Castle Hill Hospital,Dr E M BessellConsultant Clinical Oncologist, NottinghamMs R Bratt-WytonClinical Nurse Specialist, Russells HallMrs C Brown PatientMrs M BrownNurse Lecturer in Haematology, ThamesMs T BurgoyneNurse Lecturer/Practitioner inCentral England, BirminghamDr S ClossConsultant in Palliative Medicine, TyOlwen Palliative Care Service, MorristonDr R CowanConsultant Clinical Oncologist, ChristieMrs L Czyzewska PatientDr J DaviesConsultant Haematologist, Western GeneralHospital, EdinburghMs J DowningLecturer in Cancer Care, The Centre forProfessor A FaulknerProfessor of Communication in HealthDr J FergusonClinical Director, South East LondonStrategic Health Authority 120 Mr M Geering PatientDr S GeorgeSenior Lecturer in Public Health Medicine,Miss V GoodeNurse Clinician, Christie Hospital,Professor B Hancock Professor of Clinical Oncology, WestonPark Hospital, SheffieldDr A HaynesConsultant Haematologist, Nottingham CityDr J HealeyConsultant Radiologist, Chelsea &Dr F HicksConsultant in Palliative Medicine, StDr P HoskinConsultant Clinical Oncologist, MountDr M HowardConsultant Haematologist, York DistrictMs S HuntonDirector, Bradford Cancer Support CentreDr T IllidgeConsultant Clinical Oncologist, Royal SouthDr A JackConsultant Histopathologist, The GeneralInfirmary at LeedsProfessor P JohnsonProfessor of Medical Oncology,Dr C C KibblerConsultant Medical Microbiologist, RoyalProfessor K MacLennanProfessor of Cytopathology &Dr A McMillanConsultant Haematologist, Mount VernonDr R MarcusConsultant Haematologist, AddenbrookeÕsHospital,CambridgeDr P NorrisGP, Kingston upon ThamesDr R PettengellConsultant Medical Oncologist, St GeorgeÕsMr C Pilmoor PatientProfessor R PowlesProfessor of Haematological Oncology,Dr A PrenticeConsultant Haematologist, DerrifordMs A RidehalghHaematology Clinical Nurse Specialist, TheMrs J Sale PatientDr S ScheyConsultant Haematologist, GuyÕs Hospital,Dr C SingerConsultant Haematologist, Royal United 121 Dr J SpencerConsultant Radiologist, St JamesÕsMr M SummerhayesPharmacist, GuyÕs Hospital, LondonDr G TannerGP, BridgwaterDr B Walker GP, SeascaleMr D WatsonClinical Nurse Manager, Clinical ApheresisUnit, Glasgow Royal InfirmaryProfessor J WilkinsonProfessor of Public Health, North EastDr J BarrettConsultant Clinical Oncologist and ClinicalDirector, Four Counties Cancer NetworkProfessor R A HawardProfessor of Cancer Studies, University ofProfessor J KleijnenDirector, NHS Centre for Reviews andProfessor M A RichardsSainsbury Professor of Palliative Medicine, 122 The guidance was subject to the NICE consultation process (seewww.nice.org.ukDr S AllardConsultant Haematologist, Northwick ParkMr R AndersonEconomic Adviser, Department of HealthDr B AngusSenior Lecturer in Pathology, Royal VictoriaInfirmary, Newcastle upon TyneDr D ArmstrongConsultant in Public Health Medicine,Professor P ArmstrongProfessor of Radiology, St BartholomewÕsDr D AshPresident of the Royal College ofDr R AttanoosConsultant Histopathologist, LlandoughMs L BakerSenior Haematology Nurse,Birmingham Heartlands HospitalDr M BakerGP, LincolnMr J J BannisterConsultant Surgeon, Barnsley DistrictDr J BarrettConsultant Clinical Oncologist and ClinicalDirector, Four Counties Cancer NetworkDr M BhavnaniConsultant Haematologist, Royal AlbertEdward Infirmary, WiganDr N BienzConsultant Haematologist, Wexham ParkDr D BlackGP and Chair, Nottingham ClinicalDr P BlainMember of the National CancerMs R BradleyClinical Nurse Specialist, St BartholomewÕs 123 Ms R Bratt-WytonClinical Nurse Specialist, Russells HallMr A BrennanDirector of Operational Research, Schoolof SheffieldMs J BuckhamOncology Services Pharmacist, SheffieldDr C BunchMedical Director, John Radcliffe Hospital,Mr S BurgessConsultant Obstetrician & Gynaecologist,King George Hospital, EssexMs T BurgoyneNurse Lecturer/Practitioner inCentral England, BirminghamProfessor A K Burnett Professor of Haematology, University ofWales College of Medicine, CardiffDr A ByrneConsultant in Palliative Medicine, Holmewer Marie Curie Centre, PenarthMs L BywaterClinical Nurse Specialist, John RadcliffeMs C CaffertyRadiographer, Weston Park Hospital,SheffieldDr G CarrollClinical Director, Eastern RegionProfessor J A ChildConsultant Haematologist, The GeneralInfirmary at LeedsDr D ClarkConsultant Cellular Pathologist, GranthamMs H ClementsRadiographer, The Churchill Hospital,Ms D CoatsSenior Cancer Information Nurse Specialist,Dr R ColtartConsultant Clinical Oncologist, Kent andMs J ConnellyDirector, Cancer Action Team, St ThomasÕDr B CottierHead of Cancer Services Analysis, NationalCancer Services Analysis TeamDr I CoxGP, BirminghamMs S CroftsHaematology & Myeloma Research Nurse,Royal South Hants Hospital, SouthamptonMs D CrowtherChief Executive, Wirral Holistic CareDr M H CullenConsultant Medical Oncologist, QueenElizabeth Hospital, BirminghamDr J CullisConsultant Haematologist, Salisbury DistrictDr P CumberConsultant Haematologist, West Wales 124 Dr D CunninghamConsultant Medical Oncologist, The RoyalMs E Dannie Clinical Nurse Specialist, HammersmithDr P DarraghDeputy Chief Medical Officer, DepartmentSafety, Northern IrelandMs J DavieSister, Ninewells Hospital, DundeeDr T W DaviesDirector, East Anglian Cancer Registry,Dr D DeakinConsultant Clinical Oncologist, ChristieDr S DevereuxConsultant Haematologist, KingÕs CollegeProfessor A K DixonProfessor of Radiology, AddenbrookeÕsProfessor L DonaldsonChief Medical Officer, Department ofMs S EagleRadiographer, The Royal Marsden HospitalMs A EastwoodSenior Research Fellow, NHS Centre forDr J EllershawMedical Director, Liverpool Marie CurieMs M EllisBone Marrow Transplant Co-ordinator,John Radcliffe Hospital, OxfordDr D EmpeyMedical Director, The Royal LondonMr S EvansChief Executive, The Society ofMs J FenelonMember of the National CancerDr J FergusonClinical Director, South East LondonProfessor I FinlayMedical Director, Holme Tower MarieCurie Centre, PenarthMs A FloryHaematology Sister, Royal BerkshireDr A FordGP, NottinghamDr A FraterDirector of Public Health, North HampshirePrimary Care TrustDr J GallowayGP, Kings LynnProfessor K GatterProfessor of Pathology, John RadcliffeProfessor D GeorgePresident, British Association of SurgicalDr D GilsonConsultant Clinical Oncologist, Cookridge 125 Dr J GoepelConsultant Histopathologist, RoyalHallamshire Hospital, Sheffield Professor J GoldmanProfessor of Leukaemia Biology andChairman, Department of Haematology,Professor A H GoldstoneProfessor of Haematology, UniversityProfessor E C Professor of Haematology, St GeorgeÕs Gordon-SmithHospital Medical SchoolDr H W HabboushConsultant Haematologist, Nevill HallHospital, AbergavennyDr R HallChief Medical Officer, Welsh OfficeDr J HalpinLead Clinician, Mount Vernon CancerProfessor G W HanksProfessor of Palliative Medicine, UniversityDr J HansonCancer Services Project Co-ordinator, WelshOfficeProfessor J D HardcastleNetwork Lead Clinician, Mid Trent CancerDr M HardingConsultant in Public Health Medicine,Sutton and Merton Primary Care TrustMr T HarrisDirector, Association of Community HealthCouncils for England and WalesDr C HarrisonMedical Director, Greater ManchesterDr P HarveyConsultant Clinical Psychologist, QueenElizabeth Hospital, Birmingham Dr C HattonConsultant Haematologist, John RadcliffeDr V HempsallCancer Lead, Dorset and Somerset StrategicDr A HibbleGP, StamfordDr N HicksConsultant in Public Health Medicine, EastHampshire Primary Care TrustProfessor I HigginsonProfessor of Palliative Care and Policy,Dr R HillierConsultant Physician in Palliative Medicine,Countess Mountbatten House, SouthamptonMs H HollisClinical Nurse Specialist, Royal BerkshireProfessor A HorwichProfessor of Clinical Oncology, The RoyalDr G HoughtonGP, Birmingham Dr M HowardConsultant Haematologist, York DistrictDr P A HulseConsultant Radiologist, Christie Hospital,Ms S HuntonDirector, Bradford Cancer Support Centre 126 Professor P G IsaacsonProfessor of Histopathology, Royal FreeSir B JacksonFormer President, Royal College ofSurgeons of EnglandDr P JamesGP, BirminghamDr M JeffersonConsultant in Palliative Medicine,University of Wales College of MedicineDr R JohnsonConsultant in Diagnostic Radiology,Dr S A N JohnsonConsultant Haematologist, Taunton andSomerset Hospital, TauntonDr I D A JohnstonMedical Director, University Hospital,Dr A C JonesConsultant Clinical Oncologist, TheDr E JorgeFormer Director of Public Health,Ms H KellyRadiographer, Royal South Hants Hospital,Dr S KellyGP, Chichester, West SussexDr P R KelseyConsultant Haematologist, VictoriaMs V KelseyHaematology Clinical Nurse Specialist,Professor D KerrProfessor of Clinical Oncology, Universityof BirminghamDr N KetleyConsultant Haematologist, GreenwichDr C C KibblerConsultant Medical Microbiologist, RoyalMrs D KnupferExecutive Director of Nursing, ChristieDr A KyleConsultant Haematologist, Antrim AreaDr A K LakhaniConsultant Haematologist, FarnboroughDr R LaneConsultant in Palliative Medicine,Ms E LardnerClinical Nurse Specialist, SingletonDr A W LeeGP, ScunthorpeDr S LevyGP, StockportMs C LewisResearch Nurse, Royal Berkshire Hospital,Professor D C LinchProfessor of Haematology, Royal Free andProfessor T A ListerProfessor of Medical Oncology, St 127 Professor P LittlejohnsClinical Director, National Institute forDr P LoriganConsultant Medical Oncologist, WestonPark Hospital, Sheffield Mr G McGheeSenior Staff Nurse, Western GeneralHospital, EdinburghDr M McGovernSenior Policy/Medical Adviser, Departmentof HealthDr I MacLellan-SmithGP, Cheadle, CheshireDr A D L MacVicarConsultant Radiologist, The Royal MarsdenProfessor G McVieDirector General, Cancer ResearchDr J MaherConsultant Clinical Oncologist, MountDr A R ManhireConsultant Radiologist, Nottingham CityDr I ManifoldMedical Director, Weston Park Hospital,SheffieldProfessor R E ManselChairman, Division of Surgery, Universityof Wales College of Medicine, CardiffDr R MarcusClinical Director, British Committee forMr I MarkConsultant Urologist, Lincoln CountyDr T S MaughanConsultant Clinical Oncologist, VelindreHospital, Cardiff Dr G M Mead Consultant Medical Oncologist, RoyalSouth Hants Hospital, SouthamptonDr A B MehtaConsultant Haematologist, Royal FreeMrs R MilesChair, National Cancer AllianceDr D W MilliganConsultant Haematologist, BirminghamProfessor G MorganProfessor of Haematology, University ofMs C MorrisSister, Haematology Day Care Unit, RoyalCornwall Hospital, TruroDr T C M MorrisConsultant Haematologist, Belfast CityProfessor G J MuftiProfessor of Haemato-oncology, GuyÕs,KingÕs and St ThomasÕ School of Medicine,Dr S MundayDirector of Public Health, Southarwickshire Primary Care TrustMs M NendickNursing Officer, Department of HealthDr G NewmanConsultant Clinical Oncologist, RoyalDr P NorrisGP, Kingston upon Thames 128 Dr A J NortonSenior Lecturer in Histopathology, StDame G OliverDirector of Service Development,Dr B A OppenheimConsultant Microbiologist, WithingtonMs H OuthwaiteClinical Nurse Specialist, GuyÕs Hospital,Mrs S PaceyPharmacist, Nottingham City HospitalDr A PagliucaConsultant Haematologist, KingÕs CollegeMs J PalinProject Manager, Cancer Action Team, StDr G ParkGP, StokesleyDr M ParmarHead, Cancer Division, MRC Clinical TrialsDr H ParryConsultant Haematologist, YsbytyDr J PawadeConsultant Histopathologist, Bristol RoyalInfirmaryProfessor M PearsonDeputy Director of Human Resources,Dr S PearsonDirector of Clinical Strategy,Gloucestershire Hospitals NHS TrustMs S PerrettMacmillan Clinical Nurse Specialist forHaematology, University Hospital of Wales,CardiffDr F PittConsultant in Public Health Medicine,North Sheffield Primary Care TrustMrs E PorterfieldMember of the National CancerDr M PotterConsultant Haematologist, Royal FreeDr C PoyntonConsultant Haematologist, UniversityHospital of Wales, CardiffDr A PrenticeConsultant Haematologist, DerrifordDr T PriestmanConsultant Clinical Oncologist, New CrossHospital, WolverhamptonDr J PritchardScientific Adviser, Welsh OfficeProfessor S J ProctorProfessor of Haematological Medicine,Royal Victoria Infirmary, Newcastle uponDr E PughMedical Director, Butterwick Hospice,Stockton-on-TeesDr J RadfordConsultant Physician, Christie Hospital,Dr S RamakrishnanLead Clinician, Weston Park Hospital,Sheffield Dr A D RamsaySecretary, British Lymphoma PathologyGroup, Great Ormond Street Hospital forMr B ReesConsultant General Surgeon, UniversityHospital of Wales, CardiffDr P RevellConsultant Haematologist, StaffordshireGeneral Hospital, StaffordProfessor R H ReznekProfessor of Diagnostic Imaging, StBartholomewÕs Hospital, LondonProfessor M A RichardsSainsbury Professor of Palliative Medicine,St ThomasÕ Hospital, LondonMs A RidehalghHaematology Clinical Nurse Specialist,Ms M RiggeDirector, College of HealthDr M H RobinsonSenior Lecturer in Clinical Oncology,eston Park Hospital, Sheffield Professor P RobinsonProfessor of Clinical Radiology, St JamesÕsDr P RoderickSenior Lecturer in Public Health Medicine,Professor T RogersImperial College Medical School, LondonProfessor A Z S RohatinerProfessor of Haemato-oncology, StBartholomewÕs Hospital, LondonDr N RooneyConsultant Pathologist, Royal UnitedDr A W W RoquesConsultant Haematologist, WorthingHospital, West SussexMr R D RosinConsultant Surgeon, St MaryÕs Hospital,Dr J R Y RossConsultant Haematologist, NorthamptonProfessor G RubinGP, YarmProfessor N H RussellProfessor of Haematology, Nottingham CityDr R D Russell-JonesConsultant Dermatologist, St ThomasÕDr S Schey Director of Clinical Haematology, GuyÕsDr E A ScottImplementation Director, NHSModernisation AgencyDr M SekharConsultant Haematologist, West MiddlesexProfessor P SelbyProfessor of Cancer Medicine, St JamesÕsProfessor K SikoraProfessor of Clinical Oncology,Dr C SinnottConsultant and Senior Lecturer in PalliativeMedicine, St ThomasÕ Hospital, London 130 Dr D N SlaterConsultant Histopathologist/Dermatopathologist, Royal HallamshireHospital, Sheffield Mr J SmallwoodLead Cancer Clinician, SouthamptonMr C SmeeChief Economic Adviser, Department ofDr A G SmithConsultant Haematologist, SouthamptonDr M J SmithConsultant Physician, HeatherwoodDr S R SmithConsultant Haematologist, Torbay Hospital,Dr J SpibyConsultant in Environmental Public Health,Mr M StoneDirector, The PatientÕs AssociationMrs R StoneManager, Hogarth Haematology and BoneMarrow Transplant Unit, Nottingham CityDr N StuartConsultant Medical Oncologist, YsbytyMr M SummerhayesPrincipal Oncology Pharmacist, GuyÕsDr N SummertonClinical Senior Lecturer in Primary CareMedicine, University of HullDr P SuttonGP, Brigg, North LincolnshireDr N SykesConsultant in Palliative Medicine, StDr G TannerGP, Bridgwater, SomersetDr T TateMedical Adviser, Marie Curie Cancer CareDr J ThomasDirector of Public Health, Sunderlandeaching Primary Care TrustMrs H ThorntonChairman, ConsumersÕ Advisory Group forClinical TrialsMr A TurnerMember of the National CancerDr P TwentymanSecretary, United Kingdom Co-ordinatingDr E A VandenbergheConsultant Haematologist, RoyalHallamshire Hospital, Sheffield Dr J van der WaltConsultant Histopathologist, St ThomasÕDr J VerneDirector, South West Public HealthDr S VinnicombeConsultant Radiologist, St BartholomewÕs 131 Dr C WaineFormer Director of Health Programmes andMr D WatsonClinical Nurse Manager, Clinical ApheresisUnit, Glasgow Royal InfirmaryDr P WatsonMedical Director, Essex Strategic HealthDr B WeeConsultant in Palliative Medicine, CountessDr N C WestConsultant Haematologist, WestMrs K WestbrookRadiographer, Bristol Royal InfirmaryDr B S WilkinsSenior Lecturer in Pathology, University ofDr M V WilliamsConsultant Clinical Oncologist,Dr J Z WimperisConsultant Haematologist, Norfolk andDr H WinterSenior Lecturer in Public Health Medicine,University of BirminghamDr C WolfeReader in Public Health Medicine, GuyÕs,Dr A WotherspoonConsultant Histopathologist, The RoyalMr N YoungChief Executive, Macmillan Cancer Relief 132 Overall co-ordinatorsMs A Eastwood NHS Centre for Reviews and Dissemination, Professor J KleijnenUniversity of Yorkand Dr H McIntoshi) Literature reviewsProfessor P Johnson and Cancer Research UK Oncology Unit, Ms B Bennett-LloydCancer Sciences Division, University ofDr S AgrawalBarts and the London School of MedicineDr S GeorgeHealth Services Research Unit, CommunityContributed reviews which were used to inform guidance on Topics 1,Miss R CollinsNHS Centre for Reviews and Dissemination, and Miss M WomphreyUniversity of YorkContributed reviews which were used to inform guidance on Topics 2Ms K Misso andNHS Centre for Reviews and Dissemination, Ms G RitchieUniversity of York 133 Ms R Miles andNational Cancer Alliance, Oxfordiii) Economic reviewV AbbottSchool of Health and Related Research,R AraUniversity of SheffieldS Ward 134 Ms E AndelinAssistant Director of Patient Services,Bradford City Primary Care TrustProfessor M R BakerDirector/Lead Clinician, Yorkshire CancerMr M BellamyFormer Chief Executive, Ealing,Dr A BenghiatCancer Lead Clinician, Leicester RoyalInfirmaryDr P BevanDeputy Director of Public Health,Mr D CampbellChief Executive, Liverpool Central PrimaryCare TrustDr A ChampionAssistant Cancer Services Project Co-ordinator, Welsh OfficeDr I G CoxMacmillan GP Adviser in Cancer andPalliative Care, BirminghamMiss C EdwardsChief Executive, North TrentCommissioning Network, Barnsley PrimaryCare TrustMrs S EllisPartnership Director, West YorkshirePrimary Care Organisations, Wakefieldest Primary Care TrustMr J GrimesDirector of Finance, North & Eastorkshire and Northern LincolnshireDr J HalpinLead Clinician, Mount Vernon CancerDr V HempsallCancer Lead, Dorset and Somerset StrategicDr J KearneyDirector of Public Health, DacorumPrimary Care TrustDr A W LeeGP, ScunthorpeDr M MarshallCancer Lead, Middlesbrough Primary CareDr S MundayDirector of Public Health, Southarwickshire Primary Care Trust Dame G OliverDirector of Service Development, 135 Dr S PearsonDirector of Clinical Strategy,Gloucestershire Hospitals NHS TrustDr F A PittConsultant in Public Health Medicine,North Sheffield Primary Care TrustMr R J PriestleyFormer Chief Executive, North StaffordshireDr E A ScottImplementation Director, NHSModernisation AgencyDr J SpibyConsultant in Environmental Public Health,Dr J ThomasDirector of Public Health, Sunderlandeaching Primary Care TrustDr J VerneDirector, South West Public HealthDr P WatsonMedical Director, Essex Strategic HealthMs S OÕTooleConsultant in Health Policy andMrs V SaundersManager, Northern and Yorkshire CancerRegistry and Information Service 136 Glossary of termsA rapidly progressive cancer of the blood forming system of suddenacuteleukaemiaformed fromformed from myeloid Age-standardised incidencepopulations by removing differences in the age distributions of thoseChemicals that kill organisms e.g. herbicides and pesticides.A procedure in which a patient receives bone marrowhigh dosetherapybone marrowbelow normal.plasmacells 137 Autologous transplantation/autograftbone marrowwhich were collected prior to a course of high dosetherapybone marrow. Also see The armpit.diagnosis of a disease.in which the disease progression becomes morerapid and aggressive and the number of immature, abnormal bone marrowBlood productsProgenitor cellswhich give rise to red blood cells and immune systemBone marrowwhich develop into the three different types of blood cells: red blood 138 Bone marrow transplantation (BMT)A procedure to replace bone marrow. There are two types of transplant Ð bone marrowtype to the patient and , where the patientÕs own marrowCardiologyA branch of medicine concerned with the diagnosis and treatment ofdiseases affecting the heart and blood vessels.Central venous catheter/central lineand blood transfusions can be given. Once in place itChronicChronic leukaemiaGenerally a slowly progressing cancer of the blood, usually of gradual. In some types of chronic leukaemiathe blood cells are not over-produced but fail to die when theyChronic lymphocytic leukaemia (CLL)chronic leukaemiaformed from lymphoid Chronic myeloid leukaemia (CML)chronic leukaemiaformed from myeloid , but may also use talking and practising specific types of voluntary activity. This groupof interventions can include, for example, relaxation training,counselling, and psychological approaches to pain control.bone marrow Core biopsyexamination. This test uses a slightly larger needle than the one usedfine needle aspiration(FNA)and is usually done under localCryopreservationCytogenetic abnormalitiesAbnormalities of chromosomes.The study of chromosomes and chromosomal abnormalities.specific effects on other cells. Some cytokines help the body todestroy abnormal cells. Examples of cytokine treatment includeinterferon and interleukins.oxic to cells. This term is used to describe drugs which kill cancer 140 DermatologistThe study of populations in order to determine the frequency andthat lines internal and external surfaces of the body including organs,Erythrocyte sedimentation rate (ESR)cells (erythrocytes) to settle out more quickly than normal.Fibrotic tissueFibrous tissue that replaces normal tissue e.g. scars or tissue that isThe removal of cells using a fine needle for examination in theAn imaging technique sometimes used to provide further informationabout abnormalities identified on plain x-ray or Gastroenterologistincluding the liver.bone marrow transplantationbone marrowthat is an essential component of the immuneHaematological cancersCancers of the blood and blood-forming tissues. 141 A doctor who specialises in disorders of the blood and blood-formingA branch of medicine concerned with the study and treatment ofdisorders of the blood and blood-forming tissues.A branch of medicine concerned with the study and treatment ofcancers of the blood and blood-forming tissues.bone marrowAbnormal enlargement of both the liver and the Intensive treatment with to killbone marrowbone marrowbone marrowin excess and result in the progressive, painless enlargement of A particular abnormal cell,known as the Reed-Sternberg cell is found in HodgkinÕs lymphoma.HypercalcaemiaAbnormally high levels of calcium in the blood.Iatrogenic Pattern of specific proteins () present on the surfaceImmunosupressionSuppression of the immune system. 142 Drugs that interfere with the growth of some cancer cells by blockingCancer of the blood forming system in the bone marrowcharacterised by the production of abnormal bone marrowDisease or swelling of the A class of Magnetic resonance imaging (MRI)A non-invasive method of imaging which allows the form andmetabolism of tissues and organs to be visualised (also known as 143 Medical oncologistMicrobiologistA person who specialises in the study of micro-organisms such asdevelopment of treatment plans for such infections.produced in the laboratory from a single copy of a humanthat can target specific cancer cells wherever they may be inA condition in which increased numbers of abnormal significance in itself and does not require treatment. However, 20-30%Abnormal formation of blood cells in the bone marrowMyelodysplastic syndrome (MDS) bone marrowfunctions abnormallyand fails to produce enough normal blood cells. It may progress to. Also see chronic myeloid leukaemiabone marrow in many places simultaneously, it is also known as multiple myeloma. 144 Myeloproliferative disorders (MPD) marrowNeoplastic diseaseDisease characterised by new and abnormal growth of tissue (cancer).NephrologyA branch of medicine concerned with the diagnosis and treatment ofNeutropenianeutrophilsblood is below normal.Neutropenic sepsisneutrophilsNeutrophilsinclude: diffuse large B-aldenstromÕs lymphoma and marginal zone lymphomas. Extra-nodalaffecting the skin or intestine.A doctor who specialises in treating cancer.ParaproteinAn abnormal A person who specialises in the diagnosis of disease through study ofbone marrowPhiladelphia chromosomeA chromosomal abnormality found in the blood cells of all peoplechronic myeloid leukaemia. Positron emission tomography (PET)computerised image of metabolic activity of body tissues.PrecursorA substance from which another substance is formed.Progenitor cellsParent cells that give rise to progeny that serve more specialisedProphylaxisProtocolConcerned with psychological influence on social behaviour.to specifically target tumour cells. 146 A doctor who specialises in creating and interpreting pictures of areasThe use of radiation, usually x-rays or gamma rays, to kill cancerRandomised controlled trial (RCT)A type of experiment which is used to compare the effectiveness ofdifferent treatments. The crucial feature of this form of trial is thatinterventions being assessed or control treatments. RCTs offer themost reliable (i.e. least biased) form of evidence of effectiveness.RecurrenceThe return of cancer.signs of cancer or cancer-related symptoms.An organ which is part of the lymphatic system. It produces, stores blood cells, filters the bloodand removes anddestroys worn-out red blood cells.Squamous cell carcinomascales Ð found in the tissue that forms the surface of the skin, thelining of the hollow organs of the body, and the respiratory andThe extent (stage) of disease defined by internationally agreedcriteria. Staging helps determine treatment and indicates prognosis. 147 bone marrowmarrow transplantation) cells are normally found in the bone marrow.However, the bone marrow, they may be purged to destroy any remainingStem cell rescuebone marrow transplantbone marrowSteroidsSteroids are hormonal substances naturally produced in the body.steroid have been found to destroy some types of cancer cells andmore effective.ThrombosisFormation or presence of a blood clot within a blood vessel.organs within the body.immune system and are present in the blood and lymphatic system,bone marrownumber of different types of white blood cells which work together to 148 Carmustine (BCNU), etoposide, cytosineBritish Society for Bone Marrow TransplantationCPAC-VAMPDiffuse large B-cell lymphomaEar, nose and throatExternal quality assuranceHEPAHigh efficiency particulate airHICPAC Ifosfamide, carboplatin and etoposideMechlorethamine, vincristine, procarbazine andNational Institute for Clinical ExcellenceOffice for National StatisticsRevised European-American Classification ofSwedish Council on Technology Assessment inUnited Kingdom Acute Lymphoblasticorld Health Organisation 150