ha em a to logy guidelines

8/14/2019 Ha Em a to Logy Guidelines

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ASWCS Haematology

Cancer Clinical CareGuidelines

December 2005


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December 2005

Chris Knechtli on behalf of the ASWCS Haematology Site SpecialistGroup

If you need further copies of this document please telephone ASWCSon 0117 900 2324

If you need this document in a different format please telephoneASWCS on 0117 900 2324


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C:\Documents and Settings\MSanidas\Local Settings\Temporary Internet Fi les\OLK7EC\Haematology Guidelinesv2.doc

Contents Page 2

5 Treatment ------------------------------------------------------------------------------------------ 35

5.1 Indolent Lymphoproliferative Disorders------------------------------------------------------ 35

5.2 Hairy Cell Leukaemia----------------------------------------------------------------------------- 36

5.3 Mantle Cell Lymphoma -------------------------------------------------------------------------- 36

5.4 Aggressive Non-Hodgkins Lymphoma------------------------------------------------------ 36

5.5 Very Aggressive Non-Hodgkins Lymphoma----------------------------------------------- 36

5.6 Hodgkins Disease -------------------------------------------------------------------------------- 36

5.7 Hodgkins Disease / aggressive NHL Salvage--------------------------------------------- 36

5.8 Stem Cell Transplantation----------------------------------------------------------------------- 37

5.9 Myeloma--------------------------------------------------------------------------------------------- 37

5.10 Chronic Myeloid Leukaemia --------------------------------------------------------------------37

6 Follow up------------------------------------------------------------------------------------------- 38

7

Patient Involvement and Information ----------------------------------------------------- 38

7.1 Principles of Effective Patient Involvement and Information ---------------------------38

7.2 Communicating Significant News ------------------------------------------------------------- 39

7.2.1 Before a first cancer related appointment--------------------------------------------------- 39

7.2.2 Breaking Bad News Confirming a Diagnosis --------------------------------------------- 39

7.3 Holistic Needs Assessment Guidance------------------------------------------------------- 40


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Haematology Guidelines

C:\Documents and Settings\MSanidas\Local Settings\Temporary Internet Files\OLK7EC\HaematologyGuidelinesv2.doc

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1 Background

This document outlines the clinical management guidelines for Haematological cancer,which includes leukaemia, lymphoma and myeloma. These guidelines have beendiscussed and agreed at the ASWCS Network Haematology Site Specialist Group.

The Avon, Somerset and Wiltshire Cancer Services (ASWCS) Network serves apopulation of 2.096 million.

2 NICE Referral Guidelines for Haematological Cancer

A patient who presents with symptoms suggestive of haematological cancer should bereferred to a team specialising in the management of haematological cancer, dependingon local arrangements.

Haematological cancers can present with a variety of symptoms that may have a numberof different clinical explanations. Combinations of the following symptoms and signswarrant full examination, further investigation (including a blood count and film) and

possible referral: Fatigue

Drenching night sweats

Fever

Weight loss

Generalised itching

Breathlessness

Bruising

Bleeding

Recurrent infections

Bone pain

Alcohol-induced pain

Abdominal pain

Lymphadenopathy

Splenomegaly

The urgency of referral depends on the symptom severity and findings of investigations.

A patient who presents with a blood count/film reported as acute leukaemia or withspinal cord compression or renal failure suspected of being caused by myelomamust be referred immediately.

A patient who presents with persistent unexplained splenomegaly must bereferred urgently.


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2.1 Investigations

In patients with:

Persistent unexplained fatigue carry out a full blood count, blood film anderythrocyte sedimentation rate, plasma viscosity or C-reactive protein

(according to local policy). Repeat at least once if the patients conditionremains unexplained and does not improve

Unexplained lymphadenopathy carry out a full blood count, blood film anderythrocyte sedimentation rate, plasma viscosity or C-reactive protein(according to local policy)

Any of the following additional features of lymphadenopathy:

Persistence for 6 weeks or more

Lymph nodes increasing in size

Lymph nodes greater than 2 cm in size

Widespread nature

Associated splenomegaly, night sweats or weight loss

Investigate further and/or refer

Unexplained bruising, bleeding and purpura or symptoms suggestinganaemia, carry out a full blood count, blood film, clotting screen anderythrocyte sedimentation rate, plasma viscosity or C-reactive protein(according to local policy)

Persistent and unexplained bone pain, carry out a full blood count and X-

ray, urea and electrolytes, liver and bone profile, PSA test (in males) anderythrocyte sedimentation rate, plasma viscosity or C-reactive protein(according to local policy)

3 Imaging Guidelines

This guidance has been produced by the Avon Somerset & Wiltshire Cancer Services(ASWCS) Network Imaging Group and the Network Service Improvement Lead.

NICE have produced a serious of Improving Outcomes Guidance (IOG) documentswhich are cancer disease site specific. They provide a framework for the consistentapproach to the diagnosis, treatment and support of patients with suspected or confirmed

cancer.Compliance with IOG is tested through the process of External Peer Review. This is anaudit process using standards (quality measures) defined in the Manual of QualityMeasures (QMs). There are now specific QMs for radiology against which radiologydepartments will be externally audited at peer review.

In the newly revised Manual of QMs (May 2004), at a disease site specific level, there is arequirement for network based site specialist groups (SSGs) to define:

Imaging for diagnosis

Imaging for staging

Imaging for surveillance


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Both locally and nationally The Cancer Services Collaborative Improvement Project haveidentified that access to diagnostics (including radiology, pathology and endoscopy)represents the biggest bottleneck along the patient journey. Ironically, IOGrecommendations have directly contributed to the problem. In the drive to achieve anetworked/specialist approach to care, patients now frequently travel to hospitals around

the ASWCS Network for different aspects of their overall care package. In common withother patients from other networks across the UK, patients are frequently investigatedseveral times for the same thing in the different hospitals they attend on this journey. Thiscauses unnecessary duplication of investigations contributing to the shortage of capacity.This common practice may also be at odds with recommendations set out in the IRMAregulations.

This guidance, proposed by the Network Imaging Group seeks to:

Help SSGs, trusts, disease site multidisciplinary teams and the network to comply withIOG and QMs

Provide a framework for the consistent approach to diagnosis, staging and surveillance end post code variations in practice

Assist radiology departments in controlling demand and manage capacity


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3.1 Screening Guidance for women who have received supraclavicularradiotherapy for Hodgkins Disease

(Ref Cheryl Cavanagh, Cancer Policy Team, DoH, November 03: IncreasedRisk of Breast Cancer after Radiotherapy for Hodgkins Disease PatientNotification Exercise)

Age at timeof RT

Age to startScreening

Type ofscreening

Frequency / Notes

16 Not applicable None

17 25 MRI

18 26 MRI

19 27 MRI

20 28 MRI

21 29 MRI

ANNUALLY - UP TO THE AGE OF 30 THEN BASELINE MAMMOGRAM:

Group 1: Predominantly Fatty Breast Tissue Annual 2-view Mammography

Group 2:Dense Breast Tissue Annual 2-viewMammography Plus MRI Unless:

1 = There are contra-indications

2 = Patient cannot tolerate MRI3 = Patient chooses not to have MRI

If any of 1-3 apply = Annual MammographyPLUS ultra-sound

22 30 Mammogram

23 31 Mammogram

24 32 Mammogram

25 33 Mammogram

26 34 Mammogram

27 35 Mammogram

28 36 Mammogram

29 37 Mammogram

30 38 Mammogram

31 39 Mammogram

32 40 Mammogram

33 41 Mammogram

34 42 Mammogram

35 43 Mammogram

Annually for anyone in this category up theage of 50.

This includes women who had RT within the

age range 17 and 35 and who are now agedbetween 43 and 49.

Following Baseline Mammogram:

Group 1: Predominantly Fatty Breast Tissue Annual 2-view Mammography

Group 2:Dense Breast Tissue Annual 2-viewMammography Plus MRI Unless:

1 = There are contra-indications

2 = Patient cannot tolerate MRI3 = Patient chooses not to have MRI

If any of 1-3 apply = Annual MammographyPLUS ultra-sound

36 Not required NoneWomen who had radiotherapy agedbetween 17 and 35 and who arenow aged 50 should be in theNHSBSP

Mammogram 3 yearly

Note: The DoH guidance recommends that MRI be carried out in MARIBSScanning Centres. Guys is the nearest MARIBS Scanning Centre for Kent &

Medway patients. Specialist Commissioners are still discussing financial details.


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4 Pathology Guidelines

4.1 Clinical Guidelines on Leukaemia

This document is written to facilitate a standard approach to the management of

acute and chronic leukaemia across the ASWCS network. It is anticipated that itwill provide minimal acceptable standards for management of such patients.

This document is necessary to allow compliance with the Department of HealthCancer Services Peer Review measure 1C-124.

This document is principally aimed at health care professionals involved in thecare of patients with acute and chronic leukaemia:

General Practitioners

Consultant Haematologists

Consultant Medical and Clinical Oncologists Consultants in Radiotherapy

Specialist Registrars in Haematology and Oncology

Haematology Clinical Nurse Specialists

Haematology Nursing Staff

This document details the approach that should be taken to the followingconditions:

Acute Myeloid Leukaemia (AML)

Acute Lymphoblastic Leukaemia (ALL)

Chronic Myeloid Leukaemia (CML)

Chronic Lymphocytic Leukaemia (CLL)

The estimated annual incidence of acute and chronic leukaemia in England andWales is outlined in the following table:

Disease AnnualIncidence

Per 1,000,000 Per 500,000 Per 250,000

Acute Leukaemia 2400 48 24 12

CML 500 10 5 2-3

CLL 4000 80 40 20

4.1.1 Presentation / Referral Recommendations

A patient presenting with symptoms or signs suggesting leukaemia shouldbe referred to a team specialising in the management of leukaemia.

Combinations of the following symptoms or signs may suggest leukaemiaand warrant full examination, blood count/blood film examination and

possible referral:


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fatigue

drenching night sweats

fever

weight loss

breathlessness

bruising

bleeding

recurrent infections

bone pain

abdominal pain

lymphadenopathy

splenomegaly

The urgency of referral depends on the severity of the symptoms andsigns, and the findings of the blood count/blood film examination.

In patients with a blood count or blood film reported as acute leukaemia,an immediate referral should be made. In patients with persistentunexplained splenomegaly or blood count/blood film appearancesconsistent with CML, an urgent referral (to be seen within 2 weeks) shouldbe made. Uncomplicated CLL can be referred for non urgent clinic reviewbut the associated presence of cytopenias (anaemia or thrombocytopenia)or bulky lymphadenopathy/organomegaly should also precipitate an urgent

request for review.

4.1.2 Acute Myeloid Leukaemia

Initial Management

Admit the patient to a haemato-oncology in-patient bed as a matterof urgency.

Take blood for the following:

FBC, film, (immunophenotyping if sufficient blast count)

PT, aPTT, fibrinogen

G&S

U&E, creatinine, LFTs, calcium, magnesium, uric acid

Full tissue typing of patient and siblings (if allo-SCT is likelyto be a future treatment option)

Perform bone marrow aspirate (and trephine, if difficult aspirate)and send for morphological, (cytochemical), immunophenotypic andcytogenetic analysis. Document findings/MDT discussion.

CXR


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Check ECG and consider echocardiogram/MUGA scan to assessLV function particularly in patients with symptoms and/or signssuggestive of cardiac dysfunction.

Subsequent Management

This will depend on the age and performance status of the patient.

The optimum treatment of AML is intensive chemotherapy.Induction chemotherapy is given initially to induce a remission,defined as a normocellular marrow with less than 5% blasts.Consolidation or post-remission chemotherapy is then necessary toprevent early relapse and increase the chance of cure. This mayinclude stem cell transplantation.

Intensive induction chemotherapy for AML should only be given onan approved BCSH level 2 Haematology Unit.

Ideally, patients with AML should be treated within MRC trials.

Risk stratification is used to determine consolidation therapy.

For a list of induction and consolidation chemotherapy regimensused in both the trial and non-trial setting, please see relevantsection in the ASWCS Chemotherapy Handbook.

Patients not suitable for intensive chemotherapy may beconsidered for less aggressive palliative treatment including lowdose ara C and should be given best supportive care.

4.1.3 Acute Lymphoblastic Leukaemia

Initial Management



FBC, film, (immunophenotyping if sufficient blast count)

PT, aPTT, fibrinogen

G&S

U&E, creatinine, LFTs, calcium, magnesium, uric acid


Perform bone marrow aspirate (and trephine, if difficult aspirate)and send for morphological, (cytochemical), immunophenotypic andcytogenetic analysis. Document findings/MDT discussion.

CXR

Check ECG and consider echocardiogram/MUGA scan to assessLV function particularly in patients with symptoms and/or signssuggestive of cardiac dysfunction.


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Consider early lumbar puncture (LP) in order to assess CSFcytology, glucose and protein if symptoms/signs suggestive of CNSdisease.


This will depend on the age and performance status of the patient.

Multi-agent chemotherapy is the optimum treatment for ALL.Induction chemotherapy is given initially to induce a remission,defined as a normocellular marrow with less than 5% blasts.Consolidation, intensification (including CNS prophylaxis) andmaintenance chemotherapy is then necessary to prevent earlyrelapse and increase the chance of cure. Stem cell transplantationis an important treatment consideration in the management of ALLin adult patients.

Intensive induction chemotherapy for ALL should only be given onan approved BCSH level 2 Haematology Unit.

Ideally, patients with ALL should be treated within MRC trials.UKALL XII is the current MRC trial for adult patients between theages of 18 to 55.

Serious consideration should be given to allogeneic stem celltransplantation in the management of Philadelphia chromosomepositive disease.

For a list of induction, consolidation, intensification andmaintenance chemotherapy regimens used in the management ofALL, please see relevant sections in the UKALL XII protocol.

Patients not suitable for the intensive chemotherapy scheduleemployed in UKALL XII can be treated with palliativesteroids/vincristine and supportive care.

4.1.4 Chronic Myeloid Leukaemia

Initial Management


FBC, film, manual differential

U&E, creatinine, LFTs, calcium, LDH, uric acid

Quantitative RT-PCR for BCR-ABL


Perform bone marrow aspirate and trephine biopsy, and sendsample of aspirate for cytogenetic analysis. Documentfindings/MDT discussion.

Clinical (+/- ultrasound) assessment of spleen size.

Consider buffy coat cryopreservation in all patients in whom SCT isa potential treatment option.

In patients with symptoms of leucostasis consideration should begiven to therapeutic leucopheresis.


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Patients with chronic phase disease should be encouraged to enterthe international SPIRIT trial.

If trial entry is declined then standard NICE approved management

in this situation is imatinib 400mg daily. Close monitoring of response with regular FBC, quantitative PCR

for BCR-ABL and marrow cytogenetics is recommended.

Suboptimal responders to imatinib (and patients


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Other options, especially for relapsed disease, include single agentfludarabine, and combination therapy with fludarabine andcyclophosphamide.

Patients who are refractory to fludarabine may gain benefit fromCHOP, high dose methylprednisolone or alemtuzumab(CAMPATH).

4.1.6 Addendum Patient information and support regarding a diagnosisof Leukaemia

All patients and their families should be fully informed regarding the type ofleukaemia, management plan and treatment intent. Patients should beoffered written information about the disease, together with details on otheruseful information sources. Patients must be informed of their Key Workerwithin the MDT. Clear information about access to the range of servicesoffered by the MDT must be communicated. The management plan needsto be communicated simply to the patient and his/her carer anddocumented so that the information is readily accessible to other members

of the multi-disciplinary specialist team.

Patients should be given the opportunity of receiving more than onemedical opinion.

4.2 Clinical Guidelines on Lymphoproliferative disorders

This protocol is written to facilitate a standard approach to the management ofsuspected and proven lymphoproliferative disorders across the ASWCS Network.It is anticipated that this will provide fundamental guidance on the minimalacceptable standards for the management of such patients. The document isnecessary to allow the Network SSG to comply with the DoH Cancer ServicesPeer Review measure 1C-125 and allow local MDTs to comply with measure 2H-

138.

The document is principally aimed at the following health care professionals:

GPs


Consultant Medical and Clinical Oncologists

SpRs in Haematology and Oncology


Senior nurses working on Haematology wards and in Haematology Out-Patient Departments

This document details the approach that should be taken to the followingconditions:

Low grade B cell lymphoproliferative disorders

follicular lymphoma (grades 1 and 2) (FL)

lymphocytic lymphoma (LL)

chronic lymphocytic leukaemia (CLL)

lymphoplasmacytoid lymphoma (LPL)


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Waldenstrms macroglobulinaemia (WM)

splenic lymphoma with villous lymphocytes (SLVL)

marginal zone lymphoma (MZL)

hairy cell leukaemia (HCL)

prolymphocytic leukaemia (PLL)

Intermediate grade B cell lymphoproliferative disorders

mantle cell lymphoma (MCL)

High grade B cell lymphoproliferative disorders

diffuse large B cell non-Hodgkins lymphoma (DLBCL)

T cell-rich B cell non-Hodgkins lymphoma

Mediastinal sclerosing B cell lymphoma

grade 3 follicular non-Hodgkins lymphoma

Very high grade B cell lymphoproliferative disorders

Burkitt lymphoma

Burkitt-like lymphoma

B cell lymphoblastic lymphoma

Hodgkins lymphoma

Nodular lymphocyte predominant Hodgkins lymphoma (NLPHL)

Classical Hodgkins lymphoma

nodular sclerosing

lymphocyte-rich

mixed cellularity

lymphocyte-depleted

Low grade T cell lymphoproliferative disorders

High grade T cell lymphoproliferative disorders

Anaplastic large cell lymphomas

4.2.1 Initial Presentation

This patient group can present in a wide variety of ways. The NICE ClinicalGuidance for Suspected Cancer (CG27, published June 2005, pages 75-77)advises that the following symptoms or signs warrant a full clinical examination,further investigation and possible referral to a specialist in haemato-oncology:

Fatigue

Drenching night sweats

Fever (unexplained)


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Superior vena caval obstruction

Severe sepsis

Hyperviscosity syndrome

Of course, some of these symptoms are not individually specific to

malignancies of haematological origin and haemato-oncology specialistsrely on GPs to refer to the appropriate clinical teams for initial patient work-up. The following are suggested routes of referral for given clinical signs:

Drenching night sweats Haemato-Oncologist

Weight loss depends on other clinical findings

Generalised itching Dermatologist or Haemato-Oncologist

Breathlessness at rest or minimal exertion (esp if pleural effusion) Respiratory Physician

Bruising or bleeding (unexplained) - Haemato-Oncologist

Lymphadenopathy neck ENT surgeon

axilla breast surgeon

groin general surgeon

Splenomegaly - Haemato-Oncologist

4.2.2 Initial Specialist Assessment

The focus of investigations should be to establish a tissue diagnosisassoon as possible. This may be afforded by the full blood count (FBC),

inspection of the peripheral blood film and immuno-phenotyping. However,in most patients, a proper diagnosis will require removal of an adequatepiece of affected tissue. Fine needle aspiration biopsy is invariablyinsufficient to establish a diagnosis of lymphoma. Where possible, excisionbiopsy of a lymph node or a significant part of a lymph node mass shouldbe attempted. In a minority of cases this will not be possible and a needlebiopsy (usually image-guided) should be performed e.g. of lymph nodemass, liver or bone marrow. In very rare circumstances this may also provedifficult, in which case attempts should be made to sample otherappropriate diagnostic material e.g. cerebro-spinal, pleural and/or asciticfluids.

Surgeons are urged to bisect the diagnostic material. One half should besent in formalin and the other dry (unfixed) to the histopathologylaboratory. The latter needs to be processed urgently if live cells arerequired for immunophenotyping or cytogenetic analysis. It is not presentlyroutine practice (outside clinical trials) to request cytogenetic analysis ofdiagnostic material exceptin the rare cases where Burkitt lymphoma issuspected. In these situations, demonstration of either one of the typicalkaryotypes, t(8;14), t(2;8) and t(8;22), is crucial in confirming the diagnosis.In this situation, it is mandatory for cytogenetic analysis to be requested onany available solid or liquid diagnostic tissue.

The DoH access targets (31 day decision-to-treat to treatment & 62 dayGP referral to treatment) present a significant challenge for clinicians

investigating patients presenting with lymphoma. It is crucialthat thediagnosis is established as speedily as possible in order to give enough


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time for pre-treatment assessment, including staging investigations andreferral to the Chemotherapy or Radiotherapy Services.

4.2.3 Pathological Assessment

A separate ASWCS protocol is available for the histopathologicalinvestigation of lymph node or other solid tissue biopsy material.

For patients with a clear population of lymphoid cells evident in theperipheral blood, a precise diagnosis may be obtained from inspection ofthe peripheral blood film and immunophenotyping. The latter should beperformed on the gated population of lymphoid cells of interest with apanel of antibodies directed at the following antigens: CD3, CD4, CD5,CD8, CD10, CD19, CD23 in the first instance. A secondary panel ofantibodies may be employed e.g. anti-CD25 and FMC7 to confirm asuspected diagnosis of hairy cell leukaemia. Cytogenetic and/or FISHanalysis may also prove useful e.g. to identify poor risk CLL (11q- or 17p-)in a young patient or to confirm a diagnosis of mantle cell lymphoma(t(11;14)).

4.2.4 Pre-Treatment Evaluation

Low / intermediate grade B or T cell lymphoproliferative disorders

Document precise pathological sub-type of lymphoproliferativedisorder according to WHO Classification.

Document full clinical history and examination.

Document FBC, U&E, creatinine, LFTs, serum proteinelectrophoresis, immunoglobulin levels and a direct antiglobulintest.

Additional staging including CT scan of chest, abdomen and pelvisand bone marrow aspirate and trephine biopsy should beperformed in some cases particularly those patients with follicular,marginal zone or mantle cell lymphomas.

For patients with follicular lymphoma, the Follicular LymphomaInternational Prognostic Index (FLIPI) score (Blood2004; 104: 1258- 1265) can be recorded according to the following proforma:

- Pre-treatment criteria (Risk factors) Score 0 Score 1

Age (years) 60 >60

Hb (g/dl) 12Serum LDH 1 x normal >1 x normalStage (Ann Arbor) I or II III or IV

No. of sites 4 >4

Risk groups: 10 year survivalgood (0 or 1 risk factor) 71%intermediate (2 risk factors) 51%poor (3 - 5 risk factors) 27%

Record patient height and weight and calculate surface area.


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Age adjusted IPI (aa-IPI) risk groups (for patients60 years):[dependent only on stage, performance status and LDH]Low (0 risk factors)Low intermediate (1 risk factors)High intermediate (2 risk factors)High (3 risk factors)


In patients with a history of cardiac disease record ECG andechocardiogram to assess LV function.

Give adequate verbal/written information to patients and relativesconcerning patients disease, treatment strategy and potential sideeffects of treatment.

Discuss potential risk of infertility with patient and relatives.

Refer to Haematology Clinical Nurse Specialist.

Schedule discussion of patient at next available MDT meeting.

Consider admission for intravenous hydration and tumour lysisprecautions according to local practice in patients with bulkdisease.

Very high grade lymphomas


Document histological sub-type of non-Hodgkin's lymphomaaccording to WHO Classification.

Document disease stage following:

Full clinical history (including the presence or absence of Bsymptoms)

Full clinical examination

CXR

CT scan of chest, abdomen and pelvis (consider MRI scanfor cranio-spinal involvement)

Bone marrow aspirate and trephine biopsy (includingcytogenetic analysis if Burkitt lymphoma suspected)

Lumbar puncture for cytological assessment of CSF (+protein and M, C&S). It is suggested that cytarabine 70mg isgiven intrathecally at the time of the LP if Burkitt's orlymphoblastic lymphoma is a serious diagnostic possibility.

Aspiration of pleural and/or ascitic fluid if appropriate (withcytogenetic analysis if Burkitt lymphoma suspected)

Document ECOG/WHO performance status


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Document FBC, ESR/PVisc, clotting screen (PT, aPTT andfibrinogen), U&E, creatinine, LFTs, calcium, magnesium, uric acid,LDH, immunoglobulin levels and serum protein electrophoresis.Baseline FSH, LH, oestradiol and testosterone levels should be

considered.

An HIV test should be considered as Burkitt's lymphoma is one ofthe commonest histological subtypes seen in HIV-positive patients.

Creatinine clearance (measured by 24-hour urine collection orradio-isotopic methods) must be performed before any high dosemethotrexate is given.


Consider ECG and echocardiogram/MUGA scan to assess LVfunction particularly in patients with symptoms and/or signs

suggestive of cardiac dysfunction.

Consider pulmonary function tests to assess spirometry, TLCO andKCO in patients with pre-existing lung disease.

Give adequate verbal/written information to patients and relativesconcerning patients disease, treatment strategy and potential sideeffects of treatment.

Discuss potential risk of infertility with patient and relatives andconsider sperm cryopreservation.

Refer to Haematology Clinical Nurse Specialist.

These patients are at high risk of developing tumour lysissyndrome. Start IV hydration at a rate of at least 3l/m2/day (sodium

content 75mmol/l) or as close to this figure as is tolerated. Givefrusemide as required to maintain urine output. DO NOT includepotassium supplements with the IV fluids unless serum potassiumfalls below 3.0mmol/l.

Give Rasburicase 200g/kg daily for 3 - 7 days.

An additional measure that can be employed for persistenthyperuricaemia is to add sodium bicarbonate to the IV solutions(start with 50mmol of sodium bicarbonate per litre of solution). Keep

urine pH 7.0 (by increasing the amount of sodium bicarbonate inthe infusion fluids to 100mmols/l, if necessary). Stop addingbicarbonate to infusions when urate is back within the normalrange, or serum bicarbonate >30mmol/l and/or immediately prior tocommencement of chemotherapy.

Start allopurinol at 300mg/day (100mg/day if significant renalimpairment) following discontinuation of Rasburicase.

Arrange for a Hickman or similar tunnelled central venous catheterto be inserted as soon as convenient.


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Hodgkins Lymphoma

Document precise pathological sub-type of Hodgkins diseaseaccording to WHO Classification.

Document disease stage following:

Full clinical history (including the presence or absence of Bsymptoms)

Full clinical examination

CXR

CT scan of chest, abdomen and pelvis (consider MRI scanfor cranio-spinal involvement)

Bone marrow aspirate and trephine biopsy (if abnormal FBCor film or suspicion of stage IV disease)

Other investigations should include blood tests for FBC,ESR/PVisc, U&E, creatinine, LFTs, and LDH. Baseline uric acid,FSH, LH, oestradiol and testosterone levels should also beconsidered.

Consider testing HIV serology

Hasenclever score (NEJM 1998; 339: 1506 - 1514) may becalculated based on the following parameters:

- Pre-treatment criteria (Risk factors) Score 0 Score 1

Age (years) 45 >45Sex female maleStage I III IVHaemoglobin 10.5


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Discuss potential risk of infertility with patient and relatives andconsider sperm cryopreservation.

Consider admission for intravenous hydration in patients with bulkdisease

Issue patient with DoH Irradiated blood information sheet and card:

all blood components should be irradiated indefinitely

Schedule discussion of patient at next available MDT meeting.

4.2.5 First-line Treatment

It is recommended that all patients should be considered as candidates forentry into clinical trials where a suitable clinical trial is available and thepatient is willing and able to give appropriate informed consent. Thefollowing recommendations are designed for those unsuitable for clinicaltrials or who are unwilling or unable to give consent for entry into a trial.

Ideally the treatment recommendation should be reached following

discussion at an MDT meeting. If urgent treatment is required then thetreatment protocol decided upon should be ratified at an MDT meeting assoon as possible after the treatment is initiated.

Where guidance from NICE is available, this should be adhered to unlessthere are contra-indications to giving the relevant treatment.

Specific information about the regimens referred to below can be found onthe ASWCS website athttp://www.aswcs.nhs.uk/pharmacy/ChemoHandbook/HCP/index.htm.

Follicular lymphoma (FL)

Stage 1A refer for radiotherapy as this offers a chance of cure.

If asymptomatic, watch and wait.

If symptoms or bulk disease Chlorambucil Prednisolone.

If rapid response required (e.g. compression of vital organ or verylarge bulk) consider CHOP or Fludarabine + Cyclophosphamide.

If large cell variant (histological grade 3b) treat as per DLBCL.

If transformed FL treat as per DLBCL.

If young patient consider rainy day autologous haematopoietic

stem cell collection in 1st CR.

Chronic lymphocytic leukaemia / lymphocytic lymphoma (CLL/LL)

LL Stage 1A refer for radiotherapy as this offers a chance of cure.



If rapid response required (e.g. compression of vital organ or verylarge bulk) consider CHOP or Fludarabine + Cyclophosphamide.


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Waldenstrms macrogolbulinaemia (WM)

Lymphoplasmacytic lymphoma (LPL)

Splenic MZL / Splenic Lymphoma with Villous Lymphocytes (SLVL)

Primary nodal Marginal Zone Lymphoma (monocytoid B cell

lymphoma)

Stage 1A refer for radiotherapy as this offers a chance of cure.



For splenic MZL, splenectomy can be considered for symptomcontrol.

Extra-nodal marginal zone (MALT-type) lymphoma (ENMZL)

Gastric MZL

Stage 1E Helicobacter pylori eradication as sole therapy.

Follow-up with upper GI endoscopy and biopsy every 6months for 2 years.

If more advanced stage, treat with Chlorambucil.

Surgery best avoided unless required as an emergency e.g.to control bleeding.

Radiotherapy best avoided.

Non-gastric MZL


Stage 1A refer for radiotherapy as this offers a chance ofcure.

If more advanced stage, treat with Chlorambucil.

Radiotherapy usually reserved for local symptom controlonly e.g. conjunctival disease.

CVP or CHOP could be considered for severe organ

compromise where a rapid response is desired. For transformed MZL, treat as per DLBCL.symptom control

only e.g. conjunctival disease.

Hairy cell leukaemia (HCL)

Options for treatment include:

2-Chlorodeoxyadenosine (Cladrabine)

Deoxycoformycin (Pentostatin)


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Anaplastic large cell lymphoma (ALCL) t(2;5) and / or ALK +ve

CHOP x 6-8 cycles depending on response measured after 4courses.

Primary cerebral lymphomaIn the non-immunosuppressed patient, the

following may be considered: Patients with cerebral involvement only CHOD-BVAM

Patients with cerebral and systemic involvement IDARAM

For patients not fit for the above regimens consider cranial radiotherapyalone

4.2.6 Treatment for relapsed / progressive disease

Once again:

Trial entry is encouraged.

MDT discussion of management plan is mandatory.

Compliance with NICE guidance is essential unless contra-indicated for clinical reasons.

Specific information about the regimens referred to below can befound on the ASWCS website athttp://www.aswcs.nhs.uk/pharmacy/ChemoHandbook/HCP/index.htm.

Follicular lymphoma (FL)

Re-treat with Chlorambucil Prednisolone if duration of firstresponse >1 year.

Otherwise Fludarabine is commonly used 2nd line therapy

Other options include

COP

CVP

MCP

MCD

CHOP

Fludarabine + Cyclophosphamide

FMD

Rituximab therapy should be reserved for those who are eitherchemo-resistant or chemo-intolerant in accordance with NICEguidance (technology appraisal guidance #37, published March2002).

Any use of Rituxumab outside NICE guidance should be discussed

with the local MDT and a specific source of funding identified beforetreatment is initiated.


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Chronic lymphocytic leukaemia / lymphocytic lymphoma (CLL/LL)


Otherwise Fludarabine is commonly used 2nd line therapy. Thiscomplies with NICE guidance (technology appraisal guidance #29,

published September 2001).


COP

CVP

MCP

MCD

CHOP


FMD

Any use of Campath-1H (MabCampath) should be used inaccordance with the guidelines produced by the British Committeefor Standards in Haematology (www.bcshguidelines.com) anddiscussed with the local MDT. A specific source of fundingidentified before treatment is initiated.

Waldenstrms macrogolbulinaemia (WM)

Lymphoplasmacytic lymphoma (LPL)

Splenic MZL / Splenic Lymphoma with Villous Lymphocytes (SLVL)

Primary nodal Marginal Zone Lymphoma (monocytoid B celllymphoma)


Otherwise Fludarabine is commonly used 2nd line therapy


COP

CVP

MCP

MCD

CHOP


FMD

Any use of Rituxumab should be discussed with the local MDT anda specific source of funding identified before treatment is initiated.


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Extra-nodal marginal zone (MALT-type) lymphoma (ENMZL)

Gastric MZL

Options include:

Chlorambucil

CHOP

Non-gastric MZL

for disseminated disease - treat as per follicular NHL

for large cell transformation treat as per DLBCL

Hairy cell leukaemia (HCL)

Consider (re)treatment with either/or:

2-Chlorodeoxyadenosine (Cladrabine)

Deoxycoformycin (Pentostatin)

3rd or 4th line therapy includes:

Interferon-

Splenectomy

Mantle cell lymphoma (MCL)


COP

CVP

MCP

MCD

CHOP


FMD

For younger patients, HyerCVAD Rituximab or Fludarabine +

Cyclophosphamide Rituximab followed by autologous stem celltransplantation (auto-SCT) or reduced intensity allogeneic stem celltransplantation (RIC-allo-SCT) should be considered.

Any use of Rituxumab should be discussed with the local MDT anda specific source of funding identified before treatment is initiated.

Prolymphocytic leukaemia (PLL)

Options for patients with progressive PLL are limited and need tobe discussed at the local MDT.


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Diffuse large B cell lymphoma (DLBCL)

Relapse following 1st line radiotherapy R-CHOP x 6-8

Primary refractory disease or relapse

attempt remission re-induction with one or more of the

following choices:

DHAP

ESHAP

FluDAP

IVE

Mini-BEAM

patients with responsive disease should be consolidated

with a BEAM-conditioned auto-SCT

patients resistant to one or more of the conventionalsalvage regimens may still benefit from BEAM-conditionedauto-SCT

patients relapsing after all of the above, and who are stillcandidates for treatment, a reduced intensity allo-SCTshould be considered

palliative regimens include:

COP

CVP

MCP

MCD

Cockle

Burkitt, Burkitt-type or lymphoblastic B cell lymphoma

There is no consensus as to how these patients are best treated.

Outcome would be expected to be very poor.

Treatment should be decided at MDT.

Allo-SCT may be considered for young patients after effectiveremission reinduction.

Classical Hodgkins lymphoma (cHL)

Relapse following 1st line radiotherapy or VAPEC-B chemotherapy+ radiotherapy

ABVD x 6-8


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Primary refractory disease or relapse

attempt remission re-induction with one or more of thefollowing choices:

DHAP

ESHAP

FluDAP

IVE

Mini-BEAM

patients with responsive disease should be consolidatedwith a BEAM-conditioned auto-SCT

patients resistant to one or more of the conventionalsalvage regimens may still benefit from BEAM-conditioned

auto-SCT

patients relapsing after all of the above, and who are stillcandidates for treatment, a reduced intensity allo-SCTshould be considered

Nodular lymphocyte-predominant Hodgkins lymphoma (nLPHL)

If relapse outside initial radiotherapy field, treat with IF-RT.

For relapse within initial radiotherapy field treat with R-CHOP x 6-8.

Peripheral T cell lymphoma (PTCL) These patients should be treated with a non-cross-reacting regimen

e.g. IVE, ESHAP/DHAP followed by high-dose chemotherapy withautologous SCT or reduced intensity allo-SCT.

Alternatively palliative therapy should be offered, if appropriate.

Lymphoblastic T cell lymphoma

If not already attempted, these patients should received remissionreinduction therapy and would be suitable for allo-SCT (or auto-SCT in the absence of a suitable donor).

Where SCT is unsuitable, palliative therapy only should be offered.

Anaplastic large cell lymphoma (ALCL) t(2;5) and / or ALK +ve

These patients should be treated with a non-cross-reacting regimene.g. IVE, ESHAP/DHAP followed by high-dose chemotherapy withautologous SCT or reduced intensity allo-SCT.

Alternatively palliative therapy might be offered, if appropriate.


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4.3 Clinical Guidelines on Myeloma

This document is written to facilitate a standard approach to the management ofsuspected and proven myeloma across the ASWCS network. It is anticipated thatit will provide minimal acceptable standards for management of such patients.

This document is necessary to allow compliance with the Department of HealthCancer Services Peer Review measure 1C-126. The ASWCS network acceptsthe National Guidelines on the Clinical Management of Myeloma (Reference UKMyeloma and Nordic Myeloma Study Group: Guidelines on the Diagnosis andManagement of Multiple Myeloma on behalf of the British Committee forStandards in Haematology).

This document is principally aimed at health care professionals involved in thecare of patients with myeloma

General Practitioners


Consultant Medical and Clinical Oncologists

Consultants in Radiotherapy

Specialist Registrars in Haematology and Oncology


Haematology Nursing Staff

4.3.1 Introduction

Myeloma is a plasma cell tumour, with an annual incidence in the United

Kingdom of approximately 50 per million population. The median age atpresentation is about 70 years. Most cases present de novo, a minoritywill evolve from a Monoclonal Gammopathy of Undetermined Significance.(MGUS).

Approximately 15% of patients will present at less than 60 years and afurther 15% between 60 and 65 years. 2% or less of myeloma patients areunder 40 years at diagnosis. Younger patients may be eligible for specifictypes of treatment such as high dose therapy and stem celltransplantation. The majority of patients with myeloma will be treated withoral chemotherapy.

4.3.2 Facilities and expertise required for management of myeloma

patients

A Consultant Haematologist should lead the care of patients withmyeloma, there also needs to be input from a range of other professionalsfamiliar with the range of problems likely to encountered. This should bedelivered within a multi-disciplinary team, within an approved CancerNetwork.

Effective and high quality care in myeloma requires the availability ofother specialist expertise and services, including those of renalsupport and intensive care. These services may be available locally,or at a neighbouring hospital.


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Where therapy involves autologous stem cell transplantation thismust be delivered in a Level 3 setting (BCSH 1995).

4.3.3 Criteria for referral of a patient with suspected myeloma

The clinical presentation is varied. Common presentations include bonepain, recurrent or persistent infection, anaemia, renal impairment, or a

combination of these. Some patients are asymptomatic.

4.3.4 Presenting features which require urgent specialist referral

Bone Destruction Symptoms

persistent backache associated with loss of height andosteoporosis

symptoms suggestive of spinal cord/nerve root compression

Compromised Immunity and /or bone marrow function

recurrent bacterial infections

anaemia (usually normochromic)

leucopenia and/or thrombocytopenia

Persistently elevated ESR or plasma viscosity

Impaired renal function

Hypercalcaemia

4.3.5 Investigations available in primary care for a case of suspectedmyeloma should include:

ESR or plasma viscosity

Full blood count

Serum urea, electrolytes and creatinine

Serum calcium

Serum immunoglobulins

Serum electrophoresis to confirm and type any paraprotein present

Urine analysis for Bence Jones Protein (free light chains)

Standard x-ray imaging of bones, particularly the axial skeleton

Patients presenting to primary care physicians with these criteria should bereferred to their local Haematology team via the network 2 week waitsuspected malignancy pathway.

4.3.6 Initial Specialist Assessment

Further assessment and investigations should be co-ordinated by aConsultant Haematologist. Initial specialist assessment should include, fullblood count, plasma viscosity, electrolyte and creatinine, serum calcium,serum albumin and uric acid. In addition electrophoresis of serum andconcentrated urine, followed by immunofixation to confirm and type anyparaprotein present. Quantification of serum paraprotein and/or urinarylight chain load should be undertaken.


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In addition, quantification of non-isotypic serum immunoglobulins shouldbe performed.

Standard x-rays of the skeleton should be performed, to include cervical,thoracic and lumbar spine, skull, chest, pelvis, humerus and femora.Magnetic Resonance Imaging is indicated for patients with suspectedspinal cord compression.

A bone marrow aspirate and trephine biopsy should be performed, and inyounger patients, (less than 65 years), cytogenetic analysis performed.Collection of other prognostic information may be indicated in younger

patients such as 2 microglobulin, lactate dehydrogenase (LDH) and C-reactive protein.

A summary of these findings should be discussed at a multi-disciplinaryteam meeting.

4.3.7 Confirmation of diagnosis of myeloma

The confirmation of a diagnosis of myeloma is achieved by demonstration

of a protein in serum or urine and/or lytic lesions on x-ray, together with aplasmacytosis of over 10% in bone marrow. Accepted criteria fordistinguishing myeloma and MGUS are available. Guidelines on theDiagnosis and Management of Multiple Myeloma: UK Myeloma Forum andNordic Study Group.

Patients should be presented to an MDT meeting and an initialmanagement plan established and documented.

Monitoring of myeloma related organ or tissue impairment according to theInternational Myeloma Working Group 2003 should be undertaken.

4.3.8 Indications for Starting Therapy

(Please refer to National Guideline Document)

Chemotherapy is indicated for the management of symptomatic myelomaand asymptomatic myeloma with myeloma related organ damage.Chemotherapy is not indicated for patients with MGUS, or those withequivocal /indolent or smouldering myeloma. Patients with no symptoms,normal haemoglobin, calcium and renal function may remain stable for along period without treatment. The decision to proceed to chemotherapyshould be documented at an MDT meeting.

Treatment should be delayed in this patient group until there are signs ofprogression. Three monthly monitoring with examination, measurement ofserum and urinary paraprotein, together with full blood count and renalfunction assessment is thereafter indicated.

4.3.9 Chemotherapy of Myeloma patients

There are many regimes of chemotherapy available for use in thetreatment of myeloma. The network has protocols for both oral andintravenous chemotherapy regimes. Please refer to the ASWCSchemotherapy protocols for regimes used for the treatment of myeloma.Please also refer to the National Guideline document for guidance as towhich chemotherapy regime to be used in specific patient groups.


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4.3.10 General management of myeloma patients

Optimal general management is fundamental. Patients should be informedabout the condition, its potential complications and the importance ofsupportive measures.

4.3.11 Management of specific complications of myeloma

Anaemia

A therapeutic trial of EPO should be considered in patients withsymptomatic anaemia. EPO is indicated for the treatment ofanaemia in patients with myeloma and chronic renal failure. Redcell support is indicated for patients with non-EPO responseanaemia

Bisphosphonate therapy

Long-term bisphosphonate therapy is recommended for all patientswith myeloma, whether or not bone lesions are evident.(Guidelines for use of Bisphosphonate therapy in myeloma patients- updated 2003 UKMF guideline on behalf of British Committeefor Standards in Haematology). The choice of specificbisphosphonate will be directed by both patient and physicianpreference. Caution is required in moderate to severe renal failure.

Management of patients with renal failure

Management of patients with myeloma and chronic renal failurerequires clear communication between the Haematology/Oncologyteam and Specialist Renal team. Patients presenting with acuterenal failure should be referred to a Specialist Renal Unit. Dialysis

should be offered to patients when appropriate for the managementof renal failure. Specific considerations apply to chemotherapyoptions suitable for patients with renal impairment. (See Networkprotocols).

Plasma exchange

Plasma exchange maybe considered in cases presenting withsymptomatic hyperviscosity. Patients presenting with renal failureshould be considered for entry into the MERIT trial.

Treatment of infection in myeloma patients

(Please refer to National Guideline document).

Bone pain

NSAIDs should be avoided because of their adverse effects onrenal blood flow. Opiates should be used with caution.Radiotherapy should be considered for local management of bonepain. Please also refer to the National guideline document for theextended options available for the management of bone pain

4.3.12 Patient information and support

All patients and their families should be lead to understand that although

treatment for myeloma is not curative, it will relieve symptoms and prolongsurvival and increase quality of life. Patients should be offered written


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CVP

Dexa-BEAM

FAD

Fludaradine (single agent)

Fludaradine and Cyclophosphamide

FMD

MCP

MCD

Rituximab (single agent)

5.2 Hairy Cell Leukaemia

2-Chlorodeoxyadenosine (Cladribine, Leustat)

Interferon

Pentostatin (Deoxycofromycin, Nipent)

5.3 Mantle Cell Lymphoma

CHOP

Hyper-CVAD/MA

Rituximab / Cyclophosphamide + Fludarabine

5.4 Aggressive Non-Hodgkins Lymphoma

CHOP

CHOP & Rituximab

PMitCEBO

5.5 Very Aggressive Non-Hodgkins Lymphoma

CODOX-M/IVAC

5.6 Hodgkins Disease

ABVD

CHIVPP

ChIVPP/PABIOE

PABIOE

Stanford V

VAPEC-B

5.7 Hodgkins Disease / aggressive NHL Salvage

Cockle (Oral Palliative) Regimen

DHAP


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ESHAP

FLuDAP

Gemcitabine (Single Agent)

IVE

Mini-BEAM

5.8 Stem Cell Transplantation

BEAM

Busulphan + cyclophosphamide

Cyclophosphamide PBSC Mobilisation

Cyclophosphamide +TBI

G-CSF only PBSC Mobilisation

High-dose Melphalan

LACE

5.9 Myeloma

ABCM

C-VAMP

CIDEX

Cyclophosphamide Weekly

High Dose Dexamethasone

Intermediate Dose Melphalan

Melphalan +/- Prednisolone

Thalidomide +/- pulsed Dexamethasone

VAD

VAMP

Z-DEX

5.10 Chronic Myeloid Leukaemia

Busulphan

Hydroxyurea

Imatinib Mesylate (Glivec)

Interferon


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6 Follow up

This will be taking forward during 2006.

7 Patient Involvement and Information

The ASWCS network is committed to the development of a patient centred care. With thisin mind the ASWCS User Involvement Group has produced a series of policy documentsaiming to contribute to improved patient and carer experience.

7.1 Principles of Effective Patient Involvement and Information

The following summarises the level of service that people affected by cancershould expect. This is based on the service model of the NICE Supportive andPalliative Care Guidance.

People affected by cancer should be involved in decisions about their care andtreatment. They should always be able to express their views or worries abouttheir treatment and care.

People affected by cancer can expect their health team to communicate clearlywith them. They should feel confident that the doctors, nurses and other healthstaff caring for them are honest and sensitive when talking to them, and explainthings in a way they understand.

People affected by cancer should be told where they can get help and advice. Thename and contact details of a key worker should be given to them so that they canget in touch if they need any information or advice.

People affected by cancer should be offered as much information as they want.Clinical Nurse Specialists have an important role to play in explaining the clinicalcare and treatment, while the information specialists at the Information andSupport Centres (where available) can provide information about the impact ofliving with Cancer.

Health professionals looking after service users should be aware that your needsare not only physical and medical. They should ask you about the kind of practicaland social support they may need as well and put them in touch with people andlocal organisations who can help.

Health staff should be aware that some people want emotional and spiritualsupport, and help them to find it - if that is what they want.

Service users should also be offered help living with the effects of cancer and its

treatment.Health and social care staff should ensure that families and friends are askedabout their needs, particularly at crucial times such as diagnosis or bereavement,and get all the emotional and practical support they need.

People affected by cancer should expect a speedy response at times of greatestneed.

Preferences about where and how someone wants die should be respected.

People affected by cancer should be offered an opportunity to get involved inmaking cancer services better; for example by being put in touch with the ASWCSUser Involvement Group


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Patients should have an opportunity to review what has been said duringthe consultation and also ask further questions.

Breaking Bad News Training should be made available to all staff whohave contact with cancer patients.

7.3 Holistic Needs Assessment Guidance

The Measure 1E-502 of the Manual of National Cancer Measures (2004),stipulates that the Network Partnership Group should develop a Holistic NeedsAssessment Guidance addressing the needs of people affected by cancer. Theterms holistic includes a number of different needs- physical, psychological, social,spiritual information and carers needs.

A Network Workshop was held in Bath in November 2004 which was attended bya wide range of health care professionals, the voluntary sector, service users andcarers. During the course of the Workshop all participants were asked to considerwhat they perceived to be essential core components of an holistic needsassessment at the following key points during the patient pathway:

Pre Diagnosis including GP referral

Diagnosis

Treatment

Post treatment or living with cancer

End of Life

The Network Holistic Needs Assessment Framework aims to give prompts forneeds that should be assessed throughout the cancer journey. This could beeither user led, focusing on health and well-being, or professionally led. The

workshop participants were in agreement that local solutions could be foundproviding that all the core principles as detailed in the guidance were met and thatinformation was easily transferable should users move around the Network andduplication of assessment did not take place.

The full guidance is available online athttp://www.aswcs.nhs.uk/supportivecare/holistic.htm

Agreed by:

Signed: ---------------------------------------------------------------------- Date-------------------Mr Mark Gritten, Chair, ASWCS Board

Signed: ---------------------------------------------------------------------- Date-------------------Mr Chris Knechtli, Chair, ASWCS Haematology SSG


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Mary Barnes, ASWCS DirectorDecember 2005