Indolent Lymphoma
Haematological Pathway
for
South Wales Cancer Network
Document Control Sheet
Organisation
Specialty/Project
Document Title
Document Number
South Wales Cancer Network
Haematological Site Specific Group
Indolent Lymphoma Haematological Pathway
05/017
Version
Author/s
1.0
Dr W Ingram
Approved by
South Wales Haematology
Cancer Network Group
Approval date
Ratified by
Dr W Ingram
Dr C Fegan
Date of next review
TBC
TBC
South Wales Haematology Network Guidelines on the
Diagnosis and Management of Indolent B-Cell Lymphomas
Aims and Scope
This guideline aims to cover general principles of the patient
pathway for indolent lymphomas in Wales.
The reader is directed to the excellent and comprehensive
guidelines from the British Committee for Standards in
Haematology (BCSH) for detailed guidelines on the management
of specific disease entities.
www.bcshguidelines.org.uk
There are current BCSH guidelines for:
 Follicular lymphoma
 Mantle Cell lymphoma
 Waldenstrom’s Macroglobulinaemia
 Hairy Cell Leukaemia
General Principles of Diagnosis and Staging
Where possible, excision lymph node biopsy is preferable to core
biopsy to ensure adequate tissue for diagnosis and to minimise
delays.
There should be agreed local pathways with surgeons to progress
to rapid surgical biopsy in cases where radiology core biopsy is
non-diagnostic.
All cases should be discussed at a haematology MDT meeting:
 At diagnosis and on completion of staging, to confirm
management plan and discuss any relevant clinical
trials
 At review of interim and post-treatment imaging, to
decide on appropriate management.
Histopathology procedures and standards
 Each MDT meeting should have at least one designated
Pathologist from the All Wales Lymphoma Panel (AWLP) who
will review material from all new lymphoma diagnoses.
 All lymphomas are to be reported according to the WHO
classification system and should include relevant prognostic
biomarkers where possible.
 For the majority of cases a preliminary source report should be
available within 5 working days of receiving the specimen and
an AWLP report should be available within 10 working days.
More
complex
cases,
and
those
requiring
extensive
immunohistochemistry and/or molecular analysis will take
longer
to
report.
Production
of
an
interim
report
recommended in such cases.
Staging and pre-treatment investigations
 Clinical history including any history of immunosuppression
 Documentation of presence or absence of systemic symptoms
 Clinical examination
 ECOG Performance status
is
 Calculation of relevant prognostic score where available eg
MIPI, FLIPI2
 FBC and blood film, liver and renal function, LDH, bone profile,
immunoglobulins,
beta-2
microglobulin
and
protein
electrophoresis
 HIV, HBsAg, HBcAb and HBsAb and Hep C Ab testing
 Contrast enhanced CT Neck/chest/abdomen/pelvis
 Bone marrow examination (aspirate and trephine)
 Immunophenotyping of peripheral blood or bone marrow or
lymph node biopsy material, when appropriate
 FDG-PET is of uncertain value in low grade lymphomas.
Routine use should be considered only in the setting of a
clinical trial
 In addition to staging the head and neck, MRI is the diagnostic
procedure of choice for rare patients with suspected disease in
the CNS disease including brain, leptomeninges and spinal cord
 An echocardiogram and ECG should be performed for all
patients being considered for anthracycline based therapy who
are over the age of 70 years or who have cardiac risk factors.
 Pregnancy testing in females of child bearing age prior to any
chemotherapy.
Fertility preservation
All men should be offered the option for sperm storage
All women of childbearing potential should be offered the option for
egg collection and storage prior to starting chemotherapy.
However, the following should be noted
1. CHOP based chemotherapy is unlikely to be sterilising
2. Egg collection will delay treatment starting by approximately
1 month
Patients who are unwell from their lymphoma are unlikely to get a
good egg harvest and should get on with treatment urgently
Information Required at MDT
 Clinical summary, ECOG performance status
 Final staging
 Named key worker
 WHO/ICD diagnostic code
Specific Disease Entities; special considerations
Follicular lymphoma
Covered in separate, detailed document
Mantle Cell Lymphoma
 In addition to routine staging tests, consider imaging of GI
tract, if there are gastrointestinal symptoms
 Similarly, while not recommended routinely, diagnostic
lumbar puncture should be considered in those with
symptoms suggestive of central nervous system (CNS)
disease
 Use of Rituximab containing regimes is recommended in
BCSH Guideline 2012, but there is no NICE guidance. Some
Health Boards are requiring IPFR application.
Recommended first line treatment
 Young/fit (under 65y): Nordic chemotherapy protocol
(alternating R-maxiCHOP/R-Cytarabine), followed by
consolidation with BEAM autograft.
 Older/less fit: Options include Fludarabine,
Cyclophosphamide, Rituximab (FCR), RCHOP for the fairly
fit, Chlorambucil +Rituximab (elderly,frail, comorbidities)
 Clinically indolent disease: A subset of patients, often those
with splenomegaly, but little nodal disease, appear to have a
clinically indolent course, and initial watch and wait may be
appropriate.
 Early stage disease, outside a clinical trial, consider
radiotherapy
Waldenstrom’s Macroglobulinaemia
Diagnosis, Staging and Monitoring
 To avoid difficulties of interpretation, sequential IgM
monitoring should be performed in a single laboratory using
a single methodology
 The value of SFLC ratio has not been established in WM,
and should not be used routinely
 Tissue biopsy is recommended in patients suspected of
histological transformation
 In patients with neuropathy, check anti-MAG antibodies
Treatment
 BCSH Guideline (2014) recommends that symptomatic
patients, requiring therapy, should receive a Rituximab
containing regime. Appropriate regimes include
dexamethasone, rituximab, cyclophosphamide (DRC),
bendamustine, rituximab (BR).
Fludarabine, rituximab (FR), fludarabine, cyclophosphamide,
rituximab (FCR) and cladribine,rituximab (clad-R).
As for Mantle Cell Lymphoma, in some Health Boards in
Wales, this will necessitate IPFR, there being no NICE
guidance in WM.
 Given the risk of IgM flare, careful monitoring of all
patients receiving Rituximab is required
 RCHOP should not be used as primary therapy in WM
 Chlorambucil remains suitable therapy in elderly, frail
patients
 Bortezomib is not recommended for 1st line therapy, outside
a clinical trial
IgM associated neuropathy
 Joint care with a Neurologist recommended
 Consider treatment (with a Rituximab containing regime) in
patients with rapidly progressive or disabling anti-MAG
neuropathy
Hyperviscosity Syndrome
 Plasma exchange:1-2 procedures, 1-1.5 plasma volume
recommended
Hairy Cell Leukaemia
Key points
 Purine analogues, cladribine or pentostatin are
recommended first line treatments
 Aim for complete remission, giving a second cycle of
cladribine or pentostatin if necessary
 Addition of Rituximab recommended for relapsed or
refractory disease
 Interferon alpha can be useful initial treatment in patients
with severe pancytopenia
 Hairy Cell Variant responds poorly to purine analogues, and
if treatment is required, splenectomy is probably the
treatment of choice, but there is inadequate data to make
firm recommendations.