Mature Lymphoproliferative Diseases Flashcards
Broad classification of lymphomas
- Hodgkin’s lymphoma (9%)
- Non-Hodgkin’s lymphoma (90%)
- B cell lymphomas - DLBCL (agressive) and follicular lymphoma (indolent) make up 60% of NHL
- T cell lymphomas (10% of NHL)
Presentation lymphoma
- Lymphdenopathy
- Abdominal pain with bulky disease
- Systemic symtpoms -> weight loss (> 10%), fever, sweats (drenching night sweats)
- Abnormal blood findings uncommon compared to leukaemia
- Extranodal disease in 20%
**GI extranodal disease
**Stomach -> MALT and DLBCL
Duodenal -> follicular
Small intestine -> extranodal marginal
Sigmoid -> mantle cell
**Cutaneous manifestations
**Particularly T cell lymphomas and anaplastic large cell lymphoma
- Mycoses fungoides
Clinical classification of NHL
**Indolent/low grade NHL (incurable)
**Survival of untreated disease measured in years
Follicular, MALT, marginal
**Aggressive/intermediate NHL (> 50% cured)
**Survival untreated disease measured in months
DLBCL and peripheral T cell lymphoma
?Mantle cell
**Highly aggressive/High grade NHL (> 70% cured)
**Survival untreated disease measured in weeks
Burkitt’s. T lymphoblastic lymphoma
Initial work-up for lymphoma
Staging systems for lymphoma
**Ann Arbor
**Stage 1: Involvement of a single group of nodes
Stage 2: More than 1 group, but on same side of diaphragm
Stage 3: Crosses diaphragm
Stage 4: Diffuse extranodal invovlement
**Imaging recommendations for lymphoma staging
**PET-CT should be used for routine staging FDG-avid lymphomas
High sensitivity in HL and DLBCL -> most can be spared BMB
PET-CT recommended mid-treatment assessment in place of CT if clinically indicated and for remission assessment
Reporting:
1. No uptake
2. Uptake <= medistinum
3. Uptake > mediastinum but <= liver
4. Uptake moderately higher than liver
5. Uptake markedly higher than liver +/- new lesions
Notes on follicular lymphoma
- Most common indolent/low grade lymphoma
- Median age 60 years
- Bcl 2 (anti-apoptotic) over-expression, t(14;18)
- Expression of CD 19, CD 20 (B cell antigens) and CD 10 and BCL 2 and BCL 6
- No curative strategy - median survival 20 years
- Grades 1-3 a treat as indolent lymphoma, 3b treated as DLBCL (histoligical transformation approx 4% in first decade)
Initial therapy options for follicular lymphoma
- Watch and wait - appropriate in asymptomatic patients (median duration watch and wait 18 months)
- Rituximab or Obintuzumab + CVP (Cyclo, Vincristine, Prednisone)
- More appropriate in frail elderly and reduced EF. Not much alopecia or prolonged immunosuppression - Rituximab or orbintuzumab + CHOP (cYCLO, Adriamycin, Vincristine, Prednisone)
- More cytopaenia, alopecia, more immunesuppression - Rituximab or orbintuzumab + bendamustine
- Most immunosuppressive, prolonged CD4 cytopaenia. Doesn’t cause alopecia, or same degreee of neutropaenia as CHOP (until cycle 5/6). But generally immunosuppressed for up to 2 years after therapy. Avoid in over 70s
Rituximab and orbintuzumab = Anti-CD 20
Rituximab vs orbintuzumab
Rituximab MOA
- chimeric anti CD20
- Inhibition of cell proliferation, ADCC, complement activation, apoptosis
Orbintuzmab-chemo vs rituximab-chemo in indolent NHL -> better progerssion free survival. **No advantage DLCBL
Follicular lymphoma - options for relapsed disease
- Chemo + rituximab, then rituximab maintainence
- Add anthracycline if not used before
- Obintuzumab- Bendamustine
- SCT for younh: autologous vs allogeneic
**New agents
**PI3Kinase inhibitor (idelalisib) - PBS listed double refactory patients
Lenalidomide
CAR-T cell therapy - current clinical trials
Notes on MALT lymphoma
- Extra-nodal marginal zone B cell lymphoma of Mucosa Associated Lymphoid Tissue
- Up to 50% primary gastric lymphoma
- Freq. preceding history chronic inflammatory/autoimmune issues
1. H. pylori
2. Chlamydia psittaci in conjunctival MALT
3. Sjogren’s syndrome
4. Hashimoto thyroiditis - Majority localised disease
- Treatment gastric MALT -> H pylori erradication
- Second most common site is orbit -> treatment with local radiotherapy
Notes on mantle cell lymphoma
- Indolent or agressive. Poor 5YS, generally considered incurable
- 7% adult NHL
- Diagnosis required cyclin D1 nuclear expression, or t (11;14) on cytogenetics/FISH
- Atypical small lymphoid cells in mantle zones around normal germinal centres
- Pan-b cell antigens (CD 19, CD 20) plus CD 5
- Distinguished from CLL by abscence CD 23
**Presentation
**>70% advanced stage on presentation
75% males, 60s
30% B symptoms, extranodal disease 25%, splenomegaly
**Treatment
**Rituximab + chemotherapy
Agressive therapy in young e.g. R-DHAP x 4 + ASCT
Rituximab maintainence after transplant improves OS but not pBS funded
R-bendamustine x 6 in > 60s
Ibrutinib for relapsed disease
Notes on lymphoplasmacytic lymphoma (Waldenstron’s macroglobulinaemia)
- Neoplasma of B lymphocytes & plasma cells; BM, lymph nodes, spleen
- 60s, 70s
- Whole genome sequencing: mutations in MYD88. CXCR4 mutation in minority = inferior prognosis
- Serum monoclonal protein, IgM with hyperviscosity
- Paraprotein may have autoantibody or cyroglobulin activity
- Treatment often not needed for years - very indolent progression
- Hb < 100 indication for therapy
- Treatment - alkylating agents, pruine analogues, plus rituximab
- IgM MGUS (> 10% progress to LPL). Does not progress to myeloma.
- Ibrutinib in LPL - excellent response, not yet approved in ANZ
Notes on hairy cell leukaemia
- Neoplasm of small B lyphocytes, “hairy” cytoplasmic projections
- Rare: M:F 5:1
- Present with splenomegaly and pancytopaenia
- Immunophenotype; B cell antigens and CD11c, CD 25, CD 103
- TRAP positive on histology
- > 90% CR rate to 7 days cladarabine, remissions last for years
- Virtually all patients carry BRAF V600E mutation (activates MEK-ERK pathway - specific inhibitor Vemurafenib not available in Australia but often not required anyway
DLBCL epidemiology, features, pathology
- 30% adult NHL
- 90% of all aggressive lymphomas
- Peak incidence 60s
- Early stage in 30%, extranodal disease in 30% (CNS, gastric, prostate, breast, testis)
- B symptom 30%, BM involvement in 20%
- Curable with multi-agent immuno-chemotherapy in 60%
**Pathology
** Large transformed B cells with prominent nucleoli and basophilic cytoplasm
Loss of follicular architecture
Pan-B cell markers: CD 19, CD 20, CD 22, CD79a
Ki-67 - proliferation marker - 40-90%
Gene expression prolife separates good prognosis Germinal Centre B subtype from Activated b cell type disease
10% double hit lymphoma (myc+ and bcl2/bcl6 positive) on FISH -> very poor prognosis
Treatment DLBCL
Rituximab + CHOP every 3 weeks for 6 cycles
**Adverse effects
**Cytopaenias mid cycle day 7-11
- Febrile neutropaenia - use G-CSF to reduce incidence by 25%
- Alopecia
- Nausea, vomiting
- Vincristine - sensory neuropathy, constipation
- Cardiac toxicity - ECHO before therapy
- Steroid side effects
**Relapsed disease
**Options R-DHAP, R-ICE, R-GDP, chemosensitive disease may respond well to autologous SCT
Viruses and associated lymphomas
Hodgkin’s lymphoma - pathology, epidemiology, clinical features
- Reed Sternberg cells- vast majority derived from germinal centre or post germinal centre B cells but..
- Lose typical B cell antigens, express CD 15 and CD 30
- Pathogenesis unknown. Subtypes:
1. Nodular sclerosing
2. Mixed cellularity
3. Lymphocyte rich
4. Lymphocyte depleted
**Epidemiology/clinical features
**Bimodal age distribution - 2/3rd in 20s/30s
Typically localised at presentation
Preferentially invovles cervical nodes 75%, mediastinal involvement in 60%, systemic symptoms 40% - fevers, night sweats, weight loss
90% untreated die within 2 years, 80% cured with chemotherapy
Hodgkin’s lymphoma - pathology, epidemiology, clinical features
- Reed Sternberg cells- vast majority derived from germinal centre or post germinal centre B cells but..
- Lose typical B cell antigens, express CD 15 and CD 30
- Pathogenesis unknown. Subtypes:
1. Nodular sclerosing
2. Mixed cellularity
3. Lymphocyte rich
4. Lymphocyte depleted
**Epidemiology/clinical features
**Bimodal age distribution - 2/3rd in 20s/30s
Typically localised at presentation
Preferentially invovles cervical nodes 75%, mediastinal involvement in 60%, systemic symptoms 40% - fevers, night sweats, weight loss
90% untreated die within 2 years, 80% cured with chemotherapy
Hodgkin’s lymphoma - pathology, epidemiology, clinical features
- Reed Sternberg cells- vast majority derived from germinal centre or post germinal centre B cells but..
- Lose typical B cell antigens, express CD 15 and CD 30
- Pathogenesis unknown. Subtypes:
1. Nodular sclerosing
2. Mixed cellularity
3. Lymphocyte rich
4. Lymphocyte depleted
**Epidemiology/clinical features
**Bimodal age distribution - 2/3rd in 20s/30s
Typically localised at presentation
Preferentially invovles cervical nodes 75%, mediastinal involvement in 60%, systemic symptoms 40% - fevers, night sweats, weight loss
90% untreated die within 2 years, 80% cured with chemotherapy
