Non-Hodgkin’s Lymphoma 5 th ASH Refresher Course Tanin Intragumtornchai, M.D.

Special Problems in B-Cell Lymphomas Burkitt lymphoma in adults Perkins AS, Friedberg JW, Rochestor U, NY Primary mediastinal B-cell lymphoma Johnson PWM, Davies AJ, U Southampton, UK Marginal zone lymphomas Kahl B, Yang D, U Wisconsin

Burkitt Lymphoma: Diagnostic Features High rate of proliferation (Ki-67 > 95%) Activation of MYC gene at 8q24 (Giemsa banding or FISH) Relative simplicity of karyotype No cleaves or folds in nuclear contour Lack of Tdt positivity

Key Clinical Features Bulky abdominal mass, B symptoms, laboratory evidence of tumor lysis 70% bone marrow involvement 40% leptomeningeal involvement

Treatment Intensive, short duration chemotherapy (high-dose alkylating agents, CNS prophylaxis) ALL-like regimen Therapy included consolidation with auto- SCT

OS According to Age All cases> 40 yrs CODOX-M/IVAC71%39% ALL-like51%40% Hyper-CVAD57%17% (> 60 yrs) 89% (rituximab- based)

Conclusion A highly curable malignancy Inferior outcome in patients age > 40 years Important to differentiate from “atypical Burkitt”

Primary Mediastinal B-Cell Lymphoma Median age37years Stage I/II74% Elevated LDH77% Bulk (>10 cm)75% Pleural or pericardial 50% effusion

Treatment Role of third generation regimen Role of rituximab Consolidating radiotherapy How to evaluate residual mass? Role of HDT

Role of Third Generation Regimen Three large retrospective (one population- based) studies showed superior OS for MACOP-B, VACOP-B compared to CHOP (70% vs 50%, p < 0.05)

Role of Rituximab Addition of rituximab to dose-adjusted EPOCH (n = 44) was associated with favorable EFS and OS (87% and 93%, p < 0.05) Retrospective population-based study did not showed superiority of R-CHOP over 3 rd generation regimen

Consolidating Radiotherapy Mediastinal radiotherapy is essential in patients achieving PR after initial chemotherapy (increased CR rate from 42% to 95%) Role in patients with CR is questionable in particular those treated with rituximab- based regimen

How to Evaluate Residual Mass? FDG-PET is the tool of choice All patients with positive PET relapsed compared to 26% in patients with negative PET Gallium scan is less expensive but time- consuming and low spatial resolution

Role of HDT No role in patients with first CR In chemosensitive relapse and refractory disease, the long-term OS were 40-70% and 50-60%, respectively

Nodal MZL Median age 60 years Male : female 1:1 Present in advanced stage with non-bulky widespread lymphadenopathy 1/3 had bone marrow involvement

Nodal MZL Clinical course resembled other nodal indolent lymphomas Prognosis less favourable compared to MALT, splenic MZL and FL. Roughly comparable to SLL. 16% transformed to large-cell in 4.5 years Apply same treatment approach as FL

Splenic MZL Present with moderate to massive splenomegaly Cytopenias due to splenic sequestration (main factor) and marrow involvement Best diagnostic tool is bone marrow examination Differentiate with HCL by showing negative staining to CD25 and CD103

Splenic MZL Splenectomy is the treatment of choice In asymptomatic patients using watch and wait policy, median time to treatment is 3 years Systemic chemotherapy (favored purine analogues) is indicated in patients contraindication to splenectomy or had heavy burden of disease outside spleen

Splenic MZL 5-year OS 76% Three adverse poor prognostic factors: hemoglobin ULN

Gastric MALT Lymphomas Comprised 30% of all MALT lymphomas Endoscopy showed erythema, erosions, ulceration. Masses are uncommon. Establish H. pylori status is essential (histologic examination, biopsy urease test, urea breath test, stool antigen test and selorogy). 90% of patients had H. pylori infection t(11;18) evaluation by FISH

Treatment 75% of stage IE patients with H. pylori infection and without t(11;18) will respond to H. pylori eradication Response is quite slow. Complete response is established in one year. Repeat endoscopy every 3-6 months until normalization of gastric mucosa then annually Routine biopsy of normal appearing mucosa is not recommended

Treatment Low-dose radiotherapy is indicated in patients with H-pylori negative or failure to H. pylori eradication (100% OS) Patients with advanced disease were treated with the same principle as patients with advanced stage FL

Non-gastric MALT Lymphomas Comprised 70% of all MALT lymphomas Association with infectious agents - B burgdorfi: cutaneous MALT lymphoma - C psittaci: conjunctival MALT lymphoma - C jejuni: IPSID Frequency of associations and role of antimicrobial therapy are still under investigations

Treatment Low-dose radiotherapy is the treatment of choice 5-year OS > 90% and 10-year OS > 80%

Peripheral T-Cell Lymphomas Prognosis and 1ry therapy in PTCL Kerry J Savage (BC Cancer Agency)

Addition of Etoposide to CHOP/CHOP- Like Regimen CHOEP vs CHOP : EFS 71% vs 50% (p =.01)(GNHLG) VIP/ABVD vs CHOP : no difference in OS and EFS (GOELAMS)

Subtype-Specific Therapies Cutaneous ALCL: local excision with or without radiotherapy ALK pos ALCL : CHOP Localized NK/T lymphoma, nasal type: - primary radiotherapy is the principal treatment. Chemotherapy provide additional benefit? - Initial RT vs initial CT : CR 83% vs 20% (Li et al, JCO 2006)

Conclusions Outcome is unsatisfactory with CHOP Therapies should be tailored according to the subtypes Large well-designed RCTs coorporating novel therapies are urgently needed.

WHO 2008 B-Cell Lymphomas (New Addition) Primary cutaneous follicle center cell lymphoma DLBCL, NOS - T-cell/histiocyte rich large B-cell lymphoma - Primary DLBCL of CNS - Primary cutaneous DLBCL, leg type DLBCL of chronic inflammation ALK-pos large B-cell lymphoma Plasmablastic lymphoma Large B-cell lymphoma associated with Castleman disease B-cell lymphoma, intermediate beteween DLBCL and BL B-cell lymphoma, intermediate beteween DLBCL and HL

WHO 2008 T-Cell Lymphomas (New Addition) Systemic EBV positive-T-cell lymphoproliferative diseases of childhood Hydroa vacciniiforme-like lymphoma Primary cutaneous CD30 positive T-cell lymphoproliferative disorders - lymphomatoid papulosis - primary cutaneous ALCL Primary cutaneous gamma-delta T-cell lymphoma ALCL, ALK pos

DLBCL of Chronic Inflammation Long standing chronic inflammation Associated with EBV infection Involve narrow space, body cavities Prototype : pyothorax-ass-lymphoma. Poor pg, 5-yr OS 25-30%

Hydroa Vacciniiforme-Like Lymphoma Children/adolescence of Asian, Native Americans, South Americans Associated with EBV Associated with insect bites, sun sensitivity

Lymphomatoid Papulosis Chronic relapsing papular, papulonecrotic and/or nodular skin lesions. Good prognosis