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

• CODOX-M/IVAC • ALL-like • Hyper-CVAD All cases 71% > 40 yrs 39% 51% 57% 40% 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 age • Stage I/II • Elevated LDH • Bulk (>10 cm) • Pleural or pericardial effusion 37 74% years 77% 75% 50%

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 < 12 g/dl, serum albumin < 3.5 g/dl and LDH > 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 eradication

H. pylori

• 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