Non-Hodgkin’s Lymphoma5th ASH Refresher Course

Tanin Intragumtornchai, M.D.

Special Problems in B-Cell Lymphomas

• Burkitt lymphoma in adultsPerkins AS, Friedberg JW, Rochestor U, NY

• Primary mediastinal B-cell lymphomaJohnson PWM, Davies AJ, U Southampton, UK

• Marginal zone lymphomasKahl 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/IVAC 71% 39%

• ALL-like 51% 40%

• Hyper-CVAD 57% 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 37 years

• Stage I/II 74%

• Elevated LDH 77%

• 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 3rd 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 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 PTCLKerry 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