HIV-Associated Lymphoma - New Treatments, June 19, 2003

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HIV-Associated Lymphoma

Beta-cell lymphoma occurs in between 5 and 10% of individuals with HIV infection. The incidence of lymphoma in this population has been rising and may reflect the prolongation of survival due to the use of effective antiretroviral therapy and infection prophylaxis.

Etiology is unknown. Unlike transplant-associated NHL, Epstein-Barr virus has not been shown to be associated with a majority of systemic lymphomas. However, EBV DNA is found in 100% of primary CNS lymphomas.

Other similarities exist with transplant-associated NHL. Polyclonal lymphomas have been

In vitro evidence suggests a role for interleukins 6 and 10 in pathogenesis. Inhibition of these cytokines results in growth inhibition in

Pathology

HIV-associated non-Hodgkin's lymphomas are virtually all of B-cell origin. Most are intermediate- or high-grade lymphomas categorized as large cell (60%) or small non-cleaved lymphomas (25%).

Systemic lymphomas present in individuals with a variety of levels of immune function (median approx 100/mm3). Seventy-five percent have CD4>50/mm3. Most present with

	Systemic	CNS	Primary Effusion
Histology	Large Cell (60%) SNC (30%)	Large Cell	Pleomorphic large cell
Clonality	Monoclonal polyclonal	Monoclonal	Monoclonal
EBV	Present in minority	Always present	Often present
HIV- 8	Absent	Absent	Present
Median CD4+	100	30	90
Survival (median)	6-8 months	3 months	5 months

Treatment

Treatment is frequently complicated by the occurrence of opportunistic infection and by the presence of poor bone marrow reserve both of which result in a decrease in the

Complete response occurs in 33-62%.

Relapse occurs in approximately 25% of complete responders usually within 6 months.

Reported median survival 4-8 months with about half dying of lymphoma and half of opportunistic infection. However, in recent series median survivals as long as 18 months reported.

Recently identified poor prognostic categories age >35 or 40, stage HI/IV, CD4 <100, IVDU and LDH associated with poor prognosis.

Approaches to therapy that have been used include reduced-dose chemotherapeutic regimens (low-dose mBACOD or CHOP) and the use of more standard dose regimens with the adjunctive use of hematopoietic growth factor (GM-CSF or G-CSF). Both colony stimulating feeders are effective means of reducing chemotherapy-associated myelosuppression

Low-dose mBACOD: In a non-randomized clinical trial this treatment regimen is associated with similar response and survival as has been observed with more standard treatment regimens but at the expense of

Aggressive Chemotherapy

Historically associated with higher risk of death due to opportunistic infection better tolerated in those with CD4+ >200/mm³

Unclear whether longer survival observed in one study (LNH-84) due to higher baseline CD4 alone or due to

Myeloid growth factors (G-CSF, GM-CSF) have been shown to reduce hematologic toxicity and its associated morbidity in

ACTG 142: multicenter prospective randomized trial of low-dose mBACOD vs. standard-dose mBACOD with GM-CSF support.

European intergroup study:

Patients with "intermediate" risk (ie, 1 poor prognostic factor)

110 patients randomized to CHOP or low-dose CHOP (50% reduction in

Meningeal prophylaxis (intrathecal MTX or cytosine arabinoside) clearly indicated for those with positive bone marrow, small noncleaved histology and those with paranasal or epidural involvement and perhaps for anyone with

Infusional cyclophosphamide, doxorubicin, etoposide (CDE) (Investigational)

Large phase II trial in progress (ECOG) results appear to be similar.L. Treatment recommendations: Systemic NHL

1. All patients with CD4<100/mm3: low-dose chemotherapy

2. CD4>100/mm3: consider standard-dose chemotherapy in

3. Antibiotic prophylaxis for P.carnii in all patients.

4. Meningeal prophylaxis for at least those with SNC histology, bone marrow

Primary central nervous system lymphoma in HIV infection

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