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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.

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

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.

 

  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.

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.

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.

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

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.

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.

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