Prognostic Factors in the Treatment of Human Immunodeficiency Virus-Associated Non-Hodgkin’s Lymphoma

Abstract

Chemotherapy regimens similar to those used for non-Hodgkin’s lymphoma (NHL) not associated with human immunodeficiency virus (HIV) infection have been used for patients with HIV-associated NHL with less success. In a recent trial, patients with intermediate or high-grade NHL were randomized to either low-dose chemotherapy with methotrexate, bleomycin, doxorubicin, vincristine and dexamethasone (m-BACOD) or to standard-dose m-BACOD with sargramostim (granulocyte-macrophage colony-stimulating factor, GM-CSF). With low-dose m-BACOD 41% of patients achieved a complete remission and the median survival was 35 weeks. With standard-dose m-BA-COD and sargramostim, the percentage of complete remissions was 52% with a median survival of 31 weeks (P = n.s.). Myelosuppression was greater with standard-dose chemotherapy. In univariate and multivariate analyses of 21 pretreatment features of patients in this trial, four factors emerged as adversely prognostic with respect to survival: age >35 years, intravenous drug use, CD4 counts <100/mm³ and stage III/IV disease. In an analysis using the proportional hazards model, a “favorable” group was defined by patients with 0 or 1 adverse factor (median survival 46 weeks, survival at 144 weeks 29.5%) as compared with an unfavorable group with 3 or 4 adverse factors (median survival 18 weeks, survival at 144 weeks 0). The outcome of these patients may be improving with the use of highly active antiretroviral therapy (HAART), which seems to improve immune function and tolerance of chemotherapy. A recent trial of the AIDS Malignancy Consortium found that low-dose chemotherapy (cyclophosphamide, doxorubicin, vincristine and prednisone: CHOP) and standard-dose chemotherapy had similar respon.se rates, acceptable toxicity and minimal alterations in cyclophosphamide, doxorubicin and indinavir pharmacokinetics in HIV-associated lymphoma patients also on HAART (stavudine, lamivudine and indinavir). There is a suggestion that Burkitt-type lymphomas may tend to occur in HIV-infected patients with relatively well preserved immune function and CD4 cell counts. Recent results from our institution suggest that similar outcomes are achievable with intensive chemotherapy in patients with Burkitt’s lymphomas with or without HIV infection. With improved immune status and improved bone marrow function with the use of HAART, it will probably become more possible to treat many patients with aggressive HIV-associated NHL with more intensive treatment regimens.