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-BACOD 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 response 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.