Lymphoma is a well known complication of HIV infection. Previous studies by this laboratory have identified several mechanisms of B cell activation in patients with HIV infection which may lead to lymphoma: 1) increased numbers of Epstein-Barr virus infected B cells; 2) T-cell dependent polyclonal B cell activation induced by HIV; and 3) antigen-specific B cell activation by HIV. We have recently observed that eight of 55 patients (14.5%) with AIDS or severe ARC entered onto three long-term phase I trials of azidothymidine (AZT) or AZT-containing regimens at the NCI between 1985 and 1987 developed a high-grade non-Hodgkin's lymphoma (NHL), B cell type after initiating antiretroviral treatment. The lymphomas developed a median of 23.8 months after the initiation of therapy. The estimated probability of developing lymphoma by 36 months was 46.4%. The patients who developed NHL had <100 T4 cells/mm(3) for a median of 17.8 months prior to that diagnosis. All patients presented with NHL in extranodal sites. Patients with symptomatic HIV infection who survive for up to three years on antiretroviral therapy may have a relatively high probability of developing lymphoma. As improved therapies for the treatment of HIV and its complications result in prolonged survival, NHL may become an increasingly significant problem. We are now exploring means of improving therapy in this disorder. In collaboration with Dwight Kaufman, M.D. in the Radiation Oncology Branch, we are conducting a trial of combination chemotherapy with AZT and GM-CSF. Preliminary results suggest that some patients may respond to this regimen but that toxicity can be a problem.
