This project requests support to study the clinical therapeutic role of bone marrow transplantation (BMT) in combination with antiviral chemotherapy in the treatment of patients with HIV-1 associated lymphoma. Patients will be treated with chemo-irradiation therapy in preparation of the transplant to destroy the host's tumor cells and to eradicate the host's hematopoietic-lymphoid-monocyte cellular reservoir containing HIV-1. Anti-retroviral therapy will be administered to retard the infection of the transplanted donor cells. BMT is an effective and curative therapy for patients with poor prognostic lymphomas. HIV-1 infection is associated with a high risk for developing lymphoma for which conventional chemotherapy results are less than optimal. In addition, HIV-1 results in an immune deficiency by the infection of CD4+ cells of bone marrow origin including T-cell lymphocytes, monocyte- macrophages, alveolar macrophages, Langerhans dendritic cells, and microglial cells of the central nervous system. The chemotherapy and whole body irradiation given to destroy lymphoma cells has the dual advantage of also destroying the hematopoietic-lymphoid-monocyte reservoir for HIV-1. In order to prevent the HIV-1 infection of infused donor cells, anti- retroviral chemotherapy will be co-administered during the transplantation process. Experimental design and methods will be used to perform allogeneic- syngeneic BMT in selected groups of patients with HIV-1 associated lymphoma. Patients will be treated with marrow and tumor ablative therapy consisting of cyclophosphamide and total body irradiation prior to the marrow transplant, and are to receive azidothymidine before, during and after the procedure. HIV-1 will be quantitatively monitored for by culture of plasma, peripheral blood mononuclear cells and bone marrow; and by PCR gene amplification for HIV-1 sequences. Immune reconstitution studies, adoptive immune transfer and cytotoxic lymphocyte responses will be monitored.
