The purpose of this proposal is to develop better treatment programs for patients with HIV-related lymphomas and to investigate the biology of these diseases. This will provide an opportunity to link basic biology questions to clinical correlates, and to utilize the information obtained from biologic studies to design rational therapeutic alternatives. These goals will be met by conducting clinical trials and correlative laboratory studies within a consortium of eight institutions, each of which has either clinical or basic science expertise in this area. The aims of the proposal will be 1) To determine the biologically active dose of the growth factor interleukin 3 (IL-3) in a Phase I trial in neutropenic HIV positive patients, and to asses its effect on p24 antigen expression. 2) To determine the optimal dose of IL-3, zidovudine and CHOP chemotherapy in patients with HIV-related lymphoma, and to carry out quality of life studies in patients so treated. 3) To study the effect of the novel cytotoxin IL-2/ diphtheria toxin (Seragen DAB486 IL-2) in patients with refractory or recurrent HIV-related lymphoma, and to carry out quality of life studies. 4) To study the biology of HIV-related lymphoma by a) determining DNA content, S phase and pl05 nuclear antigen expression; b) by isolating restricted idiotypes common to HIV-related lymphomas and utilizing these for therapy; c) by characterizing tissue samples for selected protooncogene or EBV sequences; d) by studying the effect of the HIV "tat" protein on transformation and tumorigenicity of cell lines derived from tissue samples and; e) by studying the mutagenic effect of zidovudine. 5) Finally we will establish a system of central pathology review and data base collection in order to conduct case control analyses for comparison to non HIV lymphomas. In this way we believe that the ultimate goal of improving therapeutic outcome for patients with these diseases will be met.