The acquired immune deficiency syndrome (AIDS) is caused by the HIV-1 retrovirus, which significantly impairs the function of the human immune system causing immunocompromise and susceptibility to opportunistic infections (OI). The loss of immune function in AIDS gives rise to an increased propensity to develop lymphoid neoplasia, particularly high grade B cell non-Hodgkin's lymphomas (NHL-B). Development of NHL-B was observed early in the AIDS epidemic, but the number of AIDS-related lymphomas (ARL) has risen sharply in the last few years, possibly due in part to better therapy with drugs such as AZT, with the incidence approaching 10% of AIDS cases in some areas of the US. ARL have proven extremely difficult to treat, due not only to the aggressive biological nature of the lymphoma cells, but also due to the immunocompromised state of the patients often precluding treatment with the aggressive chemotherapeutic regimens used to treat this type of lymphomas. This proposal will launch a multidisciplinary study group, the Houston AIDS Lymphoma Study Group (HALSG), consisting of experienced clinicians involved in the treatment of AIDS and AIDS-relater lymphoma, pathologists involved in ARL diagnosis, and basic scientists with interests and expertise in pertinent areas of immunology, molecular biology, and genetics. This interdisciplinary group will meld new approaches to the clinical treatment of ARL with laboratory studies, designed to better define and characterize the biological and genetic nature of the ARL. A new treatment protocol for ARL is presented that addresses the need for less aggressive therapy in severely immunocompromised patients, in concert with immunorestorative treatment with the biological response modifier, Thymosin, to increase T cell responses in AIDS patients. Patients with a lesser immune deficit will be treated with more standard chemotherapy, which has provided promising preliminary results in such patients. All patients will be maintained on AZT to retard the progression of HIV disease. These clinical studies will be integrated with laboratory studies to delineate the possible role of a variety of immune parameters and the aberrant expression of certain proto- oncogenes such as c-nyc and p53, that may have clinical significance in ARL cells. Cytogenetic studies, using both classical and the newer techniques will be used to identify non-random chromosomal abnormalities observed in ARL, and their possible involvement with oncogene expression.
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