High-grade B cell non-Hodgkin's lymphoma (NHL) is a frequent complication of human immunodeficiency virus (HIV) infection. The mechanisms by which these lymphomas occur is unknown. Hypotheses include: a role for Epstein- Barr virus; chromosomal translocations leading to altered expression of the c-myc oncogene; and indirect effects of HIV through alteration of T cell surveillance. The dramatic growth rate, myelosuppression, opportunistic infections, have made treatment extremely difficult.
The specific aims of this project are to: 1) Develop a collaborative team of basic and clinical researchers to develop treatment for HIV-associated NHL; 2) Develop and provide clinical trials for initial and relapse therapy for lymphoma patients tailored to the challenge of concurrent control of HIV infection; 3) Collect tumor tissue and blood to determine direct and indirect effects of HIV on B cell proliferation, temporal changes in the molecular characteristics of the tumor before, during and after chemotherapy, and the changes in quantitation of HIV during therapy; and 4) Develop experimental therapies that may provide new insights into the basic biology and pathogenesis of HIV-associated NHL. Twenty patients with HIV associated NHL were seen in 1990 at UC San Diego, a number which is likely to increase. These patients will be recruited to participate in a treatment registry with standardized data collection to characterize demographic information, past medical history, HIV risk behaviors, prior HIV complications, prior treatment with anti-retroviral and other drugs, lymphocyte subsets, p24 antigen in addition to staging. Newly diagnosed patients will be offered treatment with cyclophosphamide, adriamycin, vincristine, prednisone, and etoposide (CHOPE) with zidovudine to reduce HIV load, and rhG-CSF with rhEPO to attenuate bone marrow toxicity. Three experimental phase I monoclonal antibody (MoAb) therapies will be offered to relapsed patients: cross reactive idiotypes, transferrin receptor, and pan-B mouse/human chimeric. Therapy outcome assessment will begin, in vitro, with tumor response, changes in the molecular biology of the tumor, and changes in HIV load. At a clinical level the effects of chemotherapy, including toxicity, infections, and survival will be characterized. To summarize the impact of a treatment on survival, functioning, symptoms, utility, and prognosis we will systematically assess quality of life with a structured interview. Molecular biology, virology, and immunology have identified promising experimental therapies for HIV associated NHL. Collaboration between basic and clinical science offers hope of identifying new effective therapies.
