Purpose and Rationale: This clinical protocol proposes to examine the safety of administering EBV-specific cytotoxic T lymphocytes (EBV-CTLs) in HIV seropositive patients with EBV associated B-cell non-Hodgkin's lymphoma who have refractory or relapsed disease after completing conventional chemotherapy. As a secondary endpoint, the antitumor effect of EBV-CTLs and the effect of therapy on immunologic and virologic status will be evaluated. Study Design: Eligible patients will undergo leukapheresis, and their peripheral blood mononuclear cells will be cryopreserved. Patients with a CD4 count greater than 200 and no prior AIDS defining illnesses will be treated with CHOP chemotherapy for AIDS related lymphoma. All other eligible patients will be treated with low dose m-BACOD. Following chemotherapy, patients will be evaluated every three months. If relapse of the lymphoma occurs or the lymphoma is refractory to chemotherapy, the patients will be treated with EBV-CTLs. EBV-CTLs will be generated in vitro and infused into the patient every 2-4 weeks for a total of 4. Study Procedures: Prior to study enrollment, patients must have tissue diagnosis of lymphoma with expression of EBV antigens. At the beginning of the study, patients will undergo leukapheresis. Venipuncture will be performed at each clinic visit, and 40-100 cc of blood will be collected per visit. Clinic visits typically occur biweekly to every six months. A second lymph node or tumor biopsy will be performed to confirm lymphoma recurrence prior to administration of EBV specific CTLs. Results: One HIV infected patient with EBV positive lymphoma has been treated. The patient's lymphoma progressed after 5 cycles of CHOP chemotherapy. Following leukapheresis, the patient received three doses of EBV-CTLs. The patient tolerated all doses without evidence of adverse toxicities. Clinical follow-up by Computed Tomography showed the established hepatic lesions to have decreased in size. Future Plans: This study will help determine the safety of administering activated T-lymphocytes in HIV infected patients. It will be necessary to treat more patients before we are able to evaluate the safety of this procedure. Additional plans are in progress to study novel methods for generating even more effective EBV-specific CTLs.
Showing the most recent 10 out of 128 publications
