Despite dramatic advances in curative combination chemotherapy for newly diagnosed patients with aggressive non-Hodgkin's lymphomas, few patients with low-grade lymphomas or relapsed aggressive lymphomas of any type can be cured with conventional therapy. The primary objective of this project is to investigate the therapeutic utility of a new treatment modality, radiolabeled monoclonal antibodies, for treating patients with relapsed B- cell lymphomas. Preliminary Phase I and II trials conducted using maximally tolerated doses of I-131-labeled anti-B cell antibodies in conjunction with bone marrow rescue have demonstrated that 1) 2.5 mg/kg of I-131 -anti-CD20 (""""""""B1"""""""") antibody produces better biodistributions than other antibodies or doses studied so far; 2) the maximally tolerated dose of I-131-B1 delivers approximately 2700 cGy to normal organs; and 3) patients with tumor burdens >500 cc or massive splenomegaly generally have suboptimal antibody biodistributions. In the next funding period, we propose to optimize radiolabeled antibody therapy of B cell lymphomas by continuing long-term follow-up of patients treated with I-131-B1 antibody as a single agent (Aim 1), by investigating methods of improving cure rates by combining I-131-B1 with chemotherapy (Aims 2 and 3), by analyzing the effects of cytoreductive chemotherapy and splenectomy prior to radioimmunotherapy (Aim 4), and by testing other antibodies (e.g. anti- CD19) and radionuclides (e.g. Y-90) that might be superior to those currently employed (Aim 5).
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