In Project 11 a series of studies are proposed to decrease the probability of relapse and to decrease transplant-related morbidity and mortality with the ultimate goal of improving survival in patients receiving autologous marrow transplants (AMT) for hematologic malignancies. In Project 11A we will evaluate AMT in patients with acute lymphoblastic leukemia (ALL) and malignant lymphoma (ML). For patients with advanced ML and ALL the potential effects of IL-2/LAK cell therapy on posttransplant relapses will be evaluated in conjunction with research outlined in Project 9. For patients with less advanced ML a regimen to total body irradiation (TBI), VP-16 and cyclophosphamide (CY) will be compared to a previous series of patients treated with CY (120 mg/kg) and TBI (12.0 Gy). Studies of recombinant growth factors and peripheral blood progenitor cells (PBPC) will be carried out in patients with ALL and ML in order to improve engraftment and decrease transplant-related morbidity and mortality (Project 8). In patients with ML receiving a regimen of CY, BCNU and VP16, attempts will be made to evaluate the effects of anti-inflammatory agents on regimen-related toxicity and engraftment (Project 8). In Project 11B we propose to participate in a national study through the Southwest Oncology Group (SWOG) involving timing of AMT. Patients without marrow donors will be randomized to AMT versus chemotherapy consolidation in first remission. In patients with AML not entered on the SWOG study, we propose to determine the maximum tolerated plasma level of busulphan (MTCssBU) that can be achieved through adjusting the doses to achieve a specific plasma target level. The effectiveness of treating patients with AML at the MTCssBU, cyclophosphamide (60 mg/kg) and TBI (12.0 Gy) will be determined with a Phase 2 trial. The effects of recombinant growth factors and PBPC augmentation on engraftment and transplant-related morbidity and mortality will also be carried out (Project 8). In Project 11C the toxicity and potential efficiency of bone seeking isotopes given in conjunction with BU & CY followed by AMT will be evaluated in patients with multiple myeloma.
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