Allogeneic Stem Cell Transplantation For Multiple Myeloma: A Two Step Approach To Reduce Toxicity Involving High Dose Melphalan and Autologous Stem Cell Transplant Followed By PBSC Allografting After Low Dose TBI

PRIMARY OBJECTIVES: I. To evaluate engraftment of human leukocyte antigen (HLA) identical peripheral blood stem cell (PBSC) allografts given after conditioning with total-body irradiation (TBI) (200 cGy) and post-grafting immunosuppression with cyclosporine (CSP)/mycophenolate mofetil (MMF) in myeloma patients initially cytoreduced with high-dose melphalan. II. To evaluate non-relapse mortality at day 100 post allografting. III. To evaluate the efficacy of this allografting strategy in terms of long-term progression free survival (PFS). OUTLINE: CONDITIONING REGIMEN: Patients receive high-dose melphalan intravenously (IV) over 15-20 minutes on day -2. TRANSPLANTATION: Patients undergo autologous bone marrow or PBSC transplantation (PBSCT) on day 0. NON-MYELOABLATIVE CONDITIONING REGIMEN: Beginning 40-120 days after autologous transplant, patients undergo TBI on day 0. TRANSPLANTATION: Patients undergo donor PBSCT on day 0. IMMUNOSUPPRESSION: Patients receive cyclosporine IV twice daily (BID) on days -1 and 0 and orally (PO) BID on days 1-80 with taper based on evaluation of disease response and graft-versus-host disease (GVHD). Patients also receive mycophenolate mofetil PO BID on days 0-27. POST-TRANSPLANTATION DONOR LYMPHOCYTE INFUSION (DLI): Beginning 4 weeks after immunosuppression, patients achieving persistent or progressive disease may undergo DLI over 30 minutes every 4 weeks for up to 3 treatments. After completion of study treatment, patients are followed up for 3 years.