Chemotherapy and Peripheral Stem Cell Transplantation in Treating Patients With Multiple Myeloma

OBJECTIVES: * Determine the incidence of early mortality in patients with multiple myeloma treated with melphalan and autologous peripheral blood stem cell (PBSC) transplantation followed by fludarabine, cyclophosphamide, and allogeneic PBSC transplantation. * Determine the incidence of early allogeneic graft failure (before day 100 after allogeneic PBSC transplantation) and the incidence of severe acute graft-versus-host disease (GVHD) in patients treated with this regimen. * Determine the toxicity of this regimen in these patients. * Determine the overall and disease-free survival of patients treated with this regimen. * Correlate changes in the T-cell population with clinical outcome, such as survival, in patients treated with this regimen. * Correlate changes in the T-cell population with the incidence of GVHD, use of immunosuppressive agents, and effects of fludarabine in patients treated with this regimen. * Determine the degree of chimerism after allogeneic PBSC transplantation and the time course over which it is established in patients treated with this regimen. OUTLINE: This is a multicenter study. Patients receive melphalan IV over 15 minutes on day -1. Autologous peripheral blood stem cells (PBSCs) are reinfused on day 0. Patients also receive sargramostim (GM-CSF) subcutaneously (SC) or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Beginning 100-182 days after autologous PBSC transplantation, patients receive fludarabine IV over 30 minutes on days -6 to -2 and cyclophosphamide IV over 1-2 hours on days -3 and -2. Allogeneic PBSCs are infused on day 0. Patients may receive a second allogeneic PBSC infusion on day 1. Patients also receive GM-CSF SC or IV over at least 30 minutes daily beginning on day 1 and continuing until blood counts recover. Cyclosporine is administered IV or orally twice daily as graft-versus-host disease (GVHD) prophylaxis, beginning on day -1 and continuing until day 60, followed by a taper in the absence of GVHD. Patients are followed for 5 years. PROJECTED ACCRUAL: A total 19-46 patients will be accrued for this study within 3 years.