melphalan and stem cell transplant before total-body irradiation and donor stem cell transplant in treating patients with stage i-iii multiple myeloma

Conditions: Refractory Multiple Myeloma; Stage I Multiple Myeloma; Stage II Multiple Myeloma; Stage III Multiple Myeloma

Summary: in this study donor bone marrow transplantation is divided into a two step process to try to significantly reduce the side effects of the procedure yet still provide patients with multiple myeloma the benefits of this procedure

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.

Eligibility criteria:
inclusion criteria: * meet salmon and durie criteria for initial diagnosis of multiple myeloma; transplant will be offered to patients with stage ii or iii multiple myeloma (mm) at diagnosis or have received chemotherapy and/or radiation therapy for progressive mm after initial diagnosis of stage i disease * the patient must have the capacity to give informed consent * have received at least 4 cycles of conventional dose chemotherapy for mm * donor: hla genotypically identical sibling * donor: donor must consent to filgrastim (g-csf) administration and leukapheresis for both peripheral blood stem cell (pbsc) allograft and subsequent dli * donor: donor must have adequate veins for leukapheresis or agree to placement of central venous catheter (femoral, subclavian) * donor: age \< 75, older donors may be considered after consultation by psychological consultation center (pcc) exclusion criteria: * karnofsky score less than 60, unless due solely to myeloma * left ventricular ejection fraction less than 40% * bilirubin greater than 2 x the upper limit of normal * serum glutamic pyruvic transaminase (sgpt) and serum glutamic oxaloacetic transaminase (sgot) \> 2 x the upper limit of normal * diffusion lung capacity of carbon monoxide (dlco) \< 50% (corrected) or receiving continuous supplemental oxygen * patients with poorly controlled hypertension * pregnancy * seropositive for the human immunodeficiency virus * fertile men or women unwilling to use contraceptive techniques during and for 12 months following treatment * creatinine clearance \< 40 cc/min at the time of initial autografting evaluation * prior autograft (can be treated on alternative protocol) * donor: identical twin * donor: age less than 12 years * donor: pregnancy * donor: infection with human immunodeficiency virus (hiv) * donor: inability to achieve adequate venous access * donor: known allergy to g-csf * donor: current serious systemic illness * donor: failure to meet fred hutchinson cancer research center (fhcrc) criteria for stem cell donation as described in the standard practice guidelines of the institution