High Dose Busulfan and Bortezomib in Treating Patients With High Risk Multiple Myeloma Undergoing Stem Cell Transplant

PRIMARY OBJECTIVES: I. To determine time to engraftment absolute neutrophil count (\> 0.5 x 10\^9/L for 3 consecutive days), and platelet (\> 20X 109\^/L for 3 consecutive days). 2\. Incidence and severity of acute graft-versus-host disease (GVHD) using fludarabine (fludarabine phosphate) / busulfan / bortezomib preparative regimen and triple immune suppression with tacrolimus, sirolimus and Thymoglobulin (anti-thymocyte globulin). 3\. To determine the safety related to this combination in the first six months post transplant, specifically, treatment related mortality and grade III and IV non hematologic toxicities, based on Common Terminology Criteria for Adverse Events (CTCAE) version 4 (v4). SECONDARY OBJECTIVES: I. Incidence of myeloma progression in this high risk group of patients. II. Incidence of transplant related mortality and morbidity. III. Incidence of thrombotic thrombocytopenic purpura (TTP) and sinusoidal obstructive syndrome (SOS). IV. Incidence and severity of chronic GVHD. V. Incidence of opportunistic infections including cytomegalovirus (CMV), herpes simplex virus (HSV), and Epstein-Barr virus (EBV) reactivation. I. Overall and progression free survival (PFS) at Day 100, 6 months, 1 \& 2 years post transplant. VII. To determine recovery of T-cell, B cell, and natural killer (NK) cell phenotypes post transplant. OUTLINE: CONDITIONING REGIMEN: Patients receive fludarabine phosphate intravenously (IV) on days -7 to -3, busulfan IV on days -6 to -3, and bortezomib IV on day -2. GVHD PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 to -1, sirolimus orally (PO) on day -3, and tacrolimus IV on day -3. Patients undergo allogeneic hematopoietic stem cell transplantation (HSCT) on day 0. After completion of study treatment, patients are followed up for up to 2 years.