Targeted Marrow Irradiation, Fludarabine Phosphate, and Busulfan Before Donor Progenitor Cell Transplant in Treating Patients With Hematologic Malignancies

PRIMARY OBJECTIVES: I. To determine the maximum tolerated dose of targeted marrow irradiation given in combination with fludarabine (fludarabine phosphate) and busulfan as conditioning regimen for allogeneic hematopoietic progenitor cell transplantation. SECONDARY OBJECTIVES: I. To describe the toxicity profile of the conditioning regimen of targeted marrow irradiation (TMI), fludarabine and busulfan for allogeneic hematopoietic progenitor transplantation. II. To describe the use of two techniques of delivering TMI, volumetric modulated arc therapy (VMAT) and TomoTherapy, on patient's computed tomography (CT) simulation images and describe differences in organ avoidance and target coverage, planning time, and treatment delivery time. III. To determine the disease response status 100 days after allogeneic hematopoietic progenitor cell transplantation with the conditioning regimen of TMI, fludarabine and busulfan. IV. To determine the rates of acute graft versus host disease after allogeneic hematopoietic progenitor cell transplantation with the conditioning regimen of TMI, fludarabine and busulfan. OUTLINE: This is a dose-escalation study of TMI. CONDITIONING: Patients undergo TMI twice daily (BID) on days -10 to -7. Patients also receive fludarabine phosphate intravenously (IV) over 1 hour on days -6 to -2 and busulfan IV or orally (PO) on days -5 and -4. TRANSPLANT: Patients undergo allogeneic hematopoietic progenitor cell transplant on day 0. GRAFT-VERSUS-HOST DISEASE (GVHD) PROPHYLAXIS: Patients receive anti-thymocyte globulin IV on days -3 and -2, tacrolimus IV or PO beginning on day -1 for at least 6 months with taper beginning at 4 months, and methotrexate IV on days 1, 3, 6, and 11. After completion of study treatment, patients are followed up at 100 days, 6 months, and 12 months.