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

This phase I trial studies the side effects and best dose of targeted marrow irradiation when given with fludarabine phosphate and busulfan before donor progenitor cell transplant in treating patients with hematologic malignancies. Targeted marrow irradiation is a type of specialized radiation therapy that delivers a high dose of radiation directly to the cancer cells, which may kill more cancer cells and cause less damage to normal cells. Giving targeted marrow irradiation and chemotherapy drugs, such as fludarabine phosphate and busulfan, before a donor progenitor cell transplant may help stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's progenitor cells. When the healthy progenitor cells from a donor are infused into the patient they may help the patient's bone marrow make progenitor cells, red blood cells, white blood cells, and platelets.

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.