Treo/Flu/TBI With Donor Stem Cell Transplant for Patients With Myelodysplastic Syndrome or Acute Myeloid Leukemia

This randomized phase II trial studies how well treosulfan and fludarabine phosphate, with or without total body irradiation before donor stem cell transplant works in treating patients with myelodysplastic syndrome or acute myeloid leukemia. Giving chemotherapy, such as treosulfan and fludarabine phosphate, and total-body irradiation before a donor stem cell transplant helps stop the growth of cancer cells. It may also stop the patient's immune system from rejecting the donor's stem cells. The donated stem cells may replace the patient's immune cells and help destroy any remaining cancer cells (graft-versus-tumor effect). Sometimes the transplanted cells from a donor can also make an immune response against the body's normal cells. Giving tacrolimus before and mycophenolate mofetil after the transplant may stop this from happening.

PRIMARY OBJECTIVES: I. To determine the better of two treosulfan-based conditioning regimens in patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML), by comparing 6-month progression-free survival. SECONDARY OBJECTIVES: I. Determine the effects of two conditioning regimens on changes in gene expression profiles, and evaluate the association of gene expression profiles and disease relapse. II. Determine the incidence of progression-free survival at 1 year and 2 years after hematopoietic cell transplantation (HCT). III. Evaluate overall survival (OS) at 6 months, at 1 year and at 2 years after HCT. IV. Determine the incidence of grades II-IV acute graft-versus-host disease (GVHD). V. Determine the incidence of chronic GVHD. VI. Determine donor chimerism around days +28 and +84. CONDITIONING REGIMEN: Arm A: Patients receive treosulfan intravenously (IV) over 2 hours on days -6 to -4 and fludarabine phosphate IV over 30 minutes on days -6 to -2. Arm B: Patients receive treosulfan and fludarabine phosphate as in Arm A and undergo low-dose total-body irradiation (TBI) on day 0. TRANSPLANT: Patients in both arms undergo allogeneic peripheral blood stem cell (PBSC) transplant or bone marrow transplant on day 0. GVHD PROPHYLAXIS: Patients with a related donor receive tacrolimus orally (PO) every 8 or 12 hours on days -3 to 56 with taper to day 180. Beginning 4-6 hours after PBSC infusion, patients also receive mycophenolate mofetil PO every 12 hours to day 28. Patients with an unrelated donor receive tacrolimus PO every 8 or 12 hours on days -3 to 100 with taper to day 180. Beginning 4-6 hours after PBSC infusion, patients also receive mycophenolate mofetil PO every 8 hours to day 40 with taper to day 96. NOTE: Patients with related donors eligible for FHCRC protocol 2545 may receive cyclosporine IV, instead of tacrolimus, beginning on day -3 to day 50 with a taper to day 180. After completion of study treatment, patients are followed up periodically.