• Overall survival at 2 years [ Designated as safety issue: No ]
  

• Progression-free survival [ Designated as safety issue: No ]
  
• Nonrelapse mortality at 100 days post-transplant and at 1 year post-transplant [ Designated as safety issue: Yes ]
  
• Donor cell engraftment [ Designated as safety issue: No ]
  
• Incidence of disease progression or relapse [ Designated as safety issue: No ]
  
• Interdose variability and evaluation of a limited sampling strategy with busulfan IV [ Designated as safety issue: No ]
  
• Incidence and severity of acute and chronic graft-vs-host disease [ Designated as safety issue: Yes ]
  
• Number of days hospitalized [ Designated as safety issue: Yes ]
  
• Number of transfusions post-transplant [ Designated as safety issue: No ]
  

OBJECTIVES:

Primary

• Determine whether the conditioning intensity affects outcomes after hematopoietic cell transplantation (HCT) in patients with myelodysplastic syndromes or acute myeloid leukemia who have < 5% marrow myeloblasts at the time of HCT.
• Compare the 2-year overall survival of these patients treated with myeloablative vs nonmyeloablative conditioning.

Secondary

• Compare the progression-free survival of patients treated with these regimens.
• Compare the nonrelapse mortality at day 100 and at 1 year in patients treated with these regimens.
• Compare the donor cell engraftment, incidence of disease progression/relapse, and incidence and severity of acute and chronic graft-vs-host disease in patients treated with these regimens.
• Compare the number of days hospitalized and the number of transfusions post-transplant in patients treated with these regimens.

OUTLINE: This is a prospective, randomized, open-label, multicenter study. Patients are stratified according to transplant center (FHCRC vs other), diagnosis (myelodysplastic syndromes [MDS] vs acute myeloid leukemia), donor (related [RD] vs unrelated [URD]), etiology (primary vs treatment-related), and International Prognostic Scoring System (IPSS) category for MDS (intermediate-2 vs high-risk). Patients are randomized to 1 of 2 treatment arms.

Patients with a history of treated CNS leukemia receive 2 doses of prophylactic intrathecal chemotherapy comprising either methotrexate or cytarabine prior to conditioning and 6 additional doses after transplantation, beginning on day 32.

• Arm I (nonmyeloablative regimen): Patients receive fludarabine IV on days -4 to -2 and undergo low-dose total-body irradiation on day 0. Patients undergo allogeneic peripheral blood stem cell (PBSC) infusion on day 0. Patients also receive oral or IV cyclosporine two or three times daily on days -3 to 177 with taper (RD) or -3 to 177 (URD) and oral mycophenolate mofetil every 12 hours (RD) or every 8 hours (URD) on days 0-27 (RD) or days 0-96 with taper (URD).

• Arm II (myeloablative regimen): Patients are assigned to 1 of 2 treatment regimens.

  • Regimen A: Patients receive fludarabine IV and oral busulfan four times daily or busulfan IV over 3 hours on days -5 to -2.
  • Regimen B: Patients receive cyclophosphamide IV over 1-2 hours on days -3 and -2 and oral busulfan four times daily or busulfan IV over 3 hours on days -7 to -4.

Patients undergo PBSC infusion on day 0. Patients also receive tacrolimus IV continuously or orally twice a day on days -1 to 200 (with taper) and methotrexate IV on days 1, 3, 6, and 11.

After completion of study therapy, patients are followed periodically for 5 years.

PROJECTED ACCRUAL: A total of 280 patients will be accrued for this study.