Traditional transplant conditioning regimens have a limiting factor regarding co-morbidities or old age. Therefore, reduced-intensity conditioning (RIC) regimens have been increasingly used. To define the role of RIC in AML with old age (>or=55 years) and/or co-morbidities (HCT-CI scores >or=2), we analyzed patients who received allogeneic stem cell transplantation (SCT) with Flu/Bu/TBI 400 cGy/+/-antithymocyte globulin (ATG) conditioning regimen. Seventeen men and 15 women were enrolled. The median age was 45 years (range 17-65 years). All patients were in first (n = 25) or second (n = 7) complete remission before undergoing allogeneic SCT. Patients were transplanted from HLA-mismatched unrelated donors (n = 5), matched unrelated donors (n = 10), and matched sibling (n = 17). Calcineurin inhibitor and a short course of standard dose methotrexate were used to prevent graft-versus-host disease (GVHD). All patients achieved engraftment. At a median follow-up of 18 months (range 4-40) for survivors, the estimated 2-year rates of overall survival, event-free survival, transplantation-related mortality, and relapse were 66, 63, 26, and 16%, respectively. The incidence of acute (grades II-IV) and chronic GVHD by NIH consensus criteria was 34.4 and 62.5%. This study suggests that the Flu/Bu/TBI 400 cGy or Flu/Bu/TBI 400 cGy/ATG-based conditioning regimens maybe a feasible therapeutic approach for AML with old age and/or co-morbidities.