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Busulfan (BU) has been used for approximatively four decades as a major component of chemotherapy-based conditioning before allo-HCT. At our center, IV-BU dose in MAC is 12.8 mg/kg (BU12.8) and in those not eligible for MAC, it is 9.6 mg/kg (BU9.6). The aim of this study was to compare the impact of BU9.6 to BU12.8 on outcomes in patients with acute leukemia (AL) or myelodysplastic syndromes (MDS) who received allo-HCT after BU-based conditioning from matched related or unrelated donors. This study included 181 patients: 134 AL [122 AML, 10 ALL and 2 biph. AL] and 47 (26%) MDS patients who received allo-HCT between Jan 2012 and Dec 2018 at the Ottawa Hospital. Median age at allo-HCT was 58 years (range: 18-73), 104 (57%) were males. At time of conditioning, among AL patients, 99 (74%) were in CR1, 19 (14%) in CR2 and 16 (12%) not in CR, and among MDS patients, 22 (47%) were not treated. All patients received PBSC from HLA matched related [N=68 (38%)] or unrelated [N=113 (62%)] donors. Patients were classified according to the refined Disease Risk Index (DRI): 94 (52%) intermediate, 81 (45%) high and 6 (3%) very high. GVHD prophylaxis consisted of tacrolimus and short course methotrexate for all patients. Rabbit antithymocyte globulin (rATG, Thymoglobulin) was used in all transplants from unrelated donors (n=113) and in BU12.8 transplants from related donors (n=28). Bu dose was 9.6 mg/kg for 74 (41%) patients and 12.8 mg/kg for 107 (59%). Ninety-eight % of the patients engrafted; GVHD requiring systemic immunosuppression was observed in 26/74 (35%) patients (4 acute, 22 chronic) after BU9.6, and in 45/107 (42%) patients (13 acute, 32 chronic) after BU12.8. With a median follow-up of 22 months (range: 5-74) for survivors, no significant difference in survival, relapse (REL) or NRM was observed between BU9.6 and BU12.8. Two-year OS, REL and NRM for the whole population were 65% (95%CI: 57-73), 29% (95%CI: 22-37) and 10.8% (95%CI: 6-16) respectively. When stratified according to DRI: intermediate, high and very high scores had 2-year OS of 76% (95%CI: 65-84), 53% (95%CI: 38-66) and 0% respectively, p=0.001; and 1-year REL rates of 12% (95%CI: 6-20), 31% (95%CI: 21-42) and 67% (95%CI: 12-92) respectively, p<0.001. In multivariable analysis adjusted for conditioning, DRI, the use of rATG and rATG dose, the only factors that significantly impacted OS were DRI [high-very high vs intermediate: HR=1.98 (95%CI: 1.15-3.4), p=0.013] and the use of ATG [No ATG vs ATG 4.5mg/kg: HR=2.2 (95% CI: 1.06-4.6), p=0.033], while only DRI [high-very high vs intermediate: HR=3.56 (95%CI: 1.86-6.8), p=0.0001] impacted on REL. Our results validate the efficacy of a reduced 9.6 mg/kg BU-based conditioning regimen for patients not suitable for traditional 12.8mg/kg dose. Relapse was not increased, in addition, we confirm the value of DRI in prognosticating both relapse and survival. [ABSTRACT FROM AUTHOR]