Abstract Abstract 4153 Background: better understanding of the bona fide immunological benefits derived from the donor immune effector cells resulted in development of reduced-toxicity regimens, which are associated with lesser toxicities and improved non-relapse mortality (NRM). However, reducing the toxicity of allogeneic hematopoietic cell transplantation (HCT) conditioning regimens without compromising its efficacy remains an imperative goal to broaden applicability of allogeneic HCT. We compare outcomes of two preparative regimens, known as FB2 and FB4, in patients (pts) with AML transplanted in first complete remission (CR1) at EBMT participating centers. Materials and methods: between 2003 and 2010, 437 (FB2=225 (51%), FB4=212 (49%)) pts with a median age of (FB2=57 (21–75) years, FB4=41 (18–68) years, p<0.0001), with AML in CR1, underwent allogeneic HCT. FB2 comprised intravenous (IV) busulfan cumulative dose of 6.4 ± 10% mg/kg, while FB4 cumulative dose was 12.8 ± 10% mg/kg. Cytogenetic risks groups were comparable: FB2 (good=8, int=144, poor=24) and FB4 (good=7, int=54, poor=9), p=0.27. For pts treated with FB2, donor source consisted of matched-related donors (MRD)= 112, matched unrelated donor (MUD)=80, mismatched unrelated donors (MMUD)=16, unknown=17. For FB4, donor source was MRD=160, MUD=29, MMUD=15, and unknown=8. Use of peripheral blood stem cells (PBSC) was higher in the FB2 group (96% vs. 83%, p <0.0001). Use of anti-thymocyte globulin (ATG) was also higher in FB2 group (79% vs. 33%, p<0.0001). FB4 allograft recipients (80% vs. 67%, p=0.003) and donors (77% vs. 56%, p<0.0001) had higher incidence of CMV seropositivity. Results: median follow-up time was 28 (2–89) months. Median time to absolute neutrophil count engraftment (days) was 17 (2–110) and 15 (7–45), for FB2 and FB4, respectively (p<0.0001). For pts <50 yrs. of age (n=208; FB2=56, FB4=152), the 2-year leukemia-free survival (LFS), cumulative incidence of relapse (CI-R), and of NRM was: LFS (FB2=60±7% vs. FB4=64±4%, p=0.45), CI-R (FB2=32±6% vs. FB4=20±4%, p=0.04), and NRM (FB2=7±4% vs. FB4=16±3%, p=0.17). Conversely, for pts aged ≥50 yrs. (n=229, FB2=169, FB4=60), outcomes were: LFS (FB2=63±4% vs. FB4=42±7%, p=0.02), CI-R (FB2=22±3% vs. FB4=29±6%, p=0.42), and NRM (FB2=15±3% vs. FB4=29±6%, p=0.06). Cumulative incidence of acute (≥grade 2) and chronic GVHD were similar: acute (FB2=51 (23%) and FB4=53 (26%), p=0.54) and chronic (FB2=48 ±3, FB4=44±2, p=0.51). Conclusion: in pts < 50 years of age, FB2 results in worse 2-year CI-R compared to FB4, but with similar 2-year NRM and LFS. For pts ≥50 years of age, FB2 results in superior 2-year LFS likely due to lower NRM. FB2 is a reasonable preferred option in pts ≥50 years with AML in CR1. Disclosures: No relevant conflicts of interest to declare.