Busulfan (Bu) Plus Cyclophosphamide (Cy) Versus TBI Plus Cy Conditioning for Allogeneic Stem Cell Transplantation (alloSCT) From Matched Unrelated Donors (MUD) In Adult Patients with AML in First Relapse: A Survey From the Acute Leukemia Working Party of EBMT

Abstract 161

TBY/Cy and Bu/Cy are the standard myeloablative conditioning regimens for alloSCT in adults with AML. Whether, one is associated with better outcomes compared to the other in the setting of relapsed AML is not well described. We therefore compared TBI/Cy to Bu/Cy conditioning prior to alloSCT in 158 adult patients (pts) with AML in first relapse (Rel 1) that underwent alloSCT from HLA matched (6/6) unrelated donors. 83 patients were given TBI/Cy and 75 Bu/Cy. The median age was 38 years (range, 19–62) in the TBI/Cy vs. 42 years (19–72) in the Bu/Cy group (P<0.012). FAB classifications, cytogenetic risk, time from diagnosis to alloSCT, donor gender and CMV serostatus were not different between the 2 groups. Median year of alloSCT was 2004 vs. 2007 (P<0.0001) for the TBI/Cy vs. Bu/Cy groups, respectively. Conditioning included ATG in 31% vs. 67% in the TBI/Cy and Bu/Cy groups, respectively (P<0.001). 78% of the Bu/Cy group and 80% of the TBI/Cy group, received PBSC grafts, while 22% and 20% received BM grafts, respectively (P=0.8). Median follow-up was, 23 months (range, 1–125) in TBI/Cy and 21 months (1–119) in Bu/Cy. The engraftment rate was similar between both groups with ANC>500/μL achieved at a median of 17 (10–33) and 16 (6–31) days in the TBI/Cy and Bu/Cy groups, respectively (P=0.23). Similarly, acute GVHD (≥Gr II) incidence did not differ between the 2 groups: 33% vs. 37% for the TBI/Cy vs. Bu/Cy, respectively. Death before day 100 occurred in 38% vs. 25% with TBI/Cy vs. Bu/Cy, respectively (P=0.25). 2- year NRM was similar between the 2 groups, 31±5% vs. 21±5%, respectively (P=0.15). In addition, the 2-year relapse rate did not differ between the 2 groups: 50±4% vs. 50±6%, respectively (P=0.93). Leukemia-free survival (LFS) at 2 years, was also similar between the TBI/Cy vs. Bu/Cy groups: 18 ± 5% vs. 29 ± 6 %, respectively (P=0.10). However, overall survival (OS) was significantly higher with Bu/Cy vs. TBI/Cy 38±6% vs. 21±4%, respectively (P=0.02). The main cause of death was disease relapse: 53% and 60%, with TBI/Cy vs. Bu/Cy, respectively (p=0.49). Of note, there were no differences in death from organ toxicities including VOD between the 2 groups. The rate of infection-related deaths did not differ between the groups, as well, 19% vs. 11% (p=0.25). In multivariate analysis, age, cytogenetic risk groups, use of ATG and interval from diagnosis to alloSCT were not significant prognostic factors for survival. In all, these results suggest that in AML patients in Rel 1 undergoing myeloablative alloSCT, Bu/Cy and TBI/Cy conditioning regimens can lead to similar outcomes including GVHD, NRM, disease progression and LFS. However, in terms of OS, there is a suggestion for an advantage in favor of the Bu/Cy regimen possibly due to a lower overall toxicity and improved capacity for salvage therapy.