BackgroundPatients (pts) formerly diagnosed as AML with myelodysplasia-related changes are currently recategorized according to their underlying genetic events in three different AML subgroups, namely AML with mutated TP53, AML with myelodysplasia-related gene mutations (MR-GM), and AML with myelodysplasia-related cytogenetic abnormalities (MR-CG) (International Consensus Classification 2022) (Arber AD, Blood 2022). The relevance of this new classification for transplantation (HSCT) outcome is largely unknown.MethodsWe analyzed outcomes of pts with TP53-mutated AML, pts with any of the 9 MR-GM (Arber AD, Blood 2022), and pts with MR-CG without TP53 and or MR-GM in CR1 transplanted between 2010-2022 from matched siblings, unrelated or haplo donors. Pts were hierarchically assigned to these genetic categories after excluding any pre-defined AML with recurrent genetic abnormalities (ICC 2022).Results1152 pts were included: TP53 (n=527), MR-GM (n=379), and MR-CG (n=246). Median FU was 24 mos. [IQR, 21-24]. Median age was 60.3 years (range 18.4-78.2). FLT3-ITD was more prevalent in the MR-GM group at 17.1% vs.7.4 % and 10.7% in the other 2 groups (p=0.001). A higher proportion of pts in the TP53 group had KPS <90 32.4% vs. 23.2% and 27.7% in the MR-GM and MR-CG groups (p<0.012). A higher proportion of pts in the MR-CG group received MAC at 46.5% vs. 37.8% and 37% in the TP53 and MR-GM groups (p=0.036). Finally, more pts in the MR-GM group received PTCy as GVHD prophylaxis 38.8% vs. 24.7% and 29.1% of the pts in the TP-53 and MR-GM groups (p<0.0001). On MVA, pts in the MR-GM and MR-CG groups showed a better outcome compared to. the TP53 group with lower RI: HR=0.24 (95% CI 0.18-0.33, p<0.0001) and HR=0.4 (95% CI 0.29-0.54, p<0.0001) and better LFS HR=0.37 (95% CI 0.3-0.47, p<0.0001) and HR=0.52 (95% CI 0.41-0.66, p<0.0001), OS HR=0.37 (95% CI 0.39-0.46, p<0.0001) and HR=0.5 (95% CI 0.39-0.64, p<0.0001) and GRFS HR=0.47 (95% CI 0.38-0.57, p<0.0001) and HR=0.64 (95% CI 0.51-0.79, p<0.0001), respectively. NRM, acute, and chronic GVHD did not differ significantly. In addition, pts with MR-CG showed worse outcome vs. those with MR-GM with higher RI HR=1.67 (95% CI 1.14-2.43, p=0.008) and lower LFS HR=1.39 (95% CI 1.05-1.84, p<0.021), OS HR=1.36 (95% CI 1.01-1.82, p<0.043) and GRFS HR=1.37 (95% CI 1.07-1.75, p<0.012) (Figure, univariate results). Of note, patients with sAML did not show a worse outcome than those with de novo AML after adjustment for genetic features, on MVA.ConclusionsAnalysis of HSCT outcomes in pts with myelodysplasia-related features per ICC 2022 classification demonstrated worse outcomes in pts with TP53 compared to those with MR-GM or MR-CG. Notably, the outcomes of pts with MR-GM were better than those with MR-CG. This is to our knowledge the first validation of the ICC2022 classification in AML pts with myelodysplasia-related changes undergoing transplantation.