Allogeneic Hematopoietic Cell Transplantation in Patients With Acute Myeloid Leukemia With Myelodysplasia‐Related Genetic Features: Relevance of the Genetic Underlying Category. A Retrospective Analysis on Behalf of the Acute Leukemia Working Party of the EBMT

ABSTRACT Patients (pts) with myelodysplasia‐related AML (MR‐AML) are now genetically recategorized, with three different groups in the International Consensus Classification: AML with mutated TP53 (TP53‐AML), with myelodysplasia‐related gene mutations (MR‐GM AML), and with myelodysplasia‐related cytogenetic abnormalities (MR‐CG AML). Moreover, TP53‐AML is determined by the presence of an additional complex karyotype (TP53‐mut CK and non‐CK AML, respectively). Nonetheless, the relevance of this classification to transplantation outcomes is largely unknown. We analyzed the outcomes of pts. with MR‐AML undergoing allogeneic hematopoietic cell transplantation in first complete remission between 2010 and 2022 according to these genetic categories. Overall, 1152 patients were identified: 379 (33%), 328 (28%), 246 (21%), and 199 (17%) with MR‐GM, TP53‐mut CK, MR‐CG, and TP53‐mut non‐CK AML, respectively. Median age was 60 years; median year of transplant was 2020. Unrelated donors and reduced‐intensity conditioning were used in 65% and 61% of cases, respectively. Outcomes differed markedly among genetic categories, with an increasing relapse incidence (20.2%, 29.2%, 44.6%, and 57.6% at 2 years), and decreasing LFS (60%, 55.3%, 40.6%, and 20.2% at 2 years), overall survival (65.7%, 60.1%, 47.1%, and 24.5% at 2 years), and graft‐versus‐host disease‐free, relapse‐free survival (46.9%, 39.5%, 31.9%, and 13.2% at 2 years) in MR‐GM, MR‐CG, TP53‐mut non‐CK, and TP53‐mut CK AML, respectively. These differences were confirmed in the multivariate analysis (hazard ratio for LFS: 0.21, 0.33 and 0.61 in MR‐GM, MR‐CG, and TP53‐mut non‐CK, with respect to reference TP53‐mut CK AML group). This study confirms the strong impact of genetic grouping of MR‐AML on transplant outcomes.