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

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.