Genetic risk classification in acute myeloid leukemia patients treated with hematopoietic cell transplantation and post-transplant cyclophosphamide.

We analyzed outcomes of 217 AML patients in complete remission who underwent allogeneic HCT with myeloablative conditioning and post-transplant cyclophosphamide-based GVHD prophylaxis, aiming to assess the prognostic significance of genetic risk categories. In the overall cohort, the 2-year overall survival (OS) and event-free survival (EFS) were 77% (95% CI, 71-83) and 72% (95% CI, 66- 78), respectively. ELN2022 risk stratification lacked prognostic value in HCT. Instead, we identified four risk categories with distinct impact on OS: standard risk (ELN2022 favorable/intermediate and adverse-risk without high-risk genetic under the defined subcategories), intermediate risk (≥2 myelodysplasia-related gene mutations) (HR 2.23, 95% CI 1.14-4.92), adverse risk (complex karyotype, monosomal karyotype, inv(3)/t(3;3), KMT2A rearrangement) (hazard ratio (HR) 4.24, 95% CI 2.00 - 9.02), and very adverse risk (TP53 mutations) (HR 6.81, 95% CI 3.00 - 15.5). These categories demonstrated similar predictive power for EFS and cumulative incidence of relapse. Moreover, integrating pre-transplant MRD refined risk stratification, identified MRDnegative patients with ≥2 myelodysplasia-related gene mutations whose OS and EFS were comparable to standard-risk patients. This refined classification improves the prognostic value of ELN2022 for AML patients undergoing allogeneic HCT with modern platform by integrating genetic features and MRD status to better guide post-transplant management.