Refinement of the ELN2022 genetic risk classification for patients with AML undergoing allo-HSCT

Results from a retrospective, single-center study, evaluating the prognostic value of genetic risk classification and measurable residual disease (MRD) in 217 adults with acute myeloid leukemia (AML) in complete remission (CR) undergoing allogeneic hematopoietic cell transplantation (allo-HSCT), were published in Haematologica by Villalba et al. Patients received myeloablative conditioning (MAC) and post-transplant cyclophosphamide (PTCy)-based graft-versus-host disease (GvHD) prophylaxis. A refined, four-tier genetic risk classification system was developed, including standard risk (n = 135), intermediate-risk (n = 43), adverse-risk (n = 25), and very adverse risk (n = 14) categories. The primary objective was to assess and refine the European LeukemiaNet 2022 (ELN2022) classification for predicting overall survival (OS).

Key data: According to ELN2022 risk groups, 2-year OS was 85% in favorable, 86% in intermediate, and 70% in adverse risk disease; after multivariable analysis, only adverse risk was associated with worse OS vs favorable risk (hazard ratio [HR], 2.71; p = 0.04). In contrast, the refined, four-tier genetic classification successfully stratified OS; intermediate (HR, 2.37; p = 0.02), adverse (HR, 4.24, p < 0.001), and very adverse (HR, 6.81; p < 0.001) risk were associated with progressively worse OS vs standard risk. Pre-transplant MRD positivity was associated with significantly worse OS (HR, 8.23) and event-free survival (EFS; HR, 6.51) in the intermediate risk group only. 

Key learning: The ELN2022 classification system did not adequately stratify survival outcomes in patients with AML undergoing allo-HSCT in CR, with MAC and PTCy-based treatment. A refined, transplant-specific genetic risk model, further sharpened by pre-transplant MRD, may better support prognostication and risk-adapted post-transplant strategies for this patient population.