Heterogeneous survival outcomes in molecularly defined acute myeloid leukemia with myelodysplasia-related changes

Acute myeloid leukemia with myelodysplasia-related changes (AML-MRC) is a high-risk AML subtype defined by cytogenetic or genetic changes. We evaluated the relevance of AML-MRC classifications in a contemporary cohort of intensively treated patients with AML. We retrospectively reviewed 496 consecutive patients receiving induction chemotherapy for AML between 2016 and 2023 at a single center. Patients were categorized using both World Health Organization 2017 (MRC-2017) and International Consensus Classification 2022 (MRC-2022) criteria. Outcomes were compared using χ² or Kaplan-Meier. MRC-2017 and MRC-2022 criteria identified 113 (22.8%) and 147 (29.6%) patients, respectively; 42.1% (77/183) met both definitions. Patients with AML classified by either definition had worse event-free survival (EFS) vs all patients with AML (MRC-2017: median, 1.4 vs 11.6 months; P < .001; MRC-2022: median, 1.9 vs 10.5 months; P = .019). Overall survival (OS) was inferior for MRC-2017 vs all patients with AML (median, 19.7 vs 53.1 months; P < .001) but not for MRC-2022. In the MRC-2022 mutation group, patients with a splice or transcription factor (TF) mutation had worse EFS vs mixed or chromatin modifier mutations (1.10 vs 5.35 vs 7.40 months, P = .002). Landmark analysis after allogeneic hematopoietic cell transplantation (allo-HCT) showed better 2-year OS for MRC-2022 vs non-MRC-2022 patients (77.0% vs 62.7%, P = .015). Multivariate analysis confirmed the EFS impact of TF/splice mutations (hazard ratio [HR], 1.65; 95% confidence interval [CI], 1.20-2.27; P = .002) and allo-HCT (HR, 0.49; 95% CI, 0.34-0.69; P < .001). These findings highlight the heterogeneity within the MRC-2022 group, particularly with mutation type and transplant status. Further refinement of AML-MRC risk stratification is needed.