Proposed Refinement of 2022 European LeukemiaNet Adverse-Risk Group of AML Patients Using a Real-World Cohort

Background/Objectives: The 2022 European LeukemiaNet (ELN 2022) is a widely used genotypic risk classification tool for the treatment and prognostication of acute myeloid leukemia (AML) patients. Our study evaluates its effectiveness in categorizing adverse-risk AML patients on standard therapy based on their overall survival (OS). Methods: We conducted a retrospective study involving 256 AML patients. Results: Those in the ELN 2022 adverse-risk group had the shortest OS (p < 0.0001) and were predominantly characterized by myelodysplasia-related (MR) mutations, complex karyotype (CK), monosomal karyotype (MK), and TP53 mutation (TP53 Mut). Subclassification and analysis of this adverse-risk group based on the TP53 Mut status revealed a significantly shorter OS compared to the adverse TP53 wild-type (TP53 WT) counterparts (p = 0.0036). We propose refining the ELN 2022 adverse-risk group into two categories, adverse TP53 Mut and adverse TP53 WT groups, to represent adverse- and ultra-adverse-risk groups, respectively. We used an external validation dataset to confirm our findings. Conclusions: This refinement allows for a more accurate classification of these adverse-risk patients based on their clinical outcomes.