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

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