A real-world analysis of clinical outcomes in AML with myelodysplasia-related changes: a comparison of ICC and WHO-HAEM5 criteria

Abstract

The proposed 5th edition of the WHO classification of hematolymphoid tumors (WHO-HAEM5) and International Consensus Classification (ICC) employ different definitions of acute myeloid leukemia with myelodysplasia-related genetics (AML-MR). We conducted a retrospective study which included a cohort of 432 patients treated at our institution, with 354 WHO-AML-MR patients if classified according to WHO-HAEM5 or 276 ICC-AML-MR by gene mutation or cytogenetics (ICC-AML-MR-M/CG) patients if classified according to ICC. The clinicopathological features were similar, irrespective of the classification used, except for higher rates of complex karyotype, monosomy 17, TP53 mutations, and fewer RUNX1 mutations in the WHO-AML-MR group. TP53 mutations were associated with distinct clinicopathological features and dismal outcomes (hazard ratio [HR], 2.98; p < .001). ICC-AML-MR-M/CG group had superior outcome compared to the WHO-AML-MR group (HR 0.80, p = .032), mainly due to isolating out TP53 mutated AML to form a standalone entity. In the intensively treated group, WHO-AML-MR had significantly worse outcomes than AML by differentiation (HR: 1.97, p = .024). By ICC criteria, AML-MR defined by gene mutations or by cytogenetics had more inferior outcomes than AML not otherwise specified (HR: 2.11, p = .048 and HR: 2.55, p = .028; respectively). Furthermore, changing the order of defining AML-MR (i.e. by gene mutations or cytogenetics) did not significantly impact clinical outcomes. AML-MR defined by gene mutations or cytogenetic abnormalities showed similar outcomes regardless of the order of assignment (HR: 0.92, p = .73). We propose to harmonize the two classifications by excluding TP53 mutations from WHO-HAEM5 defined AML-MR group and combining AML-MR defined by gene mutations and cytogenetics to form a unified group.