Applicability of 2022 classifications of acute myeloid leukemia in the real-world setting

The increasing knowledge of molecular genetics of acute myeloid leukemia (AML) urged the update of previous diagnostic and prognostic schemes, which resulted in the development, in 2022, of the World Health Organization (WHO), the International Consensus Classification (ICC) and the new European LeukemiaNet (ELN) recommendations. We aimed to provide a real-world application of the new models, to unravel differences and similarities, and to test their implementation in clinical AML diagnosis. A total of 1001 patients diagnosed with AML were re-classified according to the new schemes. The overall diagnostic changes between the WHO 2016, compared to WHO 2022 and ICC classifications were 22.8% and 23.7%, respectively, with a 13.1% difference in patients' distribution between ICC and WHO 2022. The 2022 ICC "not otherwise specified" and WHO "defined by differentiation" AML categories shrank as compared to WHO 2016 (24.1% and 26.8% respectively, vs 38.7%), particularly due to an expansion of the myelodysplasia (MDS)-related group. Of 397 patients with a MDS-related AML according to the ICC, 55.9% were defined by the presence of a MDS-related karyotype. The overall re-stratification between ELN 2017 and 2022 was 12.9%. The 2022 AML classifications led to a significant improvement of diagnostic schemes. In the real-world setting, conventional cytogenetics, usually rapidly available and less expensive than molecular characterization, stratified 56% of secondary AML, still maintaining a powerful diagnostic role. Considering the similarities between WHO and ICC diagnostic schemes, a tentative to generate a unified model is desirable.