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

ABSTRACT: The increasing knowledge of molecular genetics of acute myeloid leukemia (AML) necessitated the update of previous diagnostic and prognostic schemes, which resulted in the development of the World Health Organization (WHO), the International Consensus Classification (ICC), and the new European LeukemiaNet (ELN) recommendations in 2022. We aimed to provide a real-world application of the new models, unravel differences and similarities, and test their implementation in clinical AML diagnosis. A total of 1001 patients diagnosed with AML were reclassified based on the new schemes. The overall diagnostic changes between the WHO 2016 and the 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 category sizes shrank when compared with that in WHO 2016 (24.1% and 26.8% respectively, vs 38.7%), particularly because of 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 restratification between ELN 2017 and ELN 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 scheme to generate a unified model is desirable.

SUBMITTER: Attardi E

PROVIDER: S-EPMC10477447 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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

Attardi Enrico E Savi Arianna A Borsellino Beatrice B Piciocchi Alfonso A Cipriani Marta M Ottone Tiziana T Fabiani Emiliano E Divona Mariadomenica M Travaglini Serena S Pascale Maria Rosaria MR Awada Hussein H Durmaz Arda A Visconte Valeria V Della Porta Matteo Giovanni MG Venditti Adriano A Maciejewski Jaroslaw P JP Gurnari Carmelo C Voso Maria Teresa MT

Blood advances 20230901 17

The increasing knowledge of molecular genetics of acute myeloid leukemia (AML) necessitated the update of previous diagnostic and prognostic schemes, which resulted in the development of the World Health Organization (WHO), the International Consensus Classification (ICC), and the new European LeukemiaNet (ELN) recommendations in 2022. We aimed to provide a real-world application of the new models, unravel differences and similarities, and test their implementation in clinical AML diagnosis. A t ...[more]

PMID: 37327116

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Project description:Introduction: One of the mainstays of chemotherapy in acute myeloid leukemia (AML) is induction with a goal to achieve morphological complete remission (CR). However, not all patients by this remission criterion achieve long-term remission and a subset relapse. This relapse is explained by the presence of measurable residual disease (MRD). Methods: We accrued 451 consecutive patients of adult AML (from March 2012 to December 2017) after informed consent. All patients received standard chemotherapy. MRD testing was done at post-induction and, if feasible, post-consolidation using 8- and later 10-color FCM. Analysis of MRD was done using a combination of difference from normal and leukemia-associated immunophenotype approaches. Conventional karyotyping and FISH were done as per standard recommendations, and patients were classified into favorable, intermediate, and poor cytogenetic risk groups. The presence of FLT3-ITD, NPM1, and CEBPA mutations was detected by a fragment length analysis-based assay. Results: As compared to Western data, our cohort of patients was younger with a median age of 35 years. There were 62 induction deaths in this cohort (13.7%), and 77 patients (17.1%) were not in morphological remission. The median follow-up was 26.0 months. Poor-risk cytogenetics and the presence of FLT3-ITD were significantly associated with inferior outcome. The presence of post-induction MRD assessment was significantly associated with adverse outcome with respect to OS (p = 0.01) as well as RFS (p = 0.004). Among established genetic subgroups, detection of MRD in intermediate cytogenetic and NPM1 mutated groups was also highly predictive of inferior outcome. On multivariate analysis, immunophenotypic MRD at the end of induction and FLT3-ITD emerged as independent prognostic factors predictive for outcome. Conclusion: This is the first data from a resource-constrained real-world setting demonstrating the utility of AML MRD as well as long-term outcome of AML. Our data is in agreement with other studies that determination of MRD is extremely important in predicting outcome. AML MRD is a very useful guide for guiding post-remission strategies in AML and should be incorporated into routine treatment algorithms.

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

Publications

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

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