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We studied 1118 newly diagnosed AML patients (median age, 58 years; range, 18\u201386 years) who received cytarabine-based induction chemotherapy between 1999 and 2012 and compared ELN-2022 to the previous ELN-2017 risk classification. Key findings were validated in a cohort of 1160 mostly younger patients. ELN-2022 reclassified 15% of patients, 3% into more favorable, and 12% into more adverse risk groups. This was mainly driven by patients reclassified from intermediate- to adverse-risk based on additional myelodysplasia-related mutations being included as adverse-risk markers. These patients (<jats:italic>n<\/jats:italic>\u2009=\u200979) had significantly better outcomes than patients with other adverse-risk genotypes (5-year OS, 26% vs. 12%) and resembled the remaining intermediate-risk group. Overall, time-dependent ROC curves and Harrel\u2019s C-index controlling for age, sex, and AML type (de novo vs. sAML\/tAML) show slightly worse prognostic discrimination of ELN-2022 compared to ELN-2017 for OS. Further refinement of ELN-2022 without including additional genetic markers is possible, in particular by recognizing <jats:italic>TP53<\/jats:italic>-mutated patients with complex karyotypes as \u201cvery adverse\u201d. In summary, the ELN-2022 risk classification identifies a larger group of adverse-risk patients at the cost of slightly reduced prognostic accuracy compared to ELN-2017.<\/jats:p>","DOI":"10.1038\/s41375-023-01884-2","type":"journal-article","created":{"date-parts":[[2023,4,11]],"date-time":"2023-04-11T06:02:52Z","timestamp":1681192972000},"page":"1234-1244","update-policy":"http:\/\/dx.doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Validation and refinement of the 2022 European LeukemiaNet genetic risk stratification of acute myeloid leukemia"],"prefix":"10.1038","volume":"37","author":[{"ORCID":"http:\/\/orcid.org\/0000-0002-7364-5526","authenticated-orcid":false,"given":"Christian","family":"Rausch","sequence":"first","affiliation":[]},{"given":"Maja","family":"Rothenberg-Thurley","sequence":"additional","affiliation":[]},{"given":"Annika","family":"Dufour","sequence":"additional","affiliation":[]},{"given":"Stephanie","family":"Schneider","sequence":"additional","affiliation":[]},{"given":"Hanna","family":"Gittinger","sequence":"additional","affiliation":[]},{"given":"Cristina","family":"Sauerland","sequence":"additional","affiliation":[]},{"given":"Dennis","family":"G\u00f6rlich","sequence":"additional","affiliation":[]},{"given":"Utz","family":"Krug","sequence":"additional","affiliation":[]},{"given":"Wolfgang E.","family":"Berdel","sequence":"additional","affiliation":[]},{"given":"Bernhard J.","family":"Woermann","sequence":"additional","affiliation":[]},{"given":"Wolfgang","family":"Hiddemann","sequence":"additional","affiliation":[]},{"given":"Jan","family":"Braess","sequence":"additional","affiliation":[]},{"given":"Michael","family":"von Bergwelt-Baildon","sequence":"additional","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0002-5139-4957","authenticated-orcid":false,"given":"Karsten","family":"Spiekermann","sequence":"additional","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0002-9615-9432","authenticated-orcid":false,"given":"Tobias","family":"Herold","sequence":"additional","affiliation":[]},{"ORCID":"http:\/\/orcid.org\/0000-0003-3920-7490","authenticated-orcid":false,"given":"Klaus H.","family":"Metzeler","sequence":"additional","affiliation":[]}],"member":"297","published-online":{"date-parts":[[2023,4,11]]},"reference":[{"key":"1884_CR1","doi-asserted-by":"publisher","first-page":"453","DOI":"10.1182\/blood-2009-07-235358","volume":"115","author":"H D\u00f6hner","year":"2010","unstructured":"D\u00f6hner H, Estey EH, Amadori S, Appelbaum FR, B\u00fcchner T, Burnett AK, et al. 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