Sargas, ClaudiaAyala, RosaLarráyoz, María JChillón, María CRodriguez-Arboli, EduardoBilbao, CristinaPrados de la Torre, EstherMartínez-Cuadrón, DavidRodríguez-Veiga, RebecaBoluda, BlancaGil, CristinaBernal, TeresaBergua, JuanAlgarra, LorenzoTormo, MarMartínez-Sánchez, PilarSoria, ElenaSerrano, JosefinaAlonso-Dominguez, Juan MGarcía, RaimundoAmigo, María LuzHerrera-Puente, PilarSayas, María JLavilla-Rubira, EsperanzaMartinez-Lopez, JoaquinCalasanz, María JGarcía-Sanz, RamónPérez-Simón, José AGómez Casares, María TSánchez-García, JoaquínBarragán, EvaMontesinos, PauPETHEMA cooperative study group2024-09-162024-09-162023-05-12Blood Cancer J . 2023;13(1):77.https://hdl.handle.net/20.500.12105/23128Next-Generation Sequencing is needed for the accurate genetic risk stratification of acute myeloid leukemia according to European LeukemiaNet (ELN) guidelines. We validated and compared the 2022 ELN risk classification in a real-life cohort of 546 intensively and 379 non-intensively treated patients. Among fit patients, those aged ?65 years old showed worse OS than younger regardless risk classification. Compared with the 2017 classification, 14.5% of fit patients changed the risk with the 2022 classification, increasing the high-risk group from 44.3% to 51.8%. 3.7% and 0.9% FLT3-ITD mutated patients were removed from the favorable and adverse 2017 categories respectively to 2022 intermediate risk group. We suggest that midostaurin therapy could be a predictor for 3 years OS (85.2% with vs. 54.8% without midostaurin, P = 0.04). Forty-seven (8.6%) patients from the 2017 intermediate group were assigned to the 2022 adverse-risk group as they harbored myelodysplasia (MDS)-related mutations. Patients with one MDS-related mutation did not reach median OS, while patients with ?2 mutations had 13.6 months median OS (P = 0.002). Patients with TP53 � complex karyotype or inv(3) had a dismal prognosis (7.1 months median OS). We validate the prognostic utility of the 2022 ELN classification in a real-life setting providing supportive evidences to improve risk stratification guidelines.engVoRhttp://creativecommons.org/licenses/by-nc-nd/4.0/NucleophosminLeukemia, Myeloid, AcuteHumansAgedPrognosisRisk FactorsMutationAttribution-NonCommercial-NoDerivatives 4.0 Internacional371733221317710.1038/s41408-023-00835-52044-5385Blood cancer journalopen access