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000307654 1001_ $$00000-0002-6601-3096$$aHernández-Sánchez, Alberto$$b0
000307654 245__ $$aUnravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia - a HARMONY study.
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000307654 520__ $$aNPM1-mutated (NPM1-mut) acute myeloid leukemia (AML) is generally associated with a more favorable outcome, although the presence of additional gene mutations can influence patient prognosis. We analyzed intensively-treated adult NPM1-mut AML patients included in the HARMONY Alliance database. A newly developed risk classification, which included combinations of co-mutations in FLT3-ITD, DNMT3A, IDH1/IDH2, and TET2 genes, was applied to a training cohort of NPM1-mut AML patients included in clinical trials (n = 1001), an internal validation cohort more representative of real-world settings (n = 762), and an external validation cohort enrolled in UK-NCRI trials (n = 585). The HARMONY classification considered 51.8% of the NPM1-mut AML training cohort patients as favorable, 24.8% as intermediate, and 23.4% as adverse risk, with median overall survival (OS) of 14.4, 2.2, and 0.9 years, respectively; p < 0.001), thereby reclassifying 42.7% of NPM1-mut patients into a different European LeukemiaNet (ELN) 2022 risk category. These results were confirmed both in an internal and external validation cohort. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) in first complete remission (CR1) showed the highest benefit in the NPM1-mut adverse-risk subgroup. The HARMONY classification provides the basis for a refined genetic risk stratification for adult NPM1-mut AML with potential clinical impact on allo-HSCT decision-making.
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000307654 7001_ $$00000-0002-7337-7218$$aVillaverde Ramiro, Ángela$$b1
000307654 7001_ $$aSträng, Eric$$b2
000307654 7001_ $$00000-0003-1347-3360$$aTurki, Amin T$$b3
000307654 7001_ $$aAbáigar, María$$b4
000307654 7001_ $$00000-0003-2372-1663$$aVersluis, Jurjen$$b5
000307654 7001_ $$aThomas, Ian$$b6
000307654 7001_ $$aSobas, Marta$$b7
000307654 7001_ $$00000-0001-5294-6162$$aMartínez Elicegui, Javier$$b8
000307654 7001_ $$00000-0003-4892-925X$$aCastellani, Gastone$$b9
000307654 7001_ $$0P:(DE-He78)e15dfa1260625c69d6690a197392a994$$aBenner, Axel$$b10$$udkfz
000307654 7001_ $$00000-0002-3382-3674$$aAzibeiro, Raúl$$b11
000307654 7001_ $$00000-0002-0811-0824$$aTettero, Jesse M$$b12
000307654 7001_ $$00009-0005-9374-300X$$aMecklenbrauck, Rabea$$b13
000307654 7001_ $$00000-0001-7908-0063$$aMartínez-López, Joaquín$$b14
000307654 7001_ $$aPratcorona, Marta$$b15
000307654 7001_ $$00000-0002-6362-4481$$aMills, Ken I$$b16
000307654 7001_ $$00000-0002-2767-8191$$aSanz, Guillermo$$b17
000307654 7001_ $$00000-0002-6164-4761$$aVoso, Maria Teresa$$b18
000307654 7001_ $$aSören, Lehmann$$b19
000307654 7001_ $$00000-0002-3791-0548$$aRöllig, Christoph$$b20
000307654 7001_ $$00000-0003-1241-2048$$aThiede, Christian$$b21
000307654 7001_ $$00000-0003-3920-7490$$aMetzeler, Klaus H$$b22
000307654 7001_ $$00000-0002-2261-9862$$aDöhner, Konstanze$$b23
000307654 7001_ $$00000-0001-5318-9044$$aHeuser, Michael$$b24
000307654 7001_ $$00000-0003-0196-2837$$aHaferlach, Torsten$$b25
000307654 7001_ $$00000-0002-8857-9461$$aValk, Peter Jm$$b26
000307654 7001_ $$aRussell, Nigel$$b27
000307654 7001_ $$00000-0002-9661-9371$$aHernández-Rivas, Jesús María$$b28
000307654 7001_ $$00000-0003-0312-161X$$aHuntly, Brian$$b29
000307654 7001_ $$aOssenkoppele, Gert$$b30
000307654 7001_ $$00000-0003-2116-5536$$aDöhner, Hartmut$$b31
000307654 7001_ $$00000-0002-5890-5510$$aBullinger, Lars$$b32
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