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| 005 | 20260116120447.0 | ||
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| 100 | 1 | _ | |a Hernández-Sánchez, Alberto |0 0000-0002-6601-3096 |b 0 |
| 245 | _ | _ | |a Unravelling co-mutational patterns with prognostic implications in NPM1 mutated adult acute myeloid leukemia - a HARMONY study. |
| 260 | _ | _ | |a London |c 2026 |b Springer Nature |
| 336 | 7 | _ | |a article |2 DRIVER |
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| 520 | _ | _ | |a NPM1-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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| 700 | 1 | _ | |a Villaverde Ramiro, Ángela |0 0000-0002-7337-7218 |b 1 |
| 700 | 1 | _ | |a Sträng, Eric |b 2 |
| 700 | 1 | _ | |a Turki, Amin T |0 0000-0003-1347-3360 |b 3 |
| 700 | 1 | _ | |a Abáigar, María |b 4 |
| 700 | 1 | _ | |a Versluis, Jurjen |0 0000-0003-2372-1663 |b 5 |
| 700 | 1 | _ | |a Thomas, Ian |b 6 |
| 700 | 1 | _ | |a Sobas, Marta |b 7 |
| 700 | 1 | _ | |a Martínez Elicegui, Javier |0 0000-0001-5294-6162 |b 8 |
| 700 | 1 | _ | |a Castellani, Gastone |0 0000-0003-4892-925X |b 9 |
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| 700 | 1 | _ | |a Azibeiro, Raúl |0 0000-0002-3382-3674 |b 11 |
| 700 | 1 | _ | |a Tettero, Jesse M |0 0000-0002-0811-0824 |b 12 |
| 700 | 1 | _ | |a Mecklenbrauck, Rabea |0 0009-0005-9374-300X |b 13 |
| 700 | 1 | _ | |a Martínez-López, Joaquín |0 0000-0001-7908-0063 |b 14 |
| 700 | 1 | _ | |a Pratcorona, Marta |b 15 |
| 700 | 1 | _ | |a Mills, Ken I |0 0000-0002-6362-4481 |b 16 |
| 700 | 1 | _ | |a Sanz, Guillermo |0 0000-0002-2767-8191 |b 17 |
| 700 | 1 | _ | |a Voso, Maria Teresa |0 0000-0002-6164-4761 |b 18 |
| 700 | 1 | _ | |a Sören, Lehmann |b 19 |
| 700 | 1 | _ | |a Röllig, Christoph |0 0000-0002-3791-0548 |b 20 |
| 700 | 1 | _ | |a Thiede, Christian |0 0000-0003-1241-2048 |b 21 |
| 700 | 1 | _ | |a Metzeler, Klaus H |0 0000-0003-3920-7490 |b 22 |
| 700 | 1 | _ | |a Döhner, Konstanze |0 0000-0002-2261-9862 |b 23 |
| 700 | 1 | _ | |a Heuser, Michael |0 0000-0001-5318-9044 |b 24 |
| 700 | 1 | _ | |a Haferlach, Torsten |0 0000-0003-0196-2837 |b 25 |
| 700 | 1 | _ | |a Valk, Peter Jm |0 0000-0002-8857-9461 |b 26 |
| 700 | 1 | _ | |a Russell, Nigel |b 27 |
| 700 | 1 | _ | |a Hernández-Rivas, Jesús María |0 0000-0002-9661-9371 |b 28 |
| 700 | 1 | _ | |a Huntly, Brian |0 0000-0003-0312-161X |b 29 |
| 700 | 1 | _ | |a Ossenkoppele, Gert |b 30 |
| 700 | 1 | _ | |a Döhner, Hartmut |0 0000-0003-2116-5536 |b 31 |
| 700 | 1 | _ | |a Bullinger, Lars |0 0000-0002-5890-5510 |b 32 |
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