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@ARTICLE{HernndezSnchez:307654,
author = {A. Hernández-Sánchez and Á. Villaverde Ramiro and E.
Sträng and A. T. Turki and M. Abáigar and J. Versluis and
I. Thomas and M. Sobas and J. Martínez Elicegui and G.
Castellani and A. Benner$^*$ and R. Azibeiro and J. M.
Tettero and R. Mecklenbrauck and J. Martínez-López and M.
Pratcorona and K. I. Mills and G. Sanz and M. T. Voso and L.
Sören and C. Röllig and C. Thiede and K. H. Metzeler and
K. Döhner and M. Heuser and T. Haferlach and P. J. Valk and
N. Russell and J. M. Hernández-Rivas and B. Huntly and G.
Ossenkoppele and H. Döhner and L. Bullinger$^*$},
title = {{U}nravelling co-mutational patterns with prognostic
implications in {NPM}1 mutated adult acute myeloid leukemia
- a {HARMONY} study.},
journal = {Leukemia},
volume = {nn},
issn = {0887-6924},
address = {London},
publisher = {Springer Nature},
reportid = {DKFZ-2026-00115},
pages = {nn},
year = {2026},
note = {#DKTKZFB26# / epub},
abstract = {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.},
cin = {BE01 / C060},
ddc = {610},
cid = {I:(DE-He78)BE01-20160331 / I:(DE-He78)C060-20160331},
pnm = {313 - Krebsrisikofaktoren und Prävention (POF4-313)},
pid = {G:(DE-HGF)POF4-313},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:41535568},
doi = {10.1038/s41375-025-02851-9},
url = {https://inrepo02.dkfz.de/record/307654},
}