Validation and refinement of the revised 2017 European LeukemiaNet genetic risk stratification of acute myeloid leukemia.

Autor: Herold T; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany.; Research Unit Apoptosis in Hematopoietic Stem Cells, Helmholtz Zentrum München, German Research Center for Environmental Health (HMGU), Munich, Germany., Rothenberg-Thurley M; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Grunwald VV; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Janke H; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Goerlich D; Institute of Biostatistics and Clinical Research, Westfälische Wilhelms-Universität Münster, Münster, Germany., Sauerland MC; Institute of Biostatistics and Clinical Research, Westfälische Wilhelms-Universität Münster, Münster, Germany., Konstandin NP; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Dufour A; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Schneider S; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Neusser M; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Ksienzyk B; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany., Greif PA; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Subklewe M; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Faldum A; Institute of Biostatistics and Clinical Research, Westfälische Wilhelms-Universität Münster, Münster, Germany., Bohlander SK; Department of Molecular Medicine and Pathology, University of Auckland, Auckland, New Zealand., Braess J; Department of Oncology and Hematology, Hospital Barmherzige Brüder, Regensburg, Germany., Wörmann B; Charité University Hospital Berlin, Berlin, Germany., Krug U; Hospital Leverkusen, Leverkusen, Germany., Berdel WE; Department of Medicine A, University Hospital Münster, Münster, Germany., Hiddemann W; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Spiekermann K; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany.; German Cancer Research Center (DKFZ), Heidelberg, Germany., Metzeler KH; Laboratory for Leukemia Diagnostics, Department of Medicine III, University Hospital, LMU Munich, Munich, Germany. klaus.metzeler@med.uni-muenchen.de.; German Cancer Consortium (DKTK), Partner Site Munich, Munich, Germany. klaus.metzeler@med.uni-muenchen.de.; German Cancer Research Center (DKFZ), Heidelberg, Germany. klaus.metzeler@med.uni-muenchen.de.
Jazyk: angličtina
Zdroj: Leukemia [Leukemia] 2020 Dec; Vol. 34 (12), pp. 3161-3172. Date of Electronic Publication: 2020 Mar 30.
DOI: 10.1038/s41375-020-0806-0
Abstrakt: The revised 2017 European LeukemiaNet (ELN) recommendations for genetic risk stratification of acute myeloid leukemia have been widely adopted, but have not yet been validated in large cohorts of AML patients. We studied 1116 newly diagnosed AML patients (age range, 18-86 years) who had received induction chemotherapy. Among 771 patients not selected by genetics, the ELN-2017 classification re-assigned 26.5% of patients into a more favorable or, more commonly, a more adverse-risk group compared with the ELN-2010 recommendations. Forty percent of the cohort, and 51% of patients ≥60 years, were classified as adverse-risk by ELN-2017. In 599 patients <60 years, estimated 5-year overall survival (OS) was 64% for ELN-2017 favorable, 42% for intermediate-risk and 20% for adverse-risk patients. Among 517 patients aged ≥60 years, corresponding 5-year OS rates were 37, 16, and 6%. Patients with biallelic CEBPA mutations or inv(16) had particularly favorable outcomes, while patients with mutated TP53 and a complex karyotype had especially poor prognosis. DNMT3A mutations associated with inferior OS within each ELN-2017 risk group. Our results validate the prognostic significance of the revised ELN-2017 risk classification in AML patients receiving induction chemotherapy across a broad age range. Further refinement of the ELN-2017 risk classification is possible.
Databáze: MEDLINE
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