Journal Article

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

Berdel, Wolfgang E, Rothenberg-Thurley Maja, Subklewe Marion, Metzeler, Klaus H, Neusser Michaela, Faldum Andreas, Spiekermann Karsten, Bohlander, Stefan K, Grunwald, Victoria V, Wörmann Bernhard, Herold, Tobias, Janke, Hanna, Dufour Annika, Schneider, Stephanie, Konstandin, Nikola P, Krug Utz, Greif, Philipp A, Braess, Jan, Sauerland, Maria C, Goerlich, Dennis, Ksienzyk Bianka, Hiddemann Wolfgang

2020

Overview

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.

• Publisher: Nature Publishing Group
• Subject: Acute myeloid leukemia / Chemotherapy / Classification / Genetics / Karyotypes / Leukemia / Medical prognosis / Mutation / Myeloid leukemia / p53 Protein / Risk