Persistence of pre-leukemic clones during first remission and risk of relapse in acute myeloid leukemia

Leukemia
M Rothenberg-ThurleyK H Metzeler

Abstract

Some patients with acute myeloid leukemia (AML) who are in complete remission after induction chemotherapy harbor persisting pre-leukemic clones, carrying a subset of leukemia-associated somatic mutations. There is conflicting evidence on the prognostic relevance of these clones for AML relapse. Here, we characterized paired pre-treatment and remission samples from 126 AML patients for mutations in 68 leukemia-associated genes. Fifty patients (40%) retained ≥1 mutation during remission at a VAF of ≥2%. Mutation persistence was most frequent in DNMT3A (65% of patients with mutations at diagnosis), SRSF2 (64%), TET2 (55%), and ASXL1 (46%), and significantly associated with older age (p < 0.0001) and, in multivariate analyses adjusting for age, genetic risk, and allogeneic transplantation, with inferior relapse-free survival (hazard ratio (HR), 2.34; p = 0.0039) and overall survival (HR, 2.14; p = 0.036). Patients with persisting mutations had a higher cumulative incidence of relapse before, but not after allogeneic stem cell transplantation. Our work underlines the relevance of mutation persistence during first remission as a novel risk factor in AML. Persistence of pre-leukemic clones may contribute to the inferior outcome of el...Continue Reading

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Citations

Mar 13, 2019·Genes, Chromosomes & Cancer·Ing S Tiong, Andrew H Wei
Dec 7, 2018·Hematology·Gregory W Roloff, Elizabeth A Griffiths
Dec 6, 2019·British Journal of Haematology·Jack GhannamChristopher S Hourigan
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Feb 1, 2020·Current Treatment Options in Oncology·Sebastian SchwindUwe Platzbecker
Apr 3, 2019·Genes, Chromosomes & Cancer·Luise Hartmann, Klaus H Metzeler
Aug 2, 2019·Genes, Chromosomes & Cancer·Julie A I ThomsJohn E Pimanda
Dec 7, 2019·Hematology·Jacqueline CloosRichard Dillon
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Jan 10, 2021·Molecular Oncology·Myint Myat Khine AungKaren Keeshan
Nov 10, 2020·Leukemia & Lymphoma·Gráinne O'BrienChristophe Badie

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Methods Mentioned

BETA
PCR
flow cytometry

Software Mentioned

R
R Foundation for Statistical

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