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Open Access 01-07-2020 | Acute Myeloid Leukemia | Original Article

Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia

Authors: Heiko Becker, Dietmar Pfeifer, Gabriele Ihorst, Milena Pantic, Julius Wehrle, Björn H. Rüter, Lars Bullinger, Björn Hackanson, Ulrich Germing, Andrea Kuendgen, Uwe Platzbecker, Konstanze Döhner, Arnold Ganser, Anne Hagemeijer, Pierre W. Wijermans, Hartmut Döhner, Justus Duyster, Michael Lübbert

Published in: Annals of Hematology | Issue 7/2020

Abstract

TP53 aberrations reportedly predict favorable responses to decitabine (DAC) in acute myeloid leukemia (AML). We evaluated clinical features and outcomes associated with chromosome 17p loss or TP53 gene mutations in older, unfit DAC-treated AML patients in a phase II trial. Of 178 patients, 25 had loss of 17p in metaphase cytogenetics; 24 of these had a complex (CK+) and 21 a monosomal karyotype (MK+). In analyses in all patients and restricted to CK+ and MK+ patients, 17p loss tended to associate with higher rates of complete remission (CR), partial remission (PR), or antileukemic effect (ALE). Despite favorable response rates, there was no significant OS difference between patients with or without loss of 17p in the entire cohort or in the CK+ and MK+ cohort. TP53 mutations were identified in eight of 45 patients with material available. Five of the eight TP53-mutated patients had 17p loss. TP53-mutated patients had similar rates of CR/PR/ALE but shorter OS than those with TP53 wild type (P = 0.036). Moreover, patients with a subclone based on mutation data had shorter OS than those without (P = 0.05); only one patient with TP53-mutated AML had a subclone. In conclusion, 17p loss conferred a favorable impact on response rates, even among CK+ and MK+ patients that however could not be maintained. The effect of TP53 mutations appeared to be different; however, patient numbers were low. Future research needs to further dissect the impact of the various TP53 aberrations in HMA-based combination therapies. The limited duration of favorable responses to HMA treatment in adverse-risk genetics AML should prompt physicians to advance allografting for eligible patients in a timely fashion.

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Title: Monosomal karyotype and chromosome 17p loss or TP53 mutations in decitabine-treated patients with acute myeloid leukemia
Authors: Heiko Becker
Dietmar Pfeifer
Gabriele Ihorst
Milena Pantic
Julius Wehrle
Björn H. Rüter
Lars Bullinger
Björn Hackanson
Ulrich Germing
Andrea Kuendgen
Uwe Platzbecker
Konstanze Döhner
Arnold Ganser
Anne Hagemeijer
Pierre W. Wijermans
Hartmut Döhner
Justus Duyster
Michael Lübbert
Publication date: 01-07-2020
Publisher: Springer Berlin Heidelberg
Keyword: Acute Myeloid Leukemia
Published in: Annals of Hematology / Issue 7/2020
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-020-04082-7

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