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01-10-2018 | Original Article

Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15–60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials

Authors: Frédéric Baron, Marian Stevens-Kroef, Michal Kicinski, Giovanna Meloni, Petra Muus, Jean-Pierre Marie, Constantijn J. M. Halkes, Xavier Thomas, Radovan Vrhovac, Giorgina Specchia, Francois Lefrere Sr, Simona Sica, Marco Mancini, Adriano Venditti, Anne Hagemeijer, Heiko Becker, Joop H. Jansen, Sergio Amadori, Theo de Witte, Roelof Willemze, Stefan Suciu

Published in: Annals of Hematology | Issue 10/2018

Abstract

The presence of cytogenetic clonal heterogeneity has been associated with poor prognosis in patients with acute myeloid leukemia (AML). Here, we reassessed this association. The study cohort consisted of all patients with an abnormal karyotype randomized in the EORTC/GIMEMA AML-10 and AML-12 trials. Abnormal karyotypes were classified as no subclones present (cytogenetic abnormality in a single clone), defined subclones present (presence of one to three subclones), and composite karyotypes (CP) (clonal heterogeneity not allowing enumeration of individual subclones). The main endpoints were overall survival (OS) and disease-free survival (DFS). Among 1291 patients with an abnormal karyotype, 1026 had no subclones, 226 at least 1 subclone, and 39 a CP. Patients with defined subclones had an OS similar to those with no subclones (hazard ratio (HR) 1.05, 95% confidence interval (CI) 0.88–1.26), but CP patients had a shorter OS (HR = 1.58, 95% CI 1.11–2.26). However, in a multivariate Cox model stratified by protocol and adjusted for age, cytogenetic risk group, secondary versus primary AML, and performance status, clonal heterogeneity lost its prognostic importance (HR = 1.10, 95% CI 0.91–1.32 for defined subclones versus no subclones; HR = 0.96, 95% CI 0.67–1.38 for CP versus no subclones). Also, the impact of having a donor on DFS was similar in the three clonal subgroups. In summary, in patients with cytogenetic abnormality, presence of subclones had no impact on OS. The dismal outcome in patients with a CP was explained by the known predictors of poor prognosis. Trial registration: AML-10: ClinicalTrials.gov identifier: NCT00002549, retrospectively registered July 19, 2004; AML12: ClinicalTrials.gov identifier: NCT00004128, registered January 27, 2003.

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Title: Cytogenetic clonal heterogeneity is not an independent prognosis factor in 15–60-year-old AML patients: results on 1291 patients included in the EORTC/GIMEMA AML-10 and AML-12 trials
Authors: Frédéric Baron
Marian Stevens-Kroef
Michal Kicinski
Giovanna Meloni
Petra Muus
Jean-Pierre Marie
Constantijn J. M. Halkes
Xavier Thomas
Radovan Vrhovac
Giorgina Specchia
Francois Lefrere Sr
Simona Sica
Marco Mancini
Adriano Venditti
Anne Hagemeijer
Heiko Becker
Joop H. Jansen
Sergio Amadori
Theo de Witte
Roelof Willemze
Stefan Suciu
Publication date: 01-10-2018
Publisher: Springer Berlin Heidelberg
Published in: Annals of Hematology / Issue 10/2018
Print ISSN: 0939-5555
Electronic ISSN: 1432-0584
DOI: https://doi.org/10.1007/s00277-018-3396-4

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