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Ann Hematol. 2018 Oct;97(10):1785-1795. doi: 10.1007/s00277-018-3396-4. Epub 2018 Jun 20.

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.

Author information

1
Department of Hematology, GIGA-I3 and CHU, University of Liège, CHU Sart-Tilman, 4000, Liège, Belgium. f.baron@ulg.ac.be.
2
Radboud University Medical Center, Nijmegen, Netherlands.
3
EORTC Headquarters, Brussels, Belgium.
4
Sapienza University, Rome, Italy.
5
Saint Antoine Hospital, Paris, France.
6
Leiden University Medical Center, Leiden, Netherlands.
7
CHU of Lyon, Lyon, France.
8
University Hospital Centre Zagreb, Zagreb, Croatia.
9
University of Bari, Bari, Italy.
10
Necker Hospital, Paris, France.
11
Universita Cattolica Sacro Cuore, Rome, Italy.
12
University Tor Vergata, Rome, Italy.
13
University of Leuven, Leuven, Belgium.
14
Medical Center - University of Freiburg, Faculty of Medicine, University of Freiburg, Freiburg, Germany.

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.

KEYWORDS:

AML; Clonal evolution; Clonal heterogeneity; Cytogenetic; Transplantation

PMID:
29926156
DOI:
10.1007/s00277-018-3396-4
[Indexed for MEDLINE]

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