Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: A retrospective international study

Hiroto Inaba, Yinmei Zhou, Oussama Abla, Souichi Adachi, Anne Auvrignon, H. Berna Beverloo, Eveline De Bont, Tai Tsung Chang, Ursula Creutzig, Michael Dworzak, Sarah Elitzur, Alcira Fynn, Erik Forestier, Henrik Hasle, Der Cherng Liang, Vincent Lee, Franco Locatelli, Riccardo Masetti, Barbara De Moerloose, Dirk ReinhardtLaura Rodriguez, Nadine Van Roy, Shuhong Shen, Takashi Taga, Daisuke Tomizawa, Allen E J Yeoh, Martin Zimmermann, Susana C. Raimondi

Research output: Contribution to journalArticle

Abstract

Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% ± 2.7% and 49.0% ± 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n = 119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n = 44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1;22)(p13;q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9;11)(p22; q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk - 7p abnormalities; poor risk - normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk - others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes.

Original languageEnglish
Pages (from-to)1575-1584
Number of pages10
JournalBlood
Volume126
Issue number13
DOIs
Publication statusPublished - Sep 24 2015

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

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  • Cite this

    Inaba, H., Zhou, Y., Abla, O., Adachi, S., Auvrignon, A., Beverloo, H. B., De Bont, E., Chang, T. T., Creutzig, U., Dworzak, M., Elitzur, S., Fynn, A., Forestier, E., Hasle, H., Liang, D. C., Lee, V., Locatelli, F., Masetti, R., De Moerloose, B., ... Raimondi, S. C. (2015). Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: A retrospective international study. Blood, 126(13), 1575-1584. https://doi.org/10.1182/blood-2015-02-629204