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

• Published in: Blood Vol. 126; no. 13; pp. 1575 - 1584
• Main Authors: Inaba, Hiroto, Zhou, Yinmei, Abla, Oussama, Adachi, Souichi, Auvrignon, Anne, Beverloo, H. Berna, de Bont, Eveline, Chang, Tai-Tsung, Creutzig, Ursula, Dworzak, Michael, Elitzur, Sarah, Fynn, Alcira, Forestier, Erik, Hasle, Henrik, Liang, Der-Cherng, Lee, Vincent, Locatelli, Franco, Masetti, Riccardo, De Moerloose, Barbara, Reinhardt, Dirk, Rodriguez, Laura, Van Roy, Nadine, Shen, Shuhong, Taga, Takashi, Tomizawa, Daisuke, Yeoh, Allen E.J., Zimmermann, Martin, Raimondi, Susana C.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 24.09.2015; American Society of Hematology
• Subjects: Adolescent; Antimetabolites, Antineoplastic - therapeutic use; Child; Child, Preschool; Chromosome Aberrations; Cytarabine - therapeutic use; Disease-Free Survival; Female; Gene Rearrangement; Hematopoietic Stem Cell Transplantation; Humans; Infant; Kaplan-Meier Estimate; Karyotyping; Leukemia, Megakaryoblastic, Acute - diagnosis; Leukemia, Megakaryoblastic, Acute - epidemiology; Leukemia, Megakaryoblastic, Acute - genetics; Leukemia, Megakaryoblastic, Acute - therapy; Male; Myeloid Neoplasia; Prognosis; Retrospective Studies; Treatment Outcome
• ISSN: 0006-4971; 1528-0020; 1528-0020
• DOI: 10.1182/blood-2015-02-629204

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. •AMKL patients in 2000 to 2009 had better survival than those in 1989 to 1999, but outcomes for patients in 2000 to 2004 and 2005 to 2009 were comparable.•Heterogeneous cytogenetic groups can be classified into good, intermediate, and poor risk on the basis of prognosis.