title: Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study.
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.
authors.affiliation: St. Jude Children's Research Hospital, Memphis, TN;
authors.forename: Hiroto
authors.initials: H
authors.lastname: Inaba
authors.affiliation: St. Jude Children's Research Hospital, Memphis, TN;
authors.forename: Yinmei
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: The Hospital for Sick Children, Toronto, ON, Canada;
authors.forename: Oussama
authors.initials: O
authors.lastname: Abla
authors.affiliation: Kyoto University, Kyoto, Japan; Japanese Pediatric Leukemia/Lymphoma Study Group, Nagoya, Japan;
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.affiliation: French Leucémie Aigue Myeloide Enfant, Hôpital Trousseau, Paris, France;
authors.forename: Anne
authors.initials: A
authors.lastname: Auvrignon
authors.affiliation: Erasmus Medical Center, Rotterdam, The Netherlands; Dutch Childhood Oncology Group, The Hague, The Netherlands;
authors.forename: H Berna
authors.initials: HB
authors.lastname: Beverloo
authors.affiliation: Dutch Childhood Oncology Group, The Hague, The Netherlands; University Medical Center Groningen, University of Groningen, Groningen, The Netherlands;
authors.forename: Eveline
authors.initials: E
authors.lastname: de Bont
authors.affiliation: Kaohsiung Medical University Hospital, Kaohsiung, Taiwan; Taiwan Pediatric Oncology Group, Taipei, Taiwan;
authors.forename: Tai-Tsung
authors.initials: TT
authors.lastname: Chang
authors.affiliation: Medical School Hannover, Hannover, Germany; Acute Myeloid Leukemia-Berlin-Frankfurt-Munster Study Group, Essen, Germany;
authors.forename: Ursula
authors.initials: U
authors.lastname: Creutzig
authors.affiliation: St. Anna Children's Hospital, Medical University of Vienna, Vienna, Austria;
authors.forename: Michael
authors.initials: M
authors.lastname: Dworzak
authors.affiliation: Schneider Children's Medical Center of Israel, Petah-Tikva, Israel;
authors.forename: Sarah
authors.initials: S
authors.lastname: Elitzur
authors.affiliation: Children's Hospital La Plata, La Plata, Buenos Aires, Argentina; Grupo Argentino de Tratamiento de la Leucemia Aguda, Buenos Aires, Argentina;
authors.forename: Alcira
authors.initials: A
authors.lastname: Fynn
authors.affiliation: Umeå University Hospital, Umea, Sweden; Nordic Society for Pediatric Hematology and Oncology, Stockholm, Sweden;
authors.forename: Erik
authors.initials: E
authors.lastname: Forestier
authors.affiliation: Nordic Society for Pediatric Hematology and Oncology, Stockholm, Sweden; Aarhus University Hospital, Skejby, Aarhus, Denmark;
authors.forename: Henrik
authors.initials: H
authors.lastname: Hasle
authors.affiliation: Taiwan Pediatric Oncology Group, Taipei, Taiwan; Mackay Memorial Hospital, Taipei, Taiwan;
authors.forename: Der-Cherng
authors.initials: DC
authors.lastname: Liang
authors.affiliation: Prince of Wales Hospital, The Chinese University of Hong Kong, Hong Kong, China; Hong Kong Paediatric Haematology and Oncology Study Group, Hong Kong, China;
authors.forename: Vincent
authors.initials: V
authors.lastname: Lee
authors.affiliation: Istituto di Ricovero e Cura a Carattere Scientifico, Bambino Gesù Children's Hospital Rome, University of Pavia, Rome, Italy; Associazione Italiana Ematologia Oncologia Pediatrica, Bologna, Italy;
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.affiliation: Associazione Italiana Ematologia Oncologia Pediatrica, Bologna, Italy; Ospedale Sant'Orsola-Malpighi, Bologna, Italy;
authors.forename: Riccardo
authors.initials: R
authors.lastname: Masetti
authors.affiliation: Ghent University Hospital, Gent, Belgium; European Organisation for Research and Treatment of Cancer, Brussels, Belgium;
authors.forename: Barbara
authors.initials: B
authors.lastname: De Moerloose
authors.affiliation: Acute Myeloid Leukemia-Berlin-Frankfurt-Munster Study Group, Essen, Germany; University Children's Hospital, Essen, Germany;
authors.forename: Dirk
authors.initials: D
authors.lastname: Reinhardt
authors.affiliation: The Hospital for Sick Children, Toronto, ON, Canada;
authors.forename: Laura
authors.initials: L
authors.lastname: Rodriguez
authors.affiliation: Ghent University Hospital, Gent, Belgium; European Organisation for Research and Treatment of Cancer, Brussels, Belgium;
authors.forename: Nadine
authors.initials: N
authors.lastname: Van Roy
authors.affiliation: Shanghai Children's Medical Center, Shanghai Jiaotong University School of Medicine, Shanghai, China;
authors.forename: Shuhong
authors.initials: S
authors.lastname: Shen
authors.affiliation: Japanese Pediatric Leukemia/Lymphoma Study Group, Nagoya, Japan; Shiga University of Medical Science, Shiga, Japan;
authors.forename: Takashi
authors.initials: T
authors.lastname: Taga
authors.affiliation: Japanese Pediatric Leukemia/Lymphoma Study Group, Nagoya, Japan; National Center for Child Health and Development, Tokyo, Japan; and.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Tomizawa
authors.affiliation: National University Cancer Institute, National University Health System, Singapore, Singapore.
authors.forename: Allen E J
authors.initials: AE
authors.lastname: Yeoh
authors.affiliation: Medical School Hannover, Hannover, Germany; Acute Myeloid Leukemia-Berlin-Frankfurt-Munster Study Group, Essen, Germany;
authors.forename: Martin
authors.initials: M
authors.lastname: Zimmermann
authors.affiliation: St. Jude Children's Research Hospital, Memphis, TN;
authors.forename: Susana C
authors.initials: SC
authors.lastname: Raimondi
mesh_terms: D000293:Adolescent; D000964:Antimetabolites, Antineoplastic / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D003561:Cytarabine / Q000627:therapeutic use; D018572:Disease-Free Survival; D005260:Female; D015321:Gene Rearrangement; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007223:Infant; D053208:Kaplan-Meier Estimate; D007621:Karyotyping; D007947:Leukemia, Megakaryoblastic, Acute / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000628:therapy*; D008297:Male; D011379:Prognosis; D012189:Retrospective Studies; D016896:Treatment Outcome
chemical_list: D000964:Antimetabolites, Antineoplastic; D003561:Cytarabine