Hypodiploidy has Unfavorable Impact on Survival in Pediatric Acute Myeloid Leukemia: An I-BFM Study Group collaboration

Anne Sofie Borg Hammer*, Kristian Løvvik Juul-Dam, Julie Damgaard Sandahl, Jonas Abrahamsson, Malgorzata Czogala, Emmanuelle Delabesse, Iren Haltrich, Kirsi Jahnukainen, E. Anders Kolb, Gábor L Kovács, Guy Leverger, Franco Locatelli, Riccardo Masetti, Ulrika Norén-Nyström, Susana C Raimondi, Mareike Rasche, Dirk Reinhardt, Tomohiko Taki, Daisuke Tomizawa, Henrik HasleEigil Kjeldsen, Bernward Zeller, Henrik Hasle, Eigil Kjeldsen, The I-BFM-AML Study Group

*Corresponding author for this work

Research output: Contribution to journal/Conference contribution in journal/Contribution to newspaperJournal articleResearchpeer-review

Abstract

Hypodiploidy, defined as modal numbers (MNs) 45 or lower, has not been independently investigated in pediatric acute myeloid leukemia (AML) but is a well-described high-risk factor in pediatric acute lymphoblastic leukemia. We aimed to characterize and study the prognostic impact of hypodiploidy in pediatric AML. In this retrospective cohort study, we included children below 18 years of age with de novo AML and a hypodiploid karyotype diagnosed from 2000 to 2015 in 14 childhood AML groups from the International Berlin-Frankfurt-Münster (I-BFM) framework. Exclusion criteria comprised constitutional hypodiploidy, monosomy 7, composite karyotype, and t(8;21) with concurring sex chromosome loss. Hypodiploidy occurred in 81 patients (1.3%) with MNs, 45 (n = 66); 44 (n = 10) and 43 (n = 5). The most frequently lost chromosomes were chromosome 9 and sex chromosomes. Five-year event-free survival (EFS) and overall survival (OS) were 34% and 52%, respectively, for the hypodiploid cohort. Children with MN≤44 (n = 15) had inferior EFS (21%) and OS (33%) compared with children with MN = 45 (n = 66; EFS, 37%; OS, 56%). Adjusted hazard ratios (HRs) were 4.9 (P = .001) and 6.1 (P = .003). Monosomal karyotype or monosomy 9 had particular poor OS (43% and 15%, respectively). Allogeneic stem cell transplantation (SCT) in first complete remission (CR1) (n = 18) did not mitigate the unfavorable outcome of hypodiploidy (adjusted HR for OS was 1.5; P = .42). We identified pediatric hypodiploid AML as a rare subgroup with an inferior prognosis even in the patients treated with SCT in CR1.

Original languageEnglish
JournalBlood Advances
Volume7
Issue6
Pages (from-to)1045–1055
Number of pages11
ISSN2473-9529
DOIs
Publication statusPublished - Mar 2023

Keywords

  • Child
  • Humans
  • Leukemia, Myeloid, Acute/genetics
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma
  • Prognosis
  • Remission Induction
  • Retrospective Studies

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