Hypodiploidy has unfavorable impact on survival in pediatric acute myeloid leukemia: an I-BFM Study Group collaboration

Author:

Hammer Anne Sofie Borg1ORCID,Juul-Dam Kristian Løvvik1ORCID,Sandahl Julie Damgaard1,Abrahamsson Jonas2,Czogala Malgorzata3ORCID,Delabesse Emmanuelle4,Haltrich Iren5ORCID,Jahnukainen Kirsi6ORCID,Kolb E. Anders7,Kovács Gábor5ORCID,Leverger Guy8,Locatelli Franco9,Masetti Riccardo10ORCID,Noren-Nyström Ulrika11ORCID,Raimondi Susana C.12,Rasche Mareike13ORCID,Reinhardt Dirk13ORCID,Taki Tomohiko14,Tomizawa Daisuke15ORCID,Zeller Bernward16,Hasle Henrik1ORCID,Kjeldsen Eigil17

Affiliation:

1. 1Department of Pediatric and Adolescent Medicine, Aarhus University Hospital, Aarhus, Denmark

2. 2Children’s Cancer Center, Queen Silvia’s Children’s Hospital, Göteborg, Sweden

3. 3Department of Pediatric Oncology and Hematology, Jagiellonian University Medical College, Institute of Pediatrics, Krakow, Poland

4. 4Toulouse-Oncopole, Laboratoire d’Hématologie secteur Génétique des Hémopathies, Toulouse, France

5. 52nd Department of Pediatrics, Semmelweis University, Budapest, Hungary

6. 6New Children’s Hospital, Pediatric Research Center, University of Helsinki and Helsinki University Hospital, Helsinki, Finland

7. 7Nemours/Alfred I. duPont Hospital for Children, Wilmington, DE

8. 8Hopital Armand Trousseau, Assistance Publique–Hôpitaux de Paris, Service d’hematologie et d’oncologie pediatrique, Paris, France

9. 9Department of Pediatric Haematology/Oncology and Cell and Gene Therapy, IRCCS Ospedale Pediatrico Bambino Gesù, Catholic University of the Sacred Heart, Rome, Italy

10. 10Dipartimento di Scienze Mediche e Chirurgiche, Pediatric Oncology and Hematology, IRCCS Azienda Ospedaliero-Universitaria di Bologna, Bologna, Italy

11. 11Department of Clinical Sciences, Pediatrics, Umeå University, Umeå, Sweden

12. 12St Jude Children’s Research Hospital, Memphis, TN

13. 13Department of Pediatric Hematology-Oncology, Pediatrics III, University Hospital of Essen, Essen, Germany

14. 14Faculty of Health Sciences, Laboratory of Clinical Hematology, Department of Medical Technology, Kyorin University, Mitaka, Japan

15. 15Division of Leukemia and Lymphoma, Children’s Cancer Center, National Center for Child Health and Development, Tokyo, Japan

16. 16Department of Pediatric Hematology and Oncology, Oslo University Hospital, Oslo, Norway

17. 17Department of Hematology, Hemodiagnostic Laboratory, Aarhus University Hospital, Aarhus, Denmark

Abstract

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.

Publisher

American Society of Hematology

Subject

Hematology

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