Complex karyotype newly defined: the strongest prognostic factor in advanced childhood myelodysplastic syndrome

Author:

Göhring Gudrun1,Michalova Kyra2,Beverloo H. Berna34,Betts David5,Harbott Jochen6,Haas Oskar A.7,Kerndrup Gitte8,Sainati Laura9,Bergstraesser Eva5,Hasle Henrik10,Starý Jan11,Trebo Monika7,van den Heuvel-Eibrink Marry M.412,Zecca Marco13,van Wering Elisabeth R.4,Fischer Alexandra14,Noellke Peter14,Strahm Brigitte14,Locatelli Franco15,Niemeyer Charlotte M.14,Schlegelberger Brigitte1

Affiliation:

1. Institute of Cell and Molecular Pathology, Hannover Medical School, Hannover, Germany;

2. Center of Oncocytogenetics, Charles University, General Faculty Hospital, Prague, Czech Republic;

3. Department of Clinical Genetics, Erasmus University Medical Center, Rotterdam, The Netherlands;

4. Dutch Childhood Oncology Group, The Hague, The Netherlands;

5. Department of Oncology, University Children's Hospital, Zurich, Switzerland;

6. Department of Pediatric Hematology/Oncology, Justus Liebig University, Giessen, Germany;

7. St Anna Children's Hospital, Vienna, Austria;

8. Institute of Pathology, University Hospital, Odense, Denmark;

9. Clinica Oncoematologica Pediatrica, University of Padova, Padova, Italy;

10. Department of Pediatrics, Aarhus University Hospital Skejby, Aarhus, Denmark;

11. Department of Pediatric Hematology and Oncology, University Hospital Motol and Charles University, Prague, Czech Republic;

12. Department of Pediatric Oncology, Sophia Children's Hospital, Erasmus University, Rotterdam, The Netherlands;

13. Istituti di Ricovero e Cura a Carattere Scientifico Policlinico San Matteo, Department of Pediatrics, University of Pavia, Pavia, Italy;

14. Department of Adolescent and Pediatric Medicine, University Hospital, Freiburg, Germany; and

15. Department of Pediatric Hematology and Oncology, Ospedale Bambino Gesù, Rome, Italy

Abstract

Abstract To identify cytogenetic risk factors predicting outcome in children with advanced myelodysplastic syndrome, overall survival of 192 children prospectively enrolled in European Working Group of Myelodysplastic Syndrome in Childhood studies was evaluated with regard to karyotypic complexity. Structurally complex constitutes a new definition of complex karyotype characterized by more than or equal to 3 chromosomal aberrations, including at least one structural aberration. Five-year overall survival in patients with more than or equal to 3 clonal aberrations, which were not structurally complex, did not differ from that observed in patients with normal karyotype. Cox regression analysis revealed the presence of a monosomal and structurally complex karyotype to be strongly associated with poor prognosis (hazard ratio = 4.6, P < .01). Notably, a structurally complex karyotype without a monosomy was associated with a very short 2-year overall survival probability of only 14% (hazard ratio = 14.5; P < .01). The presence of a structurally complex karyotype was the strongest independent prognostic marker predicting poor outcome in children with advanced myelodysplastic syndrome.

Publisher

American Society of Hematology

Subject

Cell Biology,Hematology,Immunology,Biochemistry

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