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Differential impact of drugs on the outcome of ETV6-RUNX1 positive childhood B-cell precursor acute lymphoblastic leukaemia: results of the EORTC CLG 58881 and 58951 trials

Leukemia volume 32, pages 244–248 (2018)Cite this article

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In childhood B-cell precursor acute lymphoblastic leukaemias (BCP-ALL), the presence of an ETV6-RUNX1 fusion transcript defines one of the most prevalent genetic subgroups, together with the high hyperdiploidy (HeH) ALL. Although ETV6-RUNX1pos ALLs are associated with favourable outcome, their proper treatment strategies remain debatable, some groups suggesting crucial impact of upfront intensive treatment1 while others favour low-intensity antimetabolite-based therapy.2

To address this question, we evaluated the long-term prognostic and predictive value of ETV6-RUNX1 in BCR-ABL1 negative de novo BCP-ALL children (1–17 years old) treated in the European Organisation for Research and Treatment of Cancer (EORTC) studies 58881, opened between January 1989 and November 19983 (n=1692) and 58951 opened between December 1998 and August 20084, 5 (n=1602). Particular attention was given to the effects of the randomized treatments (Supplementary Figures S1 and S2) in the ETV6-RUNX1pos subgroup as compared with those observed in the HeH and ‘Others’ BCP-ALL subgroups, in order to reveal specific drug response profiles related to distinct oncogenic process.

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Acknowledgements

We thank all the EORTC CLG study group members. We thank the clinicians and biologists who participated in the studies. We also thank the EORTC HQ Data Management Department members (Séraphine Rossi, Lies Meirlaen, Liv Meert, Gabriel Solbu, Alessandra Busato, Aurélie Dubois, Nicole Duez, Livia Giurgea, Jan Herman, Bénédicte Marchal, Isabel VandeVelde and Christine Waterkeyn) for their essential support. We warmly thank Gaetan de Schaetzen, EORTC HQ Project Manager, for his invaluable help in this project. We also thank Prof. Martin Stanulla (Hannover medical school) for helpful discussion. This work was supported by the Kinderkankerfonds (a non-profit childhood cancer foundation under Belgian law) and by the EORTC Cancer Research Fund.

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Authors and Affiliations

  1. University Department of Pediatrics, Pediatric Onco-Hematology, CHR Citadelle, Liège, Belgium

    C Piette & M-F Dresse

  2. EORTC Headquarters, Brussels, Belgium

    S Suciu & C Gilotay

  3. Département de Génétique, Hôpital Robert Debré, Assistance Publique des Hôpitaux de Paris (AP-HP), Paris, France

    E Clappier, S Drunat & H Cavé

  4. Institut Universitaire d’Hématologie, Université Paris Diderot, Paris-Sorbonne-Cité, Paris, France

    E Clappier & H Cavé

  5. Department of Pediatric Hematology, IHOP, Hospices Civils de Lyon and Claude Bernard Lyon University, Lyon, France

    Y Bertrand

  6. Laboratory of Hematology, East Lyon University Hospital, Hospices Civils de Lyon, Lyon, France

    S Girard

  7. Assistance Publique des Hôpitaux de Paris (AP-HP), Hôpital Robert Debré, Service d’Immuno-Hématologie pédiatrique, Paris, France

    K Yakouben

  8. Department of Pediatric Onco-Hematology, Purpan University Hospital, Toulouse, France

    G Plat & N Dastugue

  9. Department of Pediatric Hematology-Oncology, Lille University Hospital, Lille, France

    F Mazingue & N Grardel

  10. Center for Medical Genetics, Ghent University, Ghent, Belgium

    N van Roy

  11. Department of Pediatrics, University Hospital Gasthuisberg, Leuven, Belgium

    A Uyttebroeck

  12. Department of Pediatrics, Portuguese Oncology Institute, Porto, Portugal

    V Costa

  13. Department of Pediatric Onco-Hematology, Caen University Hospital, Caen, France

    O Minckes

  14. Department of Pediatric Onco-Hematology, Montpellier University Hospital, Montpellier, France

    N Sirvent

  15. Department of Pediatric Onco-Hematology, Besançon University Hospital, Besançon, France

    P Simon

  16. Department of Hematology, Hautepierre University Hospital, Strasbourg, France

    P Lutz

  17. Department of Pediatric Onco-Hematology, Hôpital Universitaire des Enfants Reine Fabiola (ULB), Brussels, Belgium

    A Ferster

  18. Department of Pediatric Onco-Hematology, Reims University Hospital, Reims, France

    C Pluchart

  19. Department of Pediatric Onco-Hematology, Nice University Hospital, Nice, France

    M Poirée & P-S Rohrlich

  20. Department of Pediatric Onco-Hematology, Grenoble University Hospital, Grenoble, France

    C Freycon

  21. Department of Pediatric Onco-Hematology, Poitiers University Hospital, Poitiers, France

    F Millot

  22. Department of Pediatrics, Clinique de l'Espérance, CHC, Liège, Belgium

    C Chantrain

  23. Department of Pediatric Onco-Hematology, Universitair Ziekenhuis Brussel, Brussels, Belgium

    J van der Werff ten Bosch

  24. Pediatric Onco-Hematology Unit, Antwerp University Hospital, Antwerp, Belgium

    K Norga

  25. Department of Pediatric Hematology-Oncology, Ghent University Hospital, Ghent, Belgium

    Y Benoit

Authors
  1. C Piette
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  2. S Suciu
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  3. E Clappier
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  4. Y Bertrand
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  7. K Yakouben
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  8. G Plat
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  10. F Mazingue
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  11. N Grardel
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  13. A Uyttebroeck
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  14. V Costa
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  15. O Minckes
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  16. N Sirvent
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  17. P Simon
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  18. P Lutz
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  19. A Ferster
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  20. C Pluchart
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  21. M Poirée
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  23. M-F Dresse
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  27. K Norga
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  28. C Gilotay
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  31. H Cavé
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Corresponding authors

Correspondence to C Piette or H Cavé.

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The authors declare no conflict of interest.

Additional information

The study was presented at ASH meeting, Orlando, 7 December 2015, # 793.

Supplementary Information accompanies this paper on the Leukemia website

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Piette, C., Suciu, S., Clappier, E. et al. Differential impact of drugs on the outcome of ETV6-RUNX1 positive childhood B-cell precursor acute lymphoblastic leukaemia: results of the EORTC CLG 58881 and 58951 trials. Leukemia 32, 244–248 (2018). https://doi.org/10.1038/leu.2017.289

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