Abstract

A total of 156 patients (age range 1.3–18.0 years, median 13.2 years; 91 (58.3%) male) with newly diagnosed CML (N = 146 chronic phase (CML-CP), N = 3 accelerated phase (CML-AP), N = 7 blastic phase (CML-BP)) received imatinib up-front (300, 400, 500 mg/m2, respectively) within a prospective phase III trial. Therapy response, progression-free survival, causes of treatment failure, and side effects were analyzed in 148 children and adolescents with complete data. Event-free survival rate by 18 months for patients in CML-CP (median follow-up time 25 months, range: 1−120) was 97% (95% CI, 94.2−99.9%). According to the 2006 ELN-criteria complete hematologic response by month 3, complete cytogenetic response (CCyR) by month 12, and major molecular response (MMR) by month 18 were achieved in 98, 63, and 59% of the patients, respectively. By month 36, 86% of the patients achieved CCyR and 74% achieved MMR. Thirty-eight patients (27%) experienced imatinib failure because of unsatisfactory response or intolerance (N = 9). In all, 28/148 patients (19%) underwent stem cell transplantation (SCT). In the SCT sub-cohort 2/23 patients diagnosed in CML-CP, 0/1 in CML-AP, and 2/4 in CML-BP, respectively, died of relapse (N = 3) or SCT-related complications (N = 2). This large pediatric trial extends and confirms data from smaller series that first-line imatinib in children is highly effective.

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Acknowledgements

Meinolf Suttorp received financial support as grants from Deutsche Forschungsgemeinschaft (DFG SU 122/3-1), Sonnenstrahl e.V. Dresden, Germany, Peter-Escher Foundation, Leipzig, Germany, and Mitteldeutsche Kinderkrebsforschung Foundation, Leipzig, Germany. The work of Ingmar Glauche and Philipp Schulze was supported by the German Federal Ministry of Research and Education, Grant number 031A315 “MessAge” and Grant number 031A424 “HaematoOpt”.

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Author notes

  1. These authors contributed equally: Brigitte Schlegelberger, Christian Thiede

Affiliations

  1. Pediatric Hematology and Oncology, Department of Pediatrics, University Hospital “Carl Gustav Carus”, TU Dresden, Dresden, Germany

    • Meinolf Suttorp
    • , Christina Nowasz
    •  & Josephine T. Tauer
  2. Institute for Medical Informatics and Biometry, Faculty of Medicine “Carl Gustav Carus”, TU Dresden, Dresden, Germany

    • Philipp Schulze
    •  & Ingmar Glauche
  3. Department of Human Genetics, Hannover Medical School, Hannover, Germany

    • Gudrun Göhring
    • , Nils von Neuhoff
    •  & Brigitte Schlegelberger
  4. Department of Pediatrics III, University Hospital, University of Duisburg-Essen, Duisberg, Germany

    • Nils von Neuhoff
    •  & Bernhard Kremens
  5. Pediatric Hematology and Oncology, University Children’s Hospital, Erlangen, Germany

    • Markus Metzler
    •  & Manuela Krumbholz
  6. Pediatric Hematology and Oncology, Teaching Hospital Motol, 2nd Medical School, Charles University Motol, Prague, Czech Republic

    • Petr Sedlacek
  7. Pediatric Hematology and Oncology, University Children’s Hospital, Groningen, The Netherlands

    • Eveline S. J. M. de Bont
  8. Dutch Childhood Oncology Group (DCOG), The Hague, The Netherlands

    • Eveline S. J. M. de Bont
  9. Pediatric Hematology and Hematopoietic Stem Cell Transplantation Unit, Clinica Pediatrica Università degli Studi di Milano Bicocca, Ospedale San Gerardo, Monza, Italy

    • Adriana Balduzzi
  10. Department of Pediatric and Adolescent Medicine, University Hospital, Rigshospitalet, Copenhagen, Denmark

    • Birgitte Lausen
  11. Belarus Research Center for Pediatric Oncology, Hematology, and Immunology, Minsk, Belarus

    • Olga Aleinikova
  12. Department of Pediatrics, BMT Unit, Comenius University Children’s Hospital, Bratislava, Slovakia

    • Sabina Sufliarska
  13. Pediatric Hematology and Oncology, University Children’s Hospital, Charité Berlin, Germany

    • Günter Henze
    • , Gabriele Strauss
    •  & Angelika Eggert
  14. Pediatric Hematology and Oncology, Helios KlinikenBerlin-Buch, Berlin, Germany

    • Gabriele Strauss
  15. Pediatric Hematology and Oncology, University Children’s Hospital, Münster, Germany

    • Andreas H. Groll
  16. Pediatric Hematology and Oncology, University Children’s Hospital, Cologne, Germany

    • Frank Berthold
  17. University Children’s Hospital, Ludwig Maximilians University, Munich, Germany

    • Christoph Klein
  18. Pediatric Oncology, Hematology, Immunology, Stuttgart Cancer Center, Klinikum Stuttgart—Olgahospital, Stuttgart, Germany

    • Ute Groß-Wieltsch
  19. Paediatric Hematology and Oncology, Hannover Medical School, Hannover, Germany

    • Karl Walter Sykora
  20. Pediatric Hematology, Oncology, and Clinical Immunology, Medical Faculty, Heinrich-Heine-University, Düsseldorf, Germany

    • Arndt Borkhardt
  21. Pediatric Oncology, Hematology, and Immunology, University Children’s Hospital, Heidelberg, Germany

    • Andreas E. Kulozik
  22. Pediatric Hematology and Oncology, University Children’s Hospital, Kiel, Germany

    • Martin Schrappe
    •  & Alexander Claviez
  23. Shriners Hospitals for Children, Montréal, Canada

    • Josephine T. Tauer
  24. Oncogenetic Laboratory, Pediatric Hematology and Oncology, University Children’s Hospital, Giessen, Germany

    • Jochen Harbott
  25. Institute of Pathology, Hannover Medical School, Hannover, Germany

    • Hans H. Kreipe
  26. Medical Department I, University Hospital “Carl Gustav Carus”, TU Dresden, Dresden, Germany

    • Christian Thiede

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Conflict of interest

IG received research support (Institutional) and reimbursement for attending symposia from Bristol-Myers-Squibb. HHK received research support (Institutional) from Roche Pharma, and coverage of other expenses by Amgen, Astra Zeneca, Genomic Health, Lilly, and Roche Pharma. BS received fees for advisory board consultations (PARP inhibitors, not related to this trial) from Astra Zeneca. MSch received recent research support (Institutional) from Novartis in the time period from 2004 to 2012. MS received research support (Institutional) from Novartis and reimbursement for attending symposia organized by Bristol-Myers-Squibb, Novartis, and Pfizer. CT received research support (Institutional) from Bayer, Novartis, and Roche and is employed presently as CEO by AgenDix GmbH. The remaining authors declare that they have no conflict of interest. Neither Novartis nor any other pharmaceutical company was permitted prior insight to the results of trial CML-Paed II. Apart from the authors nobody participated in writing of the manuscript.

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Correspondence to Meinolf Suttorp.

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https://doi.org/10.1038/s41375-018-0179-9