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Additional treatment with 2-Chloro-2-Deoxyadenosine during consolidation in children with high-risk acute myeloid leukemia does not improve survival

Leukemia volume 29, pages 2260–2263 (2015)Cite this article

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The outcome in children and adolescents with high-risk (HR) acute myeloid leukemia (AML) is still unsatisfactory. Increasing the intensity of chemotherapy in these patients is difficult because toxicity has already reached a limiting level. Therefore, in study AML-BFM 2004 we aimed to improve outcome of HR patients (defined as nonstandard risk (SR) patients) by adding moderately dosed 2-chloro-2-deoxyadenosine (2-CDA) to the respective consolidation treatment backbone without increasing the toxicity.

2-CDA is one of the purine nucleoside analog drugs, which has shown remarkable efficacy alone or in combination regimens in de novo or in relapsed leukemia patients.1, 2 Different from conventional antimetabolites, 2-CDA is cytotoxic to both proliferating and quiescent cells.3, 4 In vitro studies also demonstrated a cross-resistance between cytarabine and other deoxynucleoside analogs, and a high sensitivity for 2-CDA in AML blasts, particularly in FAB type M5.5

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Acknowledgements

We thank the colleagues, data managers and technicians of the participating hospitals for their valuable cooperation, Jans-Enno Müller (Hannover) and Nora Mühlegger (Vienna) for competent data management. This study was supported by the Deutsche Krebshilfe e.V. and partly by the project (Ministry of Health, Czech Republic) for conceptual development of research organization 00064203 (the University Hospital Motol, Prague, Czech Republic).

Author Contributions

UC, MND, MZ, J-PB and DR designed and performed research and wrote and edited the paper. MZ, UC, MND and DR analyzed the data, CvN and JS performed the diagnostic studies and edited the paper, BG, GF, NG, TK, BK, TL, AvS and JS provided the study materials or patients and edited the manuscript. All the authors reviewed and approved the final version of the manuscript.

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Author notes

  1. U Creutzig and M N Dworzak: These authors contributed equally to this work.

Authors and Affiliations

  1. Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany

    U Creutzig, M Zimmermann, C von Neuhoff & D Reinhardt

  2. Department of Pediatrics, St Anna Children's Hospital and Children’s Cancer Research Institute, Medical University of Vienna, Vienna, Austria

    M N Dworzak

  3. Pediatric Hematology/Oncology, University of Zurich, Zurich, Switzerland

    J-P Bourquin

  4. Department of Pediatrics, Jena University Hospital, Jena, Germany

    B Gruhn

  5. Department of Pediatric Hematology-Oncology, University of Duisburg-Essen, Essen, Germany

    G Fleischhack, B Kremens & D Reinhardt

  6. Department of Pediatric Oncology and Hematology, Medical School, Saarland University, Homburg, Germany

    N Graf

  7. Pediatric Hematology, Oncology and Hemostaseology, University Children’s Hospital of Frankfurt/Main, Goethe-University Frankfurt/Main, Frankfurt/Main, Germany

    T Klingebiel & T Lehrnbecher

  8. Department of Pediatric Oncology/Hematology, Charité Universitätsmedizin Berlin, Berlin, Germany

    A v Stackelberg

  9. Department of Pediatric Hematology and Oncology, 2nd Faculty of Medicine, Charles University and University Hospital Motol, Czech Pediatric Hematology Working Group (CPH), Prague, Czech Republic

    J Starý

Authors
  1. U Creutzig
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  2. M N Dworzak
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  3. M Zimmermann
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  6. G Fleischhack
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  7. N Graf
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  10. T Lehrnbecher
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  11. C von Neuhoff
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  13. J Starý
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  14. D Reinhardt
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Corresponding author

Correspondence to U Creutzig.

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The authors declare no conflict of interest.

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Creutzig, U., Dworzak, M., Zimmermann, M. et al. Additional treatment with 2-Chloro-2-Deoxyadenosine during consolidation in children with high-risk acute myeloid leukemia does not improve survival. Leukemia 29, 2260–2263 (2015). https://doi.org/10.1038/leu.2015.94

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