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Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C

Leukemia volume 17, pages 2392–2400 (2003)Cite this article

Abstract

We sought to determine dynamics of BCR-ABL mRNA expression levels in 139 patients with chronic myelogenous leukemia (CML) in early chronic phase, randomized to receive imatinib (n=69) or interferon (IFN)/Ara-C (n=70). The response was sequentially monitored by cytogenetics from bone marrow metaphases (n=803) and qualitative and quantitative RT-PCR from peripheral blood samples (n=1117). Complete cytogenetic response (CCR) was achieved in 60 (imatinib, 87%) vs 10 patients (IFN/Ara-C, 14%) after a median observation time of 24 months. Within the first year after CCR, best median ratio BCR-ABL/ABL was 0.087%, (imatinib, n=48) vs 0.27% (IFN/Ara-C, n=9, P=0.025). BCR-ABL was undetectable in 25 cases by real-time PCR, but in only four patients by nested PCR. Median best response in patients with relapse after CCR was 0.24% (n=3) as compared to 0.029% in patients with continuous remission (n=52, P=0.029). We conclude that (i) treatment with imatinib in newly diagnosed CML patients is associated with a rapid decrease of BCR-ABL transcript levels; (ii) nested PCR may reveal residual BCR-ABL transcripts in samples that are negative by real-time PCR; (iii) BCR-ABL transcript levels parallel cytogenetic response, and (iv) imatinib is superior to IFN/Ara-C in terms of the speed and degree of molecular responses, but residual disease is rarely eliminated.

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Acknowledgements

We thank the members of the German CML Study Group, coinvestigators, nursing and research staff for the excellent cooperation. The study was supported by Novartis Pharma GmbH, Nürnberg, Germany, the Forschungsfonds der Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Germany, and the Competence Network ‘Acute and chronic leukemias’, sponsored by the German Bundesministerium für Bildung und Forschung (Projektträger Gesundheitsforschung; DLR e.V.- 01 GI9980/6). We are grateful to Ms Insa Gathmann, Novartis Pharmaceuticals, Basel, Switzerland, for providing clinical and cytogenetic data.

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Authors and Affiliations

  1. III. Medizinische Universitätsklinik, Fakultät für Klinische Medizin Mannheim der Universität Heidelberg, Mannheim, Germany

    M C Müller, T Lahaye, K Merx, P Paschka, H König, S Kreil, U Berger, R Hehlmann & A Hochhaus

  2. Medizinische Klinik, Universität Düsseldorf, Germany

    N Gattermann

  3. Abteilung Hämatologie, Medizinische Klinik, Universität Leipzig, Germany

    M W N Deininger

  4. Klinik für Innere Medizin, Technische Universität, Dresden, Germany

    A Berndt

  5. Medizinische Klinik und Poliklinik V, Universität Heidelberg, Germany

    S Fruehauf

  6. Abteilung Hämatologie/Onkologie, Universität Marburg, Germany

    A Neubauer

  7. Medizinische Klinik III, Universität Mainz, Germany

    T Fischer

  8. Medizinische Klinik und Poliklinik, Universitätsklinikum Eppendorf, Hamburg, Germany

    D K Hossfeld

  9. III. Medizinische Klinik und Poliklinik, Technische Universität München, Germany

    F Schneller

  10. Abteilung für Hämatologie und Internistische Onkologie, Klinikum der Universität Regensburg, Germany

    S W Krause

  11. I. Medizinische Klinik, Städtisches Krankenhaus München-Schwabing, Germany

    C Nerl

  12. Klinik und Poliklinik für Innere Medizin II, Universität Jena, Germany

    H G Sayer

  13. III. Medizinische Klinik, Universität Frankfurt, Germany

    O G Ottmann

  14. Medizinische Klinik I, Universität Freiburg, Germany

    C Waller

  15. Zentrum Innere Medizin II, Robert-Bosch-Krankenhaus Stuttgart, Germany

    W Aulitzky

  16. Medizinische Klinik, Hämatologie/Onkologie, Virchow Campus Charité Berlin, Germany

    P le Coutre

  17. Medizinische Klinik und Poliklinik, Universität Rostock, Germany

    M Freund

  18. Novartis Pharma, Nürnberg, Germany

    H Gschaidmeier

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Müller, M., Gattermann, N., Lahaye, T. et al. Dynamics of BCR-ABL mRNA expression in first-line therapy of chronic myelogenous leukemia patients with imatinib or interferon α/ara-C. Leukemia 17, 2392–2400 (2003). https://doi.org/10.1038/sj.leu.2403157

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Keywords

  • quantitative PCR
  • BCR-ABL
  • chronic myelogenous leukemia
  • imatinib
  • interferon alpha

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