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Chronic Myeloproliferative Neoplasias

Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib

Leukemia volume 28, pages 1988–1992 (2014)Cite this article

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Abstract

Early assessment of response at 3 months of tyrosine kinase inhibitor treatment has become an important tool to predict favorable outcome. We sought to investigate the impact of relative changes of BCR-ABL transcript levels within the initial 3 months of therapy. In order to achieve accurate data for high BCR-ABL levels at diagnosis, beta glucuronidase (GUS) was used as a reference gene. Within the German CML-Study IV, samples of 408 imatinib-treated patients were available in a single laboratory for both times, diagnosis and 3 months on treatment. In total, 301 of these were treatment-naïve at sample collection. Results: (i) with regard to absolute transcript levels at diagnosis, no predictive cutoff could be identified; (ii) at 3 months, an individual reduction of BCR-ABL transcripts to the 0.35-fold of baseline level (0.46-log reduction, that is, roughly half-log) separated best (high risk: 16% of patients, 5-year overall survival (OS) 83% vs 98%, hazard ratio (HR) 6.3, P=0.001); (iii) at 3 months, a 6% BCR-ABLIS cutoff derived from BCR-ABL/GUS yielded a good and sensitive discrimination (high risk: 22% of patients, 5-year OS 85% vs 98%, HR 6.1, P=0.002). Patients at risk of disease progression can be identified precisely by the lack of a half-log reduction of BCR-ABL transcripts at 3 months.

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Authors and Affiliations

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

    B Hanfstein, V Shlyakhto, R Hehlmann, S Saussele, C Dietz, P Erben, A Fabarius, U Proetel, W-K Hofmann & M C Müller

  2. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie der Ludwig-Maximilians-Universität München, München, Germany

    M Lauseker, M Pfirrmann & J Hasford

  3. MLL Münchner Leukämielabor, München, Germany

    S Schnittger

  4. Medizinische Klinik 5, Universitätsklinikum Erlangen, Erlangen, Germany

    S W Krause

  5. Klinik für Hämatologie, Onkologie und Palliativmedizin, Evangelisches Krankenhaus, Hamm, Germany

    J Schubert

  6. Medizinischen Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

    H Einsele

  7. Klinik für Innere Medizin III, Klinikum Chemnitz, Chemnitz, Germany

    M Hänel

  8. Abteilung Innere Medizin V, Medizinische Universitätsklinik, Ruprecht-Karls-Universität Heidelberg, Heidelberg, Germany

    J Dengler

  9. Medizinische Klinik 5, Klinikum Nürnberg Nord, Nürnberg, Germany

    C Falge

  10. Medizinische Klinik II, Universitätsklinikum Tübingen, Tübingen, Germany

    L Kanz

  11. Klinik für Innere Medizin, Schwerpunkt Hämatologie, Onkologie und Immunologie, Universitätsklinikum Gießen und Marburg, Marburg, Germany

    A Neubauer

  12. II. Medizinische Klinik und Poliklinik im Städtischen Krankenhaus, Universitätsklinikum Schleswig-Holstein, Kiel, Germany

    M Kneba

  13. Klinik für Innere Medizin III, Universitätsklinikum Ulm, Ulm, Germany

    F Stegelmann

  14. Innere Medizin I,

    M Pfreundschuh

  15. Universitätsklinikum des Saarlandes, Homburg, Germany

    M Pfreundschuh

  16. Klinik für Innere Medizin I, Universitätsklinikum Freiburg, Freiburg, Germany

    C F Waller

  17. Medizinische Klinik und Poliklinik III, Ludwig-Maximilians-Universität München, München, Germany

    K Spiekermann

  18. Universitätsklinik für Hämatologie, Inselspital Bern, Bern, Switzerland

    G M Baerlocher

  19. Abteilung für Hämatologie und Internistische Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

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  1. B Hanfstein
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  28. A Hochhaus
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  29. M C Müller
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for the SAKK and the German CML Study Group

Corresponding author

Correspondence to M C Müller.

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Competing interests

The CML-Study IV is supported by the Deutsche Krebshilfe (Nr. 106642), Novartis, Nürnberg, Germany, Kompetenznetz für Akute and Chronische Leukämien (BMBF 01GI0270), José-Carreras Leukämiestiftung (DJCLS H09/01f, H06/04v, H03/01) and the European LeukemiaNet (LSHC-CT-2004-503216). SS declares employment and equity ownership. The remaining authors declare no conflict of interest.

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Hanfstein, B., Shlyakhto, V., Lauseker, M. et al. Velocity of early BCR-ABL transcript elimination as an optimized predictor of outcome in chronic myeloid leukemia (CML) patients in chronic phase on treatment with imatinib. Leukemia 28, 1988–1992 (2014). https://doi.org/10.1038/leu.2014.153

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