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Chronic Myeloproliferative Neoplasias

Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML)

Leukemia volume 26, pages 2096–2102 (2012)Cite this article

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Abstract

In the face of competing first-line treatment options for CML, early prediction of prognosis on imatinib is desirable to assure favorable survival or otherwise consider the use of a second-generation tyrosine kinase inhibitor (TKI). A total of 1303 newly diagnosed imatinib-treated patients (pts) were investigated to correlate molecular and cytogenetic response at 3 and 6 months with progression-free and overall survival (PFS, OS). The persistence of BCR-ABL transcript levels >10% according to the international scale (BCR-ABLIS) at 3 months separated a high-risk group (28% of pts; 5-year OS: 87%) from a group with >1–10% BCR-ABLIS (41% of pts; 5-year OS: 94%; P=0.012) and from a group with ⩽1% BCR-ABLIS (31% of pts; 5-year OS: 97%; P=0.004). Cytogenetics identified high-risk pts by >35% Philadelphia chromosome-positive metaphases (Ph+, 27% of pts; 5-year OS: 87%) compared with ⩽35% Ph+ (73% of pts; 5-year OS: 95%; P=0.036). At 6 months, >1% BCR-ABLIS (37% of pts; 5-year OS: 89%) was associated with inferior survival compared with ⩽1% (63% of pts; 5-year OS: 97%; P<0.001) and correspondingly >0% Ph+ (34% of pts; 5-year OS: 91%) compared with 0% Ph+ (66% of pts; 5-year OS: 97%; P=0.015). Treatment optimization is recommended for pts missing these landmarks.

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Acknowledgements

We thank Insa Gathmann (Novartis, Basel, Switzerland) for statistical analysis of the validation sample. We thank Michelle Giehl, Umang Munjal, Sven Haag, Katrin Ackermann, Alla Elkovskaia, Elena Felde, Maike Haas, Melanie Hartmann, Carolin Hölting, Cathrin Huber, Vanessa Leins, Melanie Müller, Iris Palme and Irina Tarnapolscaia for reporting of laboratory results and technical assistance. The contributions of Angelika Adler, Gabriele Bartsch, Ute Berger, Sabine Dean, Christian Dietz, Michaela Hausmann, Ute Kossak, Elke Matzat, Barbara Müller, Regina Pleil-Lösch, Nicole Schomber, Annette Schreiber, Inge Stalljann, Nicole Steidl, Cornelia Willersinn, the Steering Group (Rüdiger Hehlmann, Gerhard Ehninger, Joerg Hasford, Andreas Hochhaus, Dieter Hossfeld, Hans-Jochem Kolb, Stefan Krause, Christoph Nerl, Hans Pralle, Dominik Heim, Gabriela M. Baerlocher, Hermann Heimpel) and all CML trial participants are acknowledged.

Author information

Author notes

  1. B Hanfstein: These authors contributed equally to this work.

  2. M C Müller, S Saußele and A Hochhaus: Co-senior authors.

Authors and Affiliations

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

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

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

    M Lauseker, M Pfirrmann & J Hasford

  3. MLL Münchner Leukämielabor GmbH, München, Germany

    S Schnittger & C Haferlach

  4. Institut für Zell- und Molekularpathologie, Medizinische Hochschule Hannover, Hannover, Germany

    G Göhring

  5. Medizinische Klinik und Poliklinik III, Klinikum der Universität München-Großhadern, München-Großhadern, Germany

    H-J Kolb & K Spiekermann

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

    S W Krause

  7. Abteilung für Hämatologie-Onkologie, Evangelisches Krankenhaus Hamm, Hamm, Germany

    J Schubert

  8. Medizinische Klinik und Poliklinik II, Universitätsklinikum Würzburg, Würzburg, Germany

    H Einsele

  9. Abteilung Innere Medizin V, Medizinische Klinik, Universitätsklinikum Heidelberg, Heidelberg, Germany

    J Dengler

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

    M Hänel

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

    C Falge

  12. Medizinische Klinik, Universitätsklinikum Tübingen, Tübingen, Germany

    L Kanz

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

    A Neubauer

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

    M Kneba

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

    F Stegelmann

  16. Klinik für Innere Medizin I, Universitätsklinikum des Saarlandes, Homburg, Germany

    M Pfreundschuh

  17. Abteilung Innere Medizin I, Universitätsklinikum Freiburg, Freiburg, Germany

    C F Waller

  18. Molecular Pathology, SA Pathology,, Adelaide, Australia

    S Branford

  19. School of Medicine, University of Adelaide, Adelaide, Australia

    S Branford

  20. Department of Haematology, SA Pathology, Royal Adelaide Hospital, Adelaide, Australia

    T P Hughes

  21. Universitätsklinik für Hämatologie und hämatologisches Zentrallabor, Universitätsspital Bern, Bern, Switzerland

    G M Baerlocher

  22. Abteilung für Hämatologie/Onkologie, Universitätsklinikum Jena, Jena, Germany

    A Hochhaus

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for the SAKK and the German CML Study Group

Corresponding author

Correspondence to A Hochhaus.

Additional information

Data presented in part at the Annual Meetings of the American Society of Hematology 2010 and 2011, the Annual Meeting of the European Hematology Association 2011 and the Annual Meeting of the German, Swiss and Austrian Societies of Hematology and Oncology 2011.

Author Contributions

BH, MCM, RH, SSa and AH had the primary responsibility for the publication. AH has been responsible for the organization and interpretation of the molecular analyses. PE, ML, AF, SSch, CH, GG, UP, HJK, SWK, WKH, JS, HE, JD, MH, CF, LK, AN, MK, FS, MP, CFW, KS, GMB, MP, JH, TPH and SB contributed to the design of the study, to the collection of data, to the statistical analysis and to the interpretation of the results. All authors have checked and approved the final version of the manuscript.

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Hanfstein, B., Müller, M., Hehlmann, R. et al. Early molecular and cytogenetic response is predictive for long-term progression-free and overall survival in chronic myeloid leukemia (CML). Leukemia 26, 2096–2102 (2012). https://doi.org/10.1038/leu.2012.85

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