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CML

Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia – prospective long-term results from a randomized-controlled trial

Leukemia volume 17, pages 2444–2453 (2003)Cite this article

Abstract

Marrow fibrosis (MF) has rarely been considered in therapy studies on chronic myeloid leukemia (CML), and there is a lack of long-term observations on the basis of sequential bone marrow biopsies (BMBs) taken prospectively during the course of disease. A total of 848 BMBs from 400 patients with Ph+ CML recruited in the German randomized CML study I were examined for MF before and during therapy. In total, 110 patients had been randomized to receive interferon (IFN)-α, and 290 to receive chemotherapy (hydroxyurea (HU): 154, busulfan: 136). During IFN-α and HU medication, MF was reduced or did not increase for about 2 years. Evolving or progressive MF was an independent and early predictor of therapy failure about 2 years earlier than indicated by changes in the peripheral blood, spleen size, marrow blast count and cytogenetics (P<0.00005), resulting in a significant shortening of the survival times of patients independent of the type of therapy applied including allografting (multivariate analyses; P<0.00005). The analyzed long-term observations strongly indicate that MF is an independent poor prognostic complication of CML, allowing an early prediction of therapy failure. Consideration of the fiber content in marrow may therefore significantly improve the prediction of therapy efficacy and outcome of disease.

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Acknowledgements

We thank our colleagues from the numerous other laboratories in Germany and Switzerland supporting these evaluations for sending the bone marrow biopsies of the patients recruited into the German CML study to our laboratory. This work was supported by a grant (Bu1103/2-1) from the Deutsche Forschungsgemeinschaft, Bonn, Germany.

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Authors and Affiliations

  1. Institut für Pathologie, Medizinische Hochschule Hannover, Germany

    G Buesche, A Schmeil, G Gomez, T Buhr, H-H Kreipe & A Georgii

  2. III Medizinische Klinik, Klinikum Mannheim, Universität Heidelberg, Germany

    R Hehlmann

  3. Institut für Biometrie, Medizinische Hochschule Hannover, Germany

    H Hecker, H Herrmann & M Kappler

  4. Abteilung für Innere Medizin III, Klinikum der Universität Ulm, Germany

    H Heimpel

  5. Abteilung für Innere Medizin III, Tumorzytogenetiklabor, Universität Ulm, Germany

    B Heinze

  6. Institut für Medizinische Informatik, Biometrie und Epidemiologie, Universität München, Germany

    M Pfirrmann & J Hasford

  7. Hämatologisches Zentrallabor, Inselspital, Universität Bern, Switzerland

    A Tobler

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Buesche, G., Hehlmann, R., Hecker, H. et al. Marrow fibrosis, indicator of therapy failure in chronic myeloid leukemia – prospective long-term results from a randomized-controlled trial. Leukemia 17, 2444–2453 (2003). https://doi.org/10.1038/sj.leu.2403172

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