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Explaining survival differences between two consecutive studies with allogeneic stem cell transplantation in patients with chronic myeloid leukemia

  • Original Article – Clinical Oncology
  • Published:
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Abstract

Purpose

In the two consecutive German studies III and IIIA on chronic myeloid leukemia, between 1995 and 2004, 781 patients were randomized to receive either allogeneic hematopoietic stem cell transplantation with a related donor or continued drug treatment. Despite comparable transplantation protocols and most centers participating in both studies, the post-transplant survival probabilities for patients transplanted in first chronic phase were significantly higher in study IIIA (144 patients) than in study III (113 patients). Prior to the decision on a combined analysis of both studies, reasons for this discrepancy had to be investigated.

Methods

The Cox proportional hazard cure model was used to identify prognostic factors for post-transplant survival.

Results

Donor–recipient matching for human leukocyte antigen, patient age, time between diagnosis and transplantation, and calendar time showed a significant influence on survival and/or the incidence of cure. Added as a further factor, affiliation to study IIIA had no significant impact any longer.

Conclusions

Discrepancies in influential prognostic factors explained the different post-transplant survival probabilities between the studies. The significance of calendar time suggests a lack of consistency of transplantation practice over time. Accordingly, the prerequisite for a common assessment of overall survival in the two randomized transplantation arms was not met. Moreover, our analyses provide an independent validation of established prognostic factors and their cutoffs. The statistical approach in investigating and modeling potential prognostic factors for survival sets an example for the examination of studies with unexpected outcome differences in concurrent treatment arms.

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Acknowledgments

The valuable assistance of A. Gil, C. Obolashvili, S. Eckstein, and Y. Hao is gratefully appreciated. This work was supported by the German CML Study Group; Grant no. BMBF 01GI0270 from Deutsches Kompetenznetz für Akute und Chronische Leukämien, and research funding from the companies Roche, Essex, Amgen and Pharmacia to the CML Study Group (coordinator Rüdiger Hehlmann).

Conflict of interest

No conflict of interest in relation to this article exists. The authors have full control of all primary data and allow the journal to review the data if requested. The funding sources had no influence on data collection, analysis, interpretation of the results, or on the contents of the manuscript.

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Authors and Affiliations

  1. Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie - IBE, Ludwig-Maximilians-Universität, Marchioninistraße 15, 81377, Munich, Germany

    Markus Pfirrmann & Joerg Hasford

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

    Susanne Saussele, Andreas Reiter, Ute Berger & Rüdiger Hehlmann

  3. Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena, Jena, Germany

    Andreas Hochhaus & Herbert G. Sayer

  4. II. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf (UKE), Hamburg, Germany

    Dieter K. Hossfeld

  5. Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin, Klinikum Schwabing, Munich, Germany

    Christoph Nerl

  6. Klinik I für Innere Medizin, Uniklinik Köln, Cologne, Germany

    Christof Scheid

  7. Medizinische Klinik III und Poliklinik, Klinikum der Ludwig-Maximilians-Universität München, Munich, Germany

    Karsten Spiekermann

  8. Department of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University, Brno, Czech Republic

    Jiri Mayer

  9. Department of Hematology and Transplantology, University Clinical Center, Medical University of Gdansk, Gdańsk, Poland

    Andrzej Hellmann

  10. Allgemeine Hämatologie/Hämostaseologie, Universitätsklinik für Innere Medizin I, Vienna, Austria

    Klaus Lechner

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

    Christiane Falge

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

    Donald Bunjes & Hermann Heimpel

  13. Klinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover, Hannover, Germany

    Arnold Ganser

  14. Deutsches Register für Stammzelltransplantation (DRST) und Klinik für Knochenmarktransplantation, Universitätsklinikum Essen, Essen, Germany

    Dietrich W. Beelen

  15. Abteilung für Hämatologie, Universitätshospital Basel, Basel, Switzerland

    Helen Baldomero

  16. Swiss Blood Stem Cell Transplantation (SBST), Bern, Switzerland

    Urs Schanz

  17. 3. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität, Munich, Germany

    Hans-Jochem Kolb

  18. Behandlungszentrum Stammzelltransplantation, Universitätsspital Basel, Basel, Switzerland

    Alois Gratwohl

Authors
  1. Markus Pfirrmann
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  2. Susanne Saussele
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  5. Ute Berger
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  6. Dieter K. Hossfeld
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  7. Christoph Nerl
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  13. Christiane Falge
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  14. Herbert G. Sayer
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  15. Donald Bunjes
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  16. Arnold Ganser
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  17. Dietrich W. Beelen
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  18. Helen Baldomero
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  19. Urs Schanz
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  20. Hermann Heimpel
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  21. Hans-Jochem Kolb
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  22. Joerg Hasford
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for the Schweizerische Arbeitsgemeinschaft für Klinische Forschung (SAKK) and the German CML Study Group

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Correspondence to Markus Pfirrmann.

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Pfirrmann, M., Saussele, S., Hochhaus, A. et al. Explaining survival differences between two consecutive studies with allogeneic stem cell transplantation in patients with chronic myeloid leukemia. J Cancer Res Clin Oncol 140, 1367–1381 (2014). https://doi.org/10.1007/s00432-014-1662-y

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  • DOI: https://doi.org/10.1007/s00432-014-1662-y

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