Journal of Cancer Research and Clinical Oncology

, Volume 140, Issue 8, pp 1367–1381

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

  • Markus Pfirrmann
  • Susanne Saussele
  • Andreas Hochhaus
  • Andreas Reiter
  • Ute Berger
  • Dieter K. Hossfeld
  • Christoph Nerl
  • Christof Scheid
  • Karsten Spiekermann
  • Jiri Mayer
  • Andrzej Hellmann
  • Klaus Lechner
  • Christiane Falge
  • Herbert G. Sayer
  • Donald Bunjes
  • Arnold Ganser
  • Dietrich W. Beelen
  • Helen Baldomero
  • Urs Schanz
  • Hermann Heimpel
  • Hans-Jochem Kolb
  • Joerg Hasford
  • Alois Gratwohl
  • Rüdiger Hehlmann
  • for the Schweizerische Arbeitsgemeinschaft für Klinische Forschung (SAKK) and the German CML Study Group
Original Article – Clinical Oncology

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.

Keywords

Chronic myeloid leukemia Allogeneic stem cell transplantation Post-transplant overall survival Cox cure model Prognostic factors 

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Markus Pfirrmann
    • 1
  • Susanne Saussele
    • 2
  • Andreas Hochhaus
    • 3
  • Andreas Reiter
    • 2
  • Ute Berger
    • 2
  • Dieter K. Hossfeld
    • 4
  • Christoph Nerl
    • 5
  • Christof Scheid
    • 6
  • Karsten Spiekermann
    • 7
  • Jiri Mayer
    • 8
  • Andrzej Hellmann
    • 9
  • Klaus Lechner
    • 10
  • Christiane Falge
    • 11
  • Herbert G. Sayer
    • 3
  • Donald Bunjes
    • 12
  • Arnold Ganser
    • 13
  • Dietrich W. Beelen
    • 14
  • Helen Baldomero
    • 15
  • Urs Schanz
    • 16
  • Hermann Heimpel
    • 12
  • Hans-Jochem Kolb
    • 17
  • Joerg Hasford
    • 1
  • Alois Gratwohl
    • 18
  • Rüdiger Hehlmann
    • 2
  • for the Schweizerische Arbeitsgemeinschaft für Klinische Forschung (SAKK) and the German CML Study Group
  1. 1.Institut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie - IBELudwig-Maximilians-UniversitätMunichGermany
  2. 2.III. Medizinische Klinik, Universitätsmedizin MannheimUniversität HeidelbergMannheimGermany
  3. 3.Abteilung Hämatologie/Onkologie, Klinik für Innere Medizin IIUniversitätsklinikum JenaJenaGermany
  4. 4.II. Medizinische KlinikUniversitätsklinikum Hamburg-Eppendorf (UKE)HamburgGermany
  5. 5.Klinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie und TropenmedizinKlinikum SchwabingMunichGermany
  6. 6.Klinik I für Innere MedizinUniklinik KölnCologneGermany
  7. 7.Medizinische Klinik III und PoliklinikKlinikum der Ludwig-Maximilians-Universität MünchenMunichGermany
  8. 8.Department of Internal Medicine, Hematology and OncologyUniversity Hospital Brno and Masaryk UniversityBrnoCzech Republic
  9. 9.Department of Hematology and Transplantology, University Clinical CenterMedical University of GdanskGdańskPoland
  10. 10.Allgemeine Hämatologie/HämostaseologieUniversitätsklinik für Innere Medizin IViennaAustria
  11. 11.Medizinische Klinik 5Klinikum Nürnberg NordNurembergGermany
  12. 12.Klinik für Innere Medizin IIIUniversitätsklinikum UlmUlmGermany
  13. 13.Klinik für Hämatologie, Hämostaseologie, Onkologie und StammzelltransplantationMedizinische Hochschule HannoverHannoverGermany
  14. 14.Deutsches Register für Stammzelltransplantation (DRST) und Klinik für KnochenmarktransplantationUniversitätsklinikum EssenEssenGermany
  15. 15.Abteilung für HämatologieUniversitätshospital BaselBaselSwitzerland
  16. 16.Swiss Blood Stem Cell Transplantation (SBST)BernSwitzerland
  17. 17.3. Medizinische Klinik, Klinikum rechts der IsarTechnische UniversitätMunichGermany
  18. 18.Behandlungszentrum StammzelltransplantationUniversitätsspital BaselBaselSwitzerland

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