Original Article – Clinical Oncology

Journal of Cancer Research and Clinical Oncology

, Volume 140, Issue 8, pp 1367-1381

First online:

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

  • Markus PfirrmannAffiliated withInstitut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie - IBE, Ludwig-Maximilians-Universität Email author 
  • , Susanne SausseleAffiliated withIII. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg
  • , Andreas HochhausAffiliated withAbteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena
  • , Andreas ReiterAffiliated withIII. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg
  • , Ute BergerAffiliated withIII. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg
  • , Dieter K. HossfeldAffiliated withII. Medizinische Klinik, Universitätsklinikum Hamburg-Eppendorf (UKE)
  • , Christoph NerlAffiliated withKlinik für Hämatologie, Onkologie, Immunologie, Palliativmedizin, Infektiologie und Tropenmedizin, Klinikum Schwabing
  • , Christof ScheidAffiliated withKlinik I für Innere Medizin, Uniklinik Köln
  • , Karsten SpiekermannAffiliated withMedizinische Klinik III und Poliklinik, Klinikum der Ludwig-Maximilians-Universität München
    • , Jiri MayerAffiliated withDepartment of Internal Medicine, Hematology and Oncology, University Hospital Brno and Masaryk University
    • , Andrzej HellmannAffiliated withDepartment of Hematology and Transplantology, University Clinical Center, Medical University of Gdansk
    • , Klaus LechnerAffiliated withAllgemeine Hämatologie/Hämostaseologie, Universitätsklinik für Innere Medizin I
    • , Christiane FalgeAffiliated withMedizinische Klinik 5, Klinikum Nürnberg Nord
    • , Herbert G. SayerAffiliated withAbteilung Hämatologie/Onkologie, Klinik für Innere Medizin II, Universitätsklinikum Jena
    • , Donald BunjesAffiliated withKlinik für Innere Medizin III, Universitätsklinikum Ulm
    • , Arnold GanserAffiliated withKlinik für Hämatologie, Hämostaseologie, Onkologie und Stammzelltransplantation, Medizinische Hochschule Hannover
    • , Dietrich W. BeelenAffiliated withDeutsches Register für Stammzelltransplantation (DRST) und Klinik für Knochenmarktransplantation, Universitätsklinikum Essen
    • , Helen BaldomeroAffiliated withAbteilung für Hämatologie, Universitätshospital Basel
    • , Urs SchanzAffiliated withSwiss Blood Stem Cell Transplantation (SBST)
    • , Hermann HeimpelAffiliated withKlinik für Innere Medizin III, Universitätsklinikum Ulm
    • , Hans-Jochem KolbAffiliated with3. Medizinische Klinik, Klinikum rechts der Isar, Technische Universität
    • , Joerg HasfordAffiliated withInstitut für Medizinische Informationsverarbeitung, Biometrie und Epidemiologie - IBE, Ludwig-Maximilians-Universität
    • , Alois GratwohlAffiliated withBehandlungszentrum Stammzelltransplantation, Universitätsspital Basel
    • , Rüdiger HehlmannAffiliated withIII. Medizinische Klinik, Universitätsmedizin Mannheim, Universität Heidelberg
    • , for the Schweizerische Arbeitsgemeinschaft für Klinische Forschung (SAKK) and the German CML Study Group

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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.

Keywords

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