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Acute Leukemias

Hematopoietic cell transplantation in patients with intermediate and high-risk AML: results from the randomized Study Alliance Leukemia (SAL) AML 2003 trial

Leukemia volume 29, pages 1060–1068 (2015)Cite this article

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Abstract

The optimal timing of allogeneic hematopoietic stem cell transplantation (HCT) in acute myeloid leukemia (AML) is controversial. We report on 1179 patients with a median age of 48 years who were randomized upfront. In the control arm, sibling HCT was scheduled in the first complete remission for intermediate-risk or high-risk AML and matched unrelated HCT in complex karyotype AML. In the experimental arm, matched unrelated HCT in first remission was offered also to patients with an FLT3-ITD (FMS-like tyrosine kinase 3–internal tandem duplication) allelic ratio >0.8, poor day +15 marrow blast clearance and adverse karyotypes. Further, allogeneic HCT was recommended in high-risk AML to be performed in aplasia after induction chemotherapy. In the intent-to-treat (ITT) analysis, superiority of the experimental transplant strategy could not be shown with respect to overall survival (OS) or event-free survival. As-treated analyses suggest a profound effect of allogeneic HCT on OS (HR 0.73; P=0.002) and event-free survival (HR 0.67; P<0.001). In high-risk patients, OS was significantly improved after allogeneic HCT in aplasia (HR 0.64; P=0.046) and after HCT in remission (HR 0.74; P=0.03). Although superiority of one study arm could not be demonstrated in the ITT analysis, secondary analyses suggest that early allogeneic HCT is a promising strategy for patients with high-risk AML.

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Acknowledgements

We thank the support of the DKMS, which allowed for immediate HLA-typing and provisional unrelated donor search. Further, we thank the data managers of the central study office of the Study Alliance Leukemia, especially Annett Engmann and Katrin Peschel for their extensive work and their excellent contributions to this project.

Author Contributions

Financial and administrative support: Gerhard Ehninger. Conception and design: Gerhard Ehninger, Markus Schaich, and Martin Bornhäuser. Collection and assembly of data: Kerstin Schäfer-Eckart, Matthias Hänel, Walter E Aulitzky, Hermann Einsele, Norbert Schmitz, Wolf Rösler, Matthias Stelljes, Claudia D Baldus, Anthony D Ho, Andreas Neubauer, Hubert Serve, Stefani Parmentier, Christoph Röllig, Uwe Platzbecker, Jiri Mayer, Wolfgang E Berdel, Christian Thiede, and Markus Schaich. Central diagnostics: Christian Thiede, Brigitte Mohr, Uta Oelschlägel, and Stefani Parmentier. Statistical analysis: Michael Kramer and Johannes Schetelig. Interpretation: Gerhard Ehninger, Martin Bornhäuser, Markus Schaich and Johannes Schetelig. Manuscript writing: Johannes Schetelig and Martin Bornhäuser. Final approval of manuscript: All coauthors reviewed and approved the final manuscript.

Author information

Author notes

  1. M Bornhäuser and G Ehninger: These author contributed equally to this work.Previous presentations: The results of this study were partly presented at the 54th Annual Meeting of the American Society of Hematology in Atlanta on Sunday, 9 December 2012 (Abstract 229).

Authors and Affiliations

  1. Medizinische Klinik und Poliklinik I, Universitätsklinikum Carl Gustav Carus der TU Dresden, Dresden, Germany

    J Schetelig, M Schaich, B Mohr, U Oelschlägel, S Parmentier, C Röllig, M Kramer, U Platzbecker, T Illmer, C Thiede, M Bornhäuser & G Ehninger

  2. DKMS, German Bone Marrow Donor Center, Dresden, Germany

    J Schetelig

  3. Städtisches Klinikum Nord, Medizinische Klinik 5, Nürnberg, Germany

    K Schäfer-Eckart

  4. Klinikum Chemnitz gGmbH, Klinik für Innere Medizin III, Chemnitz, Germany

    M Hänel

  5. Abteilung für Hämatologie, Robert-Bosch-Krankenhaus, Onkologie und Palliativmedizin, Stuttgart, Germany

    W E Aulitzky

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

    H Einsele

  7. Abteilung für Hämatologie, Asklepios Klinik St Georg, Onkologie und Stammzelltransplantation, Hamburg, Germany

    N Schmitz

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

    W Rösler

  9. Medizinische Klinik und Poliklinik A, Universitätsklinikum Münster, Münster, Germany

    M Stelljes & W E Berdel

  10. Charité Berlin, Campus Benjamin Franklin, Berlin, Germany

    C D Baldus

  11. Abteilung Innere Medizin V, Medizinische Klinik und Poliklinik, Hämatologie, Onkologie und Rheumatologie, Universität Heidelberg, Heidelberg, Germany

    A D Ho

  12. Kliniken für Innere Medizin, Hämatologie/Onkologie und Immunologie, Universitätsklinikum Marburg, Marburg, Germany

    A Neubauer

  13. Medizinische Klinik II, Klinikum der J.W. Goethe Universität, Frankfurt, Germany

    H Serve

  14. Department of Hemato-Oncology, University Hospital Brno, Brno, Czech Republic

    J Mayer

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  1. J Schetelig
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  18. S Parmentier
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Correspondence to J Schetelig.

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Schetelig, J., Schaich, M., Schäfer-Eckart, K. et al. Hematopoietic cell transplantation in patients with intermediate and high-risk AML: results from the randomized Study Alliance Leukemia (SAL) AML 2003 trial. Leukemia 29, 1060–1068 (2015). https://doi.org/10.1038/leu.2014.335

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