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.
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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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DOI: https://doi.org/10.1038/leu.2014.335
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