Abstract
Antithymocyte globulin (ATG) is commonly used for graft-vs.-host disease (GVHD) prophylaxis in unrelated donor allogeneic transplantation (Allo-HSCT). However, its use is still controversial in matched sibling donor (MSD) Allo-HSCT, notably after reduced intensity conditioning (RIC). ATG dose may influence the outcome, explaining in part the discordant conclusions in MSD Allo-HSCT. We, therefore, analyzed the impact of ATG doses in patients with acute myeloid leukemia in first complete remission undergoing RIC Allo-HSCT from a MSD. We analyzed 234 patients from the EBMT registry and compared outcome according to given ATG dose (high dose: ≥ 6 mg/kg, n = 39 or low dose: < 6 mg/kg, n = 195). No difference was found in the cumulative incidence of acute (grade 2–4: high dose vs. low dose: 21% vs. 13%, p = 0.334; adjusted hazard ratio (HR): 1.20, p = 0.712) and chronic GVHD (extensive: high dose vs. low dose: 19% vs. 18%, p = 0.897; adjusted HR: 1.01, p = 0.980). In contrast, high dose of ATG significantly increased the incidence of relapse (52% vs. 26%, p = 0.011; adjusted HR: 1.31, p = 0.001) leading to impaired outcome (HR progression-free survival (PFS): 1.23, p = 0.002; HR overall survival (OS): 1.17, p = 0.029; HR GVHD and relapse-free survival (GRFS): 1.20, p = 0.005). We conclude that an ATG dose <6 mg/kg is sufficient for GVHD prophylaxis, while higher doses impair disease control and outcome.
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Acknowledgements
We acknowledge all EBMT participating centers and their datamanagers (Supplemental file). We thank J.V. Melo (University of Adelaide, Australia, and Imperial College, London, UK) for critical reading of the manuscript.
Author’s contributions
DB, AN and MM designed the study. RD and ML performed statistical analyses. RD, ML, DB, AN, and MM analyzed data and wrote the manuscript. RD, PC, MPL, GS, AH, JHB, JYC, GRG, GM, DD, MM, NF, FC, FB, DB, AN and MM included patients. All authors commented and approved the manuscript.
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MM, AN, JYC, FB, and DB received lectures honoraria and research support from Sanofi whose product is discussed in this manuscript. GS received lectures honoraria from Fresenius Biotech. The remaining authors declare no conflict of interest.
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Arnon Nagler and Mohamad Mohty contributed equally to this work.
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Devillier, R., Labopin, M., Chevallier, P. et al. Impact of antithymocyte globulin doses in reduced intensity conditioning before allogeneic transplantation from matched sibling donor for patients with acute myeloid leukemia: a report from the acute leukemia working party of European group of Bone Marrow Transplantation. Bone Marrow Transplant 53, 431–437 (2018). https://doi.org/10.1038/s41409-017-0043-y
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DOI: https://doi.org/10.1038/s41409-017-0043-y
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