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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 Transplantation volume 53, pages 431–437 (2018)Cite this article

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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.

Author information

Authors and Affiliations

  1. Department of Hematology, Institut Paoli Calmettes, Marseille, France

    Raynier Devillier & Didier Blaise

  2. CRCM and Aix Marseille University, Marseille, France

    Raynier Devillier & Didier Blaise

  3. Department of Hematology, University Hospital Saint Antoine, APHP, Paris, France

    Myriam Labopin & Mohamad Mohty

  4. EBMT ALWP Office, Pierre and Marie Curie University, Paris, France

    Myriam Labopin, Arnon Nagler & Mohamad Mohty

  5. Department of Hematology, University Hospital Nantes, Nantes, France

    Patrice Chevallier

  6. Department of Hematology, University Hospital Hautepierre, Strasbourg, France

    Marie-Pierre Ledoux

  7. Department of Hematology, University Hopital St Louis, APHP, Paris, France

    Gérard Socié

  8. Department of Hematology, University Insitute of cancer of Toulouse–Oncopole, Toulouse, France

    Anne Huynh

  9. Department of Hematology, Institut Gustave Roussy, Villejuif, France

    Jean-Henri Bourhis

  10. Department of Hematology, University Hospital A. Michallon, Grenoble, France

    Jean-Yves Cahn

  11. Department of Hematology, University Hospital Nancy, Vandoeuvre-lès-Nancy, France

    Gabrielle Roth-Guepin

  12. Department of Hematology, King’s College Hospital, London, UK

    Ghulam Mufti

  13. Department of Hematology, University Hospital La Miletrie, Poitiers, France

    Déborah Desmier

  14. Department of Hematology, University Hospital Lyon Sud, Lyon, France

    Mauricette Michallet

  15. Department of Hematology, University Hospital Montpellier, Montpellier, France

    Nathalie Fegueux

  16. Department of Hematology, San Raffaele Hospital, Milano, Italy

    Fabio Ciceri

  17. Department of Hematology, University of Liège, Liège, Belgium

    Fréderic Baron

  18. Department of Hematology, Chaim Sheba Medical Center, Tel-Hashomer, Israel

    Arnon Nagler

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  1. Raynier Devillier
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Correspondence to Mohamad Mohty.

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Conflict of interest

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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