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

Raynier Devillier 1, 2 Myriam Labopin 3, 4 Patrice Chevallier 5, 6, 7 Marie-Pierre Ledoux Gerard Socie 8 Anne Huynh 9 Jean-Henri Bourhis 10 Jean-Yves Cahn 11 Gabrielle Roth-Guepin Ghulam Mufti 12 Deborah Desmier 13 Mauricette Michallet 14 Nathalie Fegueux 15 Fabio Ciceri 16 Frederic Baron 17 Didier Blaise 18, 19 Arnon Nagler 20 Mohamad Mohty 21
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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Raynier Devillier, Myriam Labopin, Patrice Chevallier, Marie-Pierre Ledoux, Gerard Socie, 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 Transplantation, Nature Publishing Group, 2018, 53 (4), pp.431-437. ⟨10.1038/s41409-017-0043-y⟩. ⟨hal-02143554⟩

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