Two dose levels of rabbit antithymocyte globulin as graft-versus-host disease prophylaxis in haploidentical stem cell transplantation: a multicenter randomized study

BACKGROUND: The optimal dose of rabbit antithymocyte globulin (ATG, ImtixSangstat) minimizing infections without increasing graft-versus-host disease (GVHD) is unknown in T cell-replete, G-CSF-primed haploidentical hematopoietic stem cell transplantation (haplo-HSCT). METHODS: Four hundred and eight patients were enrolled in this multicenter study to evaluate the effect of 7.5 mg/kg and 10.0 mg/kg rabbit ATG on viral infections and GVHD prophylaxis after haplo-HSCT. The primary endpoint was EBV DNAemia within 1 year posttransplantation. RESULTS: The 1-year incidence of EBV DNAemia was 20.7% (95% confidence interval, 15.4–26.5) and 40.0% (33.3–46.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (P < 0.001). The 100-day cumulative incidence of grade II to IV aGVHD was 27.1% (21.1–33.4) and 25.4% (19.6–31.5) in the 7.5 mg/kg and 10.0 mg/kg ATG groups, respectively (P = 0.548). The 2-year incidence of chronic GVHD was 34.6% (27.8–41.4) and 36.2% (29.1–43.2) in the 7.5 mg and 10.0 mg groups (P = 0.814). The 1-year incidence of CMV DNAemia was 73.4% (67.2–79.4) and 83.4% (77.5–87.9) in the 7.5 mg/kg and 10.0 mg/kg groups (P = 0.038). The 3-year overall survival posttransplantation was 69.5% (63.2–75.8) and 63.5% (56.2–70.8), and the disease-free survival was 62.2% (55.3–69.1) and 60.3% (53.0–67.6) in the 7.5 mg/kg and 10.0 mg/kg groups, respectively (OS: P = 0.308; DFS: P = 0.660). The counts of EBV- and CMV-specific cytotoxic T cells (CTLs) were higher in the 7.5 mg/kg group than in the 10.0 mg/kg group early posttransplantation. CONCLUSIONS: Compared with 10.0 mg/kg, 7.5 mg/kg ATG for GVHD prophylaxis was associated with reduced EBV and CMV infections without increased incidence of GVHD in haplo-HSCT, probably by affecting EBV- and CMV-specific CTLs. TRIAL REGISTRATION: clinicaltrials.gov, NCT01883180. Registered 14 June 2013. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (10.1186/s12916-019-1393-7) contains supplementary material, which is available to authorized users.