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Attempts to reduce the incidence of cGVHD include the addition of anti-thymocyte globulin (ATG) to the pretransplant conditioning regimen. METHODS: The goal of this retrospective study was to analyze the effect of ATG on allo-PBSCT outcomes for adults with Philadelphia-negative acute lymphoblastic leukemia (Ph-neg ALL). The primary endpoint was survival free from relapse, grade 3 to 4 acute graft-versus-host disease (aGVHD), and cGVHD (ie, graft-versus-host disease-free/relapse-free survival [GRFS]). Nine-hundred twenty-four patients who underwent unmanipulated allo-PBSCT in their first complete remission between 2007 and 2016 were included. ATG was used in 97 of the 494 transplants from matched sibling donors (20%) and in 307 of the 430 transplants from human leukocyte antigen-matched (8 of 8 loci) unrelated donors (71%). RESULTS: The use of ATG was an independent factor for an improved chance of GRFS (hazard ratio [HR], 0.70; P = .0009). Furthermore, it was associated with a reduced risk of both grade 2 to 4 (HR, 0.66; P = .005) and grade 3 to 4 aGVHD (HR, 0.58; P = .03). Similarly, its addition reduced the incidence of both total (HR, 0.45; P < 10(-5) ) and extensive cGVHD (HR, 0.30; P < 10(-5) ) as well as nonrelapse mortality (HR, 0.58; P = .01). No significant effect was found with respect to leukemia-free or overall survival. However, an increased risk of relapse was noted for those who received ATG (HR, 1.40; P = .04). CONCLUSIONS: Patients with Ph-neg ALL treated with allo-PBSCT benefit from the use of ATG in terms of improved GRFS. Its use may, therefore, be considered in this setting. Cancer 2018. 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