Systematic review and meta-analysis of anti-thymocyte globulin dosage as a component of graft-versus-host disease prophylaxis

Rabbit anti-thymocyte globulin (ATG) has been used in allogeneic hematopoietic stem cell transplantation (Allo-HSCT) for graft-versus-host disease (GvHD) prophylaxis. Since the best dose has not been defined yet, this study aimed to determine the efficacy and safety of different doses of ATG in Allo-HSCT. Data sources were MEDLINE/PUBMED, EMBASE, Cochrane Library, Web of Science, LILACS, and SciELO. Studies were eligible when comparing doses of ATG. The higher dose was in the intervention group. A total of 22 articles (2002-2022) were included. Higher doses (4-12 mg/kg) of ATG-T reduced the incidence of grade III-IV acute GvHD (RR 0. 60; 95%CI 0. 42-0. 84) and limited chronic GvHD (RR 0. 64 95%CI 0. 45-0. 92) compared with lower doses (2-7. 5 mg/kg). Higher doses increased the Epstein-Barr virus (RR 1. 90 95% CI 1. 49-2. 42) and Cytomegalovirus reactivation (RR, 1. 30; 95% CI 1. 03-1. 64). Relapse rates were higher in the higher dose group (RR 1. 34, 95% CI 1. 07-167). The ATG-T dose ≥7mg/kg versus the lower dose showed a number needed to treat 7. 4 for acute GvHD III-IV, with a number to harm of 7. 7 for relapse at one year in the higher dose group. A dose lower than 7 mg/kg suggests a better risk-benefit ratio than a higher one. Well-designed RCT is needed to define the best risk-benefit doses. Trial registration: Trial registration number: PROSPERO: https: //www. crd. york. ac. uk/prospero/displayᵣecord. php? ID=CRD42020173449.