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

PLoS One. 2023 Apr 18;18(4):e0284476. doi: 10.1371/journal.pone.0284476. eCollection 2023.

Abstract

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/display_record.php?ID=CRD42020173449.

Publication types

  • Meta-Analysis
  • Systematic Review
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antilymphocyte Serum / therapeutic use
  • Chronic Disease
  • Epstein-Barr Virus Infections* / complications
  • Graft vs Host Disease* / etiology
  • Hematopoietic Stem Cell Transplantation* / adverse effects
  • Herpesvirus 4, Human
  • Humans
  • Recurrence
  • Retrospective Studies
  • Transplantation, Homologous / adverse effects

Substances

  • Antilymphocyte Serum

Grants and funding

This study was supported by Funding of Incentive to Research, Hospital de Clínicas de Porto Alegre, RS, Brazil (FIPE)/HCPA), concession number: 2019-0138. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.