Meta-analysis of the actions of antithymocyte globulin in patients undergoing allogeneic hematopoietic cell transplantation

Abstract

Graft-versus-host disease (GVHD) is a serious complication associated with allogeneic hematopoietic cell transplantation (allo-HCT). Antithymocyte globulin (ATG) is widely used prior to allo-HCT for GVHD prevention, though evidence of its efficacy remains unclear. We therefore identified nine randomized controlled trials (RCTs), enrolling 1089 patients (554 in the ATG group and 535 in the non-ATG group) to conduct a meta-analysis of the actions of ATG in allo-HCT. A relative risk or risk ratio (RR) and 95% confidence interval (CI) were calculated for each outcome. Rabbit ATG reduced overall acute (a) GVHD (RR 0.77, 95% CI 0.67-0.89, P = 0.0004), grade III-IV aGVHD (RR 0.53, 95% CI 0.32-0.88, P = 0.01), overall chronic (c) GVHD (RR 0.52, 95% CI 0.42-0.64, P < 0.00001) and extensive cGVHD (RR 0.28, 95% CI 0.18-0.43, P < 0.00001), without increased risk of relapse (RR 1.17, 95% CI 0.91-1.49, P = 0.23). By contrast, horse ATG did not reduce overall aGVHD (RR 1.25, 95% CI 0.88-1.79, P = 0.22) or cGVHD (RR 1.67, 95% CI 0.96-2.91, P = 0.07). ATG marginally reduced 100-day transplant related mortality (RR 0.75, 95% CI 0.56-1.00, P = 0.05) without compromising overall survival or increased risk of infections. Further studies are required to evaluate the optimal dosage and formulation of ATG in different conditioning regimens of transplantation with varied sources of graft and donor.

Haploidentical transplantation outcomes for secondary acute myeloid leukemia: Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT) study

“…T‐cell depletion with ATG has been commonly used for prevention of acute and chronic GVHD with previous data indicating mixed results in terms of outcomes . Using univariate analysis, LFS and OS were inferior using ATG versus PTCy.…”

“…Several strategies were developed to overcome these challenges, including ex vivo and in vivo TCD as well as T‐cell replete (TCR) grafts . In vivo TCD with ATG has become a commonly used practice for GVHD prophylaxis in haploHCT, especially in China, with improvement in achieving primary engraftment, reducing RI, and minimizing GVHD . However, in vivo TCD is known to be associated with a high incidence of infection and NRM leading to increased morbidity and mortality .…”

Comparison of Different Rabbit Anti-Thymocyte Globulin Formulations in Allogeneic Stem Cell Transplantation: Systematic Literature Review and Network Meta-Analysis

“…Previous analyses [7,8,23], including only 1 NMA, have been conducted to aggregate evidence on GVHD prevention in transplantation settings. However, no conclusions have been drawn for comparisons of different formulations of rabbit ATG.…”

“…This reduces the risk of rejection while similarly depleting newly infused donor T cells, thereby potentially reducing GVHD [6]. Recent meta-analyses have provided data on outcomes of ATG therapy in reciepients of allo-SCT [7,8]; however, there is no published comparison of different formulations of ATG, although the need for it has been expressed in the literature [9,10].…”

Effect of antithymocyte globulin on HLA-mismatched unrelated transplantation

“…The use of ATG reduced the incidences of acute and/ or chronic GVHD in all of the randomized control trials and most of the retrospective studies (Tables 1, 2). This was confirmed by a meta-analysis of the randomized control trials [24][25][26][27]. In general, the risk of acute and chronic GVHD is higher in allo-HCT from MMUD than in that from MUD [4][5][6][7][8].…”