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.
Highlights
Rapid advances in allo-HCT, especially the development of haploidentical transplantation, have increased the possibility of successful treatment in patients with hematological malignancies [16]
We initially searched 824 studies, from which 20 were retrieved for detailed evaluation: eleven studies were eventually excluded for reasons explained in Figure 1, and nine randomized controlled trials (RCTs) meeting the inclusion criteria were included in the final analysis
graft-versus-host disease (GVHD) prophylaxis with small molecule immunosuppressive drugs or pure ex vivo, but not in vivo, T cell depletion may increase the rate of relapse and infections [36,37,38,39,40]
Summary
Rapid advances in allo-HCT, especially the development of haploidentical transplantation, have increased the possibility of successful treatment in patients with hematological malignancies [16]. The immunosuppressive agent antithymocyte globulin (ATG) has a relatively long half-life and suppresses or kills T cells infused with the graft [13, 14]. It has been used since the 1970s to prevent severe acute and chronic GVHD (aGVHD and cGVHD, respectively) following allogeneic hematopoietic cell transplantation (alloHCT). Prospective, randomized or nonrandomized studies evaluated the efficacy of ATG against GVHD [15,16,17,18]. We updated the randomized controlled trials (RCTs) and performed a meta-analysis to evaluate the potential benefit and risk of ATG use in allo-HCT
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