Two Doses of Antithymocyteglobulin As Graft-Versus-Host Disease Prophylaxis in Haploidentical Allogeneic Stem Cell Transplantation: A Multicenter Prospective Study

Background

Graft-versus-host disease (GVHD) is an important complication after haploidentical hematopoietic stem cell transplantation (haplo-HSCT). Antithymocyteglobulin (ATG) has been widely used for GVHD prophylaxis. However, the delay of T-cell reconstitution causes by ATG may increase the risk of opportunistic infections. In this multicenter prospective study, we compared the outcomes of the patients undergoing haplo-HSCT who received 7.5 mg/kg ATG or 10 mg/kg ATG as GVHD prophylaxis.

Methods

A total of 368 consecutive patients undergoing haplo-HSCT were randomized in 5 hospitals between May 2013 and March 2016. ATG with a total dosage of 7.5 mg/kg were administered in 184 patients and 10 mg/kg ATG were administered in 181 for GVHD prophylaxis. Three patients did not received allocated intervention and transplantation due to leukemia relapse before transplant or toxicity of conditioning regimens. The primary endpoint was the incidence of acute GVHD grade II to IV on day 100. Noninferiority of 7.5mg/kg ATG against 10mg/kg ATG was established if the difference of the 95% confidence interval (CI) in acute GVHD grade II to IV between the two groups was within 15%.

Results

The incidences of acute GVHD grade II to IV on day 100 were 31.5% and 28.2% in 7.5 mg/kg and 10 mg/kg ATG (P=0.485), respectively. The difference between these two groups was 3.3% with 95% CI of -6.1% to 12.7%, which indicated that 7.5 mg/kg ATG was not inferior to 10 mg/kg ATG. The incidences of acute GVHD grade III to IV were similar in the two groups (8.2% in 7.5 mg/kg group vs. 5.0% in 10 mg/kg group, P=0.220). No difference in chronic GVHD was found in the two groups (21.2% in 7.5 mg/kg arm vs. 19.8% in 10 mg/kg arm, P=0.748). More patients developed EBV viremia in 10 mg/kg group (37.5±3.8%) than those in 7.5 mg/kg group (25.2±3.3%, P=0.018). The 2-years overall survival were 69.5±4.3% and 66.7±4.0% for 7.5 mg/kg and 10 mg/kg group (P=0.356). And the 2-year disease-free survival were also comparative in the two groups (66.3±5.7% in 7.5 mg/kg arm vs. 66.6±3.8% in 10 mg/kg arm, P=0.288).

Conclusion

Compared with 10 mg/kg ATG, the 7.5mg/kg ATG applied in haplo-HSCT appears not to increase GVHD and might reduce the risk of EBV infection after transplantation.