Comparing two different doses of anti-thymocyte globulin in allogeneic hematopoietic stem cell transplantation for transfusion-dependent thalassemia: an open-label, randomized clinical trial

Anti-thymocyte globulin (ATG) is used as prophylaxis for graft-versus-host disease (GvHD) and graft failure (GF) in allogeneic hematopoietic stem cell transplantation (allo-HSCT) for patients with transfusion-dependent thalassemia (TDT). However, the optimal dose of ATG remains unknown.

To compare the 3-year overall survival (OS) of 8 mg/kg and 10 mg/kg ATG in allo-HSCT for patients with TDT.

We compared two different doses of ATG for patients with TDT undergoing allo-HSCT from HLA-matched sibling donors (MSDs). Between 2015 and 2023, 147 patients were randomized to the 8 mg/kg ATG group and 148 patients to the 10 mg/kg ATG group. Primary endpoints were 3-year OS and thalassemia-free survival (TFS). Survival analysis for OS and TFS was performed using the Kaplan-Meier method.

The 8 and 10 mg/kg ATG groups had similar 3-year OS and TFS (both 98.6% (95% confidence interval [CI]: 96.8-100) vs 95.3% (95% CI: 91.9-98.7), p = 0.066). There were no significant differences in graft-versus-host disease and GF between groups. In the subgroup with co-transplantation of cord blood (CB) and bone marrow (BM) as stem cell sources, the 8 mg/kg ATG group had higher 3-year OS and TFS than the 10 mg/kg ATG group (both 100% (95% CI: not applicable) vs 86.5% (95% CI: 75.5-98.2), p = 0.012).

This study provides evidence that an 8 mg/kg ATG is an effective treatment for TDT transplanted from MSDs. A notable finding was the superior survival associated with the 8 mg/kg ATG in the CB and BM co-transplantation. These results provide critical evidence for guiding ATG dosing strategies in allo-HSCT for TDT, particularly in the context of stem cell source selection.

Open-label, randomized clinical trial.

ChiCTR-IPR-15005779 (Chinese Clinical Trial Registry; https://www.chictr.org.cn/showproj.html?proj=10208; date of registration: December 29, 2014).