Randomized trial of anti-thymocyte globulin plus low-dose post-transplant cyclophosphamide to prevent graft-versus-host disease in haploidentical transplantation

The combination of anti-thymocyte globulin (ATG) and posttransplant cyclophosphamide (PTCy) appears to be a potentially effective graft-versus-host disease (GVHD) prevention strategy for haploidentical transplantation. However, the majority of the evidence originated from retrospective studies without uniform protocols. Our previous findings indicated that 10 mg/kg ATG plus low-dose PTCy could decrease GVHD among high-risk populations transplanted from maternal or collateral relatives. We designed an open-label, phase III, randomized controlled trial to compare patients receiving granulocyte colony-stimulating factor (G-CSF)/ATG-based haploidentical transplantation with or without low-dose PTCy (14.5 mg/kg on days 3 and 4) in non-maternal, non-collateral haploidentical transplants from fathers, children or siblings. A total of 66 patients were randomly assigned to ATG-PTCy (N=44) or ATG (N=22) when the first interim analysis was performed. The interim analysis revealed that the 100-day cumulative incidences of grade 2-4 (18.2%, 95% confidence interval [CI]: 6.6-29.7 vs. 18.2%, 95% CI: 1.7-34.7; P=0.996) and 3-4 acute GVHD (2.3%, 95% CI: 0-6.7 vs. 0; P=0.480) were comparable between the ATG-PTCy and ATG cohorts, as was chronic GVHD at 1 year. The estimated 1-year disease-free survival (DFS) rates were also similar between ATG-PTCy and ATG cohorts (95.5%, 95% CI: 89.5-100 vs. 95.2%, 95% CI: 86.6-100; P=0.979). These results suggested that ATG/PTCy (low-dose) had no advantage over 10 mg/kg ATG-based prophylaxis in patients with haploidentical transplantation other than that of maternal donors or collateral relatives. Future work needs to focus on identifying which populations might benefit from the combined strategy in the context of G-CSF/ATG-based protocols (clinicaltrials gov. Identifier: NCT06108739).