Randomized trial of GvHD Prophylaxis in Haploidentical PBSC Transplantation: ATG, PTCy, and Low-Dose Combination Therapy

The optimal graft-versus-host disease (GvHD) prophylaxis strategy in haploidentical peripheral blood stem cell transplantation (haplo-PBSCT) remains controversial. In this open-label, phase Ⅲ study, patients aged 14-70 years with acute myeloid leukemia or myelodysplastic syndromes with excess blasts Ⅰ or Ⅱ were randomized (2:1:1) to receive low-dose ATG (5 mg/kg)/PTCy (50 mg/kg), standard-dose ATG (total dose 10 mg/kg), or a PTCy (total dose 100 mg/kg)-based regimen for GvHD prophylaxis. The co-primary endpoints were the cumulative incidence (CI) of grade Ⅱ-Ⅳ acute GvHD (aGvHD) by day 100 and GvHD/relapse-free survival (GRFS) at 1 year post-transplant. A total of 407 patients were randomized to receive ATG/PTCy (185 patients), ATG (113 patients), or PTCy (109 patients) regimen for GvHD prophylaxis. By day +100, the CI of grade Ⅱ-Ⅳ aGvHD did not differ significantly among the three groups (P=0.210). Although the overall incidence of chronic GvHD (cGvHD) was comparable across all groups (P=0.110), the 2-year CI of moderate-to-severe cGvHD was numerically lower in the ATG/PTCy (17.4%) and ATG (17.3%) groups compared to the PTCy group (28.3%), without reaching statistical significance (P=0.095). No significant differences were observed in survival outcomes among the three groups. Notably, the cumulative incidence of neutrophil and platelet recovery was significantly higher in the ATG/PTCy group compared to the other groups (P<0.001). This trial suggested that the three GvHD prophylaxis strategies presented similar efficacy in preventing grade II-IV aGvHD and yielded comparable survival. This trial was registered at www.clinicaltrials.gov as NCT03608059.