A randomized trial of GVHD prophylaxis in haploidentical PBSC transplantation: ATG, PTCy, and low-dose combination therapy
Abstract
Abstract The optimal graft-versus-host disease (GVHD) prophylaxis strategy in haploidentical peripheral blood stem cell transplantation remains controversial. In this open-label, phase 3 study, patients aged 14 to 70 years with acute myeloid leukemia or myelodysplastic syndromes with excess blasts Ⅰ or Ⅱ were randomized (2:1:1) to receive low-dose antithymocyte globulin (ATG; 5 mg/kg) plus posttransplant cyclophosphamide (PTCy; 50 mg/kg; referred to as ATG/PTCy), standard-dose ATG (total dose, 10 mg/kg), or a PTCy-based (total dose, 100 mg/kg) regimen for GVHD prophylaxis. The coprimary end points were the cumulative incidence (CI) of grade 2 to 4 acute GVHD (aGVHD) by day 100 and GVHD-free, relapse-free survival at 1 year after transplant. A total of 407 patients were randomized to receive an ATG/PTCy (185 patients), ATG (113 patients), or PTCy (109 patients) regimen for GVHD prophylaxis. By day +100, the CI of grade 2 to 4 aGVHD did not differ significantly among the 3 groups (P = .210). Although the overall incidence of chronic GVHD (cGVHD) was comparable across all groups (P = .110), the 2-year CI of moderate-to-severe cGVHD was numerically lower in the ATG/PTCy (17.4%) and ATG (17.3%) groups than the PTCy group (28.3%), without reaching statistical significance (P = .095). No significant differences were observed in survival outcomes among the 3 groups. Notably, the CI of neutrophil and platelet recovery was significantly higher in the ATG/PTCy group than in the other groups (P< .001). This trial suggested that the 3 GVHD prophylaxis strategies presented similar efficacy in preventing grade 2 to 4 aGVHD and yielded comparable survival. This trial was registered at www.clinicaltrials.gov as NCT03608059.
Article Details
Authors (20)
Jun Yang
Yannan Jia
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Xiaoxia Hu
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Fang Zhou
Institute of Hydrobiology, Chinese Academy of Sciences
Xiong Ni
Jiangbo Wan
5Department of Hematology, Shanghai Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Yi Ding
Mei Kang
7Clinical Research Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Xiaolin Yu
China-Russia Belt and Road Joint Laboratory for Intelligent Chemistry and Advanced Materials of Liaoning Province, School of Chemistry
Chuanhe Jiang
1Shanghai Institute of Hematology, State Key Laboratory of Medical Genomics, National Research Center for Translational Medicine at Shanghai, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China
Luxiang Wang
State Key Laboratory of Chemistry and Utilization of Carbon Based Energy Resources College of Chemistry Xinjiang University Urumqi China
Liping Wan
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Yu Cai
Chongmei Huang
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Huiying Qiu
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Xueying Ding
7Clinical Research Center, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Yin Tong
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Baoxia Dong
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China
Kun Zhou
Key Laboratory of Animal Virology, Ministry of Agricultural and Rural Affairs of China and Zhejiang Provincial Engineering Research Center of Animal Biological Products, Department of Veterinary Medicine, Zhejiang University College of Animal Sciences
Xianmin Song
1Department of Hematology, Shanghai General Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China