Ying-Jun Chang1, De-Pei Wu2, Yong-Rong Lai3, Qi-Fa Liu4, Yu-Qian Sun1, Jiong Hu5, Yu Hu6, Jian-Feng Zhou7, Juan Li8, Shun-Qing Wang9, Wei Li10, Xin Du11, Dong-Jun Lin12, Han-Yun Ren13, Fang-Pin Chen14, Yu-Hua Li15, Xi Zhang16, He Huang17, Yong-Ping Song18, Ming Jiang19, Jian-Da Hu20, Ying-Min Liang21, Jing-Bo Wang22, Yang Xiao23, Xiao-Jun Huang1. 1. Peking University People's Hospital, Peking University Institute of Hematology, National Clinical Research Center for Hematologic Disease, Beijing Key Laboratory of Hematopoietic Stem Cell Transplantation, and Peking-Tsinghua Center for Life Sciences, Beijing, China. 2. Jiangsu Institute of Hematology, The First Affiliated Hospital of Soochow University, Suzhou, China. 3. Department of Hematology, First Affiliated Hospital of Guangxi Medical University, Nanning, China. 4. Nanfang Hospital Affiliated to Southern Medical University, Guangzhou, China. 5. State Key Laboratory for Medical Genomics, Department of Hematology, Shanghai Institute of Hematology, and Collaborative Innovation Center of Hematology, Rui-Jin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China. 6. Union Hospital Affiliated With Huazhong University of Science and Technology, Wuhan, China. 7. Department of Hematology, Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. 8. Department of Hematology, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, China. 9. Department of Hematology, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, China. 10. The First Hospital of Jilin University, Changchun, China. 11. Guangdong General Hospital, Guangzhou, China. 12. Third Hospital of Sun Yat-sen University, Guangzhou, China. 13. Department of Hematology, Peking University First Hospital, Beijing, China. 14. Department of Hematology, Xiangya Hospital, Central South University, Changsha, China. 15. Department of Hematology, Zhujiang Hospital, Southern Medical University, Guangzhou, China. 16. Xinqiao Hospital Affiliated to Third Military Medical University, Chongqing, China. 17. Bone Marrow Transplantation Center, The First Affiliated Hospital, School of Medicine, Zhejiang University, Zhejiang, China. 18. The Affiliated Cancer Hospital of Zhengzhou University and Henan Cancer Hospital, Zhengzhou, China. 19. The First Affiliated Hospital of Xinjiang Medical University, Urumqi, China. 20. Fujian Medical University Union Hospital, Fuzhou, China. 21. Tangdu Hospital Air Force Medical University, Xi'an, China. 22. Aerospace Center Hospital, Beijing, China. 23. Southern Theater General Hospital of the Chinese People's Liberation Army, Guangzhou, China.
Abstract
PURPOSE: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS:From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION: Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.
RCT Entities:
PURPOSE: The role of antithymocyte globulin (ATG) in preventing acute graft-versus-host disease (aGVHD) after HLA-matched sibling donor transplantation (MSDT) is still controversial. PATIENTS AND METHODS: We performed a prospective, multicenter, open-label, randomized controlled trial (RCT) across 23 transplantation centers in China. Patients ages 40-60 years with standard-risk hematologic malignancies with an HLA-matched sibling donor were randomly assigned to an ATG group (4.5 mg/kg thymoglobulin plus cyclosporine [CsA], methotrexate [MTX], and mycophenolate mofetil [MMF]) and a control group (CsA, MTX, and MMF). The primary end point of this study was grade 2-4 aGVHD on day 100. RESULTS: From November 2013 to April 2018, 263 patients were enrolled. The cumulative incidence rate of grade 2-4 aGVHD was significantly reduced in the ATG group (13.7%; 95% CI, 13.5% to 13.9%) compared with the control group (27.0%; 95% CI, 26.7% to 27.3%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 27.6% to 28.2%] v 52.5% [95% CI, 52.1% to 52.9%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 8.4% to 8.6%] v 23.2% [95% CI, 22.9% to 23.5%]; P = .029) than the control group. There were no differences between the ATG and control groups with regard to cytomegalovirus reactivation, Epstein-Barr virus reactivation, 3-year nonrelapse mortality (NRM), 3-year cumulative incidence of relapse (CIR), 3-year overall survival, or 3-year leukemia-free survival. Three-year GVHD relapse-free survival was significantly improved in the ATG group (38.7%; 95% CI, 29.9% to 47.5%) compared with the control group (24.5%; 95% CI, 16.9% to 32.1%; P = .003). CONCLUSION: Our study is the first prospective RCT in our knowledge to demonstrate that ATG can effectively decrease the incidence of aGVHD after MSDT in the CsA era without affecting the CIR or NRM.
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