Antithymocyte Globulin for Matched Sibling Donor Transplantation in Patients With Hematologic Malignancies: A Multicenter, Open-Label, Randomized Controlled Study

Author:

Chang Ying-Jun1,Wu De-Pei2,Lai Yong-Rong3,Liu Qi-Fa4,Sun Yu-Qian1,Hu Jiong5,Hu Yu6,Zhou Jian-Feng7,Li Juan8,Wang Shun-Qing9,Li Wei10,Du Xin11,Lin Dong-Jun12,Ren Han-Yun13,Chen Fang-Pin14,Li Yu-Hua15,Zhang Xi16,Huang He17,Song Yong-Ping18,Jiang Ming19,Hu Jian-Da20,Liang Ying-Min21,Wang Jing-Bo22,Xiao Yang23,Huang Xiao-Jun1

Affiliation:

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, 7.8% to 19.6%) compared with the control group (27.0%; 95% CI, 19.3% to 34.7%; P = .007). The ATG group had significantly lower incidences of 2-year overall chronic GVHD (27.9% [95% CI, 20.1% to 35.7%] v 52.5% [95% CI, 43.8% to 61.2%]; P < .001) and 2-year extensive chronic GVHD (8.5% [95% CI, 3.7% to 13.3%] v 23.2% [95% CI, 15.9% to 30.5%]; 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.

Publisher

American Society of Clinical Oncology (ASCO)

Subject

Cancer Research,Oncology

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