title: Phase II Multicenter, Randomized, Double-Blind Controlled Study of Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cells in the Prophylaxis of Chronic Graft-Versus-Host Disease After HLA-Haploidentical Stem-Cell Transplantation.
abstract: Although mesenchymal stromal cells (MSCs) possess immunomodulatory properties and exhibit promising efficacy against chronic graft-versus-host disease (cGVHD), little is known about the efficacy of MSCs in the prophylaxis of cGVHD after HLA-haploidentical hematopoietic stem-cell transplantation (HLA-haplo HSCT).
  
  
  
  In this multicenter, double-blind, randomized controlled trial, we investigated the incidence and severity of cGVHD among patients, and the changes in T, B, and natural killer (NK) cells after the repeated infusion of MSCs.
  
  
  
  The 2-year cumulative incidence of cGVHD in the MSCs group was 27.4% (95% CI, 16.2% to 38.6%), compared with 49.0% (95% CI, 36.5% to 61.5%) in the non-MSCs control group (P = .021). Seven patients in the non-MSCs control group had severe lung cGVHD, but no patients in the MSCs group developed typical lung cGVHD (P = .047). After the MSC infusions, increasing memory B lymphocytes and regulatory T cells, as well as the ratio of type 1 T helper to type 2 T helper cells, were observed, whereas the number of NK cells decreased.
  
  
  
  Our findings suggest that the repeated infusion of MSCs might inhibit cGVHD symptoms in patients after HLA-haplo HSCT, accompanied by changes in the numbers and subtypes of T, B, and NK cells, leading to the acquisition of immune tolerance.
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
authors.forename: Lei
authors.initials: L
authors.lastname: Gao
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
authors.forename: Yanqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
authors.forename: Baoyang
authors.initials: B
authors.lastname: Hu
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
authors.forename: Peiyan
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authors.lastname: Kong
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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authors.lastname: Lou
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
authors.forename: Yi
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authors.lastname: Su
authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
authors.forename: Yao
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authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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authors.affiliation: Lei Gao, Yanqi Zhang, Jia Liu, Peiyan Kong, Yao Liu, Li Gao, Cheng Zhang, Lidan Zhu, Qin Wen, Ping Wang, Xinghua Chen, Jiangfan Zhong, and Xi Zhang, Third Military Medical University, Chongqing; Baoyang Hu, Chinese Academy of Sciences, Beijing; Shifeng Lou, Second Affiliated Hospital of Chongqing Medical University, Chongqing; Yi Su, General Hospital of Chengdu Military Region of People's Liberation Army, Chengdu; Tonghua Yang, Yunnan Provincial People's Hospital; Huimin Li, Affiliated Hospital of Kunming Medical College, Kunming, China; and Jiangfan Zhong, University of Southern California, Los Angeles, CA.
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mesh_terms: D000293:Adolescent; D000328:Adult; D001402:B-Lymphocytes / Q000276:immunology; D002908:Chronic Disease; D004311:Double-Blind Method; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000628:therapy*; D006680:HLA Antigens / Q000235:genetics / Q000276:immunology; D006238:Haploidy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000379:methods; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology; D019172:Transplantation Conditioning / Q000009:adverse effects / Q000379:methods; D014184:Transplantation, Homologous; D014470:Umbilical Cord / Q000166:cytology; D055815:Young Adult
chemical_list: D006680:HLA Antigens