PMID- 38413930
OWN - NLM
STAT- MEDLINE
DCOM- 20240229
LR  - 20240301
IS  - 1741-7015 (Electronic)
IS  - 1741-7015 (Linking)
VI  - 22
IP  - 1
DP  - 2024 Feb 27
TI  - Mesenchymal stromal cells plus basiliximab improve the response of 
      steroid-refractory acute graft-versus-host disease as a second-line therapy: a 
      multicentre, randomized, controlled trial.
PG  - 85
LID - 10.1186/s12916-024-03275-5 [doi]
LID - 85
AB  - BACKGROUND: For patients with steroid-refractory acute graft-versus-host disease 
      (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal 
      stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. 
      However, clinical trials and an overall understanding of the molecular mechanisms 
      of MSCs combined with basiliximab for SR-aGVHD are limited, especially in 
      haploidentical haemopoietic stem cell transplantation (HID HSCT). METHODS: The 
      primary endpoint of this multicentre, randomized, controlled trial was the 4-week 
      complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD 
      were assigned in a 1:1 randomization schedule to the MSC group (receiving 
      basiliximab plus MSCs) or control group (receiving basiliximab alone) 
      (NCT04738981). RESULTS: Most enrolled patients (96.2%) received HID HSCT. The 
      4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the 
      control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response 
      rates at week 4, the two groups were comparable. More patients in the control 
      group used >/= 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood 
      samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive 
      cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-beta and HGF. Compared 
      to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-beta (P = 0.0243) 
      levels increased significantly 1 day after MSC infusion. At 7 days after MSC 
      infusion, the levels of HO1, GAL1, TNFIA6 and TGF-beta tended to increase; however, 
      the differences were not statistically significant. Although the 52-week 
      cumulative incidence of cGVHD in the MSC group was comparable to that in the 
      control group, fewer patients in the MSC group developed cGVHD involving >/=3 
      organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no 
      infusion-related adverse events (AEs) occurred and other AEs were also comparable 
      between the two groups. However, patients with malignant haematological diseases 
      in the MSC group had a higher 52-week disease-free survival rate than those in 
      the control group (84.8% vs. 65.9%, P = 0.031). CONCLUSIONS: For SR-aGVHD after 
      allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the 
      second-line therapy led to significantly better 4-week CR rates than basiliximab 
      alone. The addition of MSCs not only did not increase toxicity but also provided 
      a survival benefit.
CI  - (c) 2024. The Author(s).
FAU - Fu, Haixia
AU  - Fu H
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Sun, Xueyan
AU  - Sun X
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Lin, Ren
AU  - Lin R
AD  - Medical Center of Haematology, State Key Laboratory of Trauma, Burn and Combined 
      Injury, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
FAU - Wang, Yu
AU  - Wang Y
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Xuan, Li
AU  - Xuan L
AD  - Medical Center of Haematology, State Key Laboratory of Trauma, Burn and Combined 
      Injury, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China.
FAU - Yao, Han
AU  - Yao H
AD  - Department of Haematology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, 510515, China.
FAU - Zhang, Yuanyuan
AU  - Zhang Y
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Mo, Xiaodong
AU  - Mo X
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Lv, Meng
AU  - Lv M
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Zheng, Fengmei
AU  - Zheng F
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Kong, Jun
AU  - Kong J
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Wang, Fengrong
AU  - Wang F
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Yan, Chenhua
AU  - Yan C
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Han, Tingting
AU  - Han T
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Chen, Huan
AU  - Chen H
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Chen, Yao
AU  - Chen Y
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Tang, Feifei
AU  - Tang F
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Sun, Yuqian
AU  - Sun Y
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Chen, Yuhong
AU  - Chen Y
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Xu, Lanping
AU  - Xu L
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Liu, Kaiyan
AU  - Liu K
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China.
FAU - Zhang, Xi
AU  - Zhang X
AD  - Medical Center of Haematology, State Key Laboratory of Trauma, Burn and Combined 
      Injury, Xinqiao Hospital, Army Medical University, Chongqing, 400037, China. 
      zhangxxi@sina.com.
FAU - Liu, Qifa
AU  - Liu Q
AD  - Department of Haematology, Nanfang Hospital, Southern Medical University, 
      Guangzhou, 510515, China. liuqifa628@163.com.
FAU - Huang, Xiaojun
AU  - Huang X
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China. xjhrm@medmail.com.cn.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China. xjhrm@medmail.com.cn.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China. xjhrm@medmail.com.cn.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China. 
      xjhrm@medmail.com.cn.
FAU - Zhang, Xiaohui
AU  - Zhang X
AD  - Peking University People's Hospital, Peking University Institute of Haematology, 
      No. 11 Xizhimen South Street, Beijing, 100044, China. zhangxh@bjmu.edu.cn.
AD  - Collaborative Innovation Center of Haematology, Peking University, Beijing, 
      China. zhangxh@bjmu.edu.cn.
AD  - Beijing Key Laboratory of Haematopoietic Stem Cell Transplantation, Beijing, 
      China. zhangxh@bjmu.edu.cn.
AD  - National Clinical Research Center for Haematologic Disease, Beijing, China. 
      zhangxh@bjmu.edu.cn.
LA  - eng
SI  - ClinicalTrials.gov/NCT04738981
GR  - 81970113/National Natural Science Foundation of China/
GR  - 81800116/National Natural Science Foundation of China/
GR  - 81730004/Key Program of National Natural Science Foundation of China/
GR  - 2017YFA0105503/National Key Research and Development Program of China/
GR  - 7232188/Beijing Natural Science Foundation/
PT  - Journal Article
PT  - Multicenter Study
PT  - Randomized Controlled Trial
DEP - 20240227
PL  - England
TA  - BMC Med
JT  - BMC medicine
JID - 101190723
RN  - 9927MT646M (Basiliximab)
RN  - 0 (Steroids)
RN  - 0 (Transforming Growth Factor beta)
SB  - IM
MH  - Humans
MH  - Basiliximab/therapeutic use
MH  - *Graft vs Host Disease/drug therapy
MH  - *Hematopoietic Stem Cell Transplantation/adverse effects
MH  - Steroids/therapeutic use
MH  - *Mesenchymal Stem Cells
MH  - Transforming Growth Factor beta/therapeutic use
MH  - Acute Disease
MH  - *Mesenchymal Stem Cell Transplantation/adverse effects
PMC - PMC10900595
OTO - NOTNLM
OT  - Acute graft-versus-host disease
OT  - Haemopoietic stem cell transplantation
OT  - Haploidentical
OT  - Mesenchymal stromal cells
OT  - Second-line therapy
OT  - Steroid-refractory
COIS- The authors declare that they have no competing interests.
EDAT- 2024/02/28 00:43
MHDA- 2024/02/29 06:42
PMCR- 2024/02/27
CRDT- 2024/02/27 23:52
PHST- 2023/06/01 00:00 [received]
PHST- 2024/01/25 00:00 [accepted]
PHST- 2024/02/29 06:42 [medline]
PHST- 2024/02/28 00:43 [pubmed]
PHST- 2024/02/27 23:52 [entrez]
PHST- 2024/02/27 00:00 [pmc-release]
AID - 10.1186/s12916-024-03275-5 [pii]
AID - 3275 [pii]
AID - 10.1186/s12916-024-03275-5 [doi]
PST - epublish
SO  - BMC Med. 2024 Feb 27;22(1):85. doi: 10.1186/s12916-024-03275-5.