Human umbilical cord-derived mesenchymal stromal cells for the treatment of steroid refractory grades III-IV acute graft-versus-host disease with long-term follow-up

• Published in: Frontiers in immunology 2024-08, Vol.15, p.1436653
• Main Authors: Niu, Jing-Wen, Li, Yuhang, Xu, Chen, Sheng, Hongxia, Tian, Chong, Ning, Hongmei, Hu, Jiangwei, Chen, Jianlin, Li, Botao, Wang, Jun, Lou, Xiao, Liu, Na, Su, Yongfeng, Sun, Yao, Qiao, Zhuoqing, Wang, Lei, Zhang, Yu, Lan, Sanchun, Xie, Jing, Ren, Jing, Peng, Bo, Wang, Shenyu, Shi, Yanping, Zhao, Long, Zhang, Yijian, Chen, Hu, Zhang, Bin, Hu, Liangding
• Format: Article
• Language: English
• Subjects: Acute Disease; Adolescent; Adult; Child; Child, Preschool; Female; Follow-Up Studies; Graft vs Host Disease - etiology; Graft vs Host Disease - therapy; graft-versus-host disease; hematopoietic stem cell transplantation; Humans; Immunology; Infant; long-term follow-up; Male; Mesenchymal Stem Cell Transplantation - methods; Mesenchymal Stem Cells; mesenchymal stromal cells; Middle Aged; Steroids - therapeutic use; Treatment Outcome; umbilical cord; Umbilical Cord - cytology; Young Adult
• ISSN: 1664-3224; 1664-3224
• DOI: 10.3389/fimmu.2024.1436653

Mesenchymal stromal cells (MSCs) have been extensively studied as a potential treatment for steroid refractory acute graft-versus-host disease (aGVHD). However, the majority of clinical trials have focused on bone marrow-derived MSCs. In this study, we report the outcomes of 86 patients with grade III-IV (82.6% grade IV) steroid refractory aGVHD who were treated with human umbilical cord-derived mesenchymal stromal cells (UC-MSCs). The patient cohort included 17 children and 69 adults. All patients received intravenous infusions of UC-MSCs at a dose of 1 × 106 cells per kg body weight, with a median of 4 infusions (ranging from 1 to 16). The median time between the onset of aGVHD and the first infusion of UC-MSCs was 7 days (ranging from 3 to 88 days). At day 28, the overall response (OR) rate was 52.3%. Specifically, 24 patients (27.9%) achieved complete remission, while 21 (24.4%) exhibited partial remission. The estimated survival probability at 100 days was 43.7%. Following a median follow-up of 108 months (ranging from 61 to 159 months), the survival rate was approximately 11.6% (10/86). Patients who developed acute lower GI tract and liver GVHD exhibited poorer OR rates at day 28 compared to those with only acute lower GI tract GVHD (22.2% vs. 58.8%; p= 0.049). No patient experienced serious adverse events. These finding suggest that UC-MSCs are safe and effective in both children and adults with steroid refractory aGVHD. UC-MSCs could be considered as a feasible treatment option for this challenging conditon. (NCT01754454).