AUTHOR=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 TITLE=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 JOURNAL=Frontiers in Immunology VOLUME=15 YEAR=2024 URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1436653 DOI=10.3389/fimmu.2024.1436653 ISSN=1664-3224 ABSTRACT=Introduction

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.

Methods

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).

Results

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.

Discussion

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).