Efficacy and Safety of Mesenchymal Stromal Cells for Steroid-Refractory Acute Graft-versus-Host Disease: An Updated...

Steroid-refractory acute graft-versus-host disease (SR-aGVHD) is a life-threatening complication of allogeneic hematopoietic stem cell transplantation with limited effective second-line therapies. Mesenchymal stromal cells (MSCs) have emerged as a promising therapeutic option due to their immunomodulatory properties; however, their clinical efficacy and safety remain under debate.

A systematic review and meta-analysis were conducted in accordance with the PRISMA 2020 guidelines, including four randomized controlled trials (RCTs) comprising 650 patients. Primary outcomes included overall response rate (ORR), complete response (CR), and overall survival (OS). Secondary outcomes assessed organ-specific responses, adverse events (AEs), serious adverse events (SAEs), and failure-free survival.

MSC therapy significantly improved overall response rate (ORR) (RR = 1.13; 95% CI: 1.04-1.23; P = 0.005) and complete response (CR) rate (RR = 1.60; 95% CI: 1.35-1.90; P < 0.00001), particularly in patients with grade III-IV acute graft-versus-host disease (aGVHD) and those with gut and skin involvement. There was no significant improvement in OS (RR = 1.05; 95% CI: 0.90-1.23; P = 0.52), AEs (RR = 1.00; P = 0.96), or SAEs (RR = 1.01; P = 0.79). MSCs showed significant benefit in reducing multi-organ aGVHD (RR = 1.25; P = 0.007), but not for liver involvement or grade II-IV disease. Heterogeneity across studies was generally low to moderate.

MSCs demonstrate significant efficacy in improving short-term clinical responses in SR-aGVHD, without increasing adverse events, particularly in cases of severe and multi-organ disease. However, they do not confer a survival benefit. Further large-scale, standardized, randomized controlled trials (RCTs) with long-term follow-up are warranted to validate these findings and inform clinical implementation.

Not applicable.