Efficacy of Thrice-Weekly Versus Once-Weekly Umbilical Cord Mesenchymal Stromal Cell Infusions for Steroid-Refractory Severe Acute Graft-Versus-Host Disease: A Retrospective Cohort Study

Abstract

Effective treatment options for steroid-refractory acute graft-versus-host disease (SR-aGVHD) remain limited. Mesenchymal stromal cells (MSCs) offer a promising therapeutic approach, but the optimal administration protocol is undefined. This retrospective cohort study investigated the impact of MSC infusion frequency on outcomes in patients with grade III–IV SR-aGVHD who received umbilical cord-derived MSCs either once weekly (n = 25) or three times weekly (n = 18). The primary endpoints were overall response rate (ORR) and complete response (CR) at 28 days, and secondary endpoints included overall survival (OS) and changes in lymphocyte subsets. The thrice-weekly group demonstrated significantly superior ORR (77.8% vs. 48.0%, P < 0.05) and CR rates (55.6% vs. 20.0%, P < 0.05), with a particularly notable benefit in gastrointestinal aGVHD (ORR: 73.3% vs. 35.0%, P < 0.05). Immunological analysis showed a more rapid and profound decline in CD3⁺CD8⁺ T cells in the thrice-weekly group (nadir: 21.16% vs. 52.09%, P < 0.05; time to nadir: 10 vs. 21 days, P < 0.05). With a median follow-up of 423 days, the thrice-weekly regimen was associated with significantly improved 2-year OS (78.1% vs. 47.4%, P < 0.05). Despite the limitations of a retrospective design, these findings suggest that increased MSC infusion frequency might be associated with improved therapeutic efficacy and survival in severe SR-aGVHD. However, the potential confounding effect of cumulative dose cannot be excluded, and these results warrant validation in prospective randomized trials.