Mesenchymal Stromal Cell Therapy for Steroid-Refractory Acute Graft-versus-Host Disease

Abstract

Background: Steroid-refractory acute graft-versus-host disease remains a lethal complication of allogeneic transplantation,
and mesenchymal stromal cells have been given for two decades on largely uncontrolled evidence.
Objective: To examine why single-arm series and randomised trials report irreconcilable response rates.
Methods: Narrative review of single-arm cohorts, randomised trials, mechanistic studies and regulatory decisions.
Findings: Single-arm studies reported 71% overall response in 55 patients and 83% at day 28 in 69 patients, whereas
randomised trials found day-28 complete response of 45% versus 46% placebo (192 treated) and 35% versus 30% (244
treated). Placebo arms fell inside the single-arm range.
Conclusions: The evidence supports immunomodulatory activity conditional on inflammatory licensing, but not the efficacy
implied by uncontrolled response rates. Function-based potency assays are required.