Efficacy and safety of MSCs for GvHD prophylaxis and SR‑aGvHD treatment

A PROSPERO-registered systematic review and meta-analysis (CRD420251059633) of 15 randomized controlled trials (RCTs), evaluating mesenchymal stromal cells (MSCs) for graft-versus-host disease (GvHD) prevention in patients with hematological disorders undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT), and for the treatment of patients with Grade 2–4 steroid-refractory acute GvHD (SR‑aGvHD), was published in Stem Cell Research & Therapy by Wu et al. Eleven trials assessed prophylaxis and four assessed SR‑aGvHD treatment. The primary outcomes were aGvHD and chronic GvHD (cGvHD) incidence in the prophylaxis analysis (n = 499 and n = 551, respectively) and overall response rate (ORR) in the treatment analysis (n = 548).

Key data: MSC treatment was associated with a reduced incidence of aGvHD (pooled odds ratio [OR], 0.47; 95% confidence interval [CI], 0.32–0.71; p = 0.00003) and cGvHD (OR, 0.50; 95% CI, 0.34–0.74; p = 0.0005) vs non‑MSC therapy. In SR‑aGvHD, MSC treatment was associated with a higher ORR (pooled OR, 1.50; 95% CI, 1.04–2.17; p = 0.03) and complete remission (CR) rate (OR, 2.10; 95% CI, 1.31–3.37; p = 0.002) vs non‑MSC therapy. Use of MSCs was not associated with improvements in overall survival (OS), relapse incidence, cytomegalovirus (CMV) infection rate, relapse-related mortality, platelet or neutrophil engraftment, or disease-/progression-free survival (DFS/PFS). MSCs were well tolerated, with no immediate or long-term toxicity reported across trials.

Key learning: MSC therapy was associated with a reduced incidence of both aGvHD and cGvHD, and improved response rates, compared with non‑MSC therapy, supporting its continued evaluation as a clinical strategy for GvHD prevention and SR‑aGvHD management.