Mesenchymal stromal cells in the prophylaxis of graft vs host disease: A meta analysis

Abstract Introduction: Graft-versus-host disease (GVHD) is a major complication following allogeneic hematopoietic stem cell transplantation (HSCT), causing morbidity and mortality. Mesenchymal stromal cells (MSCs) show potential benefits in GVHD prophylaxis through immunomodulatory properties. Studies suggest early MSC administration may enhance immune tolerance and reduce GVHD incidence. In this meta-analysis, we aim to evaluate the safety and efficacy of MSC infusion in GVHD prophylaxis. Methods: We conducted a systematic review and meta-analysis following PRISMA guidelines. A literature search was performed across PubMed, Scopus, Embase, and Google Scholar databases up to July 2025, focusing on studies comparing efficacy and safety outcomes of Mesenchymal Stromal Cells (MSC) prophylaxis with standard care in preventing GVHD following allogeneic HSCT. Data analysis used RevMan 5.4.1, and pooled risk ratios (RRs) were calculated using the Mantel-Haenszel method. A Fixed Effects Model was selected based on study characteristics. Statistical significance was determined at p< 0.05. The risk of bias was evaluated using RoB 2.0. Results: 464 participants from three randomized controlled trials were included in this analysis. MSC treated 232 patients, with 232 patients in the control group. Our meta-analysis yielded the following results: GVHD Outcomes:Infusion of mesenchymal stem cells (MSCs) decreased the incidence of acute graft-versus-host disease (aGVHD), with occurrences in 16.47% of MSC recipients versus 41.17% in controls [RR 0.40, 95% CI (0.27-0.59), I²=0%]. This reduction was notable in severe aGVHD (grade 3-4), seen in 2.35% of patients receiving MSC infusion, versus 18.23% in controls [RR 0.13, 95% CI 0.05-0.36, I² = 0%]. The incidence of chronic GVHD (cGVHD) was also lower in the treatment group. Any grade of cGVHD occurred in 24.13% of MSC patients versus 40.08% in controls [RR 0.60, 95% CI 0.46-0.79, I² = 0%], while severe cGVHD occurred in 5.17% versus 15.08% [RR 0.34, 95% CI 0.18-0.64, I² = 0%]. MSC therapy enhanced GVHD-free relapse-free survival, reaching 61.2% versus 29.4% in controls (RR 2.08, 95% CI 1.60-2.70; I² = 0%). Overall survival and disease-free rates showed slight increases: 83.6% versus 78% [RR:1.04, 95% CI (0.97-1.13), I²=10%], and 79.31% versus 72.84% [RR:1.08, 95% CI (0.98-1.19), I²=0%]. Relapse rate and non-relapse mortality were lower in the MSC group: 15.94% versus 18.10% [RR:0.89, 95% CI (0.60-1.31), I²=0%], and 4.3% versus 8.6% [RR 0.50, 95% CI (0.24-1.05); I² = 0%]. Adverse Events and Toxicities: Adverse events occurred at similar rates in both groups [77.94% vs. 77.2%, RR 1, 95% CI (0.84-1.2), I² = 48%]. However, serious events like hemorrhagic cystitis were lower in the MSC group [14.7% vs. 23.5%; RR 0.63, 95% CI (0.40-1.00); I² = 32%]. Viral infections, specifically EBV and CMV, remained consistent between MSC and control groups [44.11% vs. 44.7%, and 40.58% vs. 41.76%]. Discussion: This meta-analysis reveals that prophylactic mesenchymal stem cell (MSC) infusion significantly decreases acute graft-versus-host disease (GVHD), severe acute GVHD, chronic GVHD, and severe chronic GVHD incidence, while enhancing GVHD-free relapse-free survival in allogeneic hematopoietic stem cell transplantation (HSCT) recipients compared to standard care. The findings were consistent across studies and achieved statistical significance. Although improved survival, reduced relapse, and mortality rates were observed in the MSC group, these did not reach statistical significance. MSC infusion did not increase adverse events or viral infections and significantly reduced hemorrhagic cystitis occurrence. These results support incorporating MSCs as a prophylactic strategy in allogeneic HSCT. Their potential to enhance immune tolerance without impacting patient morbidity underscores their role in improving transplant outcomes. Future trials are needed to validate these findings and define eligibility criteria for patients who may benefit from prophylactic MSC infusions post-HSCT.