Mesenchymal stromal cells as prophylaxis for graft-versus-host disease in haplo-identical hematopoietic stem cell transplantation recipients with severe aplastic anemia?—a systematic review and meta-analysis

BACKGROUND: Mesenchymal stromal cells (MSCs) are an emerging prophylaxis option for graft-versus-host disease (GVHD) in haplo-identical hematopoietic stem cell transplantation (haplo-HSCT) recipients with severe aplastic anemia (SAA), but studies have reported inconsistent results. This systematic review and meta-analysis evaluates the efficacy of MSCs as prophylaxis for GVHD in SAA patients with haplo-HSCT. METHODS: Studies were retrieved from PubMed, EMBASE, Cochrane, Web of Science, and http://clinicaltrials.gov from establishment to February 2020. Twenty-nine single-arm studies (n = 1456) were included, in which eight (n = 241) studies combined with MSCs and eleven (n = 1215) reports without MSCs in haplo-HSCT for SAA patients. The primary outcomes were the incidences of GVHD. Other outcomes included 2-year overall survival (OS) and the incidence of cytomegalovirus (CMV) infection. Odds ratios (ORs) were calculated to compare the results pooled through random or fixed effects models. RESULTS: Between MSCs and no MSCs groups, no significant differences were found in the pooled incidences of acute GVHD (56.0%, 95% CI 48.6–63.5% vs. 47.2%, 95% CI 29.0–65.4%; OR 1.43, 95% CI 0.91–2.25; p = 0.123), grade II–IV acute GVHD (29.8%, 95% CI 24.1–35.5% vs. 30.6%, 95% CI 26.6–34.6%; OR 0.97, 95% CI 0.70–1.32; p = 0.889), and chronic GVHD (25.4%, 95% CI 19.8–31.0% vs. 30.0%, 95% CI 23.3–36.6%; OR 0.79, 95% CI 0.56–1.11; p = 0.187). Furtherly, there was no obvious difference in 2-year OS (OR 0.98, 95% CI 0.60–1.61; p = 1.000) and incidence of CMV infection (OR 0.61, 95% CI 0.40–1.92; p = 0.018). CONCLUSIONS: Our meta-analysis indicates that the prophylactic use of MSC co-transplantation is not an effective option for SAA patients undergoing haplo-HSCT. Hence, the general co-transplantation of MSCs for SAA haplo-HSCT recipients may lack evidence-based practice.