Efficacy and Safety of Mesenchymal Stem Cells Co-Infusion in Allogeneic Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis

Abstract BackgroundHematopoietic stem cell transplantation (HSCT) is a life-saving strategy for severe hematological conditions, but its efficacy and safety need further improvement. Co-infusion of mesenchymal stem cells (MSCs) may bring promise for the overall efficacy in HSCT setting. About that there are increasing studies, while the results from different trials are conflicting. A systematic review and meta-analysis are needed to appraise the real efficacy of MSCs co-infusion in HSCT. MethodsFive medical databases were searched to identify related controlled studies, which included individuals with hematological diseases receiving allogeneic HSCT (allo-HSCT), and with MSCs co-infusion as intervention arm versus no MSCs as comparison arm. Meta-analysis was performed using RevMan 5.4.ResultsUltimately, 19 trials met the inclusion criteria. MSCs co-infusion was associated with shorter time both to ANC engraftment (4RCTs: SMD -1.20, p = 0.04; 10nRCTs: SMD -0.54, p = 0.04) and PLT engraftment (4RCTs: SMD -0.60, p = 0.04; 10nRCTs: SMD -0.70, p = 0.01), lower risk of cGVHD incidence (4RCTs: RR 0.53, p = 0.01; 10nRCTs: RR 0.50, p < 0.01), and slightly positive trend towards the risk of aGVHD incidence (3RCTs: RR 0.84, p = 0.33; 9nRCTs: RR 0.74, p < 0.01) and NRM(3RCTs: OR 0.59, p = 0.34; 3nRCTs: OR 0.18, p < 0.01); didn’t affect relapse (5RCTs: RR 1.34, p = 0.34; 4nRCTs: RR 0.74, p = 0.24) and overall survival (4RCTs: HR 1.54, p = 0.18; 6nRCTs: HR 0.60, p = 0.06). Subgroup analyses revealed that, when co-transplanted with MSCs, patients younger than 18 or those received HLA-haploidentical grafts had improved engraftment (ANC and PLT）and lower risk of NRM and GVHD (acute and chronic forms) incidence. For adults or those received HLA-identical grafts, the risk of cGVHD incidence were reduced. Patients with hematologic malignancies had lower risk of developing GVHD and NRM, patients with non-malignancies showed faster engraftment.ConclusionWithout increasing the risk of mortality or relapse, MSCs co-infusion in allo-HSCT improved engraftment of platelet and neutrophil, reduced the risk of developing cGVHD. In terms of aGVHD and NRM, the effect of MSCs co-infusion was not quite significant with current evidence.