Co-transplantation of multipotent mesenchymal stromal cells in allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis

Background aims. Allogeneic hematopoietic stem cell transplantation (HSCT) is a potentially curative treatment option for patients with hematological malignancies. Co-transplantation of multipotent mesenchymal stromal cells (MSCs) during allogeneic HSCT has been explored to enhance engraftment and decrease the risk of graft-versus-host disease (GVHD). We aimed to identify, evaluate and summarize the findings of all relevant controlled clinical studies to determine the potential benefits of MSC infusion during allogeneic HSCT, with regard to the outcomes engraftment, GVHD, post-transplant relapse and survival. Methods. We conducted a systematic search of electronic databases for relevant controlled clinical studies. Studies included patients of all ages with hematological malignancies receiving allogeneic HSCT with or without infusion of MSCs within a 24-h time frame of transplantation. Results. Nine studies met our inclusion criteria, including three randomized, one non-randomized and five historically controlled trials, representing a total of 309 patients. Our meta-analyses did not reveal any statistically significant differences in donor engraftment or GVHD. A review of data regarding relapse and overall survival may result in a positive attitude toward intervention with MSCs, but due to heterogeneous reporting, it is difficult to draw any strict conclusions. None of the studies had overall serious risks of bias, but the quality of the evidence is low. Conclusions. Meta-analysis did not reveal any statistically significant effects of MSC co-transplantation, but the results must be interpreted with caution because of the weak study design and small study populations. We discuss further needs to explore the potential effects of MSCs in a HSCT setting.