title: Co-transplantation of multipotent mesenchymal stromal cells in allogeneic hematopoietic stem cell transplantation: A systematic review and meta-analysis.
abstract: OBJECTIVE
  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.
authors.affiliation: Department for immunology and transfusion medicine, Section for Cell Therapy, Haukeland University Hospital, Bergen, Norway; Bergen University College, Centre for Evidence Based Practice.
authors.forename: Merete
authors.initials: M
authors.lastname: Kallekleiv
authors.affiliation: Norwegian Knowledge Centre for the Health Services, Oslo, Norway.
authors.forename: Lillebeth
authors.initials: L
authors.lastname: Larun
authors.affiliation: Department of Medicine, Haukeland University Hospital, Bergen, Norway; Department of Clinical Science, University of Bergen, Bergen, Norway.
authors.forename: Øystein
authors.initials: Ø
authors.lastname: Bruserud
authors.affiliation: Department of Clinical Science, University of Bergen, Bergen, Norway. Electronic address: kimberley.hatfield@uib.no.
authors.forename: Kimberley Joanne
authors.initials: KJ
authors.lastname: Hatfield
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D018572:Disease-Free Survival; D006086:Graft vs Host Disease / Q000209:etiology* / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006801:Humans; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000379:methods*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000276:immunology; D008875:Middle Aged; D009364:Neoplasm Recurrence, Local / Q000453:epidemiology*; D016896:Treatment Outcome
keywords: Allogeneic hematopoietic stem cell transplantation; Engraftment; Evidence-based practice; Graft-versus-host disease; Multipotent mesenchymal stromal cells; Systematic review