title: Survival after mesenchymal stromal cell therapy in steroid-refractory acute graft-versus-host disease: systematic review and meta-analysis.
abstract: BACKGROUND
  Graft-versus-host disease (GVHD) is the major limitation of allogeneic haemopoietic stem-cell transplantation (HSCT), for which no approved treatments are available. Use of mesenchymal stromal cells (MSCs) has become standard practice in some European countries, but controversy exists for their benefit. The aim of this meta-analysis was to analyse available evidence for the benefit of MSC treatments in steroid-resistant acute GVHD.
  
  
  METHODS
  We did a systematic review and meta-analysis to assess response to and survival after MSC treatment in patients with steroid-refractory acute GVHD. We searched MEDLINE, Embase, Ovid, and Cochrane Central databases for published studies, and we used ClinicalTrials.gov and other websites to find unpublished studies and conference abstracts. We included prospective and retrospective studies in which MSCs were administered to patients with steroid-refractory acute GVHD. Data were extracted independently by two investigators based on strict selection criteria. A random-effects model was used to pool outcomes across studies because of anticipated heterogeneity. Our primary outcome was survival at 6 months from the first infusion of MSCs.
  
  
  RESULTS
  We identified 628 citations with our search, of which 610 were excluded after review and a further five did not contain pertinent data. Thus, our meta-analysis included 13 non-randomised studies at moderate risk of bias, comprising a total of 336 patients. Six studies provided data for the primary outcome analysis (119 patients). Survival at 6 months after MSC treatment was 63% (95% CI 50-74; I(2)=41%). Survival did not differ with respect to age, MSC culture medium, or dose of MSCs delivered.
  
  
  CONCLUSIONS
  Available evidence suggests that infusion of MSCs could be an acceptable treatment for patients with steroid-refractory acute GVHD. Randomised clinical trials are needed urgently to assess different treatment modalities for steroid-refractory acute GVHD.
  
  
  BACKGROUND
  None.
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA. Electronic address: Hashmi.shahrukh@mayo.edu.
authors.forename: Shahrukh
authors.initials: S
authors.lastname: Hashmi
authors.affiliation: Department of Internal Medicine, Providence Hospital, Washington, DC, USA.
authors.forename: Mohammad
authors.initials: M
authors.lastname: Ahmed
authors.affiliation: Robert D and Patricia E Kern Center for the Science of Health Care Delivery, Mayo Clinic, Rochester, MN, USA.
authors.forename: M Hassan
authors.initials: MH
authors.lastname: Murad
authors.affiliation: Department of Internal Medicine, Mayo Clinic, Rochester, MN, USA.
authors.forename: Mark R
authors.initials: MR
authors.lastname: Litzow
authors.affiliation: Department of Pediatrics, Phoenix Children's Hospital, Phoenix, AZ, USA.
authors.forename: Roberta H
authors.initials: RH
authors.lastname: Adams
authors.affiliation: Department of Pediatrics, LUMC, Leiden, Netherlands.
authors.forename: Lynne M
authors.initials: LM
authors.lastname: Ball
authors.affiliation: Department of Pediatrics, Duke University, Durham, NC, USA.
authors.forename: Vinod K
authors.initials: VK
authors.lastname: Prasad
authors.affiliation: Department of Stem Cell Transplant, M D Anderson Cancer Center, Houston, TX, USA.
authors.forename: Partow
authors.initials: P
authors.lastname: Kebriaei
authors.affiliation: Department of Laboratory Medicine, Karolinska Institute, Solna, Sweden.
authors.forename: Olle
authors.initials: O
authors.lastname: Ringden
mesh_terms: D000208:Acute Disease; D005060:Europe; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation; D011446:Prospective Studies; D012189:Retrospective Studies; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome