title: The Potential of Mesenchymal Stromal Cells as Treatment for Severe Steroid-Refractory Acute Graft-Versus-Host Disease: A Critical Review of the Literature.
abstract: BACKGROUND
  Acute graft-versus-host disease (GvHD) is a major complication after allogeneic hematopoietic stem cell transplantation which causes high morbidity and mortality among patients who do not respond to steroid treatment. Mesenchymal stromal cells (MSCs) have immune modulatory abilities and earned their place in the treatment of GvHD after a pediatric patient remarkably recovered from steroid-refractory acute GvHD with MSC salvage therapy. Large, prospective clinical trials evaluating the potency of MSCs have however not been published.
  
  
  METHODS
  To evaluate the therapeutic potential of MSCs in the treatment of steroid-refractory acute GvHD, we conducted a systematic literature search. We included all studies that focused on MSC treatment of adult allogeneic hematopoietic stem cell transplantation recipients with grades III to IV steroid-refractory acute GvHD and were transparent about their methods and patient selection criteria.
  
  
  RESULTS
  From a total of 255 articles, 9 articles met the quality criteria for this study. The proportion of patients achieving complete resolution of all symptoms (complete response, CR) varied between 8% and 83%. Four of the 9 studies reported CR rates above 50%. The GvHD grade at the time of treatment was identified as a predictor of clinical response. Interestingly, complete response but not partial response to MSCs was associated with overall survival. No serious side effects of MSC therapy were reported.
  
  
  CONCLUSIONS
  MSC treatment does improve the outcome in steroid-refractory acute GvHD patients but well-designed, prospective randomized clinical trials are needed to confirm the potential of MSCs as salvage therapy for steroid-refractory GvHD and to identify those patients that will benefit most.
authors.affiliation: 1 Department of Hematology, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. 2 Department of Hematopoiesis, Sanquin Research and Landsteiner Laboratory, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: J Marius
authors.initials: JM
authors.lastname: Munneke
authors.forename: Melchior J A
authors.initials: MJ
authors.lastname: Spruit
authors.forename: Anne S
authors.initials: AS
authors.lastname: Cornelissen
authors.forename: Vera
authors.initials: V
authors.lastname: van Hoeven
authors.forename: Carlijn
authors.initials: C
authors.lastname: Voermans
authors.forename: Mette D
authors.initials: MD
authors.lastname: Hazenberg
mesh_terms: D000208:Acute Disease; D006086:Graft vs Host Disease / Q000628:therapy*; D006801:Humans; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D011446:Prospective Studies; D013256:Steroids / Q000627:therapeutic use
chemical_list: D013256:Steroids