title: Adult adherent stromal cells in the management of graft-versus-host disease.
abstract: BACKGROUND
  Early reports demonstrated the safety of adherent mesenchymal stromal cell (MSC) infusions in the hematopoietic stem cell transplantation (HCT) setting, as well as clinical efficacy for treatment of steroid refractory acute graft-versus-host disease (GVHD); however, two large, Phase III randomized, placebo-controlled trials of MSC for initial therapy or steroid refractory GVHD failed to meet their primary endpoints of durable complete response. Subset analyses demonstrated efficacy in selected patient populations, contributing to recent approvals of MSC for pediatric patients in Canada and New Zealand.
  
  
  METHODS
  In this review, we discuss the biologic and immunomodulatory properties of MSC and potential mechanisms involved. We review the results of prior clinical trials incorporating MSC for GVHD treatment or prophylaxis, the recent approvals in Canada and New Zealand, as well as future directions in the field.
  
  
  CONCLUSIONS
  The role of MSC infusions, in the prophylaxis and/or treatment of GVHD after HCT, continues to be under active investigation. Whether, and how, to incorporate MSC infusions is unclear, and ongoing questions include the source tissue type and culture methods, the timing and dosage of MSC product infusions, as well as the optimal clinical trial design and endpoints for assessment of clinical response.
authors.affiliation: Oregon Health and Science University, OHSU Knight Cancer Institute, Center for Hematologic Malignancies , Portland, OR 97239 , USA maziarzr@ohsu.edu.
authors.forename: Laura F
authors.initials: LF
authors.lastname: Newell
authors.forename: Robert J
authors.initials: RJ
authors.lastname: Deans
authors.forename: Richard T
authors.initials: RT
authors.lastname: Maziarz
mesh_terms: D000328:Adult; D000818:Animals; D001688:Biological Products / Q000627:therapeutic use; D002170:Canada; D002648:Child; D017326:Clinical Trials, Phase III as Topic; D017277:Drug Approval; D006086:Graft vs Host Disease / Q000517:prevention & control* / Q000628:therapy*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use; D045164:Mesenchymal Stem Cell Transplantation; D009520:New Zealand; D016032:Randomized Controlled Trials as Topic; D017154:Stromal Cells / Q000166:cytology*; D016896:Treatment Outcome
chemical_list: D001688:Biological Products; D007155:Immunologic Factors