title: Intravenous infusion of allogeneic mesenchymal stromal cells in refractory or relapsed aplastic anemia.
abstract: OBJECTIVE
  For patients with aplastic anemia (AA) who are refractory to anti-thymocyte globulin (ATG) and cyclosporine, a second course of immunosuppression is successful in only one-fourth to one-third of cases.
  
  
  METHODS
  We conducted a phase 1/2 study to evaluate the addition of two to five weekly intravenous infusions of allogeneic unrelated non-human leukocyte antigen-matched bone marrow-derived mesenchymal stromal cells (MSCs) (median, 2.7 × 10(6) cells/kg/infusion; range, 1.3-4.5) to standard rabbit ATG and cyclosporine in nine patients with refractory or relapsed AA.
  
  
  RESULTS
  After a median follow-up of 20 months, no infusion-related adverse event was observed, but four deaths occurred as the result of heart failure and bacterial or invasive fungal infections; only two patients achieved partial hematologic responses at 6 months. We failed to demonstrate by fluorescence in situ hybridization or variable number tandem repeat any MSC engraftment in patient marrow 30, 90 or 180 days after infusions.
  
  
  CONCLUSIONS
  Infusion of allogeneic MSCs in AA is safe but does not improve clinical hematologic response or engraft in recipient bone marrow. This study was registered at clinicaltrials.gov, identifier: NCT01297972.
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil; Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil. Electronic address: dvcle@hcrp.usp.br.
authors.forename: Diego V
authors.initials: DV
authors.lastname: Clé
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil; Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.
authors.forename: Barbara
authors.initials: B
authors.lastname: Santana-Lemos
authors.affiliation: Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.
authors.forename: Maria Florencia
authors.initials: MF
authors.lastname: Tellechea
authors.affiliation: Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.
authors.forename: Karen L
authors.initials: KL
authors.lastname: Prata
authors.affiliation: Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.
authors.forename: Maristela D
authors.initials: MD
authors.lastname: Orellana
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil; Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.
authors.forename: Dimas T
authors.initials: DT
authors.lastname: Covas
authors.affiliation: Department of Internal Medicine, University of São Paulo at Ribeirão Preto School of Medicine, Ribeirão Preto, SP, Brazil; Center for Cell-Based Therapy, São Paulo Research Foundation (FAPESP), Ribeirão Preto, SP, Brazil.
authors.forename: Rodrigo T
authors.initials: RT
authors.lastname: Calado
mesh_terms: D000328:Adult; D000741:Anemia, Aplastic / Q000628:therapy*; D000961:Antilymphocyte Serum / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use*; D005260:Female; D006801:Humans; D007155:Immunologic Factors / Q000627:therapeutic use*; D007165:Immunosuppression Therapy / Q000379:methods; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D017404:In Situ Hybridization, Fluorescence; D007262:Infusions, Intravenous; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation / Q000009:adverse effects; D059630:Mesenchymal Stem Cells; D008875:Middle Aged; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D000961:Antilymphocyte Serum; D007155:Immunologic Factors; D007166:Immunosuppressive Agents; D016572:Cyclosporine
keywords: aplastic anemia; immunosuppression; mesenchymal stromal cell engraftment; mesenchymal stromal cells