title: Sibling donor and recipient immune modulation with atorvastatin for the prophylaxis of acute graft-versus-host disease.
abstract: OBJECTIVE
  Graft-versus-host disease (GVHD) is major cause of morbidity and mortality after allogeneic hematopoietic cell transplantation (HCT). Atorvastatin is a potent immunomodulatory agent that holds promise as a novel and safe agent for acute GVHD prophylaxis.
  
  
  METHODS
  We conducted a phase II trial to evaluate the safety and efficacy of atorvastatin administration for GVHD prophylaxis in both adult donors and recipients of matched sibling allogeneic HCT. Atorvastatin (40 mg per day orally) was administered to sibling donors, starting 14 to 28 days before the anticipated first day of stem-cell collection. In HCT recipients (n = 30), GVHD prophylaxis consisted of tacrolimus, short-course methotrexate, and atorvastatin (40 mg per day orally).
  
  
  RESULTS
  Atorvastatin administration in healthy donors and recipients was not associated with any grade 3 to 4 adverse events. Cumulative incidence rates of grade 2 to 4 acute GVHD at days +100 and +180 were 3.3% (95% CI, 0.2% to 14.8%) and 11.1% (95% CI, 2.7% to 26.4%), respectively. One-year cumulative incidence of chronic GVHD was 52.3% (95% CI, 27.6% to 72.1%). Viral and fungal infections were infrequent. One-year cumulative incidences of nonrelapse mortality and relapse were 9.8% (95% CI, 1.4% to 28%) and 25.4% (95% CI, 10.9% to 42.9%), respectively. One-year overall survival and progression-free survival were 74% (95% CI, 58% to 96%) and 65% (95% CI, 48% to 87%), respectively. Compared with baseline, atorvastatin administration in sibling donors was associated with a trend toward increased mean plasma interleukin-10 concentrations (5.6 v 7.1 pg/mL; P = .06).
  
  
  CONCLUSIONS
  A novel two-pronged strategy of atorvastatin administration in both donors and recipients of matched sibling allogeneic HCT seems to be a feasible, safe, and potentially effective strategy to prevent acute GVHD.
authors.affiliation: All authors: West Virginia University, Morgantown, WV.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Hamadani
authors.forename: Laura F
authors.initials: LF
authors.lastname: Gibson
authors.forename: Scot C
authors.initials: SC
authors.lastname: Remick
authors.forename: Sijin
authors.initials: S
authors.lastname: Wen
authors.forename: William
authors.initials: W
authors.lastname: Petros
authors.forename: William
authors.initials: W
authors.lastname: Tse
authors.forename: Kathleen M
authors.initials: KM
authors.lastname: Brundage
authors.forename: Jeffrey A
authors.initials: JA
authors.lastname: Vos
authors.forename: Aaron
authors.initials: A
authors.lastname: Cumpston
authors.forename: Pamela
authors.initials: P
authors.lastname: Bunner
authors.forename: Michael D
authors.initials: MD
authors.lastname: Craig
mesh_terms: D000284:Administration, Oral; D000328:Adult; D000368:Aged; D000069059:Atorvastatin; D001424:Bacterial Infections / Q000209:etiology; D016207:Cytokines / Q000097:blood; D005240:Feasibility Studies; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000276:immunology / Q000517:prevention & control*; D019337:Hematologic Neoplasms / Q000276:immunology / Q000601:surgery; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000379:methods*; D006538:Heptanoic Acids / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011758:Pyrroles / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D035781:Siblings; D016019:Survival Analysis; D014019:Tissue Donors; D014181:Transplantation Immunology / Q000187:drug effects / Q000276:immunology; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D014777:Virus Diseases / Q000209:etiology; D055815:Young Adult
chemical_list: D016207:Cytokines; D006538:Heptanoic Acids; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011758:Pyrroles; D000069059:Atorvastatin