title: Sirolimus demonstrates activity in the primary therapy of acute graft-versus-host disease without systemic glucocorticoids.
abstract: BACKGROUND
  Advances in acute graft-versus-host disease therapy are needed.
  
  
  METHODS
  We examined the efficacy of sirolimus as primary therapy for acute graft-versus-host disease in 32 patients.
  
  
  RESULTS
  Acute graft-versus-host disease involved the skin in 53% of cases, gastrointestinal tract in 66%, liver in 16%. The syndrome was overall grade 1 in 12% cases, grade 2 in 75%, and grade 3 in 13%. Sirolimus was targeted to achieve serum trough levels of 5-14 ng/mL. Sixteen (50%) patients achieved sustained, complete resolution of acute graft-versus-host disease with sirolimus alone. In contrast, 19 of 32 (59%) matched historical controls treated with standard 1 mg/kg steroids achieved complete response (P=0.47). With median follow-up time for surviving patients of 16 (range 6-26) months, one year overall survival was 56% (95% CI 38-74%). The cumulative incidence of relapse at one year was 37% (95% CI 23-60%), and mortality in remission was 20% (95% CI 10-42%). The cumulative incidence of chronic graft-versus-host disease was 55% (95% CI 39-79%). Thrombotic microangiopathy occurred in 3 cases (grade 1 n=1; grade 2 n=2), and responded to dose reduction of calcineurin inhibitor.
  
  
  CONCLUSIONS
  In this retrospective series, sirolimus demonstrates activity comparable to that of high-dose glucocorticoids in the primary therapy of acute graft-versus-host disease. Confirmation of this activity requires prospective clinical trials.
authors.affiliation: Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, FL 33612 USA. joseph.pidala@moffitt.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Marcie
authors.initials: M
authors.lastname: Tomblyn
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.forename: Teresa
authors.initials: T
authors.lastname: Field
authors.forename: Ernesto
authors.initials: E
authors.lastname: Ayala
authors.forename: Janelle
authors.initials: J
authors.lastname: Perkins
authors.forename: Hugo
authors.initials: H
authors.lastname: Fernandez
authors.forename: Fred
authors.initials: F
authors.lastname: Locke
authors.forename: Lia
authors.initials: L
authors.lastname: Perez
authors.forename: Jose Leonel
authors.initials: JL
authors.lastname: Ochoa
authors.forename: Melissa
authors.initials: M
authors.lastname: Alsina
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage / Q000627:therapeutic use*; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D005938:Glucocorticoids; D007166:Immunosuppressive Agents; D020123:Sirolimus