title: Rapamycin for refractory acute graft-versus-host disease.
abstract: BACKGROUND
  Rapamycin, an inhibitor of mammalian target of rapamycin kinase, is a potent immunosuppressive drug that also displays antineoplastic properties and expands regulatory T cells. Steroid-refractory acute graft-versus-host disease (GVHD) remains a significant cause of mortality after allogeneic stem-cell transplantation and therapeutic options are not codified. We retrospectively evaluated the role of rapamycin in this setting.
  
  
  METHODS
  In this retrospective single-center study, 22 patients were identified, from October 2004 to February 2008, as having received rapamycin for acute GVHD refractory to one or more lines of treatment. We analyzed the efficacy and tolerance of rapamycin and the outcome of these 22 patients in this setting.
  
  
  RESULTS
  Rapamycin resulted in a rapid and sustained complete remission of GVHD in 72% of heavily pretreated patients. Cytopenias were frequent but did not require treatment interruption. Thrombotic microangiopathy developed in 36% of patients when rapamycin was associated with calcineurin inhibitors and frequently resolved after interruption of one or both drugs. At a median follow-up of 13 months, overall survival was 41%. Previous treatment with high-dose steroid pulses was associated with a worse outcome (survival 12% vs. 69%). The major cause of death was infectious complications (77%).
  
  
  CONCLUSIONS
  Despite a small and heterogeneous population of patients, these results are encouraging and provide a rationale for prospective studies that use rapamycin in steroid-refractory acute GVHD as a second- or third-line agent.
authors.affiliation: Adult Hematology Department, Hôpital Necker-Enfants Malades, Paris, France. david.ghez@nck.aphp.fr
authors.forename: David
authors.initials: D
authors.lastname: Ghez
authors.forename: Marie Thérèse
authors.initials: MT
authors.lastname: Rubio
authors.forename: Natacha
authors.initials: N
authors.lastname: Maillard
authors.forename: Felipe
authors.initials: F
authors.lastname: Suarez
authors.forename: Marie-Olivia
authors.initials: MO
authors.lastname: Chandesris
authors.forename: Richard
authors.initials: R
authors.lastname: Delarue
authors.forename: Bénédicte
authors.initials: B
authors.lastname: Deau-Fischer
authors.forename: Bruno
authors.initials: B
authors.lastname: Varet
authors.forename: Olivier
authors.initials: O
authors.lastname: Hermine
authors.forename: Agnès
authors.initials: A
authors.lastname: Buzyn
mesh_terms: D000293:Adolescent; D000328:Adult; D001424:Bacterial Infections / Q000453:epidemiology; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000453:epidemiology / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods* / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007938:Leukemia / Q000276:immunology / Q000401:mortality / Q000601:surgery*; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000276:immunology / Q000601:surgery; D008875:Middle Aged; D012189:Retrospective Studies; D020123:Sirolimus / Q000009:adverse effects / Q000627:therapeutic use*; D015996:Survival Rate; D017741:Survivors; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus