title: Sirolimus for treatment of steroid-refractory acute graft-versus-host disease.
abstract: Acute GVHD (aGVHD) is a major cause of morbidity and mortality in hematopoietic allograft recipients. The best therapy for patients failing to respond, or not tolerating, systemic glucocorticoids remains undefined. We evaluated the efficacy of sirolimus in 34 patients, median age of 49 (23-67) years, with steroid-refractory (n=31) or steroid-intolerant (n=3) aGVHD. aGVHD was diagnosed at a median of 34 (7-1042) days post allografting, and confirmed by biopsy in all cases. Initial aGVHD treatment consisted of prednisone up to 2 mg/kg. Sirolimus was initiated at a median of 9 (1-255) days after glucocorticoid initiation. A sirolimus loading dose was administered to 19 (56%) of 34 patients, median 6 (3-8) mg, followed by maintenance of 1-2 mg/day to target therapeutic trough levels between 4 and 12 ng/ml. Overall response rate was 76%. Fifteen (44%) of 34 patients achieved CR, defined as complete resolution of aGVHD sustained for at least 1 month, after sirolimus initiation without additional immunosuppressive agents. CR was achieved in 11 (42%) of 31 steroid-refractory and 2 (67%) of 3 steroid-intolerant patients. Median OS after initiation of sirolimus was 5.6 months, and 1-year OS was 44% (95% CI: 27-60%). Sirolimus is effective in controlling steroid-refractory aGVHD.
authors: Department of Blood and Marrow Transplantation, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL 33612, USA.
authors: D
authors: D
authors: Hoda
authors: J
authors: J
authors: Pidala
authors: N
authors: N
authors: Salgado-Vila
authors: J
authors: J
authors: Kim
authors: J
authors: J
authors: Perkins
authors: R
authors: R
authors: Bookout
authors: T
authors: T
authors: Field
authors: L
authors: L
authors: Perez
authors: E
authors: E
authors: Ayala
authors: J L
authors: JL
authors: Ochoa-Bayona
authors: J
authors: J
authors: Raychaudhuri
authors: M
authors: M
authors: Alsina
authors: J
authors: J
authors: Greene
authors: W
authors: W
authors: Janssen
authors: H F
authors: HF
authors: Fernandez
authors: C
authors: C
authors: Anasetti
authors: M A
authors: MA
authors: Kharfan-Dabaja
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects; D006801:Humans; D007166:Immunosuppressive Agents; D008875:Middle Aged; D011241:Prednisone / Q000627:therapeutic use; D012189:Retrospective Studies; D020123:Sirolimus / Q000008:administration & dosage*; D013256:Steroids / Q000627:therapeutic use; D015996:Survival Rate; D014184:Transplantation, Homologous; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D013256:Steroids; D011241:Prednisone; D020123:Sirolimus