title: Sirolimus as primary treatment of acute graft-versus-host disease following allogeneic hematopoietic cell transplantation.
abstract: Glucocorticoids have gone unchallenged as an essential component of primary therapy for acute graft-versus-host disease (aGVHD) after allogeneic hematopoietic cell transplantation (HCT) despite limited complete response rates and adverse effects from this therapy. The role for alternate immunosuppressive agents as primary aGHVD treatment remains unexamined. In a series of 10 patients at high risk for corticosteroid toxicity or leukemia relapse who developed biopsy-proven grade II-III aGVHD after hematopoietic cell transplantation, we report that primary therapy with sirolimus resulted in durable complete remission of aGVHD in 5 (50%) without requirement for glucocorticoids. Mild chronic GVHD (cGVHD) developed in 4 (40%). Projected overall survival (OS) at 18 months is 79% (95% confidence interval [CI]: 38.1%-94.3%), and projected relapse-free survival (RFS) at 15 months is 70% (95% CI: 32.9%-89.2%). Sirolimus was well tolerated with mild and reversible thrombotic microangiopathy occurring in 2 patients. This experience provides preliminary evidence for the efficacy of sirolimus as a sole primary therapy in the treatment of aGVHD.
authors.affiliation: Departments of Blood and Marrow Transplantation and Oncological Sciences, University of South Florida, Moffitt Cancer Center, Tampa, FL 33612-9416. joseph.pidala@moffitt.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality*; D019337:Hematologic Neoplasms / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D020123:Sirolimus / Q000008:administration & dosage*; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D007166:Immunosuppressive Agents; D020123:Sirolimus