title: Recombinant human soluble tumor necrosis factor receptor fusion protein as treatment for steroid refractory graft-versus-host disease following allogeneic hematopoietic stem cell transplantation.
abstract: Etanercept is a recombinant human soluble tumor necrosis factor (TNF-alpha) receptor fusion protein that inhibits TNF-alpha, a major mediator in the pathogenesis of graft-versus-host disease (GVHD). The purpose of our study was to evaluate the safety and efficacy of etanercept therapy in 21 patients with steroid-refractory acute GVHD (aGVHD) (n = 13) and chronic GVHD (cGVHD) (n = 8). Etanercept 25 mg was given subcutaneously twice weekly for 4 weeks followed by 25 mg weekly for 4 weeks. At the time of initiation of etanercept, 14 patients had skin, 13 had gastro-intestinal, 5 had liver, 5 had pulmonary, and 4 had oral involvement. Twelve patients (57%) completed 12 doses of therapy. Overall, 11 of 21 patients (52%) responded to the treatment with etanercept, including 6 patients (46%) with aGVHD [n = 4 complete response (CR), n = 2 partial response (PR)] and 5 patients (62%) with cGVHD (n = 1 CR, n = 4 PR). Clinical responses were most commonly seen in patients with refractory gut aGVHD with 55% of the patients having a CR and 9% having a PR. CMV reactivation occurred in 48% of patients, bacterial infections in 14% of patients, and fungal infections in 19% of patients. Fourteen patients (67%) were alive after a median follow-up of 429 days (range 71-1007 days) since initiation of etanercept. Seven patients died, 3 of infections, 2 of refractory aGVHD, and 2 of disease progression. In conclusion, our preliminary data indicate that etanercept is well tolerated and can induce a high response rate in patients with steroid-refractory aGVHD and cGVHD, particularly in the setting of GI involvement.
authors.affiliation: Bone Marrow Transplant Unit, Department of Hematology, Azienda Ospedaliera San Giovanni Battista, Turin, Italy.
authors.forename: Alessandro
authors.initials: A
authors.lastname: Busca
authors.forename: Franco
authors.initials: F
authors.lastname: Locatelli
authors.forename: Filippo
authors.initials: F
authors.lastname: Marmont
authors.forename: Cristina
authors.initials: C
authors.lastname: Ceretto
authors.forename: Michele
authors.initials: M
authors.lastname: Falda
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D001424:Bacterial Infections / Q000209:etiology / Q000401:mortality; D002908:Chronic Disease; D003587:Cytomegalovirus; D003586:Cytomegalovirus Infections / Q000209:etiology / Q000401:mortality; D018572:Disease-Free Survival; D004351:Drug Resistance / Q000187:drug effects; D000068800:Etanercept; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000209:etiology / Q000401:mortality; D019337:Hematologic Neoplasms / Q000150:complications / Q000401:mortality / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage* / Q000009:adverse effects; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000009:adverse effects; D008297:Male; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D012189:Retrospective Studies; D013256:Steroids / Q000008:administration & dosage; D015996:Survival Rate; D014184:Transplantation, Homologous
chemical_list: D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D013256:Steroids; D000068800:Etanercept