title: Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease.
abstract: Clinical and preclinical data indicate that tumor necrosis factor (TNF)-alpha is an important mediator of acute graft-versus-host disease (aGVHD) after allogeneic bone marrow transplantation. We completed a study using etanercept, a fusion protein capable of neutralizing TNF-alpha, for the initial treatment of aGVHD. Etanercept (25 mg subcutaneously) was administered twice weekly for 16 doses, along with methylprednisolone (2 mg/kg) and tacrolimus for biopsy-proven aGVHD. Twenty patients with a median age of 47 years (range, 8-63 years) were enrolled. Fourteen patients with grade II aGVHD (11 family donors and 3 unrelated donors) and 6 patients with grade III aGVHD (3 family donors and 3 unrelated donors) were treated. Twelve patients completed 16 doses of therapy, and 8 received 5 to 15 doses. Reasons for not completing all doses of etanercept included progression of aGVHD (n = 4), relapsed leukemia (n = 2), progression of pulmonary and central nervous system lesions (n = 1), and perforated duodenal ulcer (n = 1). Fifteen (75%) of 20 patients had complete resolution of aGVHD within 4 weeks of therapy. Increasing levels of soluble TNF receptor 1 plasma concentration during the first 4 weeks of therapy indicated progression of aGVHD in 5 patients. In contrast, for 15 responding patients, soluble TNF receptor 1 plasma concentration levels returned to baseline. These data demonstrate the feasibility of using cytokine blockade in the early treatment of aGVHD.
authors.affiliation: Department of Internal Medicine, Blood and Marrow Stem Cell Transplantation Program, University of Michigan, Ann Arbor, USA. ubertij@karmanos.org
authors.forename: Joseph P
authors.initials: JP
authors.lastname: Uberti
authors.forename: Lois
authors.initials: L
authors.lastname: Ayash
authors.forename: Voravit
authors.initials: V
authors.lastname: Ratanatharathorn
authors.forename: Samuel
authors.initials: S
authors.lastname: Silver
authors.forename: Christopher
authors.initials: C
authors.lastname: Reynolds
authors.forename: Michael
authors.initials: M
authors.lastname: Becker
authors.forename: Pavan
authors.initials: P
authors.lastname: Reddy
authors.forename: Kenneth R
authors.initials: KR
authors.lastname: Cooke
authors.forename: Gregory
authors.initials: G
authors.lastname: Yanik
authors.forename: Joel
authors.initials: J
authors.lastname: Whitfield
authors.forename: Dawn
authors.initials: D
authors.lastname: Jones
authors.forename: Raymond
authors.initials: R
authors.lastname: Hutchinson
authors.forename: Thomas
authors.initials: T
authors.lastname: Braun
authors.forename: James L M
authors.initials: JL
authors.lastname: Ferrara
authors.forename: John E
authors.initials: JE
authors.lastname: Levine
mesh_terms: D000293:Adolescent; D000328:Adult; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage*; D016026:Bone Marrow Transplantation; D002648:Child; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000150:complications / Q000188:drug therapy*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D007166:Immunosuppressive Agents; D008232:Lymphoproliferative Disorders / Q000097:blood / Q000628:therapy*; D008297:Male; D008775:Methylprednisolone / Q000008:administration & dosage*; D008875:Middle Aged; D010865:Pilot Projects; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000097:blood; D016559:Tacrolimus / Q000008:administration & dosage; D014184:Transplantation, Homologous; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D000893:Anti-Inflammatory Agents; D007074:Immunoglobulin G; D007166:Immunosuppressive Agents; D018124:Receptors, Tumor Necrosis Factor; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha; D000068800:Etanercept; D016559:Tacrolimus; D008775:Methylprednisolone