title: Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept.
abstract: Steroid-resistant acute GVHD (aGVHD) following allogeneic hematopoietic stem cell transplantation (alloHSCT) continues to be associated with a high mortality. We report the results of a phase II study of treatment of steroid-resistant aGVHD with the IL-2 receptor antibody daclizumab combined with the TNF-receptor fusion protein etanercept. Treatment consisted of daclizumab 1 mg/kg given i.v. on days 1, 4, 8, 15, 22 and etanercept 16 mg/m(2) s.c. on days 1, 5, 9, 13, 17. A total of 21 patients (age 15-61 years) with steroid-resistant aGVHD after alloHSCT were included in the study. Donor types were HLA-matched related (n=6), HLA-matched unrelated (n=14), and HLA-mismatched unrelated (n=1). Eight patients achieved complete, and six showed partial remission of aGVHD. Seven patients did not respond. Four of 21 patients are currently alive with a median follow-up of 586 (185-1155) days. Three patients died due to relapsed malignancy. Treatment-related mortality was due to infectious complications (n=11) or organ failure due to aGVHD (n=3). In total, 12 patients developed subsequent chronic GVHD. In conclusion, the data demonstrate an acceptable response rate of the combination of daclizumab and etanercept in the treatment of steroid-resistant aGVHD. Nevertheless, long-term mortality due to infectious complications and chronic GVHD remains high.
authors.affiliation: Division of Haematology and Oncology, Department of Internal Medicine, University of Rostock, Germany. daniel.wolff@medizin.uni-rostock.de
authors.forename: D
authors.initials: D
authors.lastname: Wolff
authors.forename: V
authors.initials: V
authors.lastname: Roessler
authors.forename: B
authors.initials: B
authors.lastname: Steiner
authors.forename: S
authors.initials: S
authors.lastname: Wilhelm
authors.forename: V
authors.initials: V
authors.lastname: Weirich
authors.forename: J
authors.initials: J
authors.lastname: Brenmoehl
authors.forename: M
authors.initials: M
authors.lastname: Leithaeuser
authors.forename: N
authors.initials: N
authors.lastname: Hofmeister
authors.forename: C
authors.initials: C
authors.lastname: Junghanss
authors.forename: J
authors.initials: J
authors.lastname: Casper
authors.forename: G
authors.initials: G
authors.lastname: Hartung
authors.forename: E
authors.initials: E
authors.lastname: Holler
authors.forename: M
authors.initials: M
authors.lastname: Freund
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000305:Adrenal Cortex Hormones / Q000627:therapeutic use; D000328:Adult; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D061067:Antibodies, Monoclonal, Humanized; D000077561:Daclizumab; D004351:Drug Resistance; D004359:Drug Therapy, Combination; D000068800:Etanercept; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D006801:Humans; D007074:Immunoglobulin G / Q000008:administration & dosage*; D008297:Male; D008875:Middle Aged; D011697:Purpura, Thrombotic Thrombocytopenic / Q000209:etiology; D018124:Receptors, Tumor Necrosis Factor / Q000008:administration & dosage*; D014184:Transplantation, Homologous
chemical_list: D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000077561:Daclizumab; D000068800:Etanercept