Treatment of steroid-resistant acute graft-versus-host disease with daclizumab and etanercept.
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.
Wolff
D
D
Division of Haematology and Oncology, Department of Internal Medicine, University of Rostock, Germany. daniel.wolff@medizin.uni-rostock.de
Roessler
V
V
Steiner
B
B
Wilhelm
S
S
Weirich
V
V
Brenmoehl
J
J
Leithaeuser
M
M
Hofmeister
N
N
Junghanss
C
C
Casper
J
J
Hartung
G
G
Holler
E
E
Freund
M
M
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
D000305:Adrenal Cortex Hormones; D000911:Antibodies, Monoclonal; D061067:Antibodies, Monoclonal, Humanized; D007074:Immunoglobulin G; D018124:Receptors, Tumor Necrosis Factor; D000077561:Daclizumab; D000068800:Etanercept