TY - JOUR
T1 - Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease
AU - Uberti, Joseph P.
AU - Ayash, Lois
AU - Ratanatharathorn, Voravit
AU - Silver, Samuel
AU - Reynolds, Christopher
AU - Becker, Michael
AU - Reddy, Pavan
AU - Cooke, Kenneth R.
AU - Yanik, Gregory
AU - Whitfield, Joel
AU - Jones, Dawn
AU - Hutchinson, Raymond
AU - Braun, Thomas
AU - Ferrara, James L.M.
AU - Levine, John E.
N1 - Funding Information:
This work was supported by National Institutes of Health grant nos. PO1 CA 039542 and K23 CA88930 and by Food and Drug Administration grant no. FD-R-002020. J.L.M.F. is the recipient of a Doris Duke Distinguished Clinical Scientist Award. K.R.C. is an Amy Strelzer Manasevit Scholar of the National Marrow Donor Program, a Fellow of the Robert Wood Johnson Foundation Harold Amos Medical Faculty Development Program, and the recipient of a Translational Research Award from the Leukemia and Lymphoma Society.
PY - 2005/9
Y1 - 2005/9
N2 - Clinical and preclinical data indicate that tumor necrosis factor (TNF)-α 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-α, 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.
AB - Clinical and preclinical data indicate that tumor necrosis factor (TNF)-α 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-α, 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.
KW - Acute graft-versus-host disease
KW - Etanercept
KW - TNF-α
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U2 - 10.1016/j.bbmt.2005.05.009
DO - 10.1016/j.bbmt.2005.05.009
M3 - Article
C2 - 16125638
AN - SCOPUS:23944444997
SN - 1083-8791
VL - 11
SP - 680
EP - 687
JO - Biology of Blood and Marrow Transplantation
JF - Biology of Blood and Marrow Transplantation
IS - 9
ER -