Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease
Pilot trial on the use of etanercept and methylprednisolone as primary treatment for acute graft-versus-host disease
复制标题
DOI：
10.1016/j.bbmt.2005.05.009
复制
发表时间：
2005-09-01
影响因子：
4.3
通讯作者：
Levine, JE
中科院分区：
文献类型：
--
作者：
Uberti, JP;Ayash, L;Levine, JE
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. (c) 2005 American Society for Blood and Marrow Transplantation.
