Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
Safety and efficacy of denileukin diftitox in patients with steroid-refractory acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation
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DOI：
10.1182/blood-2004-01-0028
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发表时间：
2004-08-15
期刊：
影响因子：
20.3
通讯作者：
Antin, JH
中科院分区：
文献类型：
--
作者：
Ho, VT;Zahrieh, D;Antin, JH
重组人白细胞介素2（IL-2）与白喉毒素融合，对表达高亲和力IL-2受体的活化淋巴细胞具有选择性细胞毒作用。我们在30例类固醇难治性急性移植物抗宿主病（GVHD）患者中进行了地尼白介素diftitox的1期研究。7例患者在第1天和第15天静脉注射9 mug/kg; 18例患者在第1、3、5、15、17和19天静脉注射9 mug/kg; 5例患者在第1 - 5天和第15 - 19天静脉注射9 mug/kg。肝转氨酶升高为剂量限制性毒性（DLT），剂量水平2为最大耐受剂量（MTD）。总体而言，71%的患者对GVHD完全缓解（112/24; 50%）或部分缓解（5/24; 21%）作出反应。24例患者中有8例（33%）在6.3至24.6个月（中位数，7.2个月）时存活。地尼白介素Diftitox是耐受的，并在类固醇难治性急性GVHD中具有有希望的活性。(C)2004年，美国血液学会。
Denileukin diftitox (Ontak), a recombinant protein composed of human interleukin 2 (IL-2) fused to diphtheria toxin, has selective cytotoxicity against activated lymphocytes expressing the high-affinity IL-2 receptor. We conducted a phase 1 study of denileukin diftitox in 30 patients with steroid refractory acute graft-versus-host disease (GVHD). Seven patients received 9 mug/kg intravenously on days 1 and 15; 18 received 9 mug/kg intravenously on days 1, 3, 5, 15, 17, and 19; and 5 received 9 mug/kg intravenously on days 1 to 5 and 15 to 19. Hepatic transaminase elevation was the dose-limiting toxicity (DLT), and dose level 2 was the maximum tolerated dose (MTD). Overall, 71% of patients responded with complete resolution (112 of 24; 50%) or partial resolution (5 of 24; 21%) of GVHD. Eight of 24 patients (33%) are alive at 6.3 to 24.6 months (median, 7.2 months). Denileukin diftitox is tolerable and has promising activity in steroid-refractory acute GVHD. (C) 2004 by The American Society of Hematology.