Tumor necrosis factor-α blockade for the treatment of acute GVHD
Tumor necrosis factor-α blockade for the treatment of acute GVHD
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DOI：
10.1182/blood-2003-12-4241
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发表时间：
2004-08-01
期刊：
影响因子：
20.3
通讯作者：
Champlin, R
中科院分区：
文献类型：
--
作者：
Couriel, D;Saliba, R;Champlin, R
尽管移植后免疫抑制治疗，急性移植物抗宿主病（GVHD）仍然是疾病和死亡的主要原因。肿瘤坏死因子-α（TNF-α）在该过程的几个步骤中涉及GVHD的病理生理学。英夫利西单抗是一种基因构建的免疫球蛋白G1（IgG 1）鼠-人嵌合单克隆抗体，可结合TNF-α的可溶性亚基和膜结合前体，阻断其与受体的相互作用，并导致产生TNF-α的细胞溶解。在这项研究中，我们回顾性评估了134例激素难治性急性GVHD患者。其中，21人接受英夫利西单抗作为单一药物进行了分析。总缓解率为67%（n = 14），13例患者（62%）出现完全缓解（CR）。5例患者（24%）没有反应，2例（10%）有进展性GVHD。没有人对英夫利西单抗有毒性反应。10名患者（48%）有18种真菌感染，包括7种曲霉菌和10种念珠菌。17例患者（81%）有细菌感染，包括32例革兰氏阳性和8例革兰氏阴性感染。14例患者（67%）发生病毒感染，主要是巨细胞病毒再激活。Kaplan-Meier估计的总生存率为38%。总之，英夫利西单抗治疗激素耐药的急性GVHD，特别是胃肠道受累的GVHD，耐受性良好且有效。类固醇耐药急性GVHD后的生存仍然是个问题。过度真菌和其他感染的可能性必须进一步探讨。
Despite posttransplantation immunosuppressive therapy, acute graft-versus-host disease (GVHD) remains a major cause of sickness and death. Tumor necrosis factor-alpha (TNF-alpha) is implicated in the pathophysiology of GVHD at several steps in the process. Infliximab is a genetically constructed immunoglobulin G1 (IgG1) murine-human chimeric monoclonal antibody that binds the soluble subunit and the membrane-bound precursor of TNF-alpha, blocking its interaction with receptors and causing lysis of cells that produce TNF-alpha. In this study we retrospectively evaluated 134 patients who had steroid-refractory acute GVHD. Of these, 21 who received infliximab as a single agent were analyzed. The overall response rate was 67% (n = 14), and 13 patients (62%) experienced complete response (CR). Five patients (24%) did not respond, and 2 (10%) had progressive GVHD. None had a toxic reaction to infliximab. Ten patients (48%) had 18 fungal infections, including Aspergillus species in 7 and Candida species in 10. Seventeen patients (81%) had bacterial infections, including 32 gram-positive and 8 gram-negative infections. Viral infections, primarily cytomegalovirus reactivation, occurred in 14 patients (67%). The Kaplan-Meier estimate of overall survival was 38%. In conclusion, infliximab was well tolerated and active for the treatment of steroid-resistant acute GVHD, particularly with gastrointestinal tract involvement. Survival after steroid-resistant acute GVHD continues to be problematic. The possibility of excessive fungal and other infections must be explored further.