Sleight B S, Chan K W, Braun T M, Serrano A, Gilman A L
Section of Pediatric Hematology/Oncology, Department of Pediatrics, Yale University, New Haven, CT, USA.
Bone Marrow Transplant. 2007 Sep;40(5):473-80. doi: 10.1038/sj.bmt.1705761. Epub 2007 Jul 9.
GVHD remains a significant complication of allogeneic hematopoietic stem cell transplantation. Tumor necrosis factor-alpha (TNF-alpha) is a major mediator of GVHD pathogenesis. Infliximab inhibits the binding of TNF-alpha with its cellular receptors and has been associated with encouraging responses in adults with severe GVHD. We retrospectively evaluated the efficacy and safety of infliximab 10 mg/kg i.v. once a week for a median of eight doses (range 1-162) in 24 children with steroid-resistant GVHD. The overall response rate in 22 evaluable children was 82% (12 CR+6 PR). Among those patients with acute GVHD, both skin and gastrointestinal involvement responded well to infliximab; however long-term outcome was poor. While infliximab may be useful to acutely control GVHD manifestations, GVHD recurs commonly upon discontinuation of infliximab. Within 100 days of the final infliximab dose, 77% of patients had bacterial infections, 32% had viral infections and 13.6% had probable or proven non-candidal invasive fungal infections. Infliximab appears to be well-tolerated and to have activity in steroid-resistant GVHD. Controlled studies to assess the pharmacokinetics and most effective dosing regimen of infliximab for the treatment of GVHD are warranted.
移植物抗宿主病（GVHD）仍然是异基因造血干细胞移植的一个重要并发症。肿瘤坏死因子-α（TNF-α）是GVHD发病机制的主要介质。英夫利昔单抗可抑制TNF-α与其细胞受体的结合，并已在患有严重GVHD的成人患者中显示出令人鼓舞的疗效。我们回顾性评估了24例对类固醇耐药的GVHD儿童患者静脉注射英夫利昔单抗10mg/kg、每周一次、中位剂量为8剂（范围1-162剂）的疗效和安全性。22例可评估儿童的总体缓解率为82%（12例完全缓解+6例部分缓解）。在急性GVHD患者中，皮肤和胃肠道受累对英夫利昔单抗反应良好；然而长期预后较差。虽然英夫利昔单抗可能有助于急性控制GVHD表现，但在停用英夫利昔单抗后GVHD通常会复发。在最后一剂英夫利昔单抗后的100天内，77%的患者发生细菌感染，32%的患者发生病毒感染，13.6%的患者发生可能或确诊的非念珠菌侵袭性真菌感染。英夫利昔单抗似乎耐受性良好，对类固醇耐药的GVHD有活性。有必要进行对照研究以评估英夫利昔单抗治疗GVHD的药代动力学和最有效的给药方案。
