Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFα antibody
Treatment of severe steroid refractory acute graft-versus-host disease with infliximab, a chimeric human/mouse antiTNFα antibody
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DOI：
10.1038/sj.bmt.1703094
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发表时间：
2001-07-01
影响因子：
4.8
通讯作者：
Haas, R
中科院分区：
文献类型：
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作者：
Kobbe, G;Schneider, P;Haas, R
急性移植物抗宿主病（Acute graft-versus-host disease，aGVHD）是异基因外周血干细胞移植（allogene peripheral blood stem cell transplantation，PBSCT）的严重并发症。对类固醇治疗无反应的严重aGVHD患者预后不良。我们用英夫利昔单抗（一种嵌合的人/小鼠抗TNF α抗体）治疗了4例类固醇难治性严重aGVHD患者。患者（CML 2例，MM 1例，AML 1例）分别在清髓性PBSCT（2例）、供者淋巴细胞输注治疗复发性CML（1例）或非清髓性PBSCT（1例）后中位34天（范围15-76）发生III-IV级GVHD。除皮肤和/或肝脏疾病外，所有患者均患有严重的肠道受累，并且除了CsA（4）和MMF（3）外，还接受了中位11天（范围5-17）的高剂量类固醇（4）治疗。英夫利西单抗（10 mg/kg）每周给药一次，直至临床改善。在4例患者中，观察到3例腹泻完全消退，皮肤和肝脏疾病显著改善。2例患者接受1次、1例患者接受2次和1例患者接受3次英夫利西单抗输注。目前，两名患者在治疗后存活>200天，其中一名患有有限的cGVHD。2例患者死亡，1例为进行性恶性疾病，1例为难治性GVHD。英夫利昔单抗显然是治疗aGVHD的活性药物。
Acute graft-versus-host disease (aGVHD) is a serious complication of allogeneic peripheral blood stem cell transplantation (PBSCT). Patients with severe aGVHD not responding to treatment with steroids have a poor prognosis. We treated four patients with severe aGVHD refractory to steroids with infliximab, a chimeric human/mouse antiTNF alpha antibody. Patients (CML 2, MM 1, AML 1) developed grade III-IV GVHD at a median of 34 days (range 15-76) after myeloablative PBSCT (two), donor lymphocyte infusion for relapsed CML (one) or non-myeloablative PBSCT (one), respectively. All patients had severe intestinal involvement in addition to skin and/or liver disease and had received treatment with high-dose steroids (four) for a median of 11 days (range 5-17) in addition to CsA (four) and MMF (three). Infliximab (10 mg/kg) was given once a week until clinical improvement. In three of four patients a complete resolution of diarrhea and significant improvement of skin and liver disease were observed. Two patients received one, one patient two and one patient three infliximab infusions. At present two patients are alive >200 days after therapy, one with limited cGVHD. Two patients died, one of progressive malignant disease without GVHD and one of refractory GVHD. Infliximab is apparently an active drug for the treatment of aGVHD.