Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies.
Treatment of acute graft-versus-host disease with anti-CD3 monoclonal antibodies.
复制标题
用抗 CD3 单克隆抗体治疗急性移植物抗宿主病。
DOI：
10.1016/s0272-6386(88)80201-4
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发表时间：
1988
期刊：
影响因子：
--
通讯作者：
Thomas,ED
中科院分区：
文献类型：
--
作者：
Martin,PJ;Hansen,JA;Anasetti,C;Zutter,M;Durnam,D;Storb,R;Thomas,ED
进行剂量递增试验以确定使用IgG 2a抗CD 3单克隆抗体治疗骨髓移植受者中的急性移植物抗宿主病（GVHD）的有效性和安全性。2例患者接受抗体作为GVHD的初始治疗，22例患者在皮质类固醇、环孢素、抗胸腺细胞球蛋白（ATG）或ATG和环孢素联合治疗失败后接受抗体。以四个剂量水平施用抗体，从约0.015mg/kg/d开始，并以三倍增量增加。抗体的初始剂量几乎总是与发热和寒战相关，并且由于无法忍受的副作用，一名患者不得不停止治疗。在0.15 mg/kg/d的剂量下可以可靠地实现皮肤病的改善，但要改善肝脏或肠道，似乎需要3倍的剂量。在任何情况下，疾病的所有表现都没有完全消失，所有在抗体治疗后存活的患者都需要额外的免疫抑制治疗。4名患者在开始抗体治疗后7至18天内发生了EB病毒（EBV）相关的淋巴组织增生性疾病。未给予抗CD 3单克隆抗体的患者发生这种并发症的总体风险<1%。抗-CD 3抗体代表了用于治疗急性GVHD的有效免疫抑制剂，但这种治疗与EBV相关淋巴增生性疾病的显著风险相关。
A dose-escalation trial was carried out to determine the efficacy and safety of using an IgG2a anti-CD3 monoclonal antibody to treat acute graft-v-host disease (GVHD) in marrow transplant recipients. Two patients received the antibody as the initial treatment of GVHD, and 22 patients received the antibody after failure of initial treatment with corticosteroids, cyclosporine, antithymocyte globulin (ATG), or combined ATG and cyclosporine. Antibody was administered at four dose levels, beginning at approximately 0.015 mglkgld and increasing by threefold increments. The initial doses of antibody were nearly always associated with fever and chills, and treatment had to be discontinued in one patient because of intolerable side effects. Improvement in skin disease could be reliably achieved at a dose of 0.15 mg/kg/d, but threefold higher doses appeared to be necessary for improvement in the liver or gut. In no case was there complete resolution of all manifestations of disease, and all patients surviving after antibody treatment required additional immunosuppressive treatment. Four patients developed Epstein-Barr virus (EBV)-associated lymphoproliferative disorders within seven to 18 days after starting antibody therapy. The overall risk of this complication in patients not given anti-CD3 monoclonal antibody is < 1 %. Anti-CD3 antibody represents an effective immunosuppressive agent for treatment of acute GVHD, but this treatment is associated with a substantial risk of EBV associated lymphoproliferative disorders.