Martin P J, Hansen J A, Anasetti C, Zutter M, Durnam D, Storb R, Thomas E D
Division of Clinical Research, University of Washington, Seattle.
Am J Kidney Dis. 1988 Feb;11(2):149-52. doi: 10.1016/s0272-6386(88)80201-4.
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 mg/kg/d 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 less than 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.
进行了一项剂量递增试验，以确定使用IgG2a抗CD3单克隆抗体治疗骨髓移植受者急性移植物抗宿主病（GVHD）的疗效和安全性。两名患者接受该抗体作为GVHD的初始治疗，22名患者在使用皮质类固醇、环孢素、抗胸腺细胞球蛋白（ATG）或联合使用ATG和环孢素进行初始治疗失败后接受该抗体治疗。抗体以四个剂量水平给药，起始剂量约为0.015mg/kg/d，并以三倍递增。抗体的初始剂量几乎总是与发热和寒战相关，一名患者因无法耐受的副作用而不得不停止治疗。在剂量为0.15mg/kg/d时可可靠地实现皮肤病的改善，但对于肝脏或肠道的改善，似乎需要三倍更高的剂量。在任何情况下，疾病的所有表现均未完全消退，抗体治疗后存活的所有患者都需要额外的免疫抑制治疗。四名患者在开始抗体治疗后7至18天内发生了与EB病毒（EBV）相关的淋巴增殖性疾病。未给予抗CD3单克隆抗体的患者发生这种并发症的总体风险小于1%。抗CD3抗体是治疗急性GVHD的一种有效免疫抑制剂，但这种治疗与发生EBV相关淋巴增殖性疾病的重大风险相关。
