抗人CD_3T淋巴细胞单克隆抗体治疗重型再生障碍性贫血的初步观察

A preliminary experience of treatment of severe aplastic anemia with murine anti-human CD_3 T lymphocyte monoclonal antibody

目的 探讨特异性免疫抑制剂鼠抗人CD3 T淋巴细胞单克隆抗体 (CD3 单抗 )对重型再生障碍性贫血 (SAA)的临床疗效。方法 13例SAA患者中位数年龄 2 2岁 ,既往未经特殊治疗者4例 ,既往治疗无效的 9例中 ,加环孢素≥ 3个月者 4例 ;给药方法 :CD3 单抗 5mg静脉滴注 ,日 1次 ,连用 10d为一疗程。结果 共随访 3～ 15个月 ,骨髓象有 8例明显好转 ;外周血WBC平均升高 1 5 9× 10 9/L ,中性粒细胞升高 0 72× 10 9/L ,Hb升高 4 0 g/L ,血小板升高 4 7× 10 9/L(Р值均 <0 0 1) ;其中 2例基本治愈 ,2例达缓解 ,7例明显进步 ,2例无效 ;T淋巴细胞亚群的变化 :CD4/CD8比值由1 12± 0 34上升至 1 4 2± 0 4 3、HLA DR的表达率由 ( 2 9 2± 13 3) %下降至 ( 15 2± 5 6 ) % (Р值均<0 0 1) ;体外培养患者外周血单个核细胞分泌下列淋巴因子含量的中位数值 (U/ml) :肿瘤坏死因子α、干扰素γ与白细胞介素 2分别由 2 6 7、784和 92降至 15 2、5 70和 5 1(Р值均 <0 0 1)。不良反应 :单抗治疗期间 ,全部病例均有发热 ,4例出现胸闷、呼吸困难 ,但无 1例死亡。结论 与其他常用的免疫抑制剂相比 ,CD3 单抗对SAA的临床疗效更快、有效率可能更高 ,且安全性较好 ;关于该单抗的长期疗效、远期不良作用 。

Objective To investigate the efficacy of the specific murine anti human CD 3 T lymphocyte monoclonal antibody(CD 3 MoAb) for severe aplastic anemia(SAA).Methods 13 SAA patients were chosen with a medium age of 22 years, including 4 untreated patients and 9 nonresponding to previous management. They were treated with 5 mg of CD 3 MoAb per day for a total 10 days.Results The response rate was 11/13, including 2 cured and 2 remission cases during a follow up of 3 to 15 months. As compared with the pretreatment condition the proliferation of bone marrow in 8 cases become better; the leukocytes, granulocytes, hemoglobin and platelets of peripheral blood increased 1.59×10 9/L,0.72×10 9/L,40 g/L and 47×10 9/L respectively ( P <0.01, respectively ); the ratio of CD 4/CD 8 of T cell subsets increased from 1.12 to 1.42 while the expression of HLA DR antigen decreased from 29.2 to 15.2( Р <0.01, respectively); TNFα、IFNγ and IL 2 secreted by peripheral blood mononuclear cells (PBMNCs) decreased obviously from 267, 784 and 92 to 152, 570 and 51 U/ml on the average respectively( Р <0.01, respectively). The main side effects were fever in all the patients and shortness of breath in 4 cases, but none died during the therapy.Conclusions In contrast to other kinds of common immune suppressor, CD 3 MoAb showed better response and probably higher efficacy and safety for SAA. It is necessary to have more cases and to follow up longer to estimate its long term effect and side effects.