联合免疫抑制治疗儿童重型和难治型再生障碍性贫血

Effects of combined immunosupressive therapy on severe aplastic anemia and refractory aplastic anemia in children

摘要:

目的 本研究旨在探索联合免疫抑制 (CIS)治疗儿童重型再障 (SAA)和难治型再障 (RAA)的疗效 ,并进行有关疗效预测和临床方法学等方面的研究。方法 应用抗胸腺细胞球蛋白 /抗淋巴细胞球蛋白、环胞菌素A和大剂量免疫球蛋白 (HDIG)等对 36例儿童SAA(n =33)和RAA(n =3)进行CIS治疗 ,随访观察疗效 ,并将以往接受单一药物免疫抑制 (SIS)治疗的 4 3例病儿 (42例SAA ,1例RAA)作为疗效对照组。同时进行外周血淋巴细胞亚群和血清细胞因子等免疫功能指标检测 ,探索儿童再障的免疫介导致病机制及其与IS疗效的关系 ,并总结临床治疗方法与经验。结果 CIS治疗儿童再障 ,总有效率为 80 .6 % (2 9/36 ) ,其中SAA有效率和显效率分别达到 78.8% (2 6 /33)和 6 0 .6 % (2 0 /33) ,均明显高于以往SIS治疗对照组 [5 7.1% (2 4 /42 ) ,2 8.6 % (12 /42 ) ]。CIS治疗3例RAA均有效 ,而SIS治疗 1例RAA无效。儿童再障的主要异常指标为CD4 /CD8比例下降 ,IL 2R、IL 8和TNF表达增高 ,所有病例均存在 2项以上指标的明显异常。疗效预测研究显示 ,治疗前 ,病程短于 6个月或网织红细胞绝对计数高于 10× 10 9/L者 ,SIS治疗有效率显著增高 ,但上述因素与CIS疗效无关。由于采用较为合理的治疗方法和副反应防治措施 ,两组未出现明显的重要

Abstract:

Objective The purpose of this study is to evaluate the therapeutic effects of combined immunosuppressive (CIS) therapy on severe aplastic anemia (SAA) and refractory aplastic anemia (RAA) in children and to study the relationship between the effectiveness of IS therapy and the immune mediated pathological mechanism. Methods Thirty-six children with SAA (n=33) and RAA (n=3) were given CIS therapy (CIS group, a combination of antithymocyte globulin, cyclosporin A and high-dose immunoglobulin). The therapeutic effects were evaluated and compared with those of 43 children with SAA (n=42) and RAA (n=1) who received the treatment of single IS agent (Control group). Peripheral blood lymphocyte subsets levels were measured with a flow cytometer. Serum interleukin and TNF levels were examined with radioimmunoassay in the two groups. Results The total response rate [ 80.6%(29/36)] in the CIS group was significantly higher than that in the Control group [ 55.8%(24/43)] (P< 0.05). Among the CIS group, 78.8% (26/33) of SAA patients had responses to CIS therapy, which was more than that of the Control group [ 57.1%(24/42)]. All of RAA patients (3/3) were responsive to CIS therapy. The results of immunological function testing showed that the CD4/CD8 ratio decreased and IL-2R, IL-8 and TNF levels increased in the two groups. In the Control group, the children whose disease duration was less than 6 months or the absolute reticulocyte counting was greater than 10×10 9/L demostrated a higher response rate to single IS therapy. The therapeutic effects in the CIS group were not associated with the disease duration and the absolute reticulocyte counts. No severe side effects and treat-related death were found in both groups. Conclusions CIS therapy is effective and safe for childhood SAA and RAA, and the therapeutic effect of CIS is better than single IS agent. Abnormal immune mediated pathological mechanism of AA might be the base of IS therapy. In order to improve the therapeutic effects, it is necessary to make a therapeutic effect prediction for choosing cases and the treatment protocol before treatment of AA with single IS agent.