中型再生障碍性贫血患儿自然病程演变及免疫抑制治疗研究

目的 分析中型再生障碍性贫血(MAA)患儿自然病程和免疫抑制(IS)治疗疗效,探讨儿童MAA的免疫介导致病机制.方法 儿童MAA 71例中36例抗胸腺细胞球蛋白(ATG)或环孢素A(CSA)治疗(治疗组),35例雄性激素等传统药物治疗(对照组).前期无效,进展为重型再障(SAA)的患儿,行ATG+CSA+大剂量免疫球蛋白(HDIG)联合IS(CIS)治疗.检测治疗前后外周血淋巴细胞亚群比例.结果 ①治疗组有效率和显效率分别为83.3%、69.4%,显著高于对照组34.3%、17.1%.进展为SAA的患儿23例,对照组(18例)明显多于治疗组(5例).②17例转化为SAA患儿接受CIS治疗,有效率和显效率分别为70.6%、41.2%.③儿童MAA治疗前存在CD4+、自然杀伤(NK)细胞比例下降,CD8+细胞比例升高.IS治疗后,治疗组NK细胞、CD4+细胞比例回升;CD8+细胞比例降低,与对照组差异均有统计学意义.结论 儿童MAA IS治疗疗效明显优于未IS治疗者;采用雄性激素等传统药物治疗,50%以上可能进展为SAA.进展为SAA,可采用CIS治疗补救,以争取较为满意的疗效.儿童MAA存在明显的免疫介导致病机制,早期采用IS治疗需引起足够重视.

Natural history of moderate aplastic anemia in children and effects of immunosuppresstve therapy

Objective In contrast to severe aplastic anemia (SAA),the appropriate management of patients with moderate aplastie anemia (MAA) is unclear.Recently,it was reported that when childhood MAA was treated with supportive care alone,2/3 of patients progressed to SAA,and therefore patients with MAA should be treated with immunosuppressive (IS) therapy in time.The present study aimed to review the natural history,the rate of progression to SAA and outcome of children with MAA seen at our institution over the past 12 years and to explore the relationship between the effectiveness of IS therapy and the immune mediated pathological mechanism.Methods Seventy-one MAA patients were included in this study.At the first stage,thirty-six children with MAA were given IS therapy (IS group,antithymocyte globulin,ATG or cyclosporin-A,CSA).The therapeutic effects were evaluated and compared with those of 35 children with MAA who received the treatment of supportive care alone (androgens,control group).At the second stage,the patients with MAA progressed to SAA were given combined immunosuppressive (CIS) therapy (CIS group,a combination of ATG,CSA and high-dose immunoglobulin).Peripheral blood lymphocyte subsets levels were measured with a flow cytometer.Results At the first stage,in the IS group,the percentage of overall and complete responders was 83.3% and 69.4%,respectively,which was significantly higher than that of the control group (34.3% and 17.1%).Twenty-three patients with MAA progressed to SAA.In the control group,18 patients with MAA progressed to SAA.In the IS group,five patients with MAA progressed to SAA.The 17 patients with MAA who progressed to SAA were given combined immunosuppressive therapy.The percentage of overall and complete responders was 70.6% and 41.2%,respectively.The level of CD4+,NK cell ratio decreased but the level of CD8+cell increased in MAA children before the treatment.The level of NK and CIM + cell was significantly higher in the IS group with the treatment than in the control group.Conclusion When childhood MAA is treated with supportive care alone,more than 50% of patients may progress to SAA.Immune mediated pathological mechanism of MAA might be the base of IS therapy.IS therapy is effective and safe for childhood MAA.CIS therapy given to patients with MAA that was progressed to SAA may also be effective.