Qiao Xiao-hong, Xie Xiao-tian, Jiang Sha-yi, Shi Wei, Li Wei, Zhou Ji-ji
Department of Pediatrics, Tongji Hospital Affiliated to Tongji University, Shanghai 200065, China.
Zhonghua Er Ke Za Zhi. 2008 Dec;46(12):909-13.
In contrast to severe aplastic anemia (SAA), the appropriate management of patients with moderate aplastic 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.
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.
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 CD4(+) cell was significantly higher in the IS group with the treatment than in the control group.
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.
与重型再生障碍性贫血（SAA）不同，中度再生障碍性贫血（MAA）患者的恰当治疗方法尚不清楚。最近有报道称，儿童MAA若仅接受支持性治疗，2/3的患者会进展为SAA，因此MAA患者应及时接受免疫抑制（IS）治疗。本研究旨在回顾过去12年在我院就诊的儿童MAA的自然病程、进展为SAA的发生率及转归，并探讨IS治疗效果与免疫介导病理机制之间的关系。
本研究纳入71例MAA患者。第一阶段，36例儿童MAA患者接受IS治疗（IS组，抗胸腺细胞球蛋白、ATG或环孢素A、CSA）。评估治疗效果，并与35例仅接受支持性治疗（雄激素，对照组）的儿童MAA患者进行比较。第二阶段，将进展为SAA的MAA患者给予联合免疫抑制（CIS）治疗（CIS组，ATG、CSA和大剂量免疫球蛋白联合应用）。用流式细胞仪检测外周血淋巴细胞亚群水平。
第一阶段，IS组的总缓解率和完全缓解率分别为83.3%和69.4%，显著高于对照组（34.3%和17.1%）。23例MAA患者进展为SAA。对照组中，18例MAA患者进展为SAA。IS组中，5例MAA患者进展为SAA。对17例进展为SAA的MAA患者给予联合免疫抑制治疗。总缓解率和完全缓解率分别为70.6%和41.2%。治疗前MAA儿童的CD4(+)、NK细胞比例水平降低，但CD8(+)细胞水平升高。治疗后IS组的NK和CD4(+)细胞水平显著高于对照组。
儿童MAA若仅接受支持性治疗，超过50%的患者可能进展为SAA。MAA的免疫介导病理机制可能是IS治疗的基础。IS治疗对儿童MAA有效且安全。对进展为SAA的MAA患者给予CIS治疗也可能有效。
