Objectives: To study the association between paroxysmal nocturnal hemoglobinuria (PNH) clone and immunosuppressive therapy (IST) in children with severe aplastic anemia (SAA).
Methods: A retrospective analysis was performed on the medical data of 151 children with SAA who were admitted and received IST from January 2012 to May 2020. According to the status of PNH clone, these children were divided into a negative PNH clone group (n=135) and a positive PNH clone group (n=16). Propensity score matching was used to balance the confounding factors, and the impact of PNH clone on the therapeutic effect of IST was analyzed.
Results: The children with positive PNH clone accounted for 10.6% (16/151), and the median granulocyte clone size was 1.8%. The children with positive PNH clone had an older age and a higher reticulocyte count at diagnosis (P<0.05). After propensity score matching, there were no significant differences in baseline features between the negative PNH clone and positive PNH clone groups (P>0.05). The positive PNH clone group had a significantly lower overall response rate than the negative PNH clone group at 6, 12, and 24 months after IST (P<0.05). The evolution of PNH clone was heterogeneous after IST, and the children with PNH clone showed an increase in the 3-year cumulative incidence rate of aplastic anemia-PNH syndrome (P<0.05).
Conclusions: SAA children with positive PNH clone at diagnosis tend to have poor response to IST and are more likely to develop aplastic anemia-PNH syndrome.
目的: 探究儿童重型再生障碍性贫血（severe aplastic anemia，SAA）中阵发性睡眠性血红蛋白尿（paroxysmal nocturnal hemoglobinuria，PNH）克隆与免疫抑制治疗（immunosuppressive therapy，IST）之间的关系。方法: 回顾性分析2012年1月至2020年5月收治且行IST的151例SAA患儿的临床资料，根据治疗前PNH克隆状态分为PNH克隆阴性组（135例）和PNH克隆阳性组（16例）。采用倾向性评分匹配控制混杂因素，分析PNH克隆对IST疗效的影响。结果: PNH克隆阳性患儿占10.6%（16/151），中位粒细胞克隆大小为1.8%。PNH克隆阳性组患儿初诊年龄偏大，初诊网织红细胞绝对值偏高（P<0.05）；倾向性评分匹配后，PNH克隆阴性组和PNH克隆阳性组患儿的基线特征差异均无统计学意义（P>0.05）。PNH克隆阳性组IST后6、12、24个月的总有效率均低于PNH克隆阴性组（P<0.05）。IST后PNH克隆演变存在一定异质性，伴PNH克隆者再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征的3年累积发病率增加（P<0.05）。结论: 初诊时PNH克隆阳性的SAA患儿对IST的反应较差，且更易进展为再生障碍性贫血-阵发性睡眠性血红蛋白尿综合征。.
Keywords: Aplastic anemia; Child; Clonal evolution; Immunosuppressive therapy; Paroxysmal nocturnal hemoglobinuria.