Objective: To evaluate the clinical characteristics and risk factors of clonal evolution after immunosuppressive therapy (IST) in children with severe/very severe aplastic anemia (SAA/VSAA).
Methods: The clinical data of 231 children with newly-diagnosed SAA/VSAA who received IST were retrospectively studied. The incidence and risk factors of clonal evolution after IST were analyzed.
Results: The 5-year overall survival rate of the 231 patients was 82.7%. Except for 18 cases of early deaths, 213 patients were evaluated for IST efficacy. Among the 231 patients, cytogenetic abnormalities for at least two chromosome metaphase were detectable in 14 (7.4%) patients, and PNH clones were detectable in either peripheral red blood cells or neutrophils for 95 patients. Among the 213 patients evaluated for IST efficacy, 15 patients experienced clonal evolution after IST. Five patients had PNH and trisomy 8 which were defined as favorable progressions, and ten patients experienced monosomy 7 and MDS/AML as unfavorable progressions. The 5-year accumulative incidence of favorable and unfavorable progression were (2.2±2.2)% and (4.8±3.3)%, respectively. Until the last follow-up, 100% (5/5) of patients with favorable progressions and 50% (5/10) of patients with unfavorable progressions survived. WBC>3.5×109/L, CD3+T cell percentage>80%, dosage of antithymocyte globulin >3.0 mg/(kg·d) and no response to IST were related to unfavorable progressions by univariate analysis. Cox multivariate analysis revealed that an increased CD3+T cell percentage (>80%) and no response to IST were independent risk factors for unfavorable progressions.
Conclusions: The children with SAA/VSAA who have an increased CD3+T cell percentage at diagnosis or have no response to IST are in high risks of unfavorable progressions.
目的: 探讨儿童重型/超重型再生障碍性贫血（SAA/VSAA）免疫抑制治疗（IST）后发生克隆演变患儿的临床特征及克隆演变发生的危险因素。
方法: 回顾性分析231例初诊并接受IST的SAA/VSAA患儿临床资料，统计IST后克隆演变的发生率，并分析克隆演变的危险因素。
结果: 231例患儿的5年总体生存率为82.7%，其中18例早期死亡，213例进行疗效评价。231例患儿初诊时14例（7.4%）检测到至少2个中期分裂象的染色体异常，95例患者外周血粒细胞或红细胞可检测到PNH克隆。213例进行疗效评价的患者中15例发生IST后克隆演变，其中包括MDS/AML和7号染色体缺失在内的不良克隆演变10例，以及PNH及+8染色体异常的良性克隆演变5例；IST后良性克隆演变与不良克隆演变的5年累积发生率为（2.2±2.2）%与（4.8±3.3）%；至末次随访，良性与不良克隆演变患儿分别100%（5/5）与50%（5/10）存活。初诊WBC > 3.5×109/L、CD3+T细胞/淋巴细胞比值 > 80%、抗胸腺细胞球蛋白每日剂量 > 3.0 mg/kg及IST后6个月的治疗反应与不良克隆演变发生相关，其中CD3+T细胞/淋巴细胞 > 80%和IST后6个月的治疗无反应为独立影响因素。
结论: SAA/VSAA患儿初诊淋巴细胞亚群CD3+T细胞/淋巴细胞比值显著增高或IST早期反应不良与IST远期发生不良克隆演变相关，尽早识别发生不良克隆演变的高危患儿对于制定合理的诊疗决策至关重要。