单用环孢素A与环孢素A联合ATG治疗儿童重型再生障碍性贫血的临床疗效比较

Comparison of clinical efficacy of cyclosporine A alone and cyclosporine A combined with ATG in the treatment of severe aplastic anemia in children

目的比较单用环孢素A(CSA)与CSA联合抗人胸腺细胞免疫球蛋白(ATG)治疗儿童重型再生障碍性贫血(SAA)的临床疗效。方法采用回顾性分析的方法,收集昆明市儿童医院血液科2014年1月—2019年12月收治的62名SAA患儿作为研究对象。单用CSA治疗的44例患儿作为CSA组,采用CSA联合ATG治疗的18例患儿作为CSA+ATG组。药物用法用量为:CSA口服起始剂量为5~10 mg/(kg·d),服药2周后监测CSA血药浓度,在保持谷浓度水平维持在100~150μg/L的前提下将峰浓度维持在300~400μg/L。疗效达平台期后12个月方可减量。ATG(即复宁)2.5~3.5mg/(kg·d),连续静脉输注5d,累计剂量达12.5~17.5 mg/kg。治疗及随访期间定期检测患儿静脉血中性粒细胞计数、血红蛋白浓度、血小板计数及输血情况。比较两组患者的短期有效率及长期生存情况。结果(1)治疗第3个月CSA组有效率34.1%,CSA+ATG组有效率44.4%,χ^(2)检验P=0.444,无统计学差异;(2)治疗第12个月CSA组有效率31.8%,CSA+ATG组有效率27.8%,χ^(2)检验示P=0.754,无统计学差异;(3)采用logrank生存分析示,ATG+CSA组经治疗后12个月未达到完全缓解影响生存预后(P=0.100),CSA组经治疗后12个月未达到完全缓解影响生存预后(P=0.000);(4)ATG+CSA组12个月的OS率为94.4%,CSA组12个月的OS率为59.1%,χ^(2)检验示P=0.006,差异具有统计学差异;(5)中位随访时间为18个月,采用Kaplan-Meier生存分析比较,结果显示两组预后无统计学差异(P=0.859)。结论SAA患儿单纯利用免疫治疗可能导致造血延迟,从而影响缓解率,未达到缓解的患儿可能因长期的输血及药物治疗最终导致无效输血或因为药物的不良反应导致病情加重。虽然ATG+CSA组第12个月的OS率明显高于单用CSA组,但是由于两组的有效缓解率低,两组患儿长期生存均较差。

Objective To compare the clinical efficacy of cyclosporin A(CSA)alone and CSA combined with anti-human thymocyte immunoglobulin(ATG)in the treatment of severe aplastic anemia(SAA)in children.Methods Retrospective analysis was performed on 62 SAA children admitted to the Department of Hematology,Kunming Children′s Hospital from January 2014 to December 2019.44 children treated with CSA alone were treated with CSA group,and 18 children treated with CSA combined with ATG were treated with CSA+ATG group.The dosage and administration were as follows:the initial oral dose of CSA was 5-10 mg/(kg·d),the blood concentration of CSA was monitored after 2 weeks of taking the drug,and the peak concentration was maintained at 300-400μg/L under the premise of maintaining the valley concentration at 100-150μg/L.The effect was reduced 12 months after reaching the plateau.ATG(Thymoglobuline)was 2.5-3.5mg/(kg·d)for continuous intravenous infusion for 5 days,and the cumulative dosage was up to 12.5-17.5mg/kg.Neutrophil count,hemoglobin,platelet count and blood transfusion were measured regularly during treatment and follow-up.The short-term efficiency and long-term survival prognosis were compared between the two groups.Results(1)In the first 3 months of treatment,effectiveness of CSA group of was 34.091%,and the CSA+ATG group was 44.4%,and the adoptedχ^(2) test P=0.444,there was no statistically significant difference.(2)In the first 12 months of treatment,effectiveness of CSA group:31.8%,CSA+ATG group:27.8%,USES theχ^(2) test P=0.754,there was no statistically significant difference.(3)LogRank survival analysis showed that the ATG+CSA group did not achieve a complete response after 12 months of treatment,which affected the survival prognosis(P=0.100),while the CSA group did not achieve a complete response after 12 months of treatment,which affected the survival prognosis(P=0.000).(4)ATG+CSA group OS rate is 94.4%in 12 months,CSA group OS rate for 12 months,59.1%,withχ^(2) test P=0.006,differences statistically.The median follow-up time was 18 months,and kaplan-Meier survival analysis showed that there was no statistically significant difference in survival prognosis between the two groups(P=0.859).Conclusions Immunotherapy alone may lead to delayed hematopoiesis in children with SAA,thus affecting the remission rate.Children who fail to achieve remission may end up with ineffective blood transfusion due to long-term blood transfusion and drug therapy,or their condition may worsen due to adverse drug reactions.Although the OS rate at 12 months in the ATG+CSA group was significantly higher than that in the CSA group alone,the long-term survival of children in both groups was poor due to the low effective remission rate in both groups.