雷帕霉素治疗儿童结节性硬化相关心脏横纹肌瘤的临床效果

Rapamycin in the treatment of cardiac rhabdomyoma associated with tuberous sclerosis complex

目的 探讨雷帕霉素治疗结节性硬化症（TSC）合并心脏横纹肌瘤的临床效果及安全性.方法 收集自2011年9月至2015年11月在解放军总医院儿童医学中心收治的合并心脏横纹肌瘤的TSC患儿.纳入符合入组标准的TSC合并心脏横纹肌瘤患儿均长期接受雷帕霉素治疗,起始剂量1 mg/（m2·d）,血药浓度维持在5～ 10μg/L.观察雷帕霉素治疗后患儿心脏横纹肌瘤的大小及个数的改变,分析临床疗效及安全性.治疗前后肿瘤最大径的比较采用Wilcoxon检验.结果 51例患儿符合入组标准,其中男30例、女21例,接受雷帕霉素治疗时年龄15.0（7.0 ～35.0）月龄.经过治疗26例（51％）患儿肿瘤完全消失,肿瘤消失时间中位数3.26（2.92 ～5.37）个月,15例（29％）肿瘤缩小50％及以上,5例（12％）肿瘤缩小不足50％,4例（8％）肿瘤无变化或进展.治疗后可测量肿瘤个数减少了77个（72％）.治疗前肿瘤最大径中位数8.7（5.9～11.3） mm,治疗后为0.0（0.0 ～4.0） mm,肿瘤最大径减少值中位数6.7 （3.9～10.0） mm,治疗前后肿瘤最大径差异有统计学意义（Z=-8.817,P＜0.01）.对患儿年龄进行分组,0～1岁消失率为50％ （12/24）;＞1 ～3岁患儿共16例,其中10例肿瘤消失;＞3岁患儿共11例,其中4例患儿肿瘤消失.治疗后3个月心脏横纹肌瘤消失速率最高.10例患儿出现雷帕霉素相关的不良事件,其中1例轻度口腔溃疡,9例血脂异常.结论雷帕霉素治疗TSC相关的心脏横纹肌瘤能够有效减少肿瘤大小和数量,且显著缩短心脏横纹肌瘤病程,并且不良反应少,耐受性好.

Objective To assess the efficacy and safety of mammalian target of rapamycin （mTOR） inhibitor rapamycin in treatment of children with cardiac rhabdomyoma,associated with tuberous sclerosis complex （TSC）.Method The clinical data of children with cardiac rhabdomyomas,who had received a diagnosis of TSC previously,were collected between September 2011 and November 2015 from Pediatric Department of the People＇s Liberation Army General Hospital.Patients in line with the inclusion criteria received long-term treatment with sirolimus.The starting doses of sirolimus was 1 mg/ （m2·d）,and the plasma concentration was maintained at 5-10 μg/L.The size and number of cardiac rhabdomyomas were analyzed after treatment with rapamycin,and the efficacy and safety were assessed.The Wilcoxon test was used to analyze data.Result All the 51 children met the inclusion and exclusion criteria,including 30 males and 21 females.The median age for rapamycin treatment was 15.0 months （7.0-35.0 months）.Tumors disappeared in 26 （51%） children,decreased by more than 50% （including 50%） in 15 （29%）children,decreased by less than 50% in 5 （12%） children,and had no change or progressed in 4 （8%）children.The number of tumors decreased by 77 （72%）.The median maximum diameter of tumor was 8.7（5.9-11.3） mm before treatment,0.0 （0.0-4.0） mm after treatment,and the median decrease of tumor size were 6.7 （3.9-10.0） mm （Z =-8.817,P 〈 0.01）.The median disappearance time was 3.26 （2.92-5.37） months.Among different age groups,after treatment by rapamycin,the rate of tumor＆#39;s disappearance was 50% （12/24） in 0-1 years group.Tumors disappeared in 10 of 16 patients in 〉 1-3 years group and in 4 of 11 patients in 〉 3 years group.The rate of tumor＆#39;s disappearance was the highest after 3 months of treatment as compared with 6 and 12 months of treatment.Ten children had adverse event that was related to rapamycin.Canker sore was reported in one child and dyslipidemia was reported in 9 children.Conclusion Rapamycin is efficacious and well tolerate in treatment of cardiac rhabdomyomas associate with TSC,and lead to a reduction in tumor size and number,in addition,significantly shorten the duration of cardiac rhabdomyoma.