激素抵抗型婴幼儿Kasabach-Merritt综合征治疗中雷帕霉素的临床应用价值探讨

目的 初步评估临床上应用雷帕霉素治疗激素抵抗型婴幼儿Kasabach-Merritt综合征的临床疗效及安全性.方法 2015年2月至2016年4月共收集8例在我科接受治疗的Kasabach-Merritt综合征患儿,其中男5例,女3例,病灶位于颌面部3例、颈部1例、四肢2例,胸腹壁2例,8例患儿均表现为激素抵抗,对激素抵抗型Kasabach-Merritt综合征采用mTOR抑制剂雷帕霉素治疗.雷帕霉素服用方法为每次0.8 mg/m2,2次/d,间隔12h,血药浓度维持10～15 ng/ml.定期监测血常规、凝血功能、肝肾功能、血脂及雷帕霉素血药浓度等指标.根据血药浓度、血小板变化、凝血功能、瘤体缩小情况及副作用可适当调整用药计划.结果 8例患儿经雷帕霉素治疗后血小板均恢复正常,瘤体萎缩,并逐步撤离了激素,有效率达到100％.雷帕霉素平均起效时间(6.8±2.7)d,平均血小板稳定时间(19.1±8.5)d,目前雷帕霉素总的用药时间为4～10个月,平均(6.0±2.2)个月,开始雷帕霉素单药治疗时间为2～8个月,平均(4.5±1.9)个月.8例患儿仍在服药进行中,均无血小板下降和病灶复发.药物使用中不良反应主要为口腔黏膜炎及口腔溃疡(2例,GradeⅡ)、呕吐(1例,Grade工)、腹泻(2例,Grade Ⅰ/GradeⅡ)、发热(2例,GradeⅡ)、皮疹(1例,Grade Ⅰ)、疼痛(1例,Grade Ⅰ)、短暂性转氨酶及血脂异常(1例,Grade Ⅰ/GradeⅡ),予对症治疗后好转,无严重不良事件,无病例退出.结论 mTOR抑制剂雷帕霉素治疗激素抵抗型Kasabach-Merritt综合征具有一定的疗效及安全性,值得临床进一步推广应用.

Efficacy and safety of rapamycin in the treatment of steroid-resistant Kasabach-Merritt syndrome in infants

Objective To explore the efficacy and safety of rapamycin in the treatment of steroid-resistant Kasabach-Merritt syndrome in infants.Methods Eight infants with steroid-resistant Kasabach-Merritt syndrome between June 2015 and April 2016 at our hospital were enrolled.There were 5 males and 3 females.The lesions were located in maxillofacial region (n =3),neck region (n =1),extremities (n =2) and trunk (n =2).Patients with steroid-resistant Kasabach-Merritt received the therapy of rapamycin.Rapamycin was started at a dose of 0.8 mg/m2,administered twice daily at approximately 12-hour intervals for maintaining a level of 10-15 ng/ml.The dose of rapamycin could be modulated according to the level of rapamycin,count of platelet,shrinkage of lesion and side effects.Results All 8 cases were diagnosed as steroid-resistant Kasabach-Merritt syndrome.There were significant improvements in clinical status,including platelet elevation,coagulation function improvement and tumor shrinkage.Steroids were withdrawn quickly.Time to initial response was (6.8± 2.7) days,average stabilization time of platelet (19.1 ± 8.5) days,average duration of rapamycin treatment (6.0± 2.2) months and average time for rapamycin alone (4.5 ± 1.9) months.There was no symptomatic relapse.The side effects were tolerable,including oral mucositis/ulcer (n =2,grade Ⅱ),vomiting (n=1,grade Ⅰ),diarrhea (n=2,grade Ⅰ/Ⅱ),fever (n=2,grade Ⅱ),skin rash (n =1,grade Ⅰ),pain (n =1,grade Ⅰ),transient elevation of serum transaminase and cholesterin (n =1,grade Ⅰ / Ⅱ).Conclusions Rapamycin therapy for infants with steroid-resistant Kasabach-Merritt syndrome is safe and efficacious so that it is worthy of wider clinical application.