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

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

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Kasabaeh-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0．8mg／m^2，2次／d，间隔12h，血药浓度维持10-15ng／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，GradeⅠ）、腹泻（2例，GradeⅠ／GradeⅡ）、发热（2例，GradeⅡ）、皮疹（1例，GradeⅠ）、疼痛（1例，GradeI）、短暂性转氨酶及血脂异常（1例，GradeⅠ／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Kasabaeh-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。

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/m^2 , 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, includin4g 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 Steroids were withdrawn quickly.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.