克拉屈滨治疗儿童难治性高危朗格汉斯细胞组织细胞增生症：13例报告并文献复习

Cladribine for 13 cases refractory high-risk children Langerhans cell histiocytosis

目的 观察改良克拉屈滨联合阿糖胞苷（2-CdA＋Ara-C）方案（CIP-LCH-2012方案）治疗儿童难治性高危朗格汉斯细胞组织细胞增生症（LCH）的疗效及不良反应.方法 回顾性分析CIP-LCH-202方案治疗13例多系统LCH（MS-LCH）患儿（年龄＜18岁）,根据2009年国际组织细胞协会LCH诊疗及评估指南进行疗效评价与疾病状态评估;根据2009年美国卫生及公共服务部、国立卫生研究院、国家癌症研究所公布的常见不良反应事件评价标准（CTCAE 4.0版）进行药物不良反应评估.结果 13例患儿中10例达到无活动性疾病（NAD）状态;3例在CIP-LCH-2012方案治疗前出现肝硬化,其中2例治疗1个疗程后放弃治疗,1例化疗后骨髓抑制期合并严重感染,死于感染性休克.所有13例患儿均出现3级血液及淋巴系统不良反应;10例患者出现1级肝胆系统及胃肠道不良反应;另3例在治疗前存在肝硬化患儿出现2～3级肝胆系统及胃肠道不良反应,1例死亡.结论 CIP-LCH-2012方案对儿童难治性高危LCH患者疗效明确,其药物不良反应主要表现为明显的骨髓抑制,多可耐受;可考虑作为MS-LCH一线治疗失败后的挽救性治疗及MS-LCH伴有危险器官受累的一线治疗方案.对于治疗前存在严重脏器功能受损,尤其是肝硬化及严重骨髓受累时,应慎用该方案或考虑调整剂量。

Objective To observe the efficacy and adverse reaction of the improvement program of cladribine combined with cytarabine （2-CdA＋Ara-C） in treatment of children with refractory high-risk Langerhans cell histiocytosis （LCH）.Methods 13 patients with refractory high-risk LCH or recurrent LCH were treated by combined 2-CdA＋Ara-C chemotherapy.The treatment efficacy and the disease state in the process were evaluated according to the Histiocyte Society Evaluation and Treatment Guidelines （2009）.The drug toxicity was evaluated according to the Common Terminology Criteria Adverse Events Version 4.0 （CTCAE v4.0,2009）.Results Of 13 patients,10 cases achieved non active disease （NAD）;2 patients with liver cirrhosis before the improvement program with CIP-LCH-2012 gave up the treatment after 1 course of therapy; 1 patient died of infectious shock after chemotherapy with severe pulmonary infection and intestinal infection.All 13 patients had grade 3 of blood and lymphatic system toxicity; 10 patients had grade 1 of hepatobiliary and gastrointestinal side effects; 3 patients with liver cirrhosis before the improvement program had grade 2 or grade 3 of hepatobiliary system and gastrointestinal system side effects,including 1 patient of death.Conclusion The improvement program of CIP-LCH-2012 had significant efficacy for children with refractory high-risk and relapsed LCH.The cladribine-associated toxicity was of significant myelosuppression,which may be tolerated in the most children patients.The program could be considered as a recommended salvage therapy for multi-system LCH （MS-LCH） after failure of first-line therapy,and as a first-line therapy for MS-LCH with risk organ injury.The program should be used with caution or dose-adjustment consideration for pre-treatment of severe organ damage exist,especially cirrhosis.