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中国循证儿科杂志

中国循证儿科杂志 ›› 2018, Vol. 13 ›› Issue (4): 259-263.

• 论著 • 上一篇    下一篇

砷剂在儿童急性早幼粒细胞白血病治疗中的安全性病例系列报告

张元元1,4，王林娅1,4，张瑞东1，林巍1，于皎乐1，吴颖1，漆佩静1，范佳1，李静1，林嘉衍1，郑雪岭1，彭晓霞2，蒋慧3，郑胡镛1   

  1. 1 国家儿童医学中心，首都医科大学附属北京儿童医院血液肿瘤中心，儿童血液病与肿瘤分子分型北京市重点实验室，儿科学国家重点学科，儿科重大疾病研究教育部重点实验室，北京 100045；2 国家儿童医学中心，首都医科大学附属北京儿童医院临床流行病学与循证医学中心，北京 100045；3 上海交通大学上海市儿童医院，上海 200040；4 共同第一作者
  • 收稿日期:2018-06-11 修回日期:2018-08-20 出版日期:2018-08-25 发布日期:2018-08-25
  • 通讯作者: 郑胡镛，蒋慧

Report of case series on the safety of arsenic using in children with acute promyelocytic leukemia

ZHANG Yuan-yuan1,4, WANG Lin-ya1,4, ZHANG Rui-dong1, LIN Wei1, YU Jiao-le1, WU Ying1, QI Pei-jing1, FAN Jia1, LI Jing1, LIN Jia-yan1, ZHENG Xue-ling1, PENG Xiao-xia2, JIANG Hui3, ZHENG Hu-yong1   

  1. 1 Beijing Key Laboratory of Pediatric Hematology Oncology; National Key Discipline of Pediatrics (Capital Medical University); Key Laboratory of Major Diseases in Children, Ministry of Education; Hematology Oncology Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; 2 Clinical Epidemiology and Evidence-Based Medicine Center, Beijing Children's Hospital, Capital Medical University, National Center for Children's Health, Beijing 100045, China; 3 Children's Hospital of Shanghai, Shanghai Jiao Tong University, Shanghai 200040, China; 4 The co-first authors
  • Received:2018-06-11 Revised:2018-08-20 Online:2018-08-25 Published:2018-08-25
  • Contact: ZHENG Hu-yong, JIANG Hui

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摘要： 目的 初探砷剂在儿童急性早幼粒细胞白血病（APL）中应用的安全性。方法 纳入2016年3月16日至2018年5月1日在首都医科大学附属北京儿童医院血液肿瘤中心初诊的APL患儿，通过检测APL患儿不同治疗时期、不同组织中砷浓度，观察治疗中、治疗结束后砷剂的不良反应，评估砷剂在儿童APL中应用的安全性。结果 15例初诊APL患儿纳入本研究，男8例，发病年龄3~16（10.4±4.0）岁。在采用中国儿童白血病协作组-急性早幼粒细胞白血病（CCLG-APL）2016方案治疗期间，15例患儿诱导期血砷浓度均在10~100 ng·mL-1有效范围；巩固治疗期除2例血砷浓度分别为 121.3和9.46 ng·mL-1，其他患儿血砷浓度均在有效范围；维持治疗期所有患儿血砷浓度均在有效范围内。停药半年后患儿血砷及尿砷浓度均降至正常水平，分别为1.7 和40.4 ng·mL-1，与治疗前血砷浓度（0.7 ng·mL-1）及尿砷浓度（13.7 ng·mL-1）相比差异无统计学意义（P分别为0.140 1和0.451 9）。头发、指甲中砷浓度在停药时达高峰，在停药后逐渐下降，停药半年后降至治疗前水平。Spearman秩相关分析显示血砷浓度与尿（r=0.778，P<0.001）、头发（r=0.641，P<0.001）及指甲（r=0.655，P<0.001）砷浓度呈正相关；尿砷浓度与头发（r=0.622，P<0.001）、指甲（r=0.688，P<0.001）砷浓度均呈正相关；头发与指甲砷浓度呈正相关（r=0.847，P<0.001）。最长随访时间25.5个月，平均随访时间（12.2±7.8）个月，尚未观察到砷剂的慢性不良反应，砷剂短期反应如脏器功能损害等在对症或砷剂减量后均可消失。结论 APL患儿各治疗阶段血砷浓度均可维持在有效范围，血、尿、头发、指甲砷浓度在停药半年后均降至正常。砷剂在儿童APL中的应用具有安全性，但仍需后期长期的随访观察。

Abstract: Objective To study the safety of arsenic using in children with acute promyelocytic leukemia(APL). Methods Fifteen children with APL diagnosed in our hospital from March 16, 2016 to May 1, 2018 were enrolled. The arsenic concentrations in different tissues including blood, urine, hair and nail, were measured during different treatment timepoints, and adverse reactions were observed to evaluate the safety of arsenic using in children with APL. Results All blood arsenic concentrations in children with CCLG-APL 2016 protocol were within the effective range of (10-100) ng·mL-1 during induction, consolidation and maintenance therapy, except for two cases were 121.3 ng·mL-1 and 9.46 ng·mL-1 during consolidation, respectively. After six months of discontinuation, the arsenic concentrations of blood and urine, with a level of 1.7 ng·mL-1 and 40.4 ng·mL-1, were reduced to normal levels as those before treatment, between which there was no significant difference (P>0.05). Arsenic concentrations in hair and nail peaked at the time of drug withdrawal and gradually decreased to the level before treatment after six months of discontinuation. In addition, it showed that blood arsenic concentration was positively correlated with urine (r=0.778, P<0.001), hair (r=0.641, P<0.001) and nail (r=0.655, P<0.001) arsenic. Arsenic concentration in urine with hair (r=0.622, P<0.001), and nail (r=0.688, P<0.001) were also positively correlated. And arsenic concentration in hair was positively correlated with nail (r=0.847, P<0.001). Up to now, with a longest follow-up period of 25.5 months and the average follow-up time of (12.2±7.8) months, the short-term response of arsenic disappeared after symptomatic therapy or arsenic reduction, and no chronic side effects of arsenic were observed. Conclusion Through the detection of arsenic concentration in different periods and different tissues, it was found that the blood arsenic concentration could be maintained within the effective concentration range in each treatment stage, and the arsenic concentration in blood, urine, hair and nails gradually decreased to normal after six months of discontinuation. The use of arsenic in children with APL is safe, but it still needs long-term follow-up.