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BCR-ABL1 TKIs 用于儿童血液肿瘤患者的特异性风险与长期毒

性分析
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温璐平 ，夏 凡，廖紫琼，周本杰，陈 卉（中山大学附属第七医院药学部，广东 深圳 518107）
中图分类号 R979.1；R969.3 文献标志码 A 文章编号 1001-0408（2026）08-1050-06
DOI 10.6039/j.issn.1001-0408.2026.08.14

摘 要 目的 分析4种BCR-ABL1酪氨酸激酶抑制剂（伊马替尼、达沙替尼、尼洛替尼和博舒替尼）用于儿童血液肿瘤患者的特异
性风险及长期毒性。方法 收集美国FDA不良事件报告系统（FAERS）2012年1月－2024年12月上报的以伊马替尼、达沙替尼、尼
洛替尼和博舒替尼为首要怀疑药物的药物不良事件（ADE）报告，采用报告比值比法和比例报告比值比法进行数据挖掘；利用《国
际医学用语词典》（26.0版）中的系统器官分类（SOC）和首选术语（PT）进行分类统计。同时，将ADE报告按年龄分为成人组（≥18
岁）和儿童组（＜18岁），比较两组的ADE差异。结果 共纳入1 512份儿童ADE报告，其中伊马替尼993份、达沙替尼391份、尼洛
替尼112份、博舒替尼16份。在已报告的ADE中，年龄以12～＜18岁为主；报告主要来源于美国、法国和日本；主要适应证为慢性
髓性白血病和急性淋巴细胞白血病。共挖掘出 5 256 个儿童 ADE 信号，其中阳性信号 235 个，累及 1 103 个 PT，涉及 27 个 SOC。
阳性信号数排名前5位的PT为恶心、发热性中性粒细胞减少症、腹痛、中性粒细胞减少症和贫血；排名前2位的SOC为全身性疾病
及给药部位各种反应、胃肠系统疾病。与成人组比较，儿童组的感染及侵染性疾病、血液及淋巴系统疾病比例相对更高。儿童的
长期毒性信号主要表现为生长迟缓、内分泌系统异常及骨代谢异常；特异性信号包括伊马替尼相关的感染性休克，达沙替尼相关
的乳糜胸，尼洛替尼相关的心电图QT间期延长。结论 儿童使用BCR-ABL1酪氨酸激酶抑制剂时应重点监测其感染风险、血液学
指标，同时长期随访身高、内分泌与骨代谢指标，对药物特异性信号进行针对性筛查与管理，以确保其长期用药的安全性。
关键词 儿童；BCR-ABL1酪氨酸激酶抑制剂；伊马替尼；达沙替尼；尼洛替尼；博舒替尼；药物不良事件

Analysis of specific risks and long-term toxicities of BCR-ABL1 TKIs in pediatric patients with
hematological malignancies
WEN Luping，XIA Fan，LIAO Ziqiong，ZHOU Benjie，CHEN Hui（Dept. of Pharmacy， the Seventh Affiliated
Hospital， Sun Yat-sen University， Guangdong Shenzhen 518107， China）

ABSTRACT OBJECTIVE To analyze the specific risks and long-term toxicities of four BCR-ABL1 tyrosine kinase inhibitors
（TKIs）（imatinib， dasatinib， nilotinib， and bosutinib） in pediatric patients with hematological malignancies. METHODS Adverse
drug event （ADE） reports submitted to the the United States FDA Adverse Event Reporting System （FAERS） from January 2012 to
December 2024， with imatinib， dasatinib， nilotinib， and bosutinib as the primary suspect drugs， were collected. Data mining was
performed using the reporting odds ratio method and proportional reporting ratio method. ADE terms were classified and
summarized by system organ class （SOC） and preferred term （PT） according to the Medical Dictionary for Drug Regulatory
Activities （MedDRA， version 26.0）. Meanwhile， the ADE reports were divided by age into the adult group （≥18 years） and the
pediatric group （＜18 years） to compare the differences in ADE between the two groups. RESULTS A total of 1 512 pediatric
ADE reports were included： 993 for imatinib， 391 for dasatinib， 112 for nilotinib， and 16 for bosutinib. Among the reported
ADEs， the patients were mainly aged 12-＜18 years； the reports mainly originated from the United States， France， and Japan； and
the primary indications were chronic myeloid leukemia and acute lymphoblastic leukemia. A total of 5 256 ADE signals were
mined， among which 235 were positive signals， involving 1 103 PT across 27 SOC. The top five PT ranked by the number of
positive signals were nausea， febrile neutropenia， abdominal pain， neutropenia， and anemia. The top two SOC were general
disorders and administration site conditions， and gastrointestinal disorders. Compared with the adult group， the pediatric group had
relatively higher proportions of events related to infections and infestations as well as blood and lymphatic system disorders.
Pediatric long-term toxicity signals primarily included growth retardation， accompanied by signals related to endocrine system
abnormalities and bone metabolism abnormalities. Specific signals included imatinib-associated septic shock， dasatinib-associated
chylothorax， and nilotinib-associated electrocardiographic QT
Δ 基金项目 国家自然科学基金项目（No.82304584） interval prolongation. CONCLUSIONS When pediatric
＊第一作者 主管药师，硕士。研究方向：临床药学。E-mail：
patients use BCR-ABL1 TKIs， priority monitoring of infection
wenluping@sysush.com
# 通信作者 副主任药师，博士。研究方向：临床药理。E-mail： risk and hematologic parameters is required， along with long-
chenhui1@sysush.com term follow-up of height， endocrine， and bone metabolism

· 1050 · China Pharmacy 2026 Vol. 37 No. 8 中国药房 2026年第37卷第8期