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BCR-ABL1TKIs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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| 篇名： | BCR-ABL1TKIs用于儿童血液肿瘤患者的特异性风险与长期毒性分析 |
| TITLE： | Analysis of specific risks and long-term toxicities of BCR-ABL1 TKIs in pediatric patients with hematological malignancies |
| 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1512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5256个儿童ADE信号，其中阳性信号235个，累及1103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。 |
| 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 interval prolongation. CONCLUSIONS When pediatric patients use BCR-ABL1 TKIs， priority monitoring of infection risk and hematologic parameters is required， along with long-term follow-up of height， endocrine， and bone metabolism parameters. Targeted screening and management of drug-specific signals should be performed to ensure the long-term safety of pediatric medication. |
| 期刊： | 2026年第37卷第08期 |
| 作者： | 温璐平；夏凡；廖紫琼；周本杰；陈卉 |
| AUTHORS： | WEN Luping，XIA Fan，LIAO Ziqiong，ZHOU Benjie，CHEN Hui |
| 关键字： | 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 |
| KEYWORDS： | pediatric； BCR-ABL1 tyrosine kinase inhibitors； imatinib； dasatinib； nilotinib； bosutinib； adverse drug event |
| 阅读数： | 9 次 |
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