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.

A 63-year-old female patient with multiple systemic metastases from lung adenocarcinoma was treated with befotertinib (75 mg orally once daily) and other symptomatic supportive treatments. Before treatments, her platelet count (PLT) was 177×10 9/L. After 35 days of medication, the patient had a transient loss of consciousness with chest tightness and shortness of breath. Computed tomography pulmonary angiography showed multiple embolism in bilateral pulmonary arteries. Laboratory tests showed that D-dimer was 35.16 g/L, and PLT was 34×10 9/L. The pulmonary embolism and throm-bocytopenia were considered to be caused possibly by befotertinib. Befotertinib was stopped, and enoxaparin sodium injection and rivaroxaban were given successively for anticoagulation. Thirteen days later, the chest tightness and shortness of breath were significantly improved, D-dimer was 0.57 g/L, and the PLT was 123×10 9/L.

A 63-year-old female patient with multiple systemic metastases from lung adenocarcinoma was treated with befotertinib (75 mg orally once daily) and other symptomatic supportive treatments. Before treatments, her platelet count (PLT) was 177×10 9/L. After 35 days of medication, the patient had a transient loss of consciousness with chest tightness and shortness of breath. Computed tomography pulmonary angiography showed multiple embolism in bilateral pulmonary arteries. Laboratory tests showed that D-dimer was 35.16 g/L, and PLT was 34×10 9/L. The pulmonary embolism and throm-bocytopenia were considered to be caused possibly by befotertinib. Befotertinib was stopped, and enoxaparin sodium injection and rivaroxaban were given successively for anticoagulation. Thirteen days later, the chest tightness and shortness of breath were significantly improved, D-dimer was 0.57 g/L, and the PLT was 123×10 9/L.