Adverse reactions of dasatinib in pediatric acute lymphoblastic leukemia: a retrospective comparative cohort study.
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BACKGROUND: Dasatinib is increasingly used in the treatment of pediatric acute lymphoblastic leukemia (ALL) for its potent efficacy. However, the specific spectrum and incidence of adverse reactions attributable to it remain incompletely defined in the pediatric population. This retrospective cohort study aims to clarify the safety profile of dasatinib by directly comparing the incidence and types of adverse reactions between pediatric ALL patients who received dasatinib and those who did not. METHODS: This retrospective cohort study enrolled children with ALL treated at Shanghai Children's Medical Center between May and September 2024. Patients were allocated into the dasatinib group (n=144) if they received oral dasatinib (80 mg/m2/day) as part of their therapy, primarily for BCR-ABL1+ or Ph-like ALL. The control group (n=130) consisted of contemporaneous ALL patients not receiving any tyrosine kinase inhibitor (TKI), matched for treatment phase. Adverse events (AEs) were systematically assessed using Common Terminology Criteria for Adverse Events (CTCAE) v4.0 and World Health Organization (WHO) criteria. Clinical characteristics, including genetic profiles from RNA sequencing (RNA-seq), were collected. Group comparisons for categorical and continuous variables were performed using Chi-squared/Fisher's exact tests and t-tests/Mann-Whitney U tests, as appropriate. RESULTS: The two groups were comparable in terms of age and sex distribution (P>0.05), though the dasatinib group, by nature of its indication, contained a higher proportion of high-risk patients (e.g., BCR-ABL1+ and Ph-like ALL). The incidence of cardiovascular adverse reactions was higher in the dasatinib group (7.65% vs. 2.67%). Comparative analysis of hematologic adverse reactions between the two groups at different treatment stages revealed that during the maintenance phase, the dasatinib group was more prone to grade 1-3 thrombocytopenia and hemoglobin reduction (anemia) (P<0.05). During the induction phase (neutropenic period), the dasatinib group showed a higher incidence of grade 1-3 thrombocytopenia (P<0.05). In the non-neutropenic induction phase, the dasatinib group had a higher incidence of grade 2 thrombocytopenia (P<0.05). In the dasatinib group, the incidence rates of pleural effusion (PE), pericardial effusion, and tricuspid regurgitation were 8.20% (5 cases), 4.92% (3 cases), and 9.84% (6 cases), respectively. In the control group, pericardial effusion and tricuspid regurgitation occurred in 4.00% (1 case) each, with no PE observed. Genetic profiling revealed BCR-ABL1+ ALL (predominantly P190 subtype, 12 cases) with frequent IKZF1 deletions (5 cases), Ph-like ALL with kinase alterations (SSBP2-CSF1R/JAK1 mutations), and distinct high-risk (TP53/IkZF1/C-myc, 11 cases) versus low-risk (ETV6-RUNX1, 3 cases) molecular subgroups, highlighting clinically actionable targets for risk-adapted therapy. CONCLUSIONS: Dasatinib is associated with a significantly increased risk of hematologic and specific cardiovascular adverse reactions in pediatric ALL patients. These findings underscore the necessity for vigilant, protocol-driven monitoring of blood counts and cardiac function (including echocardiography) during dasatinib therapy. Proactive management strategies should be considered to mitigate these risks and improve treatment safety.