Diagnostic BMI and Induction Therapy Weight Change Associated With Hepatotoxicity in Pediatric Patients With Acute Lymphoblastic Leukemia

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ABSTRACT Background Hepatotoxicity is a common treatment‐related complication in pediatric acute lymphoblastic leukemia (ALL). Excess adiposity at diagnosis has been identified as a risk factor, but the impact of weight change during therapy has not been examined. Methods We included patients aged 2–20 years newly diagnosed with ALL between 2005 and 2021. Hepatotoxicity was defined as: (1) transaminitis (ALT/AST > 10× the upper limit of normal), or (2) conjugated hyperbilirubinemia (cbili; > 3.0 mg/dL during induction/> 2.0 mg/dL post‐induction). Youden's J was used to identify optimal BMI z‐score thresholds. Cox proportional hazards regression was used to assess associations between hepatotoxicity during treatment and diagnostic BMI and post‐induction hepatotoxicity and weight change during induction. Associations were adjusted for age, race, ethnicity, and treatment risk stratification. Patients were censored at qualifying event or 1200 days post‐diagnosis. Results Among 1070 patients (median age 6 years), 45.8% developed transaminitis and 7.6% cbili. Optimal BMI z‐score cut points were −1.5 and 1.5 for transaminitis and 1.5 for cbili. A BMI z‐score ≤ −1.5 was associated with reduced transaminitis (HR = 0.58, 95% CI: 0.39–0.86; p = 0.006), while a z‐score ≥ 1.5 was associated with increased transaminitis (HR = 1.32, 95% CI: 1.06–1.65; p = 0.01). A BMI z‐score ≥ 1.5 was also associated with increased cbili (HR = 1.97, 95% CI: 1.23–3.18; p = 0.01). Weight change was not associated with transaminitis, but weight loss during induction was associated with an increase in hazard of post‐induction cbili (HR = 1.08, 95% CI: 1.04–1.11; p < 0.0001). Conclusion Diagnostic BMI z‐score and weight loss during induction were associated with increased hepatotoxicity risk, highlighting potential targets for improved risk stratification and hepatoprotective interventions.