Obesity and age ≥10 years were significant predictors of severe hepatotoxicity (obesity SHR 1.75; 95% CI 1.04-2.96) and pancreatitis (obesity SHR 2.18; 95% CI 1.01-4.67) in pediatric ALL.
Cohort (n=262)
No
Hazard Ratio: 1.75 (95% CI 1.04–2.96)
BACKGROUND: Hepatotoxicity and pancreatitis are common treatment-related toxicities (TRTs) during contemporary treatment regimens for acute lymphoblastic leukemia (ALL). Limited detailed data from Children's Oncology Group (COG) regimens has been previously reported to enable identification of patient and treatment risk factors for these toxicities and their impact on outcomes. PROCEDURE: We analyzed a retrospective pediatric ALL cohort treated at a single institution according to COG regimens from 2008 to 2015. The primary endpoint was cumulative incidence of study-defined "severe" hepatotoxicity (Common Terminology Criteria for Adverse Events CTCAE Grade ≥ 4 transaminitis or Grade ≥ 3 hyperbilirubinemia) and clinically significant pancreatitis (any grade). Pancreatitis was additionally classified using the Ponte di Legno (PdL) toxicity criteria. Secondary endpoints were chemotherapy interruptions, early disease response (end of induction EOI minimal residual disease MRD), and event-free survival (EFS). RESULTS: We identified 262 patients, of whom 71 (27%) and 28 (11%) developed hepatotoxicity and pancreatitis, respectively. Three cases of pancreatitis did not fulfill PdL criteria despite otherwise consistent presentations. Both TRTs occurred throughout therapy, but approximately 25% of hepatotoxicity (18/71) and pancreatitis (8/28) occurred during induction alone. Both obesity and age (≥10 years) were identified as predictors of hepatotoxicity (subdistribution hazard ratio SHR obesity = 1.75, 95% confidence interval 95% CI 1.04-2.96; SHR age ≥10 = 1.9, 95% CI 1.19-3.10) and pancreatitis (SHR obesity = 2.18, 95% CI 1.01-4.67; SHR age ≥ 10 = 2.76, 95% CI 1.19-6.39, P = 0.018). Dose interruptions were common but neither toxicity influenced EOI MRD nor EFS. CONCLUSIONS: Obese and/or older children are particularly at risk for hepatotoxicity and pancreatitis, and may benefit from toxicity surveillance and chemoprotective strategies to prevent or mitigate associated morbidity.
Denton et al. (Fri,) conducted a cohort in Acute lymphoblastic leukemia (ALL) (n=262). Obesity and age ≥10 years vs. Non-obese and age <10 years was evaluated on Cumulative incidence of study-defined severe hepatotoxicity and clinically significant pancreatitis (SHR 1.75, 95% CI 1.04-2.96). Obesity and age ≥10 years were significant predictors of severe hepatotoxicity (obesity SHR 1.75; 95% CI 1.04-2.96) and pancreatitis (obesity SHR 2.18; 95% CI 1.01-4.67) in pediatric ALL.
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