Severe asparaginase-associated hypertriglyceridemia in pediatric acute lymphoblastic leukemia: a single-center experience.

Background: Asparaginase-associated hypertriglyceridemia (AAHTG) is a recognized metabolic complication of asparaginase therapy in pediatric acute lymphoblastic leukemia (ALL). However, data on its incidence, clinical presentation, and optimal management remain limited. Methods: We performed a retrospective analysis of 12 pediatric patients (≤18 years) with ALL treated at King Hussein Cancer Center (KHCC) between January 2021 and February 2026 who developed severe AAHTG, defined as triglyceride levels >1,000 mg/dL following asparaginase administration. Clinical characteristics, management strategies, and outcomes were systematically reviewed and analyzed. Results: Among 598 patients with pediatric ALL treated at KHCC, 12 developed severe AAHTG (incidence 2%). Most cases (83%) were asymptomatic and identified incidentally through observation of lipemic serum on routine laboratory testing; only two patients were symptomatic-one with acute pancreatitis and one with hyperviscosity syndrome. The median age was 9.5 years, with a male predominance (83%). Most patients had B-cell ALL (75%) and high-risk disease (66%). AAHTG occurred predominantly during the maintenance phase (66%), with a median onset of 12 days after the last asparaginase dose. The median peak triglyceride level was 2,645 mg/dL (range, 2,052-6,687 mg/dL). All patients received intravenous fluids, omega-3 fatty acids, and fibrates. Continuous insulin infusion was administered in 11 patients over a median of 3 days until triglyceride levels fell below 1,000 mg/dL. Plasmapheresis was utilized in three patients-two presenting with triglycerides exceeding 6,000 mg/dL and one with hyperviscosity syndrome-with all three achieving a reduction below 1,000 mg/dL after a single treatment session. Asparaginase was resumed per protocol in eight patients; recurrence occurred in one. Permanent discontinuation was required in four patients: two with symptomatic disease, one with refractory hypertriglyceridemia, and one who developed AAHTG after the final scheduled dose. Conclusion: Severe AAHTG is frequently asymptomatic and most often identified incidentally through lipemic serum; however, it carries a risk of serious complications. Early identification and prompt intervention were associated with favorable outcomes in this cohort. Resumption of asparaginase following an AAHTG episode appears feasible, provided triglyceride levels are confirmed below 1,000 mg/dL before each subsequent dose.