Severe Hypertriglyceridemia Secondary to Long-Acting Asparaginase in Pediatric Patients With Acute Lymphoblastic Leukemia

J Pediatr Hematol Oncol. 2025 Jun 25. doi: 10.1097/MPH.0000000000003077. Online ahead of print.

Abstract

Pegylated asparaginase is now standard in US treatment protocols for acute lymphoblastic leukemia (ALL). However, they are associated with significant side effects, including severe hypertriglyceridemia. In this case series, we report 8 patients with severe (triglyceride >1000 mg/dL) hypertriglyceridemia after receiving long-acting asparaginase for ALL and describe their clinical course. The 8 patients included 3 females and 5 males (aged 2 to 14 y; median=12 y); 7 were Hispanic and 1 was Middle Eastern. The median time from dose to peak hypertriglyceridemia was 17 days and to resolution was 25 days. Presentations included isolated hypertriglyceridemia, pseudohyponatremia, hypoglycemia, and lipemia interfering with complete blood count results. Median length of hospitalization was 3.5 days. Management included hydration, a low-fat diet, omega-3 supplements, fenofibrates, statins, and levocarnitine. An insulin drip was used in 2 patients in the intensive care unit. Asparaginase treatment continued per protocol after triglyceride levels were <1000 mg/dL. In conclusion, severe hypertriglyceridemia can occur after long-acting asparaginase and is typically asymptomatic and transient, not requiring a pause or modification in treatment. We recommend monitoring for hypertriglyceridemia closely in patients with risk factors who are resuming long-acting asparaginase therapy after triglyceride levels fall <1000 mg/dL.

Keywords: acute lymphoblastic leukemia; asparaginase; chemotherapy toxicity; hyperlipidemia; hypertriglyceridemia; pediatric oncology.