SAT-LB91 Asparaginase Induced Severe Hypertriglyceridemia Requiring Multiple Plasmapheresis Sessions

Background: Asparaginase (ASP) is an essential component of chemotherapy for acute T-cell lymphoblastic lymphoma (T-ALL). Hypertriglyceridemia (HTG) is a known side effect of ASP therapy in children and adults (incidence up to 67 and 12.5%, respectively). The mechanism of HTG is multifactorial and involves lipoprotein lipase (LPL) suppression. Acute pancreatitis can occur in 13% of patients. There are no treatment guidelines currently available for ASP-induced HTG. Clinical Case: A 33 year old male with history of prediabetes, HTG and T-ALL being treated with CALGB 10403 chemotherapy protocol (vincristine, methotrexate, cytarabine and pegylated-ASP) presented to the ED with acute onset abdominal pain radiating to the back with associated nausea. He denied alcohol use. Home medications included fenofibrate, metformin and atorvastatin. His TG level prior to initiating chemotherapy was 454 mg/dL (ref range < 150) with an HbA1C of 6.5%. Upon presentation; TG level was 11,650 mg/dL, lipase was 563 U/L (13-60) with CT abdomen findings suggestive of mild pancreatitis. He was treated in the ICU with insulin drip at 0.05 - 0.1 unit/kg/hr with repeat TG level 6,490 mg/dL after 48 hours. He eventually required 5 serial plasmapheresis sessions over a 10 day hospital course in order to achieve a goal TG level under 500 mg/dL. Conclusion: ASP is part of standard multiagent chemotherapy for patients with ALL however poses the risk of developing severe HTG. This side effect may be explained by multiple mechanisms including increased synthesis of very low-density lipoprotein (VLDL), decreased LPL activity as a result of an increase in the apoCIII/apoCII ratio, and increase in serum chylomicrons. Studies have shown patients who had extreme HTG had a higher frequency of ApoE3/4 phenotype, suggesting that screening for ApoE polymorphism may identify patients at high risk for developing this. HTG secondary to ASP is often asymptomatic, with severe elevations in TG levels observed around 10 days after the 3rd administration of ASP and resolving 2-3 weeks after drug discontinuation. There are no treatment guidelines for ASP-associated HTG as there is no single typical clinical course. Management for severe HTG includes insulin infusion and plasmapheresis. Insulin rapidly activates LPL leading to mean TG reduction of 50% within the first 24 hours as compared to 66% reduction after single plasmapheresis therapy. However, there is paucity of data regarding the appropriate insulin dose and whether there is a linear dose-response in TG level reduction. Further studies are required to develop standard treatment guidelines for ASP-induced HTG which may help alleviate serious complications such as acute pancreatitis. Reference: Tozuka et al “Characterization of hypertriglyceridemia induced by L-asparaginase therapy for acute lymphoblastic leukemia and malignant lymphoma.” Annals of Clinical & Laboratory Science 1997