Abstract #1407741: Pegaspargase-Induced Severe Hyptriglyceridemia

Abstract

Pegaspargase (PEG) a critical medication for acute lymphoblastic leukemia (ALL). As a long-acting formulation of L-asparaginase, it leads to degradation and depletion of the amino acid asparagine and selective leukemic cell apoptosis. Despite significantly improving treatment response rates, its use can be challenging due to a complex toxicity profile, including thrombosis, hepatotoxicity, hyperglycemia, pancreatitis, and hypertriglyceridemia (HTG). We report a case of a young man who developed severe hypertriglyceridemia secondary to PEG. A 26-year-old man with no significant past medical history presented with refractory upper respiratory symptoms and cervical lymphadenopathy. He was subsequently found to have severe leukocytosis with 70% blasts and 7cm mediastinal mass with superior vena cava compression. Flow cytometry and bone marrow biopsy diagnosed T-cell ALL and he was started on chemotherapy via the GIMEMA LAL1913 protocol (a chemotherapy regimen that includes prephase cyclophosphamide and induction phase with vincristine, idarubicin, dexamethasone, and PEG). About 12 days after having received PEG, the patient developed unexplained acute hyponatremia to 123 mmol/L and other lab tests such as potassium and hepatic function tests were not able to be processed. Further workup revealed pseudohyponatremia and that lab interference was occurring from lipemia. A triglyceride (TG) level was found to be >4425 mg/dL. LDL direct was measured to be 95 mg/dL, and lipid analysis showed absent chylomicrons. Clinically, he had stable mild abdominal tenderness and a serum lipase level resulted marginally above the upper limit of reference range. At this point, he was transitioned to a low-fat diet (<20g per day). Omega-3-acid ethyl esters (EPA/DHA) and fenofibrate were started. In the next 2 weeks his TG steadily decreased to 163 mg/dL. His mild abdominal pain resolved and lipase normalized. The patient is currently undergoing cycle 2 of his chemotherapy and remains on low fat diet, EPA/DHA, and fenofibrate therapy. After 1 week of receiving his second dose of PEG, his triglycerides were 105 mg/dL. Apo E genotyping was performed and revealed normal E3/E3 genotype. He denies any family history of lipid disorders. The incidence of PEG-induced HTG is poorly described in the adult population, and recent studies have shown the condition is becoming more frequently recognized. Its underlying mechanism is not fully understood, but TG levels often rise dramatically and can lead to severe pancreatitis. Clinicians should be aware of this adverse effect and consider baseline lipid analysis prior to induction chemotherapy and TG surveillance, in addition to clinical monitoring for pancreatitis.