Pegylated-Asparaginase Induced Severe Hypertriglyceridemia in an Adult with Acute B-cell Lymphoblastic Leukemia

Background/Synopsis We review a case of a young woman with hypertriglyceridemia after Pegylated-Asparaginase (PEG-ASP) treatment for B-cell LL. Objective/Purpose To describe important clinical features and management of PEG-ASP induced hypertriglyceridemia. Methods Retrospective review of electronic medical records and literature review. Results A 26-year-old Guyanese woman with acute B-cell lymphoblastic leukemia presents to the emergency department (ED) after being found to have a triglyceride (TG) level of 7851 mg/dL on outpatient labs three weeks after receiving (PEG-ASP). She has no history of obesity or diabetes. She follows a vegetarian diet and does not consume alcohol. She denies any family history of premature atherosclerotic cardiovascular disease. Of note, six months ago, this patient had severe hypertriglyceridemia (HTG) from PEG-ASP treatment that required ICU admission and continuous intravenous insulin infusion. Her medications on current admission include rosuvastatin, fenofibrate, niacin, and omega-3 acid ethyl esters. She denies any symptoms. Her lipase level is 71 U/L, and a computerized tomography (CT) scan of the abdomen and pelvis shows a normal pancreas. TG levels remain elevated in the 3,000 range, but she remains asymptomatic. She is discharged after three days with outpatient lipidology follow-up. One month later, her fasting lipid profile shows total cholesterol of 157 mg/dL, high-density lipoprotein (HDL) of 37 mg/dL, calculated low-density lipoprotein (LDL) of 86 mg/dL, triglycerides of 169 mg/dL, and non-HDL of 120 mg/dL. Conclusions Severe hypertriglyceridemia has become a notable side effect of PEG-ASP containing treatment regimens. Patients are usually asymptomatic and although pancreatitis is rare, it has been reported. Clinicians need to have a strong clinical suspicion to check triglycerides in a timely manner. Usually, severe hypertriglyceridemia can occur three weeks after PEG-ASP administration which is hypothesized to be attributed to lipoprotein lipase (LPL) activity reduction. Genetic variants can also predispose to hypertriglyceridemia. Some studies discuss that Apo-E polymorphism can predispose these patients to severe hypertriglyceridemia. A case report on a gain of function (GOF) variant in the APOC-III gene illustrated severe hypertriglyceridemia after PEG-ASP treatment. PEG-ASP can also inhibit insulin production and release, and decreased insulin levels are hypothesized to inhibit LPL activity. Early recognition and management with dietary restrictions and medical therapy are vital to avoid complications. More research is needed to help identify risk factors for developing PEG-ASP-induced HTG and to provide guidance in management. External Funding No We review a case of a young woman with hypertriglyceridemia after Pegylated-Asparaginase (PEG-ASP) treatment for B-cell LL. To describe important clinical features and management of PEG-ASP induced hypertriglyceridemia. Retrospective review of electronic medical records and literature review. A 26-year-old Guyanese woman with acute B-cell lymphoblastic leukemia presents to the emergency department (ED) after being found to have a triglyceride (TG) level of 7851 mg/dL on outpatient labs three weeks after receiving (PEG-ASP). She has no history of obesity or diabetes. She follows a vegetarian diet and does not consume alcohol. She denies any family history of premature atherosclerotic cardiovascular disease. Of note, six months ago, this patient had severe hypertriglyceridemia (HTG) from PEG-ASP treatment that required ICU admission and continuous intravenous insulin infusion. Her medications on current admission include rosuvastatin, fenofibrate, niacin, and omega-3 acid ethyl esters. She denies any symptoms. Her lipase level is 71 U/L, and a computerized tomography (CT) scan of the abdomen and pelvis shows a normal pancreas. TG levels remain elevated in the 3,000 range, but she remains asymptomatic. She is discharged after three days with outpatient lipidology follow-up. One month later, her fasting lipid profile shows total cholesterol of 157 mg/dL, high-density lipoprotein (HDL) of 37 mg/dL, calculated low-density lipoprotein (LDL) of 86 mg/dL, triglycerides of 169 mg/dL, and non-HDL of 120 mg/dL. Severe hypertriglyceridemia has become a notable side effect of PEG-ASP containing treatment regimens. Patients are usually asymptomatic and although pancreatitis is rare, it has been reported. Clinicians need to have a strong clinical suspicion to check triglycerides in a timely manner. Usually, severe hypertriglyceridemia can occur three weeks after PEG-ASP administration which is hypothesized to be attributed to lipoprotein lipase (LPL) activity reduction. Genetic variants can also predispose to hypertriglyceridemia. Some studies discuss that Apo-E polymorphism can predispose these patients to severe hypertriglyceridemia. A case report on a gain of function (GOF) variant in the APOC-III gene illustrated severe hypertriglyceridemia after PEG-ASP treatment. PEG-ASP can also inhibit insulin production and release, and decreased insulin levels are hypothesized to inhibit LPL activity. Early recognition and management with dietary restrictions and medical therapy are vital to avoid complications. More research is needed to help identify risk factors for developing PEG-ASP-induced HTG and to provide guidance in management.