Characterization of hypertriglyceridemia induced by L-asparaginase therapy for acute lymphoblastic leukemia and malignant lymphoma.

Plasma lipids and apolipoproteins were determined in 19 children with acute lymphoblastic leukemia (ALL) or malignant lymphoma (ML) who were treated by L-asparaginase with prednisolone and vincristine. Extreme hypertriglyceridemia, i.e., over 10,000 mg/l of the maximum serum triglyceride concentration, was induced in 8 patients; these concentrations were not over 10,000 mg/l in the remaining 11 patients. The possibility was raised that the apolipoprotein E (apoE) isoform apoE4 (epsilon 4) participated in the induction of extreme hypertriglyceridemia, since the frequency of the apoE4/E3 phenotype in the patients with extreme hypertriglyceridemia was higher compared to those in the patients without extreme hypertriglyceridemia and control subjects (n = 248). The acute and severe hypertriglyceridemia was induced at 8 to 14 days after the end of the L-asparaginase therapy, with an earlier remarkable increase in the apoCIII/apoCII ratio and an extreme decrease of fibrinogen concentrations (a marker of the protein productivity of the liver). It is well known that apoCII and apoCIII have possible functions as an activator and an inhibitor of lipoprotein lipase (LPL), respectively. The extreme increase in the apoCIII/apoCII ratio could be one of the reasons for the accumulation of triglyceride-rich lipoproteins in plasma.