The effect of L-asparaginase on lipid metabolism during induction chemotherapy of childhood lymphoblastic leukaemia

Abstract

L-asparaginase is an effective antileukaemic drug and a potent inhibitor of hepatic protein synthesis. Its effect on lipid metabolism was studied in two cohorts of children with ALL, one of whom received L-asparaginase concomitantly with three other drugs (protocol BFM 79). In the second protocol (BFM 83) administration of L-asparaginase was arranged to follow the other three drugs in time sequence. The two major findings of this study were elevated serum levels of total cholesterol and a strong increase in serum triglycerides. The former change was due to an increase in alpha-cholesterol and could not be attributed to L-asparaginase because it was also found following protocol BFM 83 before the administration of the drug. Elevations of total triglycerides were due to high levels of exogenous chylomicron bound triglycerides and were limited in occurrence almost exclusively to the period of L-asparaginase monotherapy. Hypothyroidism was excluded as a possible pathogenetic mechanism. These changes in lipid metabolism induced by L-asparaginase during intensive remission induction chemotherapy are fully reversible.

Long-term Cardiovascular Toxicity in Children, Adolescents, and Young Adults Who Receive Cancer Therapy: Pathophysiology, Course, Monitoring, Management, Prevention, and Research Directions

“…Further long-term clinical trials are needed to assess the benefits, risks, limitations, and cost-effectiveness of universal and comprehensive childhood cholesterol screening. 370 Among different treatment modalities for childhood cancers (Table 1), radiation exposure in the presence or absence of GH deficiency 276,366 and treatment with corticosteroids 371,372 have been proposed as possible mechanisms leading to the abnormal lipid profile in cancer survivors. A number of chemotherapeutic agents have also been implicated in dyslipidemia.…”

PEG-asparaginase induced severe hypertriglyceridemia

“…The proposed mechanisms of ASP-induced HTG are decreased lipoprotein lipase activity (15), which may result in elevated exogenous chylomicrons (16), and increased endogenous very-low-density lipoprotein (VLDL) synthesis (5). Additionally, it's been suggested that ASP may cause a disturbance in lipoprotein metabolism (17).…”

“…The latter showed a significant increase of TG and chylomicrons but not of total cholesterol. The authors concluded that ASP was responsible exclusively for the increase of TG, likely by the enrichment of exogenous chylomicrons (16). Furthermore, Parson reported an elevation of TG mainly due to endogenous VLDL production during ASP therapy and increased cholesterol while receiving steroids (5).…”

Pharmacological and clinical evaluation of l-asparaginase in the treatment of leukemia

“…While many patients have had elevation in blood ammonia levels, but a correlation between ammonia levels and degree of toxicity has not been firmly established. Cremer et al [173] studied the effect of l-asparaginase on lipid metabolism during induction chemotherapy of childhood lymphoblastic leukemia and found changes in serum lipid. An account of comparative induction toxicity of native and PEG-l-asparaginase has been tabulated in Table 7.…”