Liver function studies in children with acute lymphocytic leukemia after cessation of therapy

Abstract

We investigated liver function in 27 children with acute lymphocytic leukemia (ALL) after cessation of therapy. Induction therapy consisted of prednisolone+vincristine (VP regimen) alone (16 patients) or with addition of daunorubicin (4 patients) or L-asparaginase (7 patients). Patients treated with VP regimen received short courses of VP regimen every 12 weeks for the first year of maintenance. Twenty-five patients remained in first complete remission and had completed 3-year maintenance therapy with methotrexate (MTX) and 6-mercaptopurine (6-MP) 1-7 years prior to this study. Twenty-three patients had received transfusions of packed red blood cells or fresh whole blood (1-11 units; median: 2 units) but none had evidence of either hepatitis B or hepatitis C. Alanine aminotransferase (ALT), which was measured every 3 months during maintenance therapy, had values more than three times the upper limit of the normal range in 25% of the measurements in more than half of the patients. However, by 3 months after the completion of maintenance therapy, ALT had normalized in all patients and remained normal in all but two patients until the time of this study. Serum bilirubin, serum albumin, and prothrombin time were all within normal limits. Fasting and 2-hour postprandial total serum bile acids were high in 5 of 13 patients and in 6 of 13 patients, respectively. The ratio of cholic acids+deoxycholic acids to chenodeoxycholic acids+lithocholic acids was below 1 in all but two patients, whereas this ratio was above 1 in all controls. Our bile acid profile results indicate the necessity of careful long-term follow-up of survivors of ALL treated with hepatotoxic chemotherapy during childhood.

Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

“…6MP and MTX are hepatotoxic and 2-fold elevations or more of serum aminotransferases are frequent,100,146,152–156 but usually normalize within a few weeks after discontinuation of maintenance therapy 146,153. Hypoglycemic episodes during fasting157–160 have been associated with high levels of methylated 6MP metabolites 161.…”

“…Accordingly, most study groups do not recommend dose reductions in case of high aminotransferase levels48 unless accompanied by biochemical evidence of severe hepatic dysfunction, that is, bilirubin 3 times above the upper normal limit and/or coagulation factor II-VII-X <0.50 IU/L. Such patients should be explored for other causes, including hepatotropic vira (eg, B or C virus153,154), veno-occlusive syndrome (VOD), or Gilbert syndrome with reduced glucuronyltransferase activity and elevated unconjugated bilirubin.…”

Advances in individual prediction of methotrexate toxicity: a review

“…The most commonly encountered toxicities during continuation therapy for ALL and NHL are bone‐marrow suppression (which is actually the target rather than a side effect) and hepatotoxicity, which, at least in children with leukaemia, is generally mild, and almost never leads to significant liver fibrosis (Halonen et al , 2003). The risk of hepatotoxicity is especially high among patients who are carriers of viral hepatitis virus (Bessho et al , 1994; Farrow et al , 1997).…”

L-Carnitine Ameliorates L-Asparaginase-Induced Acute Liver Toxicity in Steatotic Rat Livers

“…Steatotic-transformed livers are more susceptible to the side effects of chemotherapy than nonsteatotic livers [10], and patients with preexisting liver disorders, such as steatosis or hepatitis [11,12], experience more often complications and even fatal liver failure after chemotherapy [13]. L -Asparaginase treatment is associated with increased hepatocyte damage, which is reflected by higher serum values of liver enzymes like alanine aminotransferase (ALT) [14,15] and aspartate aminotransferase (AST) [15], and an increase in lipid components [16,17,18] and steatosis [19,20]. Adults experience more hepatotoxic reactions to L -asparaginase therapy than pediatric patients receiving comparable doses [4].…”