Related Experiment Videos
[Acute hepatotoxicity with intermediate-dose methotrexate in children with leukemia and non-Hodgkin's lymphoma]
P Exadaktylos1, T Reiss, R Schobess
1Abteilung Pädiatrische Hämatologie, Onkologie und Immunologie, Martin-Luther-Universität Halle-Wittenberg.
Insights
Methotrexate (MTX) infusions can cause liver damage in children, indicated by elevated liver enzymes like ALAT and GGTP. Pre-existing liver conditions and MTX dosage influence the severity of hepatotoxicity.
Area of Science:
- Pediatric Oncology
- Hepatology
- Pharmacology
Background:
- Methotrexate (MTX) is a common chemotherapy agent used in treating various childhood cancers.
- Assessing the acute hepatotoxicity of MTX is crucial for patient management and monitoring.
- Understanding factors influencing MTX-induced liver injury is essential for optimizing treatment protocols.
Purpose of the Study:
- To investigate the acute hepatotoxicity of methotrexate (MTX) infusions in pediatric patients.
- To correlate liver enzyme activity with MTX dosage, infusion time, and patient diagnosis.
- To identify reliable biomarkers for predicting MTX-induced hepatocellular damage.
Main Methods:
- Retrospective analysis of 49 children treated with 219 MTX infusions between 1988 and 1992.
- Monitoring of serum liver enzymes (ASAT, ALAT, GGTP) from day -1 to day 5 of MTX treatment.
- Correlation analysis of enzyme activity with MTX dosage, infusion duration, and area under the curve (AUC).
Main Results:
- Elevated liver enzyme activity (ASAT, ALAT, GGTP) correlated with the intensity and type of hepatocellular damage.
- ALAT and GGTP were identified as sensitive predictors of hepatocellular lesion.
- High enzyme activity prior to MTX indicated pre-existing liver damage.
- Serum hepatotoxicity showed a strong correlation with the AUC of MTX.
Conclusions:
- Acute MTX hepatotoxicity in children is characterized by increased serum liver enzymes.
- GGTP and ALAT are sensitive indicators of MTX-induced liver injury.
- Pre-existing liver conditions and MTX exposure levels (AUC) are key factors in MTX hepatotoxicity.
Abstract:
In the period of 1.1.1988 to 1.5.1992 49 children, 28 boys and 21 girls, were treated with 219 MTX infusions. The acute hepatotoxicity was investigated from day--1 to day 5 of treatment duration. 30 patients suffered of a ALL, 6 of a relapse of a ALL, 3 of a ANLL and 10 of a NHL. We studied the MTX dosage and the infusion time. At all patients the determination of the activity of the liver enzymes ASAT, ALAT and GGTP in the serum took place according to the treatment protocol. The increase of enzymes activity correlated with the intensity and kind of hepatocellular damage. Partly the extreme increase of lesion parameters is not the expression of an irreversible cytonecrosis. Beside the ALAT also the GGPT is a sensitive predictor of hepatocellular lesion. The high enzyme activity before the MTX application is a indicator of a preexistent cell damage of the liver. The hepatotoxicity measured in the serum was highly correlated with the AUC.