Methotrexate hepatotoxicity in children with leukemia

Area of Science:

• Pediatric Oncology
• Hepatology
• Pharmacology

Background:

• Maintenance chemotherapy with high-dose methotrexate is a standard treatment for acute lymphocytic leukemia (ALL) in children.
• Long-term methotrexate use can be associated with potential hepatotoxicity.
• Early detection of liver complications is crucial for managing treatment and preventing long-term sequelae.

Purpose of the Study:

• To investigate the prevalence of hepatic fibrosis in children with ALL receiving long-term, high-dose intravenous methotrexate.
• To evaluate the efficacy of standard liver function tests and technetium-sulfur-colloid scans in identifying methotrexate-induced liver injury.

Main Methods:

• Percutaneous liver biopsy was performed on seven children undergoing maintenance chemotherapy for ALL.
• Patients had received high-dose intravenous methotrexate for 1.5 to 2.5 years.
• Liver function tests and 99mtechnetium-sulfur-colloid scans were conducted prior to biopsy.

Main Results:

• Four out of seven children (57%) showed evidence of portal fibrosis on liver biopsy.
• An additional patient treated with oral methotrexate also exhibited portal fibrosis.
• Neither liver function tests nor 99mtechnetium-sulfur-colloid scans accurately predicted the presence of hepatic fibrosis.

Conclusions:

• Long-term, high-dose intravenous methotrexate therapy for pediatric ALL is associated with a significant risk of developing portal fibrosis.
• Clinical signs of liver disease and standard non-invasive tests were insufficient to detect this subclinical hepatic injury.
• Liver biopsy is essential for diagnosing methotrexate-induced hepatic fibrosis in this patient population, underscoring the need for careful monitoring.