High-dose methotrexate administration and acute liver damage in children treated for acute lymphoblastic leukemia. A prospective study

Haematologica. 1992 Jan-Feb;77(1):49-53.

Abstract

Background: Methotrexate-induced hepatotoxicity following chronic low-dose administration has been extensively reported. Current protocols now include high-dose methotrexate (HDMTX), but there are few studies providing data on its acute hepatotoxicity in childhood leukemia.

Methods: To evaluate the prevalence of HDMTX-induced acute hepatotoxicity, sixty-eight consecutive children with ALL were prospectively studied from diagnosis to the end of HDMTX courses with biochemical and clinical evaluation performed at regular intervals.

Results: Prevalence of HDMTX-induced acute hepatotoxicity was 1.47% (1/68 patients). ALT values did not change in 22% (15/68) and decreased in 76.4% (52/68) after HDMTX infusion. Mean ALT levels calculated in all the patients decreased significantly during HDMTX administration when compared to the values reached during induction (p less than 0.0001). Direct hyperbilirubinemia was present only in the child with HDMTX-related hepatotoxicity.

Conclusions: The use of HDMTX in the treatment of childhood ALL is not associated with major evidence of direct acute hepatotoxic effects, while it may modify the pattern of preexisting liver diseases.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Antineoplastic Combined Chemotherapy Protocols / therapeutic use*
  • Asparaginase / administration & dosage
  • Child
  • Child, Preschool
  • Cyclophosphamide / administration & dosage
  • Cytarabine / administration & dosage
  • Daunorubicin / administration & dosage
  • Female
  • Humans
  • Hyperbilirubinemia / chemically induced
  • Infant
  • Liver / pathology
  • Liver Diseases / blood
  • Liver Diseases / epidemiology
  • Liver Diseases / etiology*
  • Liver Function Tests
  • Male
  • Mercaptopurine / administration & dosage
  • Methotrexate / administration & dosage
  • Methotrexate / adverse effects*
  • Necrosis
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / complications
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Prednisone / administration & dosage
  • Prevalence
  • Prospective Studies
  • Vincristine / administration & dosage

Substances

  • Cytarabine
  • Vincristine
  • Cyclophosphamide
  • Mercaptopurine
  • Asparaginase
  • Prednisone
  • Methotrexate
  • Daunorubicin

Supplementary concepts

  • AIEOP acute lymphoblastic leukemia protocol