High-dose methotrexate administration and acute liver damage in children treated for acute lymphoblastic leukemia. A prospective study.
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.
Locasciulli
A
A
Clinica Pediatrica, Università di Milano, Ospedale S. Gerardo, Monza, Italy.
Mura
R
R
Fraschini
D
D
Gornati
G
G
Scovena
E
E
Gervasoni
A
A
Uderzo
C
C
Masera
G
G
D000293:Adolescent; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use*; D001215:Asparaginase / Q000008:administration & dosage; D002648:Child; D002675:Child, Preschool; D003520:Cyclophosphamide / Q000008:administration & dosage; D003561:Cytarabine / Q000008:administration & dosage; D003630:Daunorubicin / Q000008:administration & dosage; D005260:Female; D006801:Humans; D006932:Hyperbilirubinemia / Q000139:chemically induced; D007223:Infant; D008099:Liver / Q000473:pathology; D008107:Liver Diseases / Q000097:blood / Q000453:epidemiology / Q000209:etiology*; D008111:Liver Function Tests; D008297:Male; D015122:Mercaptopurine / Q000008:administration & dosage; D008727:Methotrexate / Q000008:administration & dosage / Q000009:adverse effects*; D009336:Necrosis; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D011241:Prednisone / Q000008:administration & dosage; D015995:Prevalence; D011446:Prospective Studies; D014750:Vincristine / Q000008:administration & dosage
D003561:Cytarabine; D014750:Vincristine; D003520:Cyclophosphamide; D015122:Mercaptopurine; D001215:Asparaginase; D011241:Prednisone; D008727:Methotrexate; D003630:Daunorubicin