Chronic liver disease related to 6-thioguanine in children with acute lymphoblastic leukaemia

J Hepatol. 2006 Feb;44(2):407-10. doi: 10.1016/j.jhep.2005.06.020. Epub 2005 Jul 18.

Abstract

Background/aims: The United Kingdom (UK) acute lymphoblastic leukaemia (ALL) 97/99 clinical trial compared 6-mercaptopurine (6MP) with 6-thioguanine (6TG) as maintenance therapy for childhood ALL. Review of interim results has led to discontinuation of the 6TG arm.

Methods: We report six children with ALL, who presented with splenomegaly after a median (range) treatment duration of 12 (6-22) months. All these children were treated in the 6TG-arm.

Results: The median (range) age at presentation was 6.6 (3.2-11.5) years. There were five boys. The presenting features were splenomegaly in all and hepatomegaly in four. AST was abnormal in one (80 IU/l, normal range 10-50). Abdominal sonography showed an altered texture of the liver parenchyma and confirmed splenomegaly. Microscopy showed findings within the spectrum of occlusive venopathy and nodular regenerative hyperplasia (NRH). After a median (range) follow-up of 23 (4-36) months splenomegaly and thrombocytopenia, suggestive of progressive portal hypertension, continue to worsen in all children.

Conclusions: 6TG is associated with chronic hepatic toxicity and progressive portal hypertension on follow-up. Microscopy showed NRH in all patients with features in keeping with an intrahepatic occlusive venopathy and variable parenchymal atrophy and loss.

Publication types

  • Comparative Study

MeSH terms

  • Antimetabolites, Antineoplastic / adverse effects*
  • Antimetabolites, Antineoplastic / therapeutic use
  • Biopsy
  • Chemical and Drug Induced Liver Injury*
  • Child
  • Child, Preschool
  • Chronic Disease
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Liver Diseases / diagnostic imaging
  • Liver Diseases / pathology
  • Male
  • Precursor Cell Lymphoblastic Leukemia-Lymphoma / drug therapy*
  • Retrospective Studies
  • Thioguanine / adverse effects*
  • Thioguanine / therapeutic use
  • Ultrasonography

Substances

  • Antimetabolites, Antineoplastic
  • Thioguanine