title: Chronic liver disease related to 6-thioguanine in children with acute lymphoblastic leukaemia.
abstract: OBJECTIVE
  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.
authors.affiliation: Department of Child Health, Paediatric Liver Unit, King's College Hospital, Denmark Hill, SE5 9RS London, UK.
authors.forename: Ruth
authors.initials: R
authors.lastname: De Bruyne
authors.forename: Bernard
authors.initials: B
authors.lastname: Portmann
authors.forename: Marianne
authors.initials: M
authors.lastname: Samyn
authors.forename: Sanjay
authors.initials: S
authors.lastname: Bansal
authors.forename: Alex
authors.initials: A
authors.lastname: Knisely
authors.forename: Giorgina
authors.initials: G
authors.lastname: Mieli-Vergani
authors.forename: Anil
authors.initials: A
authors.lastname: Dhawan
mesh_terms: D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D001706:Biopsy; D056486:Chemical and Drug Induced Liver Injury; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008107:Liver Diseases / Q000000981:diagnostic imaging / Q000473:pathology; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000188:drug therapy*; D012189:Retrospective Studies; D013866:Thioguanine / Q000009:adverse effects* / Q000627:therapeutic use; D014463:Ultrasonography
chemical_list: D000964:Antimetabolites, Antineoplastic; D013866:Thioguanine