P0157 PP LIVER DISEASE RELATED TO 6-THIOGUANINE TREATMENT IN CHILDREN WITH ACUTE LYMPHOBLASTIC LEUKAEMIA.

Abstract

Introduction: Hepatosplenomegaly after chemotherapy in children with haematologic malignancies is a matter of concern. Common causes are recurrence of the disease, infections or drug toxicity. Review of the interim results of the MRC UK ALL 97/99 protocol comparing 6-Thioguanine (6TG) with 6-Mercaptopurine in the treatment of acute lymphoblastic leukaemia (ALL) has led to the discontinuation of the 6TG-arm because of evidence of hepatotoxicity, although no information is available on liver histology. Methods: We report our experience of 6 children (referred between June 1998 and July 2003), 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 5 boys and 1 girl. The presenting features were splenomegaly in all and hepatomegaly in 4 without stigmata of chronic liver disease. None of the patients had a history of gastrointestinal bleeding. Liver function tests (transaminases, prothrombin time, albumin and bilirubin) were abnormal in one patient (AST 80 IU/l). The median (range) platelet count was 95 (74–181) 109/l. Ultrasound of the liver was interpreted as showing fatty changes in all and confirmed splenomegaly. No varices were documented in the 3 children who underwent endoscopy. Microscopy in all patients revealed some distortion of the liver architecture and variable degrees of focal sinusoidal dilatation, perisinusoidal fibrosis and hepatocellular hyperplasia with poorly delineated nodules. Steatosis was found in a single case. These findings lay within the spectrum of nodular regenerative hyperplasia. ‘Lafora-like’ bodies were seen in 2 cases, previous parenchymal loss and reticulin collapse in another 2. All children at a median (range) follow up of 22 (4–36) months continue to have increasing splenomegaly and thrombocytopenia, suggestive of progressive portal hypertension. Conclusion: In conclusion liver disease after 6TG treatment is consistent with parenchymal as well as vascular damage and appears to be progressive. Close follow up is warranted in these patients.