Long‐term Follow‐up of Children With 6‐Thioguanine‐related Chronic Hepatoxicity Following Treatment for Acute Lymphoblastic Leukaemia

Abstract

6-Thioguanine (6-TG) therapy in childhood acute lymphoblastic leukaemia results in chronic hepatotoxicity and portal hypertension. We report follow-up data in a cohort of 10 children with acute lymphoblastic leukaemia and 6-TG-related hepatotoxicity described initially in 2006. Clinically significant portal hypertension was present in the majority of patients several years after cessation of 6-TG treatment. These data reflect the natural history of noncirrhotic portal hypertension and emphasises the need to incorporate ongoing surveillance in the transition arrangement to adult services in this select group of patients.

Predictors of hepatotoxicity and pancreatitis in children and adolescents with acute lymphoblastic leukemia treated according to contemporary regimens

“…However, rare treatment‐related mortality from hepatobiliary toxicity during induction and a subtle impact of dose modifications on survival may not be evident in a single‐institution study such as this. Moreover, both toxicities confer potential for significant burden from acute and long‐term comorbidity, such as feeding intolerance, endocrine abnormalities, and hepatobiliary dysfunction . Although it is unclear that comorbidities noted in long‐term follow‐up are due to acute TRTs, it is likely that they play a role.…”

“…Moreover, both toxicities confer potential for significant burden from acute and long-term comorbidity, such as feeding intolerance, endocrine abnormalities, and hepatobiliary dysfunction. 27,30,[32][33][34][35][36] Although it is unclear that comorbidities noted in long-term follow-up 37 are due to acute TRTs, it is likely that they play a role. Of note, risk for hepatotoxicity and pancreatitis continued throughout maintenance as well.…”

Thioguanine-Related Chronic Hepatotoxicity in a Child with Acute Myeloid Leukemia: A Case Report and Review

“…Rawat ve ark. ortanca 85 ay (64-112 ay) süreyle izledikleri 10 hastanın 7'sinde portal hipertansiyon geliştiğini ve bunların çok azında tedavi kesildikten sonra tam düzelme olduğunu bildirmişlerdir (12).…”

“…6-TG kullanan ALL'li hastalarda ilaç kullanımının kesilmesi ile düzelen hepatik veno-oklüziv hastalık (VOH) oluştuğu gösterilmiştir. Ancak, son çalışmalarda 6-TG'ye bağlı karaciğer etkileniminin ilerleyerek kronik hepatotoksisite ve portal hipertansiyona yol açabileceği bildirilmektedir (9)(10)(11)(12).…”

Etiology and Management of Hemorrhagic Complications of Portal Hypertension in Children

“…Well-tolerated variceal bleeding and hypersplenism have been reported in this syndrome mainly described in Asian patients [30]. Recent reports coming from western-country children surviving from acute leukemia treated with 6-thioguanin highlights the alleged toxin exposure as one of the possible causes of the endothelial damage [31]. Management of these patients follows the same rules applied for portal vein obstruction.…”