Veno-occlusive disease in patients receiving thiopurines during maintenance therapy for childhood acute lymphoblastic leukaemia.
The case records of 99 consecutive children with acute lymphoblastic leukaemia who received either 6-thioguanine (6-TG) or 6-mercaptopurine (6-MP) as maintenance therapy for at least 1 year were reviewed for hepatic veno-occlusive disease (VOD). Overall, 12% of those on 6-TG developed VOD (all boys). Isolated persistent thrombocytopenia appeared to be the earliest indicator of incipient VOD. Multivariate analysis identified male sex and 6-TG as risk factors. In all cases, VOD was mild and reversible on withdrawing 6-TG or replacing it with 6-MP. The data implicate a sex-linked polymorphic variation in xenobiotic pathways of thiopurine metabolism in the pathogenesis of VOD.
D000964:Antimetabolites, Antineoplastic / Q000009:adverse effects* / Q000627:therapeutic use; D002648:Child; D002675:Child, Preschool; D005260:Female; D006504:Hepatic Veno-Occlusive Disease / Q000139:chemically induced*; D006801:Humans; D016015:Logistic Models; D008297:Male; D015122:Mercaptopurine / Q000009:adverse effects / Q000627:therapeutic use; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000150:complications / Q000188:drug therapy*; D012737:Sex Factors; D013866:Thioguanine / Q000009:adverse effects* / Q000627:therapeutic use; D015262:Xenobiotics / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D015262:Xenobiotics; D015122:Mercaptopurine; D013866:Thioguanine