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document
Toxicity and efficacy of 6-thioguanine versus 6-mercaptopurine in childhood lymphoblastic leukaemia : a randomised trial . BACKGROUND 6-mercaptopurine has been a standard component of long-term continuing treatment for childhood lymphoblastic leukaemia , whereas 6-thioguanine has been mainly used for intensification courses . Since preliminary data have shown that 6-thioguanine is more effective than 6-mercaptopurine , we compared the efficacy and toxicity of the two drugs for childhood lymphoblastic leukaemia . METHODS Consecutive children with lymphoblastic leukaemia diagnosed in the UK and Ireland between April , 1997 , and June , 2002 , were randomly assigned either 6-thioguanine ( 750 patients ) or 6-mercaptopurine ( 748 patients ) during interim maintenance and continuing therapy . All patients received 6-thioguanine during intensification courses . We analysed event-free and overall survival on an intention-to-treat basis . We obtained toxicity data using an adverse-event reporting system , with follow-up questionnaires to seek detailed information for specific toxicities . This trial is registered with the International Standard Randomised Controlled Number 26727615 with the name ALL97 . FINDINGS After a median follow up of 6 years , there was no difference in event-free or overall survival between the two treatment groups . Although 6-thioguanine conferred a significantly lower risk of isolated CNS relapse than did 6-mercaptopurine ( odds ratio [ OR ] 0.53 , 95 % CI 0.30-0.92 , p=0.02 ) , the benefit was offset by an increased risk of death in remission ( 2.22 , 1.20-4.14 , p=0.01 ) , mainly due to infections during continuing therapy . Additionally , 95 patients developed veno-occlusive disease of the liver . Of these , 82 were randomly assigned 6-thioguanine , representing 11 % of all 6-thioguanine recipients . On long-term follow-up , about 5 % of 6-thioguanine recipients have evidence of non-cirrhotic portal hypertension due to periportal liver fibrosis or nodular regenerative hyperplasia . INTERPRETATION Compared with 6-mercaptopurine , 6-thioguanine causes excess toxicity without an overall benefit . 6-mercaptopurine should remain the thiopurine of choice for continuing therapy of childhood lymphoblastic leukaemia .
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Intervention_Pharmacological
6-thioguanine
28324
Intervention_Pharmacological
6-mercaptopurine
28325
Intervention_Pharmacological
6-mercaptopurine
28326
Intervention_Pharmacological
6-thioguanine
28327
Intervention_Pharmacological
6-thioguanine
28328
Intervention_Pharmacological
6-mercaptopurine
28329
Intervention_Pharmacological
6-thioguanine
28330
Intervention_Pharmacological
6-mercaptopurine
28331
Intervention_Pharmacological
6-thioguanine
28332
Intervention_Pharmacological
6-thioguanine
28333
Intervention_Pharmacological
6-mercaptopurine
28334
Intervention_Pharmacological
6-thioguanine
28335
Intervention_Pharmacological
6-thioguanine
28336
Intervention_Pharmacological
6-thioguanine
28337
Intervention_Pharmacological
6-mercaptopurine
28338
Intervention_Pharmacological
6-thioguanine
28339
Intervention_Pharmacological
6-mercaptopurine
28340
Outcome_Other
Toxicity and efficacy
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Outcome_Other
efficacy and toxicity
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Outcome_Mortality
event-free and overall survival
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Outcome_Adverse-effects
toxicity
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Outcome_Mortality
event-free or overall survival
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Outcome_Physical
CNS relapse
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Outcome_Mortality
risk of death
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Outcome_Adverse-effects
veno-occlusive disease of the liver
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Outcome_Physical
non-cirrhotic portal hypertension
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Outcome_Adverse-effects
toxicity
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Outcome_Other
overall benefit
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Participant_Age
childhood
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Participant_Condition
lymphoblastic leukaemia
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Participant_Age
childhood
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Participant_Condition
lymphoblastic leukaemia
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Participant_Age
children
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Participant_Condition
lymphoblastic