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Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia

Mercaptopurine has been used in continuing treatment for childhood acute lymphoblastic leukaemia since the mid 1950s. Recent advances in the understanding of thiopurine pharmacology indicated thioguanine might be more effective than mercaptopurine. The US and UK cooperative groups began randomized t...

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Autores principales: Escherich, Gabriele M, Richards, Sue, Stork, Linda C, Vora, Ajay J
Formato: Online Artículo Texto
Lenguaje:English
Publicado: 2011
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112460/
https://www.ncbi.nlm.nih.gov/pubmed/21372841
http://dx.doi.org/10.1038/leu.2011.37
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author Escherich, Gabriele M
Richards, Sue
Stork, Linda C
Vora, Ajay J
author_facet Escherich, Gabriele M
Richards, Sue
Stork, Linda C
Vora, Ajay J
author_sort Escherich, Gabriele M
collection PubMed
description Mercaptopurine has been used in continuing treatment for childhood acute lymphoblastic leukaemia since the mid 1950s. Recent advances in the understanding of thiopurine pharmacology indicated thioguanine might be more effective than mercaptopurine. The US and UK cooperative groups began randomized thiopurine trials and agreed prospectively to a meta-analysis. All randomized trials of thioguanine versus mercaptopurine were sought and data on individual patients were analysed by standard methods. Combining three trials (from US, UK and Germany), the overall event free survival (EFS) was not significantly improved with thioguanine (Odds ratio (OR) = 0.89; 95% confidence interval 0·78–1·03). Apparent differences in results between trials may be partly explained by the different types of patients studied. The larger treatment effect reported in males in the US trial was confirmed in the other trials. There was heterogeneity between sex/age subgroups (p=0·001), with significant EFS benefit of thioguanine only seen for males aged under 10 years old (OR=0·70; 0·58–0·84), although this did not result in a significant difference in overall survival (OR=0·83; 0·62–1·10). Additional toxicity occurs with thioguanine. Mercaptopurine remains the standard thiopurine of choice, but further study of thioguanine may be warranted to determine whether it may benefit particular subgroups.
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spelling pubmed-31124602011-12-01 Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia Escherich, Gabriele M Richards, Sue Stork, Linda C Vora, Ajay J Leukemia Article Mercaptopurine has been used in continuing treatment for childhood acute lymphoblastic leukaemia since the mid 1950s. Recent advances in the understanding of thiopurine pharmacology indicated thioguanine might be more effective than mercaptopurine. The US and UK cooperative groups began randomized thiopurine trials and agreed prospectively to a meta-analysis. All randomized trials of thioguanine versus mercaptopurine were sought and data on individual patients were analysed by standard methods. Combining three trials (from US, UK and Germany), the overall event free survival (EFS) was not significantly improved with thioguanine (Odds ratio (OR) = 0.89; 95% confidence interval 0·78–1·03). Apparent differences in results between trials may be partly explained by the different types of patients studied. The larger treatment effect reported in males in the US trial was confirmed in the other trials. There was heterogeneity between sex/age subgroups (p=0·001), with significant EFS benefit of thioguanine only seen for males aged under 10 years old (OR=0·70; 0·58–0·84), although this did not result in a significant difference in overall survival (OR=0·83; 0·62–1·10). Additional toxicity occurs with thioguanine. Mercaptopurine remains the standard thiopurine of choice, but further study of thioguanine may be warranted to determine whether it may benefit particular subgroups. 2011-03-04 2011-06 /pmc/articles/PMC3112460/ /pubmed/21372841 http://dx.doi.org/10.1038/leu.2011.37 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
spellingShingle Article
Escherich, Gabriele M
Richards, Sue
Stork, Linda C
Vora, Ajay J
Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
title Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
title_full Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
title_fullStr Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
title_full_unstemmed Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
title_short Meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
title_sort meta-analysis of randomized trials comparing thiopurines in childhood acute lymphoblastic leukaemia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3112460/
https://www.ncbi.nlm.nih.gov/pubmed/21372841
http://dx.doi.org/10.1038/leu.2011.37
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