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Event\u2010free survival (<jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content>) for patients heterozygous for the more common <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content>*1\/*3A<\/jats:italic> variant allele (<jats:italic>n<\/jats:italic>\u00a0=\u00a099, 5\u2010year <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> 88%) was better than for both wild\u2010type <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content>*1\/*1<\/jats:italic> (<jats:italic>n<\/jats:italic>\u00a0=\u00a01206, <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> 80%, <jats:italic>P\u00a0<\/jats:italic>=\u00a00\u00b705) and <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content>*1\/*3C<\/jats:italic> patients (<jats:italic>n<\/jats:italic>\u00a0=\u00a017, <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> 53%, <jats:italic>P\u00a0<\/jats:italic>=\u00a00\u00b7002); outcomes supported by a multivariate Cox regression analysis. Poor compliance without subsequent clinician intervention was associated with a worse <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> (<jats:italic>P\u00a0<\/jats:italic>=\u00a00\u00b702) and such non\u2010compliance may have contributed to the poorer outcome for <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content>*1\/*3C<\/jats:italic> patients. Patients prescribed escalated doses had a worse <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> (<jats:italic>P\u00a0<\/jats:italic>=\u00a00\u00b704), but there was no difference in <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> by dose intensity or duration of cytopenias. In contrast to reports from some <jats:styled-content style=\"fixed-case\">USA<\/jats:styled-content> and Nordic trials, <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> heterozygosity was not associated with a higher rate of second cancers. In conclusion, <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content>*1\/*3A<\/jats:italic> heterozygotes had a better <jats:styled-content style=\"fixed-case\">EFS<\/jats:styled-content> than <jats:italic><jats:styled-content style=\"fixed-case\">TPMT<\/jats:styled-content><\/jats:italic> wild\u2010type patients. Thiopurine induced cytopenias were not detrimental to treatment outcome.<\/jats:p>","DOI":"10.1111\/bjh.13240","type":"journal-article","created":{"date-parts":[[2014,11,29]],"date-time":"2014-11-29T06:51:37Z","timestamp":1417243897000},"page":"228-240","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":48,"title":["Thiopurine dose intensity and treatment outcome in childhood lymphoblastic leukaemia: the influence of thiopurine methyltransferase pharmacogenetics"],"prefix":"10.1111","volume":"169","author":[{"given":"Lynne","family":"Lennard","sequence":"first","affiliation":[{"name":"Academic Unit of Clinical Pharmacology University of Sheffield Sheffield UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cher S.","family":"Cartwright","sequence":"additional","affiliation":[{"name":"Academic Unit of Clinical Pharmacology University of Sheffield Sheffield 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