{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T06:51:59Z","timestamp":1760079119846},"reference-count":23,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2005,8,5]],"date-time":"2005-08-05T00:00:00Z","timestamp":1123200000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2006,2]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>To group patients receiving treatment for acute lymphoblastic leukemia (ALL) according to their oral mercaptopurine (6\u2010MP) metabolite levels and to establish cut\u2010off points to screen for potential poor clinical outcome.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedure<\/jats:title><jats:p>Methodological study using 6\u2010MP metabolite levels from 48 adolescent ALL patients enrolled in a multicenter adherence study. Cluster analysis was the primary analytical technique. We used two validation methods (a split\u2010sampling and a simulation technique) for validating the results.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Four clusters were retained in our initial analysis using our first group of patients (n\u2009=\u200927). Three clusters (labeled 1, 2, and 4) exhibited the expected negative correlation between the two metabolites, that is, \u201chigh\u201d values of one were associated with \u201clow\u201d values of the other. One cluster (labeled 3) had \u201clow\u201d levels for both TGN and MMP. Five of the 27 adolescents had their 6\u2010MP \u201cheld\u201d during the study. Post\u2010hoc examination of the results revealed that all five grouped in Cluster 3 during the time that their medications were stopped, but grouped in other clusters at other times. The median ANC was highest in Cluster 3, consistent with low therapeutic drug levels. Parameters were reproducible with both validation methods. Values below the respective 75th centile for <jats:italic>both<\/jats:italic> TGN and MMP in Cluster 3 for the complete sample (n\u2009=\u200948) are suggested as representing a potentially higher risk for relapse.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study provides an objective method for identifying patients at risk for treatment failure due to suboptimal 6\u2010MP therapy; the clinical significance of this approach should be examined in future studies. \u00a9 2005 Wiley\u2010Liss, Inc.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.20518","type":"journal-article","created":{"date-parts":[[2005,8,5]],"date-time":"2005-08-05T22:16:41Z","timestamp":1123280201000},"page":"187-192","source":"Crossref","is-referenced-by-count":14,"title":["How low is too low? Use of cluster analysis to define low levels of mercaptopurine metabolites"],"prefix":"10.1002","volume":"46","author":[{"given":"Fatoumata","family":"Traore","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mary Ann","family":"O'Riordan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Myers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Karen","family":"Groth","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ahna","family":"Hoff","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Angiolillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Susan","family":"Rheingold","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dennis","family":"Drotar","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eric","family":"Kodish","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,12,20]]},"reference":[{"key":"e_1_2_6_2_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V93.9.2817"},{"key":"e_1_2_6_3_2","doi-asserted-by":"crossref","first-page":"1816","DOI":"10.1200\/JCO.1989.7.12.1816","article-title":"Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia","volume":"12","author":"Lennard L","year":"1989","journal-title":"J Clin Oncol"},{"key":"e_1_2_6_4_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF02220605"},{"key":"e_1_2_6_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0928-0987(99)00027-5"},{"key":"e_1_2_6_6_2","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2002-08-2372"},{"key":"e_1_2_6_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(94)92400-7"},{"key":"e_1_2_6_8_2","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.1995.13.2.345"},{"key":"e_1_2_6_9_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002800050816"},{"key":"e_1_2_6_10_2","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1007\/BF00279977","article-title":"Intraindividual variation in 6\u2010mercaptopurine pharmacokinetics during oral maintenance therapy of children with acute lymphoblastic leukaemia","volume":"40","author":"Lafolie P","year":"1991","journal-title":"Eur J Clin Pharmacol"},{"key":"e_1_2_6_11_2","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/91.23.1983"},{"key":"e_1_2_6_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2402373"},{"key":"e_1_2_6_13_2","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.1995.450"},{"key":"e_1_2_6_14_2","volume-title":"Cluster analysis, in Multivariate data analysis with readings","author":"Hair JF","year":"1995"},{"key":"e_1_2_6_15_2","doi-asserted-by":"publisher","DOI":"10.1002\/1097-0142(19860901)58:5<1179::AID-CNCR2820580534>3.0.CO;2-E"},{"key":"e_1_2_6_16_2","doi-asserted-by":"crossref","first-page":"551","DOI":"10.1093\/clinchem\/44.3.551","article-title":"Simultaneous determination of 6\u2010thioguanine and methyl 6\u2010mercaptopurine nucleotides of azathioprine in red blood cells by HPLC","volume":"44","author":"Dervieux T","year":"1998","journal-title":"Clin Chem"},{"key":"e_1_2_6_17_2","doi-asserted-by":"crossref","first-page":"2511","DOI":"10.1093\/clinchem\/44.12.2511","article-title":"Identification of 6\u2010methylmercaptopurine derivative formed during acis hydrolysis of thiopurine nucleotides in erythrocytes using liquid chromatography\u2010mass spectrometry, infrared spectroscopy and nuclear madnetic resonance assay","volume":"44","author":"Dervieux T","year":"1998","journal-title":"Clin Chem"},{"key":"e_1_2_6_18_2","volume-title":"Two factor index of social position","author":"Hollingshead A","year":"1975"},{"key":"e_1_2_6_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/adc.76.4.365"},{"key":"e_1_2_6_20_2","doi-asserted-by":"publisher","DOI":"10.1097\/00007691-199708000-00003"},{"key":"e_1_2_6_21_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1986.178"},{"key":"e_1_2_6_22_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM198304283081705"},{"key":"e_1_2_6_23_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1365-2125.1997.t01-1-00607.x"},{"key":"e_1_2_6_24_2","doi-asserted-by":"publisher","DOI":"10.1038\/clpt.1994.4"}],"container-title":["Pediatric Blood &amp; 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