{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T02:21:49Z","timestamp":1788142909695,"version":"build-2803163510"},"reference-count":10,"publisher":"American Society of Hematology","issue":"8","content-domain":{"domain":["ashpublications.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2003,10,15]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The German cooperative study group for childhood acute lymphoblastic leukemia (COALL-92) was designed to examine the clinical effectiveness of thioguanine (TG) versus mercaptopurine (MP) in maintenance treatment of childhood acute lymphoblastic leukemia (ALL) in a randomized multicenter trial. TG and MP are prodrugs and have to be converted intracellularly to 6-thioguanine nucleotides (TGNs) for cytostatic activity. TG is converted into TGN in fewer steps and has been shown to be more cytotoxic in equimolar doses in vitro compared with 6-MP. Therefore, a higher effectiveness of TG in maintenance treatment was postulated. Of 521 patients enrolled into the protocol, 474 were randomized to receive either MP or TG during maintenance therapy in a daily oral dose. After a median observation time of 6.6 years, the probability of event-free survival was 79% \u00b1 3% for the MP group (238 children) and 78% \u00b1 3% in the TG group (236 patients). In spite of TGN levels, exceeding those of the MP group 7 times, treatment with TG did not improve the outcome but was more complicated to handle due to a specific toxicity profile of prolonged myelosuppression with marked thrombocytopenia. Therefore, MP should remain the preferred drug for maintenance treatment of ALL, unless other studies demonstrate superiority of TG in larger trials or selected patient groups.<\/jats:p>","DOI":"10.1182\/blood-2002-08-2372","type":"journal-article","created":{"date-parts":[[2003,7,8]],"date-time":"2003-07-08T00:23:14Z","timestamp":1057623794000},"page":"2736-2740","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":72,"title":["Thioguanine offers no advantage over mercaptopurine in maintenance treatment of childhood ALL: results of the randomized trial COALL-92"],"prefix":"10.1182","volume":"102","author":[{"given":"Do\u0308rthe O.","family":"Harms","sequence":"first","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrich","family":"Go\u0308bel","sequence":"additional","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans J.","family":"Spaar","sequence":"additional","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ulrike B.","family":"Graubner","sequence":"additional","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Norbert","family":"Jorch","sequence":"additional","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Gutjahr","sequence":"additional","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gritta E.","family":"Janka-Schaub","sequence":"additional","affiliation":[{"name":"From the Children's University Hospital, Hamburg, Germany; the Children's University Hospital, Du\u0308sseldorf, Germany; the Children's University Hospital, Munich, Germany; the Children's Hospital Prof-Hess, Bremen, Germany; the Children's Hospital Gilead, Bielefeld, Germany; and the Children's University Hospital, Mainz, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"for the COALL Study Group","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"key":"2020021217272743800_REF1","doi-asserted-by":"crossref","unstructured":"Lennard L, Rees CA, Lilleyman JS, Maddocks JL. Childhood leukaemia: a relationship between intracellular 6-mercaptopurine metabolites and neutropenia. Br J Clin Pharmacol. 1983;16: 359-363.","DOI":"10.1111\/j.1365-2125.1983.tb02178.x"},{"key":"2020021217272743800_REF2","unstructured":"Nelson JA, Carpenter JW, Rose LM, Adamson DJ. Mechanisms of action of 6-thioguanine, 6-mercaptopurine, and 8-azaguanine. Cancer Res. 1975;35: 2872-2878."},{"key":"2020021217272743800_REF3","doi-asserted-by":"crossref","unstructured":"Lennard L, Lilleyman JS. Variable mercaptopurine metabolism and treatment outcome in childhood lymphoblastic leukemia [erratum appears in J Clin Oncol. 1990;8:567]. J Clin Oncol. 1989;7: 1816-1823.","DOI":"10.1200\/JCO.1989.7.12.1816"},{"key":"2020021217272743800_REF4","doi-asserted-by":"crossref","unstructured":"Lilleyman JS, Lennard L. Mercaptopurine metabolism and risk of relapse in childhood lymphoblastic leukaemia. Lancet. 1994;343: 1188-1190.","DOI":"10.1016\/S0140-6736(94)92400-7"},{"key":"2020021217272743800_REF5","doi-asserted-by":"crossref","unstructured":"Adamson PC, Poplack DG, Balis FM. The cytotoxicity of thioguanine vs mercaptopurine in acute lymphoblastic leukemia. Leuk Res. 1994;18: 805-810.","DOI":"10.1016\/0145-2126(94)90159-7"},{"key":"2020021217272743800_REF6","unstructured":"Bene MC, Castoldi G, Knapp W, et al. Proposals for the immunological classification of acute leukemias: European Group for the Immunological Characterization of Leukemias (EGIL). Leukemia. 1995;9: 1783-1786."},{"key":"2020021217272743800_REF7","doi-asserted-by":"crossref","unstructured":"Kaplan EL, Meier P. Non-parametric estimation from incomplete observations. J Am Stat Assoc. 1958;53: 457-481.","DOI":"10.1080\/01621459.1958.10501452"},{"key":"2020021217272743800_REF8","doi-asserted-by":"crossref","unstructured":"Cox DR. Regression models and life-tables [with discussion]. J R Stat Soc B. 1972;34: 187-220.","DOI":"10.1111\/j.2517-6161.1972.tb00899.x"},{"key":"2020021217272743800_REF9","doi-asserted-by":"crossref","unstructured":"Harms DO, Janka-Schaub GE. Co-operative study group for childhood acute lymphoblastic leukemia (COALL): long-term follow-up of trials 82, 85, 89 and 92. Leukemia. 2000;14: 2234-2239.","DOI":"10.1038\/sj.leu.2401974"},{"key":"2020021217272743800_REF10","doi-asserted-by":"crossref","unstructured":"Erb N, Harms DO, Janka-Schaub G. Pharmacokinetics and metabolism of thiopurines in children with acute lymphoblastic leukemia receiving 6-thioguanine versus 6-mercaptopurine. Cancer Chemother Pharmacol. 1998;42: 266-272.","DOI":"10.1007\/s002800050816"}],"container-title":["Blood"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/102\/8\/2736\/1691979\/h82003002736.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"http:\/\/ashpublications.org\/blood\/article-pdf\/102\/8\/2736\/1691979\/h82003002736.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,12,13]],"date-time":"2024-12-13T04:42:07Z","timestamp":1734064927000},"score":1,"resource":{"primary":{"URL":"https:\/\/ashpublications.org\/blood\/article\/102\/8\/2736\/17729\/Thioguanine-offers-no-advantage-over"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,10,15]]},"references-count":10,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2003,10,15]]}},"URL":"https:\/\/doi.org\/10.1182\/blood-2002-08-2372","relation":{},"ISSN":["0006-4971","1528-0020"],"issn-type":[{"value":"0006-4971","type":"print"},{"value":"1528-0020","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,10,15]]}}}