{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T18:51:25Z","timestamp":1770749485604,"version":"3.50.0"},"reference-count":28,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T00:00:00Z","timestamp":1752624000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"funder":[{"name":"National Hospital"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Cancer Chemother Pharmacol"],"published-print":{"date-parts":[[2025,12]]},"abstract":"<jats:title>Abstract<\/jats:title>\n          <jats:sec>\n            <jats:title>Purpose<\/jats:title>\n            <jats:p>Adherence to 6-mercaptopurine (6-MP)\/methotrexate maintenance treatment for acute lymphoblastic leukemia (ALL) is pivotal to preventing relapse, and the 6-MP metabolite DNA-incorporated thioguanine (DNA-TG) is associated with relapse risk. In the ALLTogether-1 (A2G1) Maintenance sub-study (EU CT nr 2022-501050-11-01), DNA-TG, thioguanine nucleotides (TGN), and methylated mercaptopurine metabolites (MeMP) are analyzed regularly. Upon levels below preset limits (TGN\u2009&lt;\u200950, or MeMP\u2009&lt;\u2009200 or &lt;\u2009100 nmol\/mmol hemoglobin for thiopurine S-methyltransferase (TPMT) wild type and heterozygous patients, respectively), the treating physician is informed of potential non-adherence. We investigated the feasibility of using DNA-TG as the primary flagging of potential non-adherence.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods<\/jats:title>\n            <jats:p>We analyzed 6-MP metabolites in 3,074 blood samples from 368 children enrolled in the A2G1 Maintenance sub-study.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results<\/jats:title>\n            <jats:p>In 6% of samples, TGN (median 212, 95% range 40\u2013642), MeMP (median 4,959, 95% range 135\u201323,880) or both were below the flagging potential non-adherence limits. DNA-TG was associated with TGN (estimate\u2009=\u20091.72, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), MeMP (estimate\u2009=\u20091.10, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001), and prescribed 6-MP dose (estimate\u2009=\u20091.083 and 1.132, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.0001, for TPMT wild type and heterozygous patients) in linear effects models, and the predicted probability of treatment interruption in logistic regression models. DNA-TG was below 200 fmol TG\/\u00b5g DNA (13th percentile of all measurements, median 569, 95% range 73\u20131,823) in all samples with both TGN and MeMP below the flagging potential non-adherence limits.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion<\/jats:title>\n            <jats:p>DNA-TG can provide a cost-effective guidance on when to measure TGN and MeMP to determine whether non-adherence should be suspected, which is an additional benefit to monitoring DNA-TG during maintenance therapy.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s00280-025-04784-7","type":"journal-article","created":{"date-parts":[[2025,7,16]],"date-time":"2025-07-16T07:00:23Z","timestamp":1752649223000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["DNA-incorporated thioguanine to detect potential non-adherence to maintenance therapy in acute lymphoblastic leukemia"],"prefix":"10.1007","volume":"95","author":[{"given":"Mathilde R\u00f8nne","family":"Koch","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4997-2914","authenticated-orcid":false,"given":"Anna Sofie","family":"Buhl Rasmussen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bodil","family":"Als-Nielsen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5332-0284","authenticated-orcid":false,"given":"Ximo","family":"Duarte","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriele","family":"Escherich","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mats","family":"Heyman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kristi","family":"Lepik","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Johan","family":"Malmros","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9144-7972","authenticated-orcid":false,"given":"Jacob","family":"Nersting","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inga","family":"Johannsdottir","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Riitta","family":"Niinim\u00e4ki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0531-8531","authenticated-orcid":false,"given":"Malene Johanne","family":"Petersen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3604-7850","authenticated-orcid":false,"given":"Heidi","family":"Segers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Inge Margriet","family":"van der Sluis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9950-5911","authenticated-orcid":false,"given":"Maria","family":"Thastrup","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Goda","family":"Vaitkeviciene","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0829-4993","authenticated-orcid":false,"given":"Kjeld","family":"Schmiegelow","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9871-7637","authenticated-orcid":false,"given":"Linea Natalie","family":"Toksvang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,7,16]]},"reference":[{"key":"4784_CR1","doi-asserted-by":"publisher","first-page":"2524","DOI":"10.3324\/haematol.2020.247031","volume":"105","author":"H Inaba","year":"2020","unstructured":"Inaba H, Mullighan CG (2020) Pediatric acute lymphoblastic leukemia. 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Oral and written consent was obtained from parents\/caregivers and patients when appropriate. The study was approved on October 28th, 2020, in the European voluntary harmonization process (VHP1557\/SA1[VHP2019111\/SA1], current amendment accepted November 12th, 2021; VHP1557\/SA3[VHP2019111\/SA3]), followed by individual approval in participating countries by ethics committees.","order":3,"name":"Ethics","group":{"name":"EthicsHeading","label":"Ethical approval"}}],"article-number":"76"}}