{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:58:06Z","timestamp":1791190686820,"version":"4.1.0"},"reference-count":27,"publisher":"S. Karger AG","license":[{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"},{"start":{"date-parts":[[2026,7,23]],"date-time":"2026-07-23T00:00:00Z","timestamp":1784764800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/karger.com\/pages\/terms-and-conditions"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Acta Haematol"],"abstract":"<jats:p>Introduction: Treatment-free remission (TFR) is an established goal for patients with chronic myeloid leukemia in chronic phase (CML-CP) who achieve sustained deep molecular response (DMR) on tyrosine kinase inhibitor (TKI) therapy. However, the relationship between pre-discontinuation dose intensity (DI) and TFR outcome remains poorly characterized. Methods: We retrospectively analyzed 146 patients with CML-CP who attempted TFR at Samsung Medical Center between 2003 and 2025. The DI was defined as the time-weighted average ratio of actual to standard TKI dose during the 2-year period preceding discontinuation. The association between DI and TFR failure was modeled using Cox regression with restricted cubic splines (RCSs) in the DI subcohort (n = 126), using a DI of 1.0 as the reference. Results: In the full cohort, at median follow-up of 22.3 months, 50 (34.2%) patients experienced molecular relapse. TFR probability was 79.5% at 6 months and 61.9% at 48 months. In the DI subcohort, an unadjusted RCS model suggested a nonlinear, inverted U-shaped pattern, but the overall DI effect was not significant (likelihood ratio, p = 0.101; p for nonlinearity = 0.045). In exploratory post hoc groups, intermediate DI showed the highest TFR failure rate (49.0% vs. 25.0% and 28.6%; p = 0.035). The pattern did not reach significance after adjustment for TKI generation (p for nonlinearity = 0.074). Conclusion: These exploratory findings suggest that the biology underlying DMR maintenance, rather than the absolute pre-discontinuation dose, may influence TFR outcome. Given the modest sample size and post hoc design, this hypothesis-generating observation requires confirmation in independent cohorts.<\/jats:p>","DOI":"10.1159\/aha\/abkag001","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T13:04:17Z","timestamp":1786021457000},"page":"1-1","source":"Crossref","is-referenced-by-count":0,"title":["Inverted U-Shaped Relationship between Pre-Discontinuation Tyrosine Kinase Inhibitor Dose Intensity and Treatment-Free Remission Outcome in Chronic Myeloid Leukemia"],"prefix":"10.1159","author":[{"given":"Dae-Ho","family":"Choi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Ho","family":"Jang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Won","family":"Jung","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"127","published-online":{"date-parts":[[2026,7,23]]},"reference":[{"key":"ref1","doi-asserted-by":"publisher","DOI":"10.1038\/243290a0"},{"key":"ref2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"ref3","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.66.2866"},{"key":"ref4","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-020-0776-2"},{"key":"ref5","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"ref6","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2013-02-483750"},{"key":"ref7","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00196-9"},{"key":"ref8","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.63"},{"key":"ref9","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-742205"},{"key":"ref10","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30192-X"},{"key":"ref11","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30235-2"},{"key":"ref12","doi-asserted-by":"publisher","DOI":"10.1080\/10428194.2019.1675879"},{"key":"ref13","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2020.5774"},{"key":"ref14","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.2914"},{"key":"ref15","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.139899"},{"key":"ref16","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2334-x"},{"key":"ref17","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30094-8"},{"key":"ref18","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2015.29"},{"key":"ref19","doi-asserted-by":"publisher","DOI":"10.1002\/sim.4780080504"},{"key":"ref20","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01647"},{"key":"ref21","doi-asserted-by":"publisher","DOI":"10.1002\/hon.70126"},{"key":"ref22","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00469"},{"key":"ref23","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.360"},{"key":"ref24","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.165001"},{"key":"ref25","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.17447"},{"key":"ref26","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.115"},{"key":"ref27","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-01-694265"}],"container-title":["Acta Haematologica"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/karger.com\/article-pdf\/doi\/10.1159\/aha\/abkag001","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T08:47:07Z","timestamp":1791190027000},"score":1,"resource":{"primary":{"URL":"https:\/\/karger.com\/article\/doi\/10.1159\/aha\/abkag001"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,23]]},"references-count":27,"URL":"https:\/\/doi.org\/10.1159\/aha\/abkag001","archive":["Portico"],"relation":{"is-supplemented-by":[{"id-type":"doi","id":"10.6084\/m9.figshare.33070490","asserted-by":"subject"}]},"ISSN":["0001-5792","1421-9662"],"issn-type":[{"value":"0001-5792","type":"print"},{"value":"1421-9662","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,23]]}}}