{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T23:43:31Z","timestamp":1792280611991,"version":"4.4.0"},"reference-count":40,"publisher":"Wiley","issue":"15","license":[{"start":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T00:00:00Z","timestamp":1754870400000},"content-version":"vor","delay-in-days":10,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2025,8,1]],"date-time":"2025-08-01T00:00:00Z","timestamp":1754006400000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100017102","name":"Friends of Leukemia Research Fund","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100017102","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["21K16245"],"award-info":[{"award-number":["21K16245"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["24K11518"],"award-info":[{"award-number":["24K11518"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2025,8]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>While tyrosine kinase inhibitor (TKI) discontinuation is an established therapeutic goal, up to 60% of patients relapse after the first attempt. The feasibility of a second or third attempt at TKI discontinuation remains uncertain. Immune surveillance, particularly T\u2010cell and natural killer (NK) cell responses, may influence treatment\u2010free remission (TFR), although no definitive biomarkers for predicting sustained TFR have been identified.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>This retrospective study included 57 chronic myeloid leukemia (CML) patients who attempted TKI discontinuation. Clinical outcomes after the first, second, and third TFR attempts were analyzed, and T cell receptor (TCR) and B\u2010cell receptor (BCR) repertoire analyses were conducted on peripheral blood samples from 14 patients to investigate the immune landscape associated with TFR.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      TFR1 at 1 year was 67.9% (95% confidence interval [CI], 53.9%\u201378.4%). Sixteen patients attempted a second discontinuation, achieving a 1\u2010year TFR2 rate of 31.2% (95% CI, 11.4%\u201353.6%). Patients maintaining\n                      <jats:italic>BCR::ABL1<\/jats:italic>\n                      mRNA levels below MR\n                      <jats:sup>4.5<\/jats:sup>\n                      at 3\u2009months post\u2010TKI discontinuation had a significantly lower risk of relapse (HR, 0.099; 95% CI, 0.012\u20130.829;\n                      <jats:italic>p<\/jats:italic>\n                      \u2009=\u20090.033). TCR repertoire analysis did not reveal distinct clonal expansions of T cells; however, a significant age\u2010related decline in T\u2010cell diversity was observed.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>T\u2010cell immunity in CML patients who have achieved a deep molecular response (DMR) may closely approximate that observed in healthy individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cam4.71142","type":"journal-article","created":{"date-parts":[[2025,8,11]],"date-time":"2025-08-11T10:28:36Z","timestamp":1754908116000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Clinical Features and T\u2010Cell Repertoire of Chronic Myeloid Leukemia Patients Who Attempt Discontinuation of Tyrosine Kinase Inhibitors: The\n                    <scp>ISAC<\/scp>\n                    \u2010\n                    <scp>TFR<\/scp>\n                    Study"],"prefix":"10.1002","volume":"14","author":[{"given":"Hiroshi","family":"Ureshino","sequence":"first","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine Faculty of Medicine Saga University  Saga Japan"},{"name":"Department of Drug Discovery and Biomedical Sciences Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yukio","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Repertoire Genesis Inc.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yemima","family":"Budirahardja","sequence":"additional","affiliation":[{"name":"Repertoire Genesis Inc.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Iwao","family":"Nozawa","sequence":"additional","affiliation":[{"name":"Repertoire Genesis Inc.  Osaka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Kidoguchi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine Faculty of Medicine Saga University  Saga Japan"},{"name":"Department of Drug Discovery and Biomedical Sciences Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuharu","family":"Kamachi","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine Faculty of Medicine Saga University  Saga Japan"},{"name":"Department of Drug Discovery and Biomedical Sciences Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1717-6208","authenticated-orcid":false,"given":"Shinya","family":"Kimura","sequence":"additional","affiliation":[{"name":"Division of Hematology, Respiratory Medicine and Oncology, Department of Internal Medicine Faculty of Medicine Saga University  Saga Japan"},{"name":"Department of Drug Discovery and Biomedical Sciences Faculty of Medicine Saga University  Saga Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2025,8,11]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1609324"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00196-9"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30235-2"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.63"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.23.01647"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.26550"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2019.106273"},{"issue":"284","key":"e_1_2_9_10_1","first-page":"1313","article-title":"Phylogenetic Perspectives in Innate Immunity","volume":"1999","author":"Hoffmann J.","year":"1979","journal-title":"Science"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-09-077438"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.165001"},{"key":"e_1_2_9_13_1","first-page":"2935","article-title":"Long\u2010Lasting Memory of Cellular Immunity in a Chronic Myeloid Leukemia Patient Maintains Molecular Response 5 After Cessation of Dasatinib","volume":"15","author":"Jo T.","year":"2018","journal-title":"Oncology Letters"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2017.9"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0462"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bneo.2024.100001"},{"key":"e_1_2_9_17_1","doi-asserted-by":"publisher","DOI":"10.1080\/2162402X.2017.1405204"},{"key":"e_1_2_9_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.30885"},{"key":"e_1_2_9_19_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.18796"},{"key":"e_1_2_9_20_1","first-page":"1","article-title":"Final Report of TKI Discontinuation Trial With Dasatinib for the Second Attempt of Treatment\u2010Free Remission After Failing the First Attempt With Imatinib: Treatment\u2010Free Remission Accomplished by Dasatinib (TRAD) Study","volume":"6","author":"Perusini M. 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