{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T00:00:54Z","timestamp":1791331254706,"version":"4.3.1"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2020,6,26]],"date-time":"2020-06-26T00:00:00Z","timestamp":1593129600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002491","name":"Bristol-Myers Squibb","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002491","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2020,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>This study presents the final report of the multicenter, prospective tyrosine kinase inhibitor discontinuation study, D\u2010STOP, after a 3\u2010year follow\u2010up of 54 patients with chronic CML who discontinued dasatinib after a sustained deep molecular response (DMR) for \u22652\u00a0years with dasatinib treatment. Estimated treatment\u2010free remission (TFR) rates at 12 and 36\u00a0months were 63.0% [95% confidence interval (CI): 48.7\u201074.3] and 59.3% (95% CI: 45.0\u201071.0), respectively. CD3<jats:sup>\u2212<\/jats:sup>CD56<jats:sup>+ <\/jats:sup>NK, CD16<jats:sup>+<\/jats:sup>CD56<jats:sup>+ <\/jats:sup>NK, and CD57<jats:sup>+<\/jats:sup>CD56<jats:sup>+ <\/jats:sup>NK large granular lymphocyte (NK\u2010LGL), CD8<jats:sup>+<\/jats:sup>CD4<jats:sup>\u2013<\/jats:sup> cytotoxic T cell, and CD57<jats:sup>+<\/jats:sup>CD3<jats:sup>+ <\/jats:sup>T\u2010LGL cell numbers were relatively elevated throughout the 24\u2010month consolidation only in failed patients who molecularly relapsed within 12\u00a0months. In successful patients, these subsets elevated transiently after 12\u00a0months, but returned to basal levels after 24\u2010month consolidation. Therefore, smaller changes in NK\/T, particularly the NK subset throughout consolidation, reflected higher TFR rates. TFR rates of those patients exhibiting elevation in CD3<jats:sup>\u2212<\/jats:sup>CD56<jats:sup>+ <\/jats:sup>NK &gt;376\u00a0cells\/\u03bcL, CD16<jats:sup>+<\/jats:sup>CD56<jats:sup>+ <\/jats:sup>NK\u00a0&gt;\u00a0241\u00a0cells\/\u03bcL, or CD57<jats:sup>+<\/jats:sup>CD56<jats:sup>+ <\/jats:sup>NK\u2010LGL &gt;242\u00a0cells\/\u03bcL during consolidation compared with others were 26.7% (8.3%\u201049.6%) vs 78.3% (55.4%\u201090.3%), HR 0.032 (0.0027\u20100.38; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.0064), 31.2% (11.4%\u201053.6%) vs 85.0% (60.4%\u201094.9%), HR 0.039 (0.0031\u20100.48; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.011), or 36.8% (16.5%\u201057.5%) vs 77.3% (53.7%\u201089.8%), HR 0.21 (0.065\u20100.69; <jats:italic>P<\/jats:italic>\u00a0=\u00a0.010), respectively. Therefore, silent responses of T\/NK subsets to dasatinib throughout consolidation were significant for longer TFR. Elevated NK\/T, particularly NK lymphocytes responsive to dasatinib, may be immunologically insufficient to maintain TFR. Their decline, subsequently replaced by altered lymphocyte population with less response to dasatinib during sustained DMR, might be immunologically significant. (D\u2010STOP, NCT01627132).<\/jats:p>","DOI":"10.1111\/cas.14518","type":"journal-article","created":{"date-parts":[[2020,6,7]],"date-time":"2020-06-07T14:16:00Z","timestamp":1591539360000},"page":"2923-2934","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Silent NK\/T cell reactions to dasatinib during sustained deep molecular response before cessation are associated with longer treatment\u2010free remission"],"prefix":"10.1111","volume":"111","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-6850-4545","authenticated-orcid":false,"given":"Takashi","family":"Kumagai","sequence":"first","affiliation":[{"name":"Department of Hematology Ome Municipal General Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chiaki","family":"Nakaseko","sequence":"additional","affiliation":[{"name":"Department of Hematology Chiba University Hospital Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kaichi","family":"Nishiwaki","sequence":"additional","affiliation":[{"name":"Division of Clinical Oncology and Hematology Department of Internal Medicine Jikei University School of Medicine Kashiwa Hospital Chiba Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikashi","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Mito Medical Center Higashiibarakigun Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuteru","family":"Ohashi","sequence":"additional","affiliation":[{"name":"Hematology Division Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Naoki","family":"Takezako","sequence":"additional","affiliation":[{"name":"Department of Hematology National Hospital Organization Disaster Medical Center Tachikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hina","family":"Takano","sequence":"additional","affiliation":[{"name":"Department of Hematology Musashino Red Cross Hospital Musashino Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasuji","family":"Kouzai","sequence":"additional","affiliation":[{"name":"Department of Hematology Tokyo Metropolitan Tama Synthesis Medical Center Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tadashi","family":"Murase","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Dokkyo Medical University Koshigaya Hospital Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8669-9865","authenticated-orcid":false,"given":"Kosei","family":"Matsue","sequence":"additional","affiliation":[{"name":"Division of Hematology\/Oncology Department of Internal Medicine Kameda Medical Center Kamogawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Satoshi","family":"Morita","sequence":"additional","affiliation":[{"name":"Department of Biomedical Statistics and Bioinformatics Kyoto University Graduate School of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junichi","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Tokai Central Hospital Kakamigahara Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Wakita","sequence":"additional","affiliation":[{"name":"Division of Hematology and Oncology Japanese Red Cross Society Narita Red Cross Hosp Narita Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hisashi","family":"Sakamaki","sequence":"additional","affiliation":[{"name":"Hematology Division Tokyo Metropolitan Cancer and Infectious Diseases Center Komagome Hospital Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Koiti","family":"Inokuchi","sequence":"additional","affiliation":[{"name":"Department of Hematology Nippon Medical School Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"name":"the Kanto CML, Shimousa Hematology Study Groups","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2020,6,26]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa062867"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.64.8899"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2015.66.2866"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1001\/jamaoncol.2015.5932"},{"key":"e_1_2_7_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djw003"},{"key":"e_1_2_7_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(10)70233-3"},{"key":"e_1_2_7_8_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2016.68.2914"},{"key":"e_1_2_7_9_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-017-2334-x"},{"key":"e_1_2_7_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(18)30192-X"},{"key":"e_1_2_7_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(15)00196-9"},{"key":"e_1_2_7_12_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-09-742205"},{"key":"e_1_2_7_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2016.360"},{"key":"e_1_2_7_14_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-013-1483-9"},{"key":"e_1_2_7_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2009-12-256800"},{"key":"e_1_2_7_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/cas.13430"},{"key":"e_1_2_7_17_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10147-011-0328-x"},{"key":"e_1_2_7_18_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20060772"},{"key":"e_1_2_7_19_1","doi-asserted-by":"publisher","DOI":"10.1038\/bmt.2012.244"},{"key":"e_1_2_7_20_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.139899"},{"key":"e_1_2_7_21_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2017.00469"},{"key":"e_1_2_7_22_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-10-745992"},{"key":"e_1_2_7_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12185-018-2517-0"},{"key":"e_1_2_7_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29933"},{"key":"e_1_2_7_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/leu.2010.185"},{"key":"e_1_2_7_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2005-07-2947"},{"key":"e_1_2_7_27_1","first-page":"285","article-title":"Cell stem cell article myeloproliferative neoplasia remodels the endosteal bone marrow niche into a self\u2010reinforcing leukemic niche","volume":"13","author":"Schepers K","year":"2013","journal-title":"Stem Cell"},{"key":"e_1_2_7_28_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2013.01.026"},{"key":"e_1_2_7_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2018.02.014"},{"key":"e_1_2_7_30_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.03152"},{"key":"e_1_2_7_31_1","doi-asserted-by":"publisher","DOI":"10.3389\/fimmu.2018.02433"},{"key":"e_1_2_7_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.critrevonc.2013.10.005"},{"key":"e_1_2_7_33_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2009.25.0779"},{"key":"e_1_2_7_34_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2017.165001"},{"key":"e_1_2_7_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(19)30235-2"},{"key":"e_1_2_7_36_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.24096"},{"key":"e_1_2_7_37_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2008-04-151407"},{"key":"e_1_2_7_38_1","doi-asserted-by":"publisher","DOI":"10.1158\/2326-6066.CIR-17-0498"},{"key":"e_1_2_7_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.leukres.2018.01.010"},{"key":"e_1_2_7_40_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.stem.2015.02.014"}],"container-title":["Cancer Science"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1111%2Fcas.14518","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14518","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1111\/cas.14518","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1111\/cas.14518","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,1]],"date-time":"2023-09-01T13:33:55Z","timestamp":1693575235000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1111\/cas.14518"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,6,26]]},"references-count":39,"journal-issue":{"issue":"8","published-print":{"date-parts":[[2020,8]]}},"alternative-id":["10.1111\/cas.14518"],"URL":"https:\/\/doi.org\/10.1111\/cas.14518","archive":["Portico"],"relation":{},"ISSN":["1347-9032","1349-7006"],"issn-type":[{"value":"1347-9032","type":"print"},{"value":"1349-7006","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,6,26]]},"assertion":[{"value":"2020-01-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-01","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2020-06-26","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}