{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T20:42:52Z","timestamp":1781728972022,"version":"3.54.5"},"reference-count":39,"publisher":"Wiley","issue":"8","license":[{"start":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T00:00:00Z","timestamp":1649635200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Pediatric Blood &amp; Cancer"],"published-print":{"date-parts":[[2022,8]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>The feasibility of tyrosine kinase inhibitor (TKI) discontinuation in pediatric chronic myeloid leukemia (CML) remains to be fully elucidated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Procedures<\/jats:title><jats:p>TKI was prospectively discontinued in patients who were diagnosed with CML at &lt;20\u00a0years of age, treated with TKI for \u22653\u00a0years, and sustained molecular response 4.0 (MR4.0) for \u22652\u00a0years. Molecular relapse was defined as a single loss of major molecular response (MMR) (<jats:italic>BCR\u2010ABL1<\/jats:italic><jats:sup>IS<\/jats:sup> &gt;0.1%). Relapsed patients resumed the same TKI therapy administered before discontinuation.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Twenty\u2010two patients with chronic\u2010phase CML were enrolled, and the median ages at diagnosis and at TKI discontinuation were 9 (range: 1\u201314) years and 16 (5\u201326) years, respectively. The median follow\u2010up time after TKI discontinuation was 37\u00a0months (range: 24\u201341\u00a0months). The median duration of TKI treatment before discontinuation was 100 (42\u2013178) months, and that of MR4.0 was 53.5 (25\u2013148) months. The treatment\u2010free remission (TFR) rate at 12\u00a0months was 50.0% (90% confidence interval: 31.7%\u201365.8%). Eleven patients experienced loss of MMR within 4\u00a0months after TKI discontinuation and resumed TKI as originally prescribed. No progression was observed, and all 11 patients regained MR4.0 after TKI resumption. No patient had a withdrawal syndrome. The quality\u2010of\u2010life analysis suggested that successful TFR may improve academic performance in some patients. In patients who discontinued TKI therapy before puberty, the possibility of improvement in growth velocity upon TKI discontinuation was observed.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>TKI could be discontinued safely in patients with pediatric CML showing a sustained deep MR.<\/jats:p><\/jats:sec>","DOI":"10.1002\/pbc.29699","type":"journal-article","created":{"date-parts":[[2022,4,11]],"date-time":"2022-04-11T12:13:13Z","timestamp":1649679193000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Discontinuation of tyrosine kinase inhibitors in pediatric chronic myeloid leukemia"],"prefix":"10.1002","volume":"69","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3432-8832","authenticated-orcid":false,"given":"Haruko","family":"Shima","sequence":"first","affiliation":[{"name":"Department of Pediatrics Keio University School of Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akiko","family":"Kada","sequence":"additional","affiliation":[{"name":"Clinical Research Center National Hospital Organization Nagoya Medical Center  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0990-2508","authenticated-orcid":false,"given":"Akihiko","family":"Tanizawa","sequence":"additional","affiliation":[{"name":"Sugita Genpaku Memorial Obama Municipal Hospital  Fukui Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6244-6591","authenticated-orcid":false,"given":"Iori","family":"Sato","sequence":"additional","affiliation":[{"name":"Department of Family Nursing, Division of Health Sciences and Nursing, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chikako","family":"Tono","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Iwate Prefectural Chubu Hospital  Iwate Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masaki","family":"Ito","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Soma General Hospital  Fukushima Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuki","family":"Yuza","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Tokyo Metropolitan Children's Medical Center  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akihiro","family":"Watanabe","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Niigata Cancer Center Hospital  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiyoko","family":"Kamibeppu","sequence":"additional","affiliation":[{"name":"Department of Family Nursing, Division of Health Sciences and Nursing, Graduate School of Medicine The University of Tokyo  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hideko","family":"Uryu","sequence":"additional","affiliation":[{"name":"Department of Pediatrics National Center for Global Health and Medicine  Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsuyoshi","family":"Koh","sequence":"additional","affiliation":[{"name":"Department of Hematology\/Oncology Saitama Children's Medical Center  Saitama Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7435-3464","authenticated-orcid":false,"given":"Chihaya","family":"Imai","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Niigata University Graduate School of Medical and Dental Sciences  Niigata Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3783-2121","authenticated-orcid":false,"given":"Nao","family":"Yoshida","sequence":"additional","affiliation":[{"name":"Department of Hematology and Oncology, Children's Medical Center Japanese Red Cross Nagoya First Hospital  Aichi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0056-9988","authenticated-orcid":false,"given":"Yuhki","family":"Koga","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Graduate School of Medical Sciences Kyushu University  Fukuoka Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1879-880X","authenticated-orcid":false,"given":"Naoto","family":"Fujita","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Hiroshima Red Cross Hospital &amp; 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