{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T11:29:24Z","timestamp":1788262164694,"version":"build-2803163510"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T00:00:00Z","timestamp":1562198400000},"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":["Br J Haematol"],"published-print":{"date-parts":[[2019,11]]},"abstract":"<jats:title>Summary<\/jats:title><jats:p>The effectiveness of tyrosine kinase inhibitors (TKIs) has made it possible to consider treatment discontinuation in chronic myeloid leukaemia (CML) patients that achieve an excellent response. However, a few of the patients included in the Europe Stop Tyrosine Kinase Inhibitors (EURO\u2010SKI) trial reported musculoskeletal pain shortly after stopping TKIs, considered as a withdrawal syndrome (WS). To identify factors that may predispose to TKI WS, we analysed the pharmacovigilance declarations for the 6\u00a0months after stopping TKIs in a large cohort of CML (<jats:italic>n<\/jats:italic>\u00a0=\u00a0427) that combined the French patients included in the STop IMatinib 2 (STIM2; <jats:italic>n<\/jats:italic>\u00a0=\u00a0224) and EURO\u2010SKI (<jats:italic>n<\/jats:italic>\u00a0=\u00a0203) trials. Among these patients, 23% (99\/427) developed TKI WS after stopping imatinib (77\/373; 20\u00b74%), nilotinib (12\/29; 41\u00b74%) or dasatinib (10\/25; 40%). WS concerned mainly the upper body joints, and required multiple symptomatic treatments in 30% of patients. Univariate and multivariate analyses identified two risk factors: duration of TKI treatment [risk ratio (RR)\u00a0=\u00a01\u00b768 (1\u00b702\u20132\u00b774)] with a 93\u2010month cut\u2010off time, and history of osteoarticular symptoms [RR\u00a0=\u00a01\u00b784 (1\u00b704\u20133\u00b728)]. These findings confirm that WS is a TKI class effect. CML patients should be carefully screened before treatment initiation to identify pre\u2010existent osteoarticular symptoms. Moreover, before TKI discontinuation, patients should be informed of the possibility of WS, particularly after a long treatment period.<\/jats:p>","DOI":"10.1111\/bjh.16083","type":"journal-article","created":{"date-parts":[[2019,7,4]],"date-time":"2019-07-04T13:11:03Z","timestamp":1562245863000},"page":"337-346","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":40,"title":["Longer treatment duration and history of osteoarticular symptoms predispose to tyrosine kinase inhibitor withdrawal syndrome"],"prefix":"10.1111","volume":"187","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1858-0587","authenticated-orcid":false,"given":"Marc G.","family":"Berger","sequence":"first","affiliation":[{"name":"CHU Clermont\u2010Ferrand, H\u00f4pital Estaing, H\u00e9matologie Biologique Clermont\u2010Ferrand Cedex France"},{"name":"Service d\u2019H\u00e9matologie Clinique Adulte et Th\u00e9rapie Cellulaire CHU Clermont\u2010Ferrand, H\u00f4pital Estaing Clermont\u2010Ferrand Cedex France"},{"name":"Universit\u00e9 Clermont Auvergne, EA 7453 CHELTER Clermont\u2010Ferrand Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Pereira","sequence":"additional","affiliation":[{"name":"D\u00e9l\u00e9gation de la Recherche Clinique et de l\u2019Innovation CHU Clermont\u2010Ferrand Clermont\u2010Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philippe","family":"Rousselot","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie et d\u2019Oncologie CH de Versailles Le Chesnay France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1633-6479","authenticated-orcid":false,"given":"Pascale","family":"Cony\u2010Makhoul","sequence":"additional","affiliation":[{"name":"Service H\u00e9matologie Clinique Centre Hospitalier Annecy Genevois Pringy France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Gardembas","sequence":"additional","affiliation":[{"name":"Service des Maladies du Sang CHU Angers Angers France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Laurence","family":"Legros","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie Clinique H\u00f4pital Paul\u2010Brousse (AP\u2010HP) Villejuif France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Escoffre\u2010Barbe","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie Clinique CHU Rennes Rennes France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck\u2010Emmanuel","family":"Nicolini","sequence":"additional","affiliation":[{"name":"H\u00e9matologie Clinique et INSERM U1052 Centre L\u00e9on B\u00e9rard Lyon France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sandrine","family":"Saugues","sequence":"additional","affiliation":[{"name":"CHU Clermont\u2010Ferrand, H\u00f4pital Estaing, H\u00e9matologie Biologique Clermont\u2010Ferrand Cedex France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C\u00e9line","family":"Lambert","sequence":"additional","affiliation":[{"name":"D\u00e9l\u00e9gation de la Recherche Clinique et de l\u2019Innovation CHU Clermont\u2010Ferrand Clermont\u2010Ferrand France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5379-7461","authenticated-orcid":false,"given":"Delphine","family":"R\u00e9a","sequence":"additional","affiliation":[{"name":"Groupe Hospitalier Saint\u2010Louis Service d\u2019H\u00e9matologie Lariboisi\u00e8re, Fernand\u2010Widal (AP\u2010HP) Paris France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Agn\u00e8s","family":"Guerci\u2010Bresler","sequence":"additional","affiliation":[{"name":"Service d\u2019H\u00e9matologie Clinique CHRU Nancy\u2010Brabois Vandoeuvre France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"St\u00e9phane","family":"Giraudier","sequence":"additional","affiliation":[{"name":"Laboratoire d\u2019H\u00e9matologie H\u00f4pital H. 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