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The availability for first-, second-, or subsequent-line use of 6 different TKIs, each with definite and often nonoverlapping features in terms of mechanism of action, potency, activity against resistance mutations, and tolerability profile provides a reassuring opportunity to rescue an optimal response, but it must be exploited carefully to avoid hasty or inappropriate choices. When and how to sequence TKIs, and whether and when to consider transplant are very important issues. \u201cOne-for-all\u201d rules cannot be formulated, because for each individual patient the decision process requires investigation and integration of a series of clinical and biological factors. After discussing how resistance is defined, we aim here to provide practical guidance to therapeutic reassessment, discussing which laboratory investigations should be performed, how they should be interpreted, which additional clinical considerations are mandatory, and how these factors should be weighed and reasonably concur to the final decision.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1182\/blood.2024026511","type":"journal-article","created":{"date-parts":[[2025,5,15]],"date-time":"2025-05-15T16:18:15Z","timestamp":1747325895000},"page":"337-346","update-policy":"https:\/\/doi.org\/10.1182\/blood.2019cm0000","source":"Crossref","is-referenced-by-count":4,"title":["How I evaluate and treat resistance and relapse in CML"],"prefix":"10.1182","volume":"147","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4508-0353","authenticated-orcid":false,"given":"Simona","family":"Soverini","sequence":"first","affiliation":[{"name":"1Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0602-2628","authenticated-orcid":false,"given":"Fausto","family":"Castagnetti","sequence":"additional","affiliation":[{"name":"1Department of Medical and Surgical Sciences, University of Bologna, Bologna, Italy"},{"name":"2IRCCS Azienda Ospedaliero-Universitaria di Bologna, Istituto di Ematologia \u201cSer\u00e0gnoli,\u201d Bologna, Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"234","reference":[{"issue":"11","key":"2026012211220809900_bib1","doi-asserted-by":"crossref","first-page":"2191","DOI":"10.1002\/ajh.27443","article-title":"Chronic myeloid leukemia: 2025 update on diagnosis, therapy, and monitoring","volume":"99","author":"Jabbour","year":"2024","journal-title":"Am J Hematol"},{"issue":"4","key":"2026012211220809900_bib2","doi-asserted-by":"crossref","first-page":"966","DOI":"10.1038\/s41375-020-0776-2","article-title":"European LeukemiaNet 2020 recommendations for treating chronic myeloid leukemia","volume":"34","author":"Hochhaus","year":"2020","journal-title":"Leukemia"},{"key":"2026012211220809900_bib3","unstructured":"NCCN clinical practice guidelines in oncology - chronic myeloid leukemia. 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