{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T02:47:20Z","timestamp":1789958840501,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T00:00:00Z","timestamp":1548979200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["acsjournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer"],"published-print":{"date-parts":[[2019,5,15]]},"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Stopping tyrosine kinase inhibitor (TKI) treatment has become a realistic and safe objective for patients who have chronic myeloid leukemia (CML). Both a sustained deep molecular response (sDMR) and the lack of a molecular recurrence after TKI discontinuation are required to reach a durable treatment\u2010free remission (TFR).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>The potential predictive role of BCR\u2010ABL transcripts in attaining an sDMR and a TFR was analyzed in a strictly consecutive, unselected series of 194 patients who were diagnosed and treated with TKIs at the authors\u2019 center.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Of 173 fully evaluable patients, 67 (38.7%) had the e13a2 transcript, and 106 (61.3%) had the e14a2 transcript. Complete cytogenetic and major molecular remissions were not affected, whereas the achievement of both a DMR (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.008) and an sDMR (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.004) was favored significantly in patients who had the e14a2 transcript. After a median of 68\u00a0months, the sDMR rate was 39.6% in those with the e14a2 transcript and 19.4% in those with the e13a2 transcript. In addition to transcript type, both the early achievement of a molecular response and starting treatment with a second\u2010generation TKI positively affected the attainment of an sDMR in multivariate analysis. The use of a second\u2010generation TKI as frontline treatment increased the sDMR rate in both transcript types. However, in patients who had the e13a2 transcript, the probability of attaining an sDMR was 37% after 60\u00a0months and did not increase further despite continuing therapy. Among 51 of 60 patients who attained an sDMR after discontinuing TKIs, 24 experienced a molecular relapse, but all regained molecular remission after resuming TKI treatment. Again, transcript type influenced TFR maintenance (\n                      <jats:italic>P<\/jats:italic>\n                      \u00a0=\u00a0.005), because only 2 patients (3%) with the e13a2 transcript enjoyed a durable TFR compared with 25 (23.5%) of those with the e14a2 transcript.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>The e13a2 transcript hinders the achievement of deep responses and the possibility of stopping TKI treatment in patients with CML.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cncr.31977","type":"journal-article","created":{"date-parts":[[2019,2,1]],"date-time":"2019-02-01T16:23:06Z","timestamp":1549038186000},"page":"1674-1682","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":61,"title":["The e13a2 BCR\u2010ABL transcript negatively affects sustained deep molecular response and the achievement of treatment\u2010free remission in patients with chronic myeloid leukemia who receive tyrosine kinase inhibitors"],"prefix":"10.1002","volume":"125","author":[{"given":"Mariella","family":"D'Adda","sequence":"first","affiliation":[{"name":"Department of Hematology Local Social Health Authority (ASST) Spedali Civili Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2980-9028","authenticated-orcid":false,"given":"Mirko","family":"Farina","sequence":"additional","affiliation":[{"name":"Department of Hematology Local Social Health Authority (ASST) Spedali Civili Brescia Brescia Italy"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Schieppati","sequence":"additional","affiliation":[{"name":"Department of Hematology Local Social Health Authority (ASST) Spedali Civili Brescia Brescia 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