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Even in the current era of BCR-ABL1 tyrosine kinase inhibitors (TKIs), the outcomes of blast phase CML remain poor with no consensus frontline treatment approach.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Methods<\/jats:title>\n                <jats:p>We retrospectively analyzed the response rates and survival outcomes of 104 consecutive patients with myeloid blast phase CML (CML-MBP) treated from 2000 to 2019 based on 4 different frontline treatment approaches: intensive chemotherapy (IC)\u2009+\u2009TKI (<jats:italic>n<\/jats:italic>\u2009=\u200920), hypomethylating agent (HMA)\u2009+\u2009TKI (<jats:italic>n<\/jats:italic>\u2009=\u200920), TKI alone (<jats:italic>n<\/jats:italic>\u2009=\u200956), or IC alone (<jats:italic>n<\/jats:italic>\u2009=\u20098). We also evaluated the impact of TKI selection and subsequent allogeneic stem cell transplant (ASCT) on patient outcomes.<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Results<\/jats:title>\n                <jats:p>Response rates were similar between patients treated with IC\u2009+\u2009TKI and HMA\u2009+\u2009TKI. Compared to treatment with TKI alone, treatment with IC\/HMA\u2009+\u2009TKI resulted in a higher rate of complete remission (CR) or CR with incomplete count recovery (CRi) (57.5% vs 33.9%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), a higher complete cytogenetic response rate (45% vs 10.7%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.001), and more patients proceeding to ASCT (32.5% vs 10.7%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.01). With a median follow-up of 6.7\u00a0years, long-term outcomes were similar between the IC\u2009+\u2009TKI and HMA\u2009+\u2009TKI groups. Combination therapy with IC\/HMA\u2009+\u2009TKI was superior to therapy with TKI alone, including when analysis was limited to those treated with a 2nd\/3rd-generation TKI. When using a 2nd\/3rd-generation TKI, IC\/HMA\u2009+\u2009TKI led to lower 5-year cumulative incidence of relapse (CIR; 44% vs 86%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and superior 5-year event-free survival (EFS; 28% vs 0%, <jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05) and overall survival (OS; 34% vs 8%, <jats:italic>p<\/jats:italic>\u2009=\u20090.23) compared to TKI alone. Among patients who received IC\/HMA\u2009+\u2009TKI, EFS and OS was superior for patients who received a 2nd\/3rd generation TKI compared to those who received imatinib-based therapy. In a landmark analysis, 5-year OS was higher for patients who proceeded to ASCT (58% vs 22%, <jats:italic>p<\/jats:italic>\u2009=\u20090.12).<\/jats:p>\n              <\/jats:sec><jats:sec>\n                <jats:title>Conclusions<\/jats:title>\n                <jats:p>Compared to patients treated with TKI alone for CML-MBP, treatment with IC\u2009+\u2009TKI or HMA\u2009+\u2009TKI led to improved response rates, CIR, EFS, and OS, particularly for patients who received a 2nd\/3rd-generation TKI. Combination therapy with IC\u2009+\u2009TKI or HMA\u2009+\u2009TKI, rather than a TKI alone, should be considered the optimal treatment strategy for patients with CML-MBP.<\/jats:p>\n              <\/jats:sec>","DOI":"10.1186\/s13045-021-01106-1","type":"journal-article","created":{"date-parts":[[2021,6,15]],"date-time":"2021-06-15T10:03:59Z","timestamp":1623751439000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Impact of frontline treatment approach on outcomes of myeloid blast phase CML"],"prefix":"10.1186","volume":"14","author":[{"given":"Kapil","family":"Saxena","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elias","family":"Jabbour","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ghayas","family":"Issa","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Koji","family":"Sasaki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Farhad","family":"Ravandi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abhishek","family":"Maiti","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Naval","family":"Daver","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tapan","family":"Kadia","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Courtney D.","family":"DiNardo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marina","family":"Konopleva","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jorge E.","family":"Cortes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Musa","family":"Yilmaz","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelly","family":"Chien","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sherry","family":"Pierce","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hagop","family":"Kantarjian","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2983-2738","authenticated-orcid":false,"given":"Nicholas J.","family":"Short","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2021,6,15]]},"reference":[{"key":"1106_CR1","unstructured":"Swerdlow SH, Campo E, Harris NL, Jaffe ES, Pileri S, Stein H, et al. 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The other authors report no relevant conflicts of interest.","order":4,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"94"}}