{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,29]],"date-time":"2026-03-29T20:45:41Z","timestamp":1774817141475,"version":"3.50.1"},"reference-count":19,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T00:00:00Z","timestamp":1774224000000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,3,1]],"date-time":"2026-03-01T00:00:00Z","timestamp":1772323200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["HemaSphere"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Response to cytoreductive therapy according to\n                    <jats:italic>CALR<\/jats:italic>\n                    mutation type,\n                    <jats:italic>CALR<\/jats:italic>\n                    variant allele frequency (VAF), and additional mutations has not been previously studied in essential thrombocythemia (ET). The impact of the molecular profile on treatment response and the main clinical outcomes was analyzed in 557\n                    <jats:italic>CALR<\/jats:italic>\n                    ET patients (\n                    <jats:italic>CALR<\/jats:italic>\n                    Type 1,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009339, median VAF 36%; and\n                    <jats:italic>CALR<\/jats:italic>\n                    Type 2,\n                    <jats:italic>n<\/jats:italic>\n                    \u2009=\u2009218, median VAF 35%). NGS data on additional mutations were available for 257 patients.\n                    <jats:italic>CALR<\/jats:italic>\n                    Type 2 showed a significantly higher rate of complete hematological response (CHR) to first\u2010line cytoreduction. However, in the multivariate analysis, the effect of\n                    <jats:italic>CALR<\/jats:italic>\n                    mutation type in response rates was no longer significant once\n                    <jats:italic>CALR<\/jats:italic>\n                    VAF was considered, whereas high VAF remained independently associated with a lower likelihood of achieving CHR (hazard ratio [HR] = 0.482, 95% confidence interval (CI): 0.297\u20130.781; P\u2009=\u20090.003). Moreover, high VAF was also associated with an increased risk of arterial thrombosis (HR\u2009=\u20094.135, 95% CI: 1.093\u201315.645; P\u2009=\u20090.037), and progression to MF (HR\u2009=\u20092.631, 95% CI: 1.004\u20136.890; P\u2009=\u20090.049). Although allele burden affects overall survival (OS) in the entire population, its impact was surpassed by the presence of high molecular risk (HMR) mutations (HR\u2009=\u20092.114, 95% CI: 1.070\u20134.176; P\u2009=\u20090.031). Furthermore, the HMR profile was also associated with a higher risk of progression to acute leukemia, while it did not influence the probability of CHR or progression to MF. In conclusion,\n                    <jats:italic>CALR<\/jats:italic>\n                    VAF and HMR profile appear to be more important than\n                    <jats:italic>CALR<\/jats:italic>\n                    mutation type regarding treatment response and major clinical outcomes in ET.\n                  <\/jats:p>","DOI":"10.1002\/hem3.70325","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T16:41:08Z","timestamp":1774284068000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Response to therapy and prognosis according to molecular characterization in\n                    <i>CALR<\/i>\n                    \u2010mutated essential thrombocythemia"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8293-5779","authenticated-orcid":false,"given":"Marta","family":"Santaliestra","sequence":"first","affiliation":[{"name":"Hospital 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Hospitalet del Llobregat Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eduardo","family":"Arellano\u2010Rodrigo","sequence":"additional","affiliation":[{"name":"Hospital Cl\u00ednic de Barcelona, IDIBAPS Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neus","family":"Garcia\u2010Gisbert","sequence":"additional","affiliation":[{"name":"Hospital del Mar Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Raquel","family":"Longar\u00f3n","sequence":"additional","affiliation":[{"name":"Hospital del Mar Barcelona Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Manuel","family":"P\u00e9rez\u2010Encinas","sequence":"additional","affiliation":[{"name":"Complexo Hospitalario Universitario de Santiago Universidad de Santiago de Compostela Santiago de Compostela 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