{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:24:03Z","timestamp":1790713443840,"version":"4.1.0"},"reference-count":21,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2018,10,17]],"date-time":"2018-10-17T00:00:00Z","timestamp":1539734400000},"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":["American J Hematol"],"published-print":{"date-parts":[[2019,1]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>First\u2010line cytoreductive drug of choice in high risk essential thrombocythemia (ET) is currently hydroxyurea, a practice based on the results of a randomized study; second\u2010line drugs of choice include pegylated interferon\u2010\u03b1, busulfan and anagrelide. Anagrelide clinical trials were pioneered by the late Murray N. Silverstein (1928\u20101998) of the Mayo Clinic whose studies led to FDA approval in March 1997. The current study represents a retrospective examination of the potential impact of anagrelide therapy on survival and disease complications in ET. 1076 patients with ET were considered (median age 58\u2009years; females 63%); risk distribution, according to the international prognostic score for ET (IPSET), was 28% high, 42% intermediate, and 30% low. Overall (OS), myelofibrosis\u2010free (MFFS) and thrombosis\u2010free survival data were compared for ET patients diagnosed before and after the 1997 FDA approval date for anagrelide; a significant difference was apparent in OS (<jats:italic>P<\/jats:italic>\u2009=\u2009.006; HR 1.4, 95% CI 1.1\u20101.7) and MFFS (<jats:italic>P<\/jats:italic>\u2009&lt;\u2009.001; HR 4.2, 95% CI 2.7\u20106.5), in favor of patients diagnosed prior to 1997; the difference was sustained during multivariable analysis that included IPSET. Similarly stratified survival data in polycythemia vera (<jats:italic>n<\/jats:italic>\u2009=\u2009665) and primary myelofibrosis (<jats:italic>n<\/jats:italic>\u2009=\u20091282) showed no similar impact on survival (<jats:italic>P<\/jats:italic>\u2009=\u2009.3 and .17, respectively). The current study represents a retrospective analysis and suggests significantly decreased OS and MFFS in ET patients diagnosed after the FDA approval date of anagrelide. Whether or not anagrelide therapy was to blame for the worsening of OS and MFFS over time cannot be assumed and requires validation in a prospective study.<\/jats:p>","DOI":"10.1002\/ajh.25294","type":"journal-article","created":{"date-parts":[[2018,9,25]],"date-time":"2018-09-25T16:11:45Z","timestamp":1537891905000},"page":"5-9","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Decreased survival and increased rate of fibrotic progression in essential thrombocythemia chronicled after the FDA approval date of anagrelide"],"prefix":"10.1002","volume":"94","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4605-3821","authenticated-orcid":false,"given":"Ayalew","family":"Tefferi","sequence":"first","affiliation":[{"name":"Divisions of Hematology Mayo Clinic  Rochester 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