{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,16]],"date-time":"2026-07-16T22:47:53Z","timestamp":1784242073351,"version":"3.55.0"},"reference-count":22,"publisher":"Wiley","issue":"7","license":[{"start":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T00:00:00Z","timestamp":1673222400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2023,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Recognizing intolerance or resistance to hydroxyurea (HU), which is related to the high risk of a disease transformation and reduced survival in essential thrombocythemia (ET), is crucial to making a reasonable decision about second\u2010line therapy. We assessed the prognostic impact of the modified European LeukemiaNet (mELN) criteria used in a recent MAJIC\u2010ET trial by analyzing the incidence of resistance or intolerance to HU and the survival outcome compared with those of the ELN criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We retrospectively compared the development of HU resistance or intolerance according to the ELN and mELN criteria for 148 high\u2010risk ET patients receiving HU between 2014 and 2018. The maximum tolerated dose for defining HU resistance was used in the mELN criteria.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The median age of patients was 65\u2009years (range, 36\u201387), with a median follow\u2010up of 3.6\u2009years (range, 1.1\u20136.4). Two thromboembolic events were observed during HU treatment. When applying the ELN criteria, 10 patients (6.9%) were resistant (<jats:italic>n<\/jats:italic>\u00a0=\u00a05 [3.4%]) or intolerant (<jats:italic>n<\/jats:italic>\u00a0=\u00a05 [3.4%]) to HU in comparison with 22 patients (15%, 14 [9.8%]) resistant and 8 [5.5%] intolerant when applying the mELN criteria. Transformation to myelofibrosis and acute myeloid leukemia occurred in 2 (1.4%) patients and 1 (0.7%) patient, respectively, as defined by the ELN criteria compared with 3 (2.1%) and 2 (1.4%) patients as defined by the mELN criteria. In multivariate analysis of transformation\u2010free survival, HU resistance defined by the mELN criteria but not the ELN criteria was an independent prognostic factor. In addition, HU resistance as defined by both sets of criteria was an independent risk factor for inferior overall survival. Intolerance of HU did not have any prognostic impact on survival.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>The mELN criteria are useful for identifying high\u2010risk ET patients who might be eligible for second\u2010line therapy in practice, which should be validated in a prospective setting.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cam4.5602","type":"journal-article","created":{"date-parts":[[2023,1,9]],"date-time":"2023-01-09T16:24:37Z","timestamp":1673281477000},"page":"8073-8082","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Prognostic value of modified criteria for hydroxyurea resistance or intolerance in patients with high\u2010risk essential thrombocythemia"],"prefix":"10.1002","volume":"12","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4516-7990","authenticated-orcid":false,"given":"Young Hoon","family":"Park","sequence":"first","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Internal Medicine Ewha Womans University Mokdong Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sewon","family":"Lee","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Internal Medicine Ewha Womans University Mokdong Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeung\u2010Chul","family":"Mun","sequence":"additional","affiliation":[{"name":"Division of Hematology\u2010Oncology, Department of Internal Medicine Ewha Womans University Mokdong Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dong Jin","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Laboratory Medicine Ewha Womans University Mokdong Hospital  Seoul Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2023,1,9]]},"reference":[{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajh.25303"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMcp1816082"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.6004\/jnccn.2018.7095"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2016-05-643346"},{"key":"e_1_2_11_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.clml.2016.02.029"},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1038\/bcj.2015.94"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199504273321704"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-07-443770"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa043800"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0609.2007.00940.x"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2010.31.8436"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.leu.2404473"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2010.08430.x"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-05-785790"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000189381"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2012.083097"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.mayocp.2015.05.014"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.thromres.2015.02.023"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.3346\/jkms.2016.31.10.1579"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11239-015-1218-2"},{"key":"e_1_2_11_22_1","first-page":"1333","article-title":"Pegylated 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