{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,14]],"date-time":"2026-03-14T06:44:57Z","timestamp":1773470697377,"version":"3.50.1"},"reference-count":35,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T00:00:00Z","timestamp":1551916800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000027","name":"Institute of Cancer Research","doi-asserted-by":"publisher","award":["153291"],"award-info":[{"award-number":["153291"]}],"id":[{"id":"10.13039\/501100000027","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009447","name":"Leukemia and Lymphoma Society of Canada","doi-asserted-by":"publisher","award":["operating grant"],"award-info":[{"award-number":["operating grant"]}],"id":[{"id":"10.13039\/100009447","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2019,4]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Methods to deepen clinical responses to ibrutinib are needed to improve outcomes for patients with chronic lymphocytic leukemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>). This study aimed to determine the safety and efficacy of combining a janus kinase (<jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>)\u2010inhibitor with ibrutinib because <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\u2010mediated cytokine\u2010signals support <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cells and may not be inhibited by ibrutinib. The <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>1\/2 inhibitor ruxolitinib was prescribed to 12 <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patients with abnormal serum beta\u20102 microglobulin levels after 6\u00a0months or persistent lymphadenopathy or splenomegaly after 12\u00a0months on ibrutinib using a 3\u00a0+\u00a03 phase 1 trial design (<jats:styled-content style=\"fixed-case\">NCT<\/jats:styled-content>02912754). Ibrutinib was continued at 420\u00a0mg daily and ruxolitinib was added at 5, 10, 15, or 20\u00a0mg <jats:styled-content style=\"fixed-case\">BID<\/jats:styled-content> for 3\u00a0weeks out of five for seven cycles. The break was mandated to avoid anemia and thrombocytopenia observed with ruxolitinib as a single agent in <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>. The combination was well\u2010tolerated without dose\u2010limiting toxicities. Cyclic changes in platelets, lymphocytes, and associated chemokines and thrombopoietic factors were observed and partial response criteria were met in 2 of 12 patients. The results suggest that <jats:styled-content style=\"fixed-case\">JAK<\/jats:styled-content>\u2010signaling helps <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cells persist in the presence of ibrutinib and ruxolitinib with ibrutinib is well\u2010tolerated and may be a useful regiment to use in combination therapies for <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>.<\/jats:p>","DOI":"10.1002\/cam4.2042","type":"journal-article","created":{"date-parts":[[2019,3,7]],"date-time":"2019-03-07T13:47:36Z","timestamp":1551966456000},"page":"1540-1550","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":18,"title":["Persistent janus kinase\u2010signaling in chronic lymphocytic leukemia patients on ibrutinib: Results of a phase I trial"],"prefix":"10.1002","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0783-7554","authenticated-orcid":false,"given":"David E.","family":"Spaner","sequence":"first","affiliation":[{"name":"Biology Platform Sunnybrook Research Institute Toronto Canada"},{"name":"Department of Medical Biophysics University of Toronto Toronto Canada"},{"name":"Sunnybrook Odette Cancer Center Toronto Canada"},{"name":"Department of Medicine University of Toronto Toronto Canada"},{"name":"Department of Immunology University of Toronto Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lindsay","family":"McCaw","sequence":"additional","affiliation":[{"name":"Biology Platform Sunnybrook Research Institute Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guizhei","family":"Wang","sequence":"additional","affiliation":[{"name":"Biology Platform Sunnybrook Research Institute Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hubert","family":"Tsui","sequence":"additional","affiliation":[{"name":"Department of Immunology University of Toronto Toronto Canada"},{"name":"Division of Hematopathology Sunnybrook Health Sciences Center Toronto Canada"},{"name":"Department of Laboratory Medicine and Pathobiology University of Toronto Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yonghong","family":"Shi","sequence":"additional","affiliation":[{"name":"Biology Platform Sunnybrook Research Institute Toronto Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2019,3,7]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-10-606038"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-02-622472"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2017-01-761536"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-12-618678"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.11618"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-15-1965"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-11-682906"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110557"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30558-7"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.3324\/haematol.2015.135418"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S2352-3026(16)30194-6"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1002\/prp2.156"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.29794"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.acra.2013.01.011"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1093\/jnci\/djp079"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/0021-9681(61)90060-1"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2007-06-093906"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/S1470-2045(16)30029-8"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.1995.tb05291.x"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V99.7.2612"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.4049\/jimmunol.1200310"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI89756"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.autrev.2013.10.010"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1158\/1535-7163.MCT-14-0448"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2012-08-452607"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M408481200"},{"key":"e_1_2_8_28_1","first-page":"109","article-title":"In vivo suppression of erythropoiesis by tumor necrosis factor\u2010alpha (TNF\u2010alpha): reversal with exogenous erythropoietin (EPO)","volume":"18","author":"Johnson CS","year":"1990","journal-title":"Exp Hematol"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood.V79.4.942.942"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2014-03-560441"},{"key":"e_1_2_8_31_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2141.2000.02314.x"},{"key":"e_1_2_8_32_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41375-019-0381-4"},{"key":"e_1_2_8_33_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2018-05-853564"},{"key":"e_1_2_8_34_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2015-12-687814"},{"key":"e_1_2_8_35_1","doi-asserted-by":"publisher","DOI":"10.1111\/bjh.15613"},{"key":"e_1_2_8_36_1","doi-asserted-by":"publisher","DOI":"10.1182\/blood-2010-05-285999"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fcam4.2042","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2042","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.2042","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.2042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,1,2]],"date-time":"2024-01-02T21:15:10Z","timestamp":1704230110000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.2042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,3,7]]},"references-count":35,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2019,4]]}},"alternative-id":["10.1002\/cam4.2042"],"URL":"https:\/\/doi.org\/10.1002\/cam4.2042","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,3,7]]},"assertion":[{"value":"2018-11-30","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-02-04","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2019-03-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}