{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T02:19:52Z","timestamp":1760149192698,"version":"build-2065373602"},"reference-count":65,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2023,7,5]],"date-time":"2023-07-05T00:00:00Z","timestamp":1688515200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Research Manitoba CLLuster","award":["761063860","761127734"],"award-info":[{"award-number":["761063860","761127734"]}]},{"name":"Janssen Pharmaceuticals","award":["761063860","761127734"],"award-info":[{"award-number":["761063860","761127734"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Current Oncology"],"abstract":"<jats:p>FISH cytogenetics, TP53 sequencing, and IGHV mutational status are increasingly used as prognostic and predictive markers in chronic lymphocytic leukemia (CLL), particularly as components of the CLL International Prognostic Index (CLL-IPI) and in directing therapy with novel agents. However, testing outside of clinical trials is not routinely available in Canada. As a centralized CLL clinic at CancerCare Manitoba, we are the first Canadian province to evaluate clinical outcomes and survivorship over a long period of time, incorporating the impact of molecular testing and the CLL-IPI score. We performed a retrospective analysis on 1315 patients diagnosed between 1960 and 2018, followed over a 12-year period, where 411 patients had molecular testing and 233 patients had a known CLL-IPI score at the time of treatment. Overall, 40.3% (n = 530) of patients received treatment, and 47.5% (n = 252) of patients received multiple lines of therapy. High-risk FISH and CLL-IPI (4-10) were associated with higher mortality (HR 2.03, p = 0.001; HR 2.64, p = 0.002), consistent with other studies. Over time, there was an increase in the use of targeted agents in treated patients. The use of Bruton\u2019s tyrosine kinase inhibitors improved survival in patients with unmutated IGHV and\/or TP53 aberrations (HR 2.20, p = 0.001). The major cause of death in patients who received treatment was treatment\/disease-related (32%, n = 42) and secondary malignancies (57%, n = 53) in those who were treatment-na\u00efve. Our data demonstrate the importance of molecular testing in determining survivorship in CLL and underpinning the likely immune differences in outcomes for those treated for CLL.<\/jats:p>","DOI":"10.3390\/curroncol30070472","type":"journal-article","created":{"date-parts":[[2023,7,6]],"date-time":"2023-07-06T00:54:41Z","timestamp":1688604881000},"page":"6411-6431","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Clinical Outcomes in a Large Canadian Centralized CLL Clinic Based on Treatment and Molecular Factors over a Decade"],"prefix":"10.3390","volume":"30","author":[{"given":"Jiayu","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lin","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bryan","family":"Tordon","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oliver","family":"Bucher","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zoann","family":"Nugent","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan","family":"Landego","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nicole","family":"Bourrier","sequence":"additional","affiliation":[{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kelsey","family":"Uminski","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Kevin","family":"Brown","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mandy","family":"Squires","sequence":"additional","affiliation":[{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Aaron J.","family":"Marshall","sequence":"additional","affiliation":[{"name":"Department of Immunology, Max Rady College of Medicine, University of Manitoba, Rady Faculty of Health Sciences, Winnipeg, MB R3E 0T5, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sachin","family":"Katyal","sequence":"additional","affiliation":[{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Department of Pharmacology and Therapeutics, Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Salah","family":"Mahmud","sequence":"additional","affiliation":[{"name":"Department of Community Health Sciences, Max Rady College of Medicine Community Health Sciences, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0044-7545","authenticated-orcid":false,"given":"Kathleen","family":"Decker","sequence":"additional","affiliation":[{"name":"Department of Epidemiology, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"},{"name":"Department of Community Health Sciences, Max Rady College of Medicine Community Health Sciences, Winnipeg, MB R3E 0W2, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marc","family":"Geirnaert","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9762-3156","authenticated-orcid":false,"given":"David E.","family":"Dawe","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0119-732X","authenticated-orcid":false,"given":"Spencer B.","family":"Gibson","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Genetics Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6614-083X","authenticated-orcid":false,"given":"James B.","family":"Johnston","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7415-8818","authenticated-orcid":false,"given":"Versha","family":"Banerji","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Department of Biochemistry and Medical Genetics Max Rady College of Medicine, Rady Faculty of Health Sciences, University of Manitoba, Winnipeg, MB R3E 3P4, Canada"},{"name":"Paul Albrechtsen Research Institute CancerCare Manitoba, Winnipeg, MB R3E 0V9, Canada"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1463","DOI":"10.1016\/j.leukres.2009.06.013","article-title":"High incidence of chronic lymphocytic leukemia (CLL) diagnosed by immunophenotyping: A population-based Canadian cohort","volume":"33","author":"Seftel","year":"2009","journal-title":"Leuk. 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