{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T06:26:34Z","timestamp":1783578394002,"version":"3.55.0"},"reference-count":30,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2025,12,1]],"date-time":"2025-12-01T00:00:00Z","timestamp":1764547200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000054","name":"National Cancer Institute","doi-asserted-by":"publisher","award":["UO1CA257679"],"award-info":[{"award-number":["UO1CA257679"]}],"id":[{"id":"10.13039\/100000054","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,4,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Elevated absolute lymphocyte count is often used as a first indication for diagnostic investigation of chronic lymphocytic leukemia (CLL). The absolute risk of CLL as a function of age, sex, and absolute lymphocyte count has not been described.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We used information about prediagnostic absolute lymphocyte cell count on 475\u2009399 longitudinally followed research participants from UK Biobank, with a median follow-up of 11.6\u2009years, during which 854 participants were diagnosed with CLL. A CLL risk model was developed based on sex, age at recruitment, and prediagnostic absolute lymphocyte count using flexible parametric survival modelling.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Compared with research participants who had absolute lymphocyte counts below 2 \u00d7\u2009109\/L, the risk of CLL was almost 8 times higher for individuals with absolute lymphocyte counts of 3 to 4 \u00d7\u2009109\/L (hazard ratio\u2009=\u20097.76, 95% CI\u2009=\u20096.24 to 9.65). The absolute risk of CLL was 2-fold higher in male than in female individuals. For 60-year-old persons with absolute lymphocyte counts of 5 \u00d7109\/L, 10-year CLL risk was estimated at 6.5% (95% CI\u2009=\u20095.6% to 7.5%) for men and 3.5% (95% CI\u2009=\u20093.0% to 4.1%) for women. The 10-year risk of CLL for participants with absolute lymphocyte counts of 5 \u00d7109\/L varied between 0.91% (95% CI\u2009=\u20090.68% to 1.2%) for a 40-year-old woman and 12% (95% CI\u2009=\u200911% to 15%) for a 70-year-old man.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>The absolute risk of CLL is strongly influenced by age, sex, and absolute lymphocyte count. A crude absolute lymphocyte count cutoff to indicate further investigation for CLL without taking age and sex into consideration will identify some individuals who are at low risk. These results may be considered when establishing guidelines for clinical management in patients with elevated absolute lymphocyte counts.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/jnci\/djaf338","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T13:05:53Z","timestamp":1764162353000},"page":"636-642","source":"Crossref","is-referenced-by-count":1,"title":["Lymphocyte count and risk of chronic lymphocytic leukemia"],"prefix":"10.1093","volume":"118","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3541-2027","authenticated-orcid":false,"given":"Simon","family":"Pahnke","sequence":"first","affiliation":[{"name":"Department of Immunology, Genetics and Pathology, Cancer Precision Medicine, Uppsala University , Uppsala,","place":["Sweden"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2308-9880","authenticated-orcid":false,"given":"Karine","family":"Alcala","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC\/World Health Organization) , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Connie","family":"Bulos Salim","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC\/World Health Organization) , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2847-1993","authenticated-orcid":false,"given":"Ricardo","family":"Cortez Cardoso Penha","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC\/World Health Organization) , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8055-3729","authenticated-orcid":false,"given":"Hanla A","family":"Park","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC\/World Health Organization) , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1787-3874","authenticated-orcid":false,"given":"James","family":"Mckay","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC\/World Health Organization) , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3116-5081","authenticated-orcid":false,"given":"Mattias","family":"Johansson","sequence":"additional","affiliation":[{"name":"Genomic Epidemiology Branch, International Agency for Research on Cancer (IARC\/World Health Organization) , Lyon,","place":["France"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,12,1]]},"reference":[{"key":"2026040911353519800_djaf338-B1","doi-asserted-by":"publisher","first-page":"5446","DOI":"10.1182\/blood-2007-06-093906","article-title":"Guidelines for the diagnosis and treatment of chronic lymphocytic leukemia: a report from the International Workshop on Chronic Lymphocytic Leukemia updating the National Cancer Institute\u2013Working Group 1996 guidelines","volume":"111","author":"Hallek","year":"2008","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B2","doi-asserted-by":"publisher","first-page":"2745","DOI":"10.1182\/blood-2017-09-806398","article-title":"iwCLL guidelines for diagnosis, indications for treatment, response assessment, and supportive management of CLL","volume":"131","author":"Hallek","year":"2018","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B3","doi-asserted-by":"publisher","first-page":"23","DOI":"10.1016\/j.annonc.2020.09.019","article-title":"Chronic lymphocytic leukaemia: ESMO Clinical Practice Guidelines for diagnosis, treatment and follow-up","volume":"32","author":"Eichhorst","year":"2021","journal-title":"Ann Oncol"},{"key":"2026040911353519800_djaf338-B4","doi-asserted-by":"publisher","first-page":"e247020","DOI":"10.6004\/jnccn.2024.7020","article-title":"Clinical risks for chronic lymphocytic leukemia","volume":"22","author":"Brown","year":"2024","journal-title":"J Natl Compr Canc Netw"},{"key":"2026040911353519800_djaf338-B5","doi-asserted-by":"publisher","first-page":"647","DOI":"10.3324\/haematol.2008.003632","article-title":"Elevated risk of chronic lymphocytic leukemia and other indolent non-Hodgkin\u2019s lymphomas among relatives of patients with chronic lymphocytic leukemia","volume":"94","author":"Goldin","year":"2009","journal-title":"Haematologica"},{"key":"2026040911353519800_djaf338-B6","doi-asserted-by":"publisher","first-page":"2046","DOI":"10.1182\/blood.2020006322","article-title":"Natural history of monoclonal B-cell lymphocytosis among relatives in CLL families","volume":"137","author":"Slager","year":"2021","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B7","doi-asserted-by":"publisher","first-page":"454","DOI":"10.1182\/blood-2015-02-585059","article-title":"Monoclonal B-cell lymphocytosis and early-stage chronic lymphocytic leukemia: diagnosis, natural history, and risk stratification","volume":"126","author":"Strati","year":"2015","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B8","doi-asserted-by":"publisher","first-page":"918","DOI":"10.1001\/jama.2023.1946","article-title":"Diagnosis and treatment of chronic lymphocytic leukemia: a review","volume":"329","author":"Shadman","year":"2023","journal-title":"JAMA"},{"key":"2026040911353519800_djaf338-B9","doi-asserted-by":"publisher","first-page":"747","DOI":"10.1038\/s41375-020-0980-0","article-title":"Antimicrobial use before chronic lymphocytic leukemia: a retrospective cohort study","volume":"35","author":"Andersen","year":"2021","journal-title":"Leukemia"},{"key":"2026040911353519800_djaf338-B10","doi-asserted-by":"publisher","first-page":"575","DOI":"10.1056\/NEJMoa075290","article-title":"Monoclonal B-cell lymphocytosis and chronic lymphocytic leukemia","volume":"359","author":"Rawstron","year":"2008","journal-title":"N Engl J Med"},{"key":"2026040911353519800_djaf338-B11","doi-asserted-by":"publisher","first-page":"e1001779","DOI":"10.1371\/journal.pmed.1001779","article-title":"UK Biobank: an open access resource for identifying the causes of a wide range of complex diseases of middle and old age","volume":"12","author":"Sudlow","year":"2015","journal-title":"PLoS Med"},{"key":"2026040911353519800_djaf338-B12","doi-asserted-by":"publisher","first-page":"361","DOI":"10.1007\/s00103-015-2297-0","article-title":"Genetics, lifestyle and environment. UK Biobank is an open access resource following the lives of 500,000 participants to improve the health of future generations","volume":"59","author":"Trehearne","year":"2016","journal-title":"Bundesgesundheitsblatt Gesundheitsforschung Gesundheitsschutz"},{"key":"2026040911353519800_djaf338-B13","author":"Froggatt","year":"2017"},{"key":"2026040911353519800_djaf338-B14","doi-asserted-by":"publisher","first-page":"396","DOI":"10.1097\/PPO.0b013e31826cda2d","article-title":"Small lymphocytic lymphoma and chronic lymphocytic leukemia: are they the same disease?","volume":"18","author":"Santos","year":"2012","journal-title":"Cancer J"},{"key":"2026040911353519800_djaf338-B15","doi-asserted-by":"publisher","first-page":"622","DOI":"10.6004\/jnccn.2022.0031","article-title":"NCCN Guidelines\u00ae insights: chronic lymphocytic leukemia\/small lymphocytic lymphoma, version 3.2022: featured updates to the NCCN guidelines","volume":"20","author":"Wierda","year":"2022","journal-title":"J Natl Compr Cancer Network"},{"key":"2026040911353519800_djaf338-B16","doi-asserted-by":"publisher","first-page":"1506","DOI":"10.1056\/NEJM199805213382104","article-title":"Chlorambucil in indolent chronic lymphocytic leukemia. French Cooperative Group on Chronic Lymphocytic Leukemia","volume":"338","author":"Dighiero","year":"1998","journal-title":"N Engl J Med"},{"key":"2026040911353519800_djaf338-B17","doi-asserted-by":"publisher","first-page":"2038","DOI":"10.1038\/s41375-020-0747-7","article-title":"Early treatment with FCR versus watch and wait in patients with stage Binet A high-risk chronic lymphocytic leukemia (CLL): a randomized phase 3 trial","volume":"34","author":"Herling","year":"2020","journal-title":"Leukemia"},{"key":"2026040911353519800_djaf338-B18","doi-asserted-by":"publisher","first-page":"3182","DOI":"10.1002\/cncr.25853","article-title":"Experience with rituximab immunotherapy as an early intervention in patients with Rai stage 0 to II chronic lymphocytic leukemia","volume":"117","author":"Ferrajoli","year":"2011","journal-title":"Cancer"},{"key":"2026040911353519800_djaf338-B19","doi-asserted-by":"publisher","first-page":"819","DOI":"10.1309\/DU0B-EBFL-3EXY-VUFP","article-title":"Transient stress lymphocytosis: an immunophenotypic characterization of the most common cause of newly identified adult lymphocytosis in a tertiary hospital","volume":"117","author":"Karandikar","year":"2002","journal-title":"Am J Clin Pathol"},{"key":"2026040911353519800_djaf338-B20","doi-asserted-by":"publisher","first-page":"458","DOI":"10.1093\/ajcp\/aqz057","article-title":"Establishing absolute lymphocyte count thresholds for further review of peripheral blood lymphocytosis to judiciously screen for monoclonal B-cell populations in older adults","volume":"152","author":"Muscara","year":"2019","journal-title":"Am J Clin Pathol"},{"key":"2026040911353519800_djaf338-B21","doi-asserted-by":"publisher","first-page":"512","DOI":"10.1038\/leu.2009.287","article-title":"Monoclonal B-cell lymphocytosis (MBL): biology, natural history and clinical management","volume":"24","author":"Shanafelt","year":"2010","journal-title":"Leukemia"},{"key":"2026040911353519800_djaf338-B22","doi-asserted-by":"publisher","first-page":"1557","DOI":"10.1182\/blood.2021012890","article-title":"High-risk subtypes of chronic lymphocytic leukemia are detectable as early as 16 years prior to diagnosis","volume":"139","author":"Kolijn","year":"2022","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B23","doi-asserted-by":"publisher","first-page":"784","DOI":"10.1111\/bjh.17857","article-title":"Chronic lymphocytic leukaemia clones are detectable decades before diagnosis","volume":"196","author":"Vojdeman","year":"2022","journal-title":"Br J Haematol"},{"key":"2026040911353519800_djaf338-B24","doi-asserted-by":"publisher","first-page":"3613","DOI":"10.1200\/JCO.21.01785","article-title":"Absolute risk of oropharyngeal cancer after an HPV16-E6 serology test and potential implications for screening: results from the Human Papillomavirus Cancer Cohort Consortium","volume":"40","author":"Robbins","year":"2022","journal-title":"J Clin Oncol"},{"key":"2026040911353519800_djaf338-B25","doi-asserted-by":"publisher","first-page":"161","DOI":"10.1038\/s41408-022-00756-9","article-title":"Chronic lymphocytic leukemia treatment algorithm 2022","volume":"12","author":"Hampel","year":"2022","journal-title":"Blood Cancer J"},{"key":"2026040911353519800_djaf338-B26","first-page":"92","article-title":"Early intervention in asymptomatic chronic lymphocytic leukemia","volume":"19","author":"Muchtar","year":"2021","journal-title":"Clin Adv Hematol Oncol"},{"key":"2026040911353519800_djaf338-B27","doi-asserted-by":"publisher","first-page":"2630","DOI":"10.1182\/blood-2021-144780","article-title":"Randomized, phase III study of early intervention with venetoclax and obinutuzumab versus delayed therapy with venetoclax and obinutuzumab in newly diagnosed asymptomatic high-risk patients with chronic lymphocytic leukemia\/small lymphocytic lymphoma (CLL\/SLL): EVOLVE CLL\/SLL study (SWOG S1925; NCT#04269902","volume":"138(suppl 1)","author":"Stephens","year":"2021","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B28","doi-asserted-by":"crossref","first-page":"2541","DOI":"10.1182\/blood-2017-11-814608","article-title":"Association of polygenic risk score with the risk of chronic lymphocytic leukemia and monoclonal B-cell lymphocytosis","volume":"131","author":"Kleinstern","year":"2018","journal-title":"Blood"},{"key":"2026040911353519800_djaf338-B29","doi-asserted-by":"publisher","first-page":"119","DOI":"10.1038\/s41375-021-01344-9","article-title":"Polygenic risk score and risk of monoclonal B-cell lymphocytosis in Caucasians and risk of chronic lymphocytic leukemia (CLL) in African Americans","volume":"36","author":"Kleinstern","year":"2022","journal-title":"Leukemia"},{"key":"2026040911353519800_djaf338-B30","doi-asserted-by":"publisher","first-page":"1399","DOI":"10.1182\/blood.2023019609","article-title":"Genetic drivers in the natural history of chronic lymphocytic leukemia development as early as 16 years before diagnosis","volume":"142","author":"Kolijn","year":"2023","journal-title":"Blood"}],"container-title":["JNCI: Journal of the National Cancer Institute"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/jnci\/advance-article-pdf\/doi\/10.1093\/jnci\/djaf338\/65667159\/djaf338.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/4\/636\/65667159\/djaf338.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/jnci\/article-pdf\/118\/4\/636\/65667159\/djaf338.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,4,9]],"date-time":"2026-04-09T15:50:12Z","timestamp":1775749812000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/jnci\/article\/118\/4\/636\/8362230"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,12,1]]},"references-count":30,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2025,12,1]]},"published-print":{"date-parts":[[2026,4,1]]}},"URL":"https:\/\/doi.org\/10.1093\/jnci\/djaf338","relation":{},"ISSN":["0027-8874","1460-2105"],"issn-type":[{"value":"0027-8874","type":"print"},{"value":"1460-2105","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,4]]},"published":{"date-parts":[[2025,12,1]]}}}