{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T04:28:57Z","timestamp":1789964937732,"version":"4.0.1"},"reference-count":32,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T00:00:00Z","timestamp":1462492800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000402","name":"Kay Kendall Leukaemia Fund","doi-asserted-by":"publisher","award":["KKL584"],"award-info":[{"award-number":["KKL584"]}],"id":[{"id":"10.13039\/501100000402","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C328\/A2738"],"award-info":[{"award-number":["C328\/A2738"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000289","name":"Cancer Research UK","doi-asserted-by":"publisher","award":["C328\/A2737"],"award-info":[{"award-number":["C328\/A2737"]}],"id":[{"id":"10.13039\/501100000289","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Br J Haematol"],"published-print":{"date-parts":[[2016,9]]},"abstract":"<jats:title>Summary<\/jats:title>\n                  <jats:p>\n                    Historically, an increase in the percentage and number of circulating prolymphocytes in chronic lymphocytic leukaemia (\n                    <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>\n                    ) has been associated with strong expression of surface immunoglobulin, trisomy 12 and a poor outcome. This study re\u2010examines the biological and clinical significance of increased peripheral blood prolymphocytes in 508 patients at entry into the randomized\n                    <jats:styled-content style=\"fixed-case\">UK<\/jats:styled-content>\n                    Leukaemia Research Fund\n                    <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>\n                    4 trial. It also investigates the associations between increased prolymphocytes and a comprehensive array of biomarkers. 270 patients (53%) had &lt;5% prolymphocytes, 167 (33%) had 5\u20139%, 60 (12%) had 10\u201314% and 11 (2%) had \u226515% prolymphocytes. We show that a higher proportion of prolymphocytes (\u226510%) was independently associated with\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">NOTCH<\/jats:styled-content>\n                      1\n                    <\/jats:italic>\n                    mutations (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00\u00b7006), absence of 13q deletion (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00\u00b7001), high\n                    <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>\n                    38 expression (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00\u00b702) and unmutated\n                    <jats:italic>\n                      <jats:styled-content style=\"fixed-case\">IGHV<\/jats:styled-content>\n                    <\/jats:italic>\n                    genes (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00\u00b701). Deaths due to Richter syndrome were significantly more common amongst patients who had \u226510% vs &lt;10% prolymphocytes (13% vs 2%) respectively (\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00\u00b70001). \u226510% prolymphocytes was also associated with a shorter progression\u2010free survival (Hazard ratio [\n                    <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\n                    ] 1\u00b750 [95% confidence interval [\n                    <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n                    ]: 1\u00b716\u20131\u00b793],\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0=\u00a00\u00b7002) and overall survival (\n                    <jats:styled-content style=\"fixed-case\">HR<\/jats:styled-content>\n                    1\u00b799 [95%\n                    <jats:styled-content style=\"fixed-case\">CI<\/jats:styled-content>\n                    : 1\u00b753\u20132\u00b759],\n                    <jats:italic>P<\/jats:italic>\n                    \u00a0&lt;\u00a00\u00b70001). Our data support the routine examination of blood films in\n                    <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>\n                    and suggest that a finding of an increased proportion of prolymphocytes may be a trigger for further evaluation of clinical and laboratory features of progressive disease.\n                  <\/jats:p>","DOI":"10.1111\/bjh.14132","type":"journal-article","created":{"date-parts":[[2016,5,6]],"date-time":"2016-05-06T03:18:48Z","timestamp":1462504728000},"page":"767-775","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":36,"title":["The morphology of CLL revisited: the clinical significance of prolymphocytes and correlations with prognostic\/molecular markers in the LRF CLL4 trial"],"prefix":"10.1111","volume":"174","author":[{"given":"David","family":"Oscier","sequence":"first","affiliation":[{"name":"Department of Molecular Pathology Royal Bournemouth Hospital Bournemouth UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Monica","family":"Else","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Estella","family":"Matutes","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ricardo","family":"Morilla","sequence":"additional","affiliation":[{"name":"Division of Molecular Pathology The Institute of Cancer Research London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan C.","family":"Strefford","sequence":"additional","affiliation":[{"name":"Cancer Sciences Faculty of Medicine University of Southampton Southampton 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