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Overall survival (<jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content>) was similar in the three randomized arms. With fludarabine\u2010plus\u2010cyclophosphamide (<jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content>), progression\u2010free survival (<jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content>) was significantly longer (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001), but <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> after progression significantly shorter, than in the chlorambucil or fludarabine arms (<jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001). 614\/777 patients progressed; 524 received second\u2010line and 260 third\u2010line therapy, with significantly better complete remission (<jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>) rates compared to first\u2010line in the chlorambucil arm (7% vs. 13% after second\u2010, 18% after third\u2010line), but worse in the <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content> arm (38% vs. 15% after both second and third\u2010line). <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> 10\u00a0years after progression was better after a second\u2010line <jats:styled-content style=\"fixed-case\">CR <\/jats:styled-content><jats:italic>versus<\/jats:italic> a partial response (36% vs. 16%) and better with <jats:styled-content style=\"fixed-case\">FC<\/jats:styled-content>\u2010based second\u2010line therapy (including rituximab in 20%) or a stem cell transplant (28%) <jats:italic>versus<\/jats:italic> all other treatments (10%, <jats:italic>P<\/jats:italic>\u00a0&lt;\u00a00\u00b70001). The 176 (24%) 10\u2010year survivors tended to be aged &lt;70\u00a0years, with a \u201cgood risk\u201d prognostic profile, stage A\u2010progressive, achieving at least one <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content>, with a first\u2010line <jats:styled-content style=\"fixed-case\">PFS<\/jats:styled-content> &gt;3\u00a0years and receiving \u22642 lines of treatment. In conclusion, clinical\/biological features and salvage treatments both influence the long\u2010term outcome. Second\u2010line therapies that induce a <jats:styled-content style=\"fixed-case\">CR<\/jats:styled-content> can improve <jats:styled-content style=\"fixed-case\">OS<\/jats:styled-content> in <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patients.<\/jats:p>","DOI":"10.1111\/bjh.13824","type":"journal-article","created":{"date-parts":[[2015,10,13]],"date-time":"2015-10-13T08:24:24Z","timestamp":1444724664000},"page":"228-237","update-policy":"http:\/\/dx.doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["The long\u2010term outcome of patients in the <scp>LRF CLL<\/scp>4 trial: the effect of salvage treatment and biological markers in those surviving 10\u00a0years"],"prefix":"10.1111","volume":"172","author":[{"given":"Monica","family":"Else","sequence":"first","affiliation":[{"name":"Division of Molecular Pathology The Institute of Cancer Research London 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