{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,14]],"date-time":"2026-09-14T13:13:52Z","timestamp":1789391632750,"version":"build-2803163510"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2015,5,20]],"date-time":"2015-05-20T00:00:00Z","timestamp":1432080000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["European J of Haematology"],"published-print":{"date-parts":[[2016,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The management of patients with chronic lymphocytic leukaemia (<jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content>) has improved with the utilisation of ofatumumab as a novel anti\u2010<jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>20 monoclonal antibody. However, as half of the patients fail to respond to the treatment, the aim of this study was to evaluate circulating <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cell depletion and clinical response according to the context of complement activation and Fc\u03b3<jats:styled-content style=\"fixed-case\">RIIIA<\/jats:styled-content> polymorphism in ten <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patients with relapsed\/refractory disease. At the end of the treatment, results indicated that circulating <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>5<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>19<jats:sup>+<\/jats:sup> <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cell depletion was major (&lt;0.01\u00a0\u00d7\u00a010<jats:sup>9<\/jats:sup>\/L) in 4 of 10 patients, partial (&gt;50% decrease) in 4 of 10 patients and ineffective for the two other patients. No clinical modifications were observed following ofatumumab introduction. Ofatumumab administration leads to a rapid and important exhaustion of complement C4 levels in patients with initial lymphocytosis. C4 exhaustion was accelerated in a non\u2010responder patient, and incomplete in two patients with partial circulating depletion. Moreover, delaying weekly to monthly ofatumumab injections improved <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cell depletion in two patients. Fc\u03b3<jats:styled-content style=\"fixed-case\">RIIIA<\/jats:styled-content> 158 polymorphism (<jats:styled-content style=\"fixed-case\">FF <\/jats:styled-content><jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>6 and <jats:styled-content style=\"fixed-case\">VF <\/jats:styled-content><jats:italic>n\u00a0<\/jats:italic>=<jats:italic>\u00a0<\/jats:italic>4) was not associated with major and\/or partial circulating <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> cell depletion. In conclusion, ofatumumab induces an important C4 exhaustion that needs to be taken into account when treating <jats:styled-content style=\"fixed-case\">CLL<\/jats:styled-content> patients with ofatumumab.<\/jats:p>","DOI":"10.1111\/ejh.12573","type":"journal-article","created":{"date-parts":[[2015,4,24]],"date-time":"2015-04-24T08:45:49Z","timestamp":1429865149000},"page":"229-235","source":"Crossref","is-referenced-by-count":14,"title":["Ofatumumab capacity to deplete B cells from chronic lymphocytic leukaemia is affected by C4 complement exhaustion"],"prefix":"10.1111","volume":"96","author":[{"given":"Adrian","family":"Tempescul","sequence":"first","affiliation":[{"name":"Department of Clinical Haematology Institute of Oncology and Haematology CHRU morvan Brest France"},{"name":"INSERM ESPRI ERI29 Laboratory of Immunotherapy and B Cell Diseases Reseau Epigenetique et Reseau Canaux Ioniques du Canc\u00e9ropole Grand Ouest Brest 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