CD52 is a glycoprotein expressed on normal as well as leukemic immune cells and shed as soluble CD52 (sCD52). We studied sCD52 levels in three CLL cohorts: the 'early', the 'high-risk', and the 'ibrutinib-treated'. The 'high-risk' patients had significantly higher sCD52 levels than the 'early' patients. For the 'early' patients, high sCD52 levels were associated with a significantly shorter time to first treatment. Regarding prognostic factors, no clear correlations with stage, IGHV, or beta-2-microglobulin were found; in a cox multivariate analysis of the 'early' patients, sCD52 and IGHV both had independent prognostic value. Following chemo-immunotherapy, sCD52 decreased in parallel with leukocytes while during ibrutinib treatment and ibrutinib-induced ymphocytosis, sCD52 decreased along with lymph node reductions. In vitro IgM stimulation of CLL cells led to increased sCD52 levels in the medium. Our findings indicate that sCD52 reflects disease activity and potentially treatment efficacy in CLL.

b Department of Clinical Biochemistry Bispebjerg Frederiksberg Hospital Copenhagen Denmark

c Hematology Branch National Heart Lung and Blood Institute National Institutes of Health Bethesda MD USA

Department of Clinical Hematology 3rd Faculty of Medicine Charles University Hospital Kralovske Vinohrady Prague Czech Republic

Department of Hematology Rigshospitalet Copenhagen Denmark

Department of Microbiology Rigshospitalet Copenhagen Denmark

e Department of Hematology Leiden University Medical Centre Leiden The Netherlands

f Department of Hematology Oslo University Hospital and Institute of Clinical Medicine University of Oslo Oslo Norway

g Department of Hematology Turku Central University Hospital Turku Finland

h Division of Hematology Department of Medicine at Huddinge Karolinska Institute Stockholm Sweden

i Department of Hematology Hadassah University Hospital Hebrew University Medical School Jerusalem Israel

j Department of Hematology Stuivenberg Hospital Antwerpen Belgium

k Department of Hematology Erasmus MC Cancer Center Rotterdam The Netherlands

l HOVON Data Centre Erasmus MC Rotterdam The Netherlands

m Department of Internal Medicine Gelderse Vallei Hospital Amersfoort The Netherlands

o Lymphoid Malignancies Maria Sklodowska Curie Memorial Institute and Oncology Centre Warszawa Poland

p Department of Hematology Academisch Medisch Centrum Amsterdam The Netherlands

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