title: Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: a prospective study.
abstract: Immune-related deficiencies are well-known complications of chronic lymphocytic leukemia (CLL). Although recent data indicate that almost all CLL patients are preceded by a monoclonal B-cell lymphocytosis precursor state, patterns of immune defects preceding CLL diagnosis are unclear. We identified 109 persons who developed CLL from the prospective and nationwide Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with 77 469 participants, with serially collected prediagnostic serum samples. We assayed monoclonal (M)-proteins, kappa/lambda free light chains (FLCs) in prediagnostic obtained up to 9.8 years before CLL diagnosis. The prevalence of an abnormal FLC ratio, M-protein, and hypogamma-globulinemia before CLL diagnosis was 38% (95% confidence interval, 29%-47%), 13% (7%-21%), and 3% (1%-8%), respectively. M-proteins and abnormal FLC ratios were detected up to 9.8 years before CLL diagnosis in a total of 48 persons (44%). Hypogammaglobulinemia was not present until 3 years before the diagnosis of CLL. Among 37 patients with information on tumor cell immunophenotype, an association between immunophenotype and involved FLC (P = .024, Fisher exact test) was observed. Among 61 persons with a normal FLC ratio and without an M-protein, 17 had elevated kappa and/or lambda FLC levels, indicating polyclonal B-cell activation in 17 of 109 (16%) patients. These findings support a role for chronic immune stimulation in CLL genesis.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
authors.forename: Huei-Ting
authors.initials: HT
authors.lastname: Tsai
authors.forename: Neil E
authors.initials: NE
authors.lastname: Caporaso
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kyle
authors.forename: Jerry A
authors.initials: JA
authors.lastname: Katzmann
authors.forename: Angela
authors.initials: A
authors.lastname: Dispenzieri
authors.forename: Richard B
authors.initials: RB
authors.lastname: Hayes
authors.forename: Gerald E
authors.initials: GE
authors.lastname: Marti
authors.forename: Maher
authors.initials: M
authors.lastname: Albitar
authors.forename: Paolo
authors.initials: P
authors.lastname: Ghia
authors.forename: S Vincent
authors.initials: SV
authors.lastname: Rajkumar
authors.forename: Ola
authors.initials: O
authors.lastname: Landgren
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D001402:B-Lymphocytes / Q000276:immunology; D005260:Female; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000097:blood*; D007136:Immunoglobulins / Q000097:blood*; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000097:blood* / Q000150:complications / Q000276:immunology*; D008213:Lymphocyte Activation / Q000276:immunology; D008297:Male; D008875:Middle Aged; D015337:Multicenter Studies as Topic; D016032:Randomized Controlled Trials as Topic
chemical_list: D007147:Immunoglobulin Light Chains; D007136:Immunoglobulins; C009823:M-proteins (Myeloma)