Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: A prospective study

Division of Cancer Epidemiology and Genetics, National Cancer Institute (NCI), National Institutes of Health (NIH), Bethesda, MD, USA.
Blood (Impact Factor: 10.45). 10/2009; 114(24):4928-32. DOI: 10.1182/blood-2009-08-237651
Source: PubMed


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.

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Available from: Gerald E Marti
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    • "During this procedure a small excess amount of light chains are produced and released in the plasma/serum in the form of serum immunoglobulin free light chains (sFLC). It has recently been found that 38% of patients eventually developing CLL displayed abnormal sFLC ratio (FLCR) up to 10 years before CLL diagnosis and another 16% had polyclonal sFLC elevation in the same time frame preceding diagnosis [8]. "
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    ABSTRACT: Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLC-kappa plus FLC-lambda in a CLL patients' series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients' followup was 32 months (range 4-228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment (P = 0.0005 and P = 0.000003, resp.) and overall survival (P = 0.05 and P = 0.003, resp.). They also correlated with β 2-microglobulin (P = 0.009 and P = 0.03, resp.), serum albumin (P = 0.009 for summated sFLC), hemoglobin (P < 0.001), abnormal LDH (P = 0.037 and P = 0.001, resp.), Binet stage (P < 0.05) and with the presence of beta symptoms (P = 0.004 for summated sFLC). Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.
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    • "The increased incidence of second malignancies in CLL has been partly attributed to the profound immune deficiency seen in this disease (Tsai et al, 2009). An increased incidence of NMSCs has been closely related to immunosuppression after renal transplantation and other immunosuppressed individuals (Greene et al, 1978; García et al, 2013). "
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    ABSTRACT: Background: Chronic lymphocytic leukaemia (CLL) patients have an increased risk of other malignancies. This may be due to surveillance bias, treatment or immunosuppression. Methods: Cohort study of 612 consecutively diagnosed CLL patients in a Canadian province, with comparisons to follicular lymphoma (FL) patients. Results: Treated CLL patients had a 1.7-fold increased risk of second cancers compared with untreated CLL patients. As compared with untreated FL patients, untreated CLL patients had a two-fold increased incidence of second malignancies. Conclusion: Chronic lymphocytic leukaemia patients have an inherent predisposition to second cancers and the incidence is further increased by treatment.
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