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Evidence of serum immunoglobulin abnormalities up to 9.8 years prior to diagnosis of chronic lymphocytic leukemia: A prospective study
Blood, 10/30/09

Tsai HT et al. – 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.The findings of this study support a role for chronic immune stimulation in CLL-genesis.

Methods

109 individuals who developed CLL from prospective and nationwide PLCO (Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial with 77,469 participants, with serially-collected pre-diagnostic serum samples

Results

Assayed monoclonal-(M)-proteins, kappa/lambda free light chains (FLCs) in pre-diagnostic obtained up to 9.8 years before CLL diagnosis
Prevalence of abnormal FLC-ratio, M-protein, and hypogammaglobulinemia prior to CLL diagnosis 38% (95%CI 29-47%), 13% (7-21%), and 3% (1-8%), respectively
M-proteins and abnormal FLC-ratios detected up to 9.8 years before CLL diagnosis in total of 48 individuals (44%)
Hypogammaglobulinemia not present until 3 years prior to diagnosis of CLL
Among 37 patients with information on tumor cell immunophenotype, association between immunophenotype and involved FLC observed
Among 61 individuals with normal FLC-ratio and without M-protein, 17 had elevated kappa and/or lambda FLC levels, indicating polyclonal B-cell activation in 17/109 (16%) patients

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