Evidence of serum immunoglobulin abnormalities up to 9.8 years prior to diagnosis of chronic lymphocytic leukemia: a prospective study.

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Evidence of serum immunoglobulin abnormalities up to 9.8 years prior to

diagnosis of chronic lymphocytic leukemia: a prospective study.

Huei-Ting Tsai, Neil E Caporaso, A , Jerry A Katzmann,

Dispenzieri, B , Gerald E Marti, Maher Albitar, Paolo Ghia, S

Rajkumar, and Ola Landgren

Blood, October 14, 2009;

National Cancer Institute, National Institutes of Health, United States;

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

individuals who developed CLL from the prospective and nationwide PLCO

(Prostate, Lung, Colorectal and Ovarian) Cancer Screening Trial with 77,469

participants, with serially-collected pre-diagnostic serum samples. We assayed

monoclonal-(M)-proteins, kappa/lambda free light chains (FLCs) in pre-diagnostic

obtained up to 9.8 years before CLL diagnosis. The prevalence of an abnormal

FLC-ratio, M-protein, and hypogammaglobulinemia prior to CLL diagnosis was 38%

(95%CI 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 individuals (44%). Hypogammaglobulinemia was not present until 3

years prior to the diagnosis of CLL. Among 37 patients with information on tumor

cell immunophenotype, an association between immunophenotype and involved FLC

(p=0.024, Fisher's exact test) was observed. Among 61 individuals 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 17/109 (16%) patients. These

findings support a role for chronic immune stimulation in CLL-genesis.

PMID: 19828698

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