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

Huei Ting Tsai, Neil E. Caporaso, Robert A. Kyle, Jerry A. Katzmann, Angela Dispenzieri, Richard B. Hayes, Gerald E. Marti, Maher Albitar, Paolo Ghia, S. Vincent Rajkumar, Ola Landgren

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

Immune-related deficiencies are wellknown 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, κ/λ 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 κ and/or λ 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.

Original languageEnglish (US)
Pages (from-to)4928-4932
Number of pages5
JournalBlood
Volume114
Issue number24
DOIs
StatePublished - Dec 3 2009

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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    Tsai, H. T., Caporaso, N. E., Kyle, R. A., Katzmann, J. A., Dispenzieri, A., Hayes, R. B., Marti, G. E., Albitar, M., Ghia, P., Rajkumar, S. V., & Landgren, O. (2009). Evidence of serum immunoglobulin abnormalities up to 9.8 years before diagnosis of chronic lymphocytic leukemia: A prospective study. Blood, 114(24), 4928-4932. https://doi.org/10.1182/blood-2009-08-237651