The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia

Fortunato Morabito, Rosaria De Filippi, Luca Laurenti, Katja Zirlik, Anna Grazia Recchia, Massimo Gentile, Emanuela Morelli, Ernesto Vigna, Vincenzo Gigliotti, Rosa Calemma, Barbara Amoroso, Antonino Neri, Giovanna Cutrona, Manlio Ferrarini, Stefano Molica, Giovanni Del Poeta, Claudio Tripodo, Antonio Pinto

Research output: Contribution to journalArticlepeer-review


Identification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). Although application of established biomarkers is limited by intrinsic detection/readout complexities, abnormality of κ and λ serum-free light chain ratio [sFLC (κ/λ)] was proposed as a straightforward prognosticator in CLL. By analyzing 449 therapy-naive patients, we show that an abnormal sFLC(κ/λ), along with CD38, ZAP-70, IGHV mutations, cytogenetics and stage, independently predicts treatment-free survival (TFS) but becomes prognostically irrelevant if the cumulative amount of clonal and nonclonal FLCs [sFLC(κ + λ)], a variable associated with cytogenetic risk, exceeds the threshold of 60.6 mg/mL. Patients with sFLC(κ + λ) above cutoff displayed a poorer TFS outcome, irrespective of sFLC(κ/λ). Only ZAP-70, cytogenetics, stage, and TFS remained associated with sFLC(κ + λ) in a multivariate model. By assigning 1 point each for these variables, the 3-year probability of TFS was 94.8%, 84.5%, 61.6%, and 21.1% for patients scoring 0, 1, 2, and 3 + 4, respectively (P <.0001). These data, and the demonstration that monoclonal and polyclonal B cells concur to FLC synthesis in tumor tissues, suggest that sFLC(κ/λ) and sFLC(κ + λ) mirror distinct biologic processes in CLL. sFLC(κ + λ) assessment represents a sensitive and cost-effective tool for identifying CLL patients requiring early treatment.

Original languageEnglish
Pages (from-to)6353-6361
Number of pages9
Issue number24
Publication statusPublished - Dec 8 2011

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology


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