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 journalArticle

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Abstract

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
JournalBlood
Volume118
Issue number24
DOIs
Publication statusPublished - Dec 8 2011

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B-Cell Chronic Lymphocytic Leukemia
Light
Biomarkers
Serum
Cytogenetics
Tumors
Mirrors
Demonstrations
Survival
Cells
Tissue
Therapeutics
Costs
Disease Progression
B-Lymphocytes
Costs and Cost Analysis
Mutation
Neoplasms

ASJC Scopus subject areas

  • Hematology
  • Biochemistry
  • Cell Biology
  • Immunology

Cite this

Morabito, F., De Filippi, R., Laurenti, L., Zirlik, K., Recchia, A. G., Gentile, M., ... Pinto, A. (2011). The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. Blood, 118(24), 6353-6361. https://doi.org/10.1182/blood-2011-04-345587

The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. / Morabito, Fortunato; De Filippi, Rosaria; Laurenti, Luca; Zirlik, Katja; Recchia, Anna Grazia; Gentile, Massimo; Morelli, Emanuela; Vigna, Ernesto; Gigliotti, Vincenzo; Calemma, Rosa; Amoroso, Barbara; Neri, Antonino; Cutrona, Giovanna; Ferrarini, Manlio; Molica, Stefano; Del Poeta, Giovanni; Tripodo, Claudio; Pinto, Antonio.

In: Blood, Vol. 118, No. 24, 08.12.2011, p. 6353-6361.

Research output: Contribution to journalArticle

Morabito, F, De Filippi, R, Laurenti, L, Zirlik, K, Recchia, AG, Gentile, M, Morelli, E, Vigna, E, Gigliotti, V, Calemma, R, Amoroso, B, Neri, A, Cutrona, G, Ferrarini, M, Molica, S, Del Poeta, G, Tripodo, C & Pinto, A 2011, 'The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia', Blood, vol. 118, no. 24, pp. 6353-6361. https://doi.org/10.1182/blood-2011-04-345587
Morabito F, De Filippi R, Laurenti L, Zirlik K, Recchia AG, Gentile M et al. The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. Blood. 2011 Dec 8;118(24):6353-6361. https://doi.org/10.1182/blood-2011-04-345587
Morabito, Fortunato ; De Filippi, Rosaria ; Laurenti, Luca ; Zirlik, Katja ; Recchia, Anna Grazia ; Gentile, Massimo ; Morelli, Emanuela ; Vigna, Ernesto ; Gigliotti, Vincenzo ; Calemma, Rosa ; Amoroso, Barbara ; Neri, Antonino ; Cutrona, Giovanna ; Ferrarini, Manlio ; Molica, Stefano ; Del Poeta, Giovanni ; Tripodo, Claudio ; Pinto, Antonio. / The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. In: Blood. 2011 ; Vol. 118, No. 24. pp. 6353-6361.
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AU - Morelli, Emanuela

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AU - Ferrarini, Manlio

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