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

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

Risultato della ricerca: Article

24 Citazioni (Scopus)

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 cut-off 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.
Lingua originaleEnglish
pagine (da-a)6353-6361
Numero di pagine9
RivistaBlood
Volume118
Stato di pubblicazionePublished - 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

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

Cita questo

Tripodo, C., Calemma, R., Zirlik, K., Molica, S., Gigliotti, V., Morelli, E., ... Pinto, A. (2011). The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. Blood, 118, 6353-6361.

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

In: Blood, Vol. 118, 2011, pag. 6353-6361.

Risultato della ricerca: Article

Tripodo, C, Calemma, R, Zirlik, K, Molica, S, Gigliotti, V, Morelli, E, Recchia, AG, Neri, A, Amoroso, B, Vigna, E, De Filippi, R, Del Poeta, G, Cutrona, G, Ferrarini, M, Laurenti, L, Gentile, M, Morabito, F & Pinto, A 2011, 'The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.', Blood, vol. 118, pagg. 6353-6361.
Tripodo C, Calemma R, Zirlik K, Molica S, Gigliotti V, Morelli E e altri. The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. Blood. 2011;118:6353-6361.
Tripodo, Claudio ; Calemma, Rosa ; Zirlik, Katja ; Molica, Stefano ; Gigliotti, Vincenzo ; Morelli, Emanuela ; Recchia, Anna Grazia ; Neri, Antonino ; Amoroso, Barbara ; Vigna, Ernesto ; De Filippi, Rosaria ; Del Poeta, Giovanni ; Cutrona, Giovanna ; Ferrarini, Manlio ; Laurenti, Luca ; Gentile, Massimo ; Morabito, Fortunato ; Pinto, Antonio. / The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia. In: Blood. 2011 ; Vol. 118. pagg. 6353-6361.
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title = "The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.",
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 cut-off 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.",
author = "Claudio Tripodo and Rosa Calemma and Katja Zirlik and Stefano Molica and Vincenzo Gigliotti and Emanuela Morelli and Recchia, {Anna Grazia} and Antonino Neri and Barbara Amoroso and Ernesto Vigna and {De Filippi}, Rosaria and {Del Poeta}, Giovanni and Giovanna Cutrona and Manlio Ferrarini and Luca Laurenti and Massimo Gentile and Fortunato Morabito and Antonio Pinto",
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T1 - The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia.

AU - Tripodo, Claudio

AU - Calemma, Rosa

AU - Zirlik, Katja

AU - Molica, Stefano

AU - Gigliotti, Vincenzo

AU - Morelli, Emanuela

AU - Recchia, Anna Grazia

AU - Neri, Antonino

AU - Amoroso, Barbara

AU - Vigna, Ernesto

AU - De Filippi, Rosaria

AU - Del Poeta, Giovanni

AU - Cutrona, Giovanna

AU - Ferrarini, Manlio

AU - Laurenti, Luca

AU - Gentile, Massimo

AU - Morabito, Fortunato

AU - Pinto, Antonio

PY - 2011

Y1 - 2011

N2 - 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 cut-off 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.

AB - 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 cut-off 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.

UR - http://hdl.handle.net/10447/99033

M3 - Article

VL - 118

SP - 6353

EP - 6361

JO - Blood

JF - Blood

SN - 0006-4971

ER -