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 language | English |
|---|---|
| Pages (from-to) | 6353-6361 |
| Number of pages | 9 |
| Journal | Blood |
| Volume | 118 |
| Issue number | 24 |
| DOIs | |
| Publication status | Published - Dec 8 2011 |
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ASJC Scopus subject areas
- Hematology
- Biochemistry
- Cell Biology
- Immunology
Cite this
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 journal › Article
}
TY - JOUR
T1 - The cumulative amount of serum-free light chain is a strong prognosticator in chronic lymphocytic leukemia
AU - Morabito, Fortunato
AU - De Filippi, Rosaria
AU - Laurenti, Luca
AU - Zirlik, Katja
AU - Recchia, Anna Grazia
AU - Gentile, Massimo
AU - Morelli, Emanuela
AU - Vigna, Ernesto
AU - Gigliotti, Vincenzo
AU - Calemma, Rosa
AU - Amoroso, Barbara
AU - Neri, Antonino
AU - Cutrona, Giovanna
AU - Ferrarini, Manlio
AU - Molica, Stefano
AU - Del Poeta, Giovanni
AU - Tripodo, Claudio
AU - Pinto, Antonio
PY - 2011/12/8
Y1 - 2011/12/8
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 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.
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 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.
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U2 - 10.1182/blood-2011-04-345587
DO - 10.1182/blood-2011-04-345587
M3 - Article
VL - 118
SP - 6353
EP - 6361
JO - Blood
JF - Blood
SN - 0006-4971
IS - 24
ER -