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.
authors: Onco-Hematology Unit, Azienda Ospedaliera Annunziata, Cosenza, Italy. fortunato_morabito@tin.it
authors: Fortunato
authors: F
authors: Morabito
authors: Rosaria
authors: R
authors: De Filippi
authors: Luca
authors: L
authors: Laurenti
authors: Katja
authors: K
authors: Zirlik
authors: Anna Grazia
authors: AG
authors: Recchia
authors: Massimo
authors: M
authors: Gentile
authors: Emanuela
authors: E
authors: Morelli
authors: Ernesto
authors: E
authors: Vigna
authors: Vincenzo
authors: V
authors: Gigliotti
authors: Rosa
authors: R
authors: Calemma
authors: Barbara
authors: B
authors: Amoroso
authors: Antonino
authors: A
authors: Neri
authors: Giovanna
authors: G
authors: Cutrona
authors: Manlio
authors: M
authors: Ferrarini
authors: Stefano
authors: S
authors: Molica
authors: Giovanni
authors: G
authors: Del Poeta
authors: Claudio
authors: C
authors: Tripodo
authors: Antonio
authors: A
authors: Pinto
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000465:Algorithms; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000378:metabolism / Q000473:pathology; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007147:Immunoglobulin Light Chains / Q000032:analysis*; D007145:Immunoglobulin kappa-Chains / Q000032:analysis; D007146:Immunoglobulin lambda-Chains / Q000032:analysis; D015451:Leukemia, Lymphocytic, Chronic, B-Cell / Q000175:diagnosis / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008198:Lymph Nodes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D016019:Survival Analysis
chemical_list: D015415:Biomarkers; D007147:Immunoglobulin Light Chains; D007145:Immunoglobulin kappa-Chains; D007146:Immunoglobulin lambda-Chains