The cumulative amount of serum free light chain is a strong prognosticator in chronic lymphocytic leukemia
Cette étude (449 cas) montre une association entre le niveau sérique cumulé des chaînes légères libres Kappa et Lambda et la survie des patients atteints d'une leucémie lymphocytaire chronique
Identification of patients at risk of early disease progression is the mainstay of tailored management in chronic lymphocytic leukemia (CLL). While 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-naïve patients, we showed 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 non-clonal 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(&][kappa]/λ). Only ZAP70, 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 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 biological processes in CLL. sFLC(κ+λ) assessment represents a sensitive and cost-effective tool to identify CLL patients requiring early treatment.
Blood , résumé, 2011