Monoclonal and polyclonal serum free light chains and clinical outcome in chronic lymphocytic leukemia (original) (raw)
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Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia
Advances in Hematology, 2013
Background. Serum free light chains (sFLC), the most commonly detected paraprotein in CLL, were recently proposed as useful tools for the prognostication of CLL patients. Objective. To investigate the prognostic implication of sFLC and the summated FLCkappa plus FLC-lambda in a CLL patients' series. Patients and Methods. We studied 143 CLL patients of which 18 were symptomatic and needed treatment, while 37 became symptomatic during follow-up. Seventy-two percent, 18%, and 10% were in Binet stage A, B and C, respectively. Median patients' followup was 32 months (range 4-228). Results. Increased involved (restricted) sFLC (iFLC) was found in 42% of patients, while the summated FLC-kappa plus FLC-lambda was above 60 mg/dL in 14%. Increased sFLC values as well as those of summated FLC above 60 were related to shorter time to treatment ( = 0.0005 and = 0.000003, resp.) and overall survival ( = 0.05 and = 0.003, resp.). They also correlated with 2-microglobulin ( = 0.009 and = 0.03, resp.), serum albumin ( = 0.009 for summated sFLC), hemoglobin ( < 0.001), abnormal LDH ( = 0.037 and = 0.001, resp.), Binet stage ( < 0.05) and with the presence of beta symptoms ( = 0.004 for summated sFLC). Conclusion. We confirmed the prognostic significance of sFLC in CLL regarding both time to treatment and survival and showed their relationship with other parameters.
Blood, 2011
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 variabl...
Blood Cancer Journal, 2019
Chronic lymphocytic leukemia (CLL) and its precursor, monoclonal B-cell lymphocytosis (MBL), are heritable. Serumfree light-chain (sFLC) measures are a prognostic factor for CLL, but their role in susceptibility to CLL is not clear. We investigated differences between sFLC measurements in pre-treatment serum from five groups to inform the association of sFLC with familial and sporadic CLL: (1) familial CLL (n = 154), (2) sporadic CLL (n = 302), (3) familial MBL (n = 87), (4) unaffected first-degree relatives from CLL/MBL families (n = 263), and (5) reference population (n = 15,396). The percent of individuals having elevated monoclonal and polyclonal sFLCs was compared using age-stratified and age- and sex-adjusted logistic regression models. In age groups >50 years, monoclonal sFLC elevations were increased in sporadic and familial CLL cases compared to the reference population (p’s < 0.05). However, there were no statistically significant differences in sFLC monoclonal or po...
Immunoglobulin free light chains: do they have a role in plasma cell leukemia?
Hematology, 2008
The assay of serum free light chains (FLCs) is established in the diagnosis and prognosis of several plasma cell dyscrasias, but its significance in plasma cell leukemia (PCL) has not been reported so far. PCL is a rare and aggressive disease with a poor prognosis. The authors describe two cases of PCL with divergent clinical profiles where the serum FLC assay was available. Although both patients had greatly elevated serum b 2-microglobulin, one patient had much higher levels of serum FLCs and evidence of renal impairment, which were absent in the other; however, the latter, who had multisystem involvement, showed a more rapidly downhill course with early mortality.
American Journal of Clinical Pathology, 2012
Serum free light chain (sFLC) assays were shown to improve detection, management, and prognostication in plasma cell disorders. Recently, sFLC assays improved detection of M proteins when combined with standard methods of protein electrophoresis/ immunofixation in patients with non-Hodgkin lymphoma/chronic lymphocytic leukemia (NHL/CLL). Incidence of abnormal sFLC ratio (sFLCr) varied from 0% to 36% and 29.7% to 59% in NHL and CLL, respectively. Increased sFLC levels or abnormal sFLCr predict shorter overall survival in early-stage CLL. Furthermore, abnormal sFLCr correlated with advanced disease stage and poorer outcome. In diffuse large B-cell lymphomas, increased sFLC was demonstrated as an independent, adverse prognostic factor for overall/event-free survival. Moreover, abnormal sFLCr can be a diagnostic tool in central nervous system lymphomas. Finally, the quantitative FLC assay has the potential to become a new, easily measured biomarker for predicting prognosis and enhanced detection in NHL/CLL. It may be used serially at follow-up evaluations to provide clues to relapse.
American Journal of Hematology, 2011
The serum free light chain (FLC) assay quantitates free immunoglobulin kappa and lambda light chains, which has prognostic value in plasma cell dyscrasias. However, there is limited data on serum FLC in lymphoid malignancies. We analyzed the association of pretreatment FLC with event-free survival (EFS) and overall survival (OS) in 100 patients with Hodgkin lymphoma (HL). Elevated polyclonal FLC were present in 30% of patients; these patients had an inferior EFS (HR 5 4.84; 95% CI: 1.84-12.7) and OS (HR 5 8.87; 95% CI: 2.35-33.52) compared to patients with normal FLC. Further studies of FLC in HL are warranted. Am. J. Hematol. 86:998-1000,
South Asian Journal of Cancer
Background The role of serum free light chain (FLC) as a prognostic biomarker in lymphoproliferative diseases is being increasingly studied. In this study we present the 5-year survival outcome for patients with aggressive B-cell non-Hodgkin's lymphoma (NHL) and their relation to FLC and other known prognostic markers. Materials and Methods This is a prospective study conducted in patients diagnosed with aggressive B-cell NHL. Serum FLC level and ratio were estimated prior to initiation of treatment. Results A total of 100 patients were included in the study from December 2013 to December 2015 with a median age of 53 years. Thirty-eight patients (38%) had elevated FLC level of which 26% were polyclonal and 12% were monoclonal elevations. Abnormal FLC ratio was noted in 12% patients. Median follow-up duration of the study was 75 months. Five-year relapse-free survival (RFS) for the study population was 54.4%. Five-year RFS was 64.1% for early stage and 48.2% for advanced stage di...
Blood, 2009
Immune-related deficiencies are well-known complications of chronic lymphocytic leukemia (CLL). Although recent data indicate that almost all CLL patients are preceded by a monoclonal B-cell lymphocytosis precursor state, patterns of immune defects preceding CLL diagnosis are unclear. We identified 109 persons who developed CLL from the prospective and nationwide Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial with 77 469 participants, with serially collected prediagnostic serum samples. We assayed monoclonal (M)–proteins, κ/λ free light chains (FLCs) in prediagnostic obtained up to 9.8 years before CLL diagnosis. The prevalence of an abnormal FLC ratio, M-protein, and hypogamma-globulinemia before CLL diagnosis was 38% (95% confidence interval, 29%-47%), 13% (7%-21%), and 3% (1%-8%), respectively. M-proteins and abnormal FLC ratios were detected up to 9.8 years before CLL diagnosis in a total of 48 persons (44%). Hypogammaglobulinemia was not present until 3 years bef...