Prognostic Significance of Serum Free Light Chains in Chronic Lymphocytic Leukemia

Abstract

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 FLC-kappa 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 (P = 0.0005 and P = 0.000003, resp.) and overall survival (P = 0.05 and P = 0.003, resp.). They also correlated with β2-microglobulin (P = 0.009 and P = 0.03, resp.), serum albumin (P = 0.009 for summated sFLC), hemoglobin (P < 0.001), abnormal LDH (P = 0.037 and P = 0.001, resp.), Binet stage (P < 0.05) and with the presence of beta symptoms (P = 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.

A new risk model to predict time to first treatment in chronic lymphocytic leukemia based on heavy chain immunoparesis and summated free light chain

“…Accordingly, in our cohort, severe HLC immunoparesis and elevated ΣFLC levels were independent risk factors for time to treatment initiation. ΣFLC has previously been associated with a shorter TTFT in CLL patients, even after adjusting for Binet stage, ZAP‐70 expression and cytogenetic abnormalities . Our novel observation is that ΣFLC, in combination with severe HLC immunoparesis, identified a very‐high‐risk group of patients with a median time to first treatment of only 1.3 months.…”

Elevated IgM and abnormal free light chain ratio are increased in relatives from high-risk chronic lymphocytic leukemia pedigrees

“…Abnormal FLC ratio is used clinically to indicate clonal plasma cells in plasma cell disorders. There is also evidence that aFLC ratio is associated with survival and time to first treatment in CLL 19–23 , suggesting it as an important biomarker for clonal B-cell development. In the context of a precursor, a biomarker for active clonal development has the potential to capture important information on progression toward overt disease.…”

Recent progress of prognostic biomarkers and risk scoring systems in chronic lymphocytic leukemia

“…It is significantly associated with increased expressions of CD38 and ZAP70 [26]. Increased serum free light chains (sFLC) correlates with s-β2M, serum albumin, hemoglobin, abnormal LDH and regards to shorter time to treatment and OS [27]. Lipoprotein lipase (LPL) is an indicator of OS for CLL patients, while LPL mRNA expression, correlating with IGHV mutation status, also has a significant impact on survival [28].…”