Abnormal Free Light Chain Ratios are Significantly Associated with Clinical Progression in Chronic Lymphocytic Leukemia

Abstract

Serum Free Light Chains (FLC) have prognostic significance in diverse plasma cell dyscrasias. Although monoclonal protein secretion is a typical feature of these diseases, it can also be detected in other B cell malignancies including chronic lymphocytic leukemia. Recent data suggests a significant correlation between abnormal ratio of FLC and outcome. Therefore, we investigated the role of FLC in a large cohort of 135 patients and the correlation to immunofixation (IF) and flow cytometry. Abnormal FLC ratios were found in 78 patients (58%) whereas the IF was positive in only 32 cases (24%). In 55 cases the FLC ratio was positive while IF was negative and in only 9 cases IF was positive while the FLC ratio was normal. In 52 of 98 patients (53%) light chain restriction determined by flow cytometry was concordant with the monoclonal FLC whereas in 5 patients they did not agree. In 41 of 98 patients (42%) a normal ratio of FLC was observed while the immunophenotype was positive for lambda or kappa. Patients with an abnormal FLC ratio for lambda had a significantly shorter time to first therapy (TFT) than patients with an abnormal ratio for kappa FLC or with a normal FLC ratio (median TFT: 34 versus 76 versus 88 months, p for trend=0.039). Additionally, monoclonal FLC had a significantly shorter time to first treatment compared to polyclonal normal and abnormal FLC ratios (p for trend=0.0489). As expected, polyclonal sFLC correlated significantly with normal and abnormal serum-creatinine (p<0.0001). Future studies are warranted to elucidate the role of FLC as biomarkers of disease and as a prognostic factor for response.