Establishment and validation of serum free light chain reference intervals in an ethnic Chinese population.

BACKGROUND: Quantification of serum free light chains (FLC) and calculation of a kappa/lambda ratio using polyclonal antisera based immunoassays provide laboratories with a sensitive alternative to urine protein electrophoresis (UPE). However, the published 0.26 - 1.65 serum FLC kappa/lambda ratio reference intervals may not be suitable for different ethnic populations (such as the Han Chinese population presented) and require validation. This is particularly important where there are significant differences in ethnicity, and hence HLA prevalence, in the population studied. METHODS: Serum FLC reference intervals were determined using 326 Han Chinese blood donor volunteers. Sensitivities and specificities for the (i) serum FLC kappa/lambda ratio reference interval and (ii) UPE analyses were determined using 68 pre-treatment, serum immunofixation (sIFE) positive multiple myeloma (MM) patient samples, 54 sera from MM patients undergoing treatment, and 56 sIFE-negative samples from patients with no plasma cell dyscrasia (PCD). RESULTS: The 100% range for the serum FLC kappa/lambda ratio in this Han Chinese population was 0.32 - 1.52. Both Han Chinese blood donors and published kappa/lambda ratio reference ranges demonstrated higher diagnostic sensitivity and specificity for PCD than was seen with UPE. Highly abnormal serum FLC kappa/lambda ratios were observed in 68% of MM patients who had a negative UPE. Furthermore, a MM screening panel of SPE plus serum FLC assays achieved 100% diagnostic sensitivity compared to 97% for a UPE plus SPE algorithm. For MM patients undergoing therapy, 70% of UPE negative samples displayed an abnormal FLC ratio. CONCLUSIONS: This study confirms the requirement to verify normal FLC reference ranges in local populations. This Han Chinese reference range is narrower than the published range. FLC testing provides a robust, sensitive, and specific alternative to classic UPE assessment.

Abnormal serum free light chain ratio predicts poor overall survival in mantle cell lymphoma.

Serum free light Chain (sFLC) ratios have been correlated with survival outcomes in Hodgkin and non-Hodgkin lymphoma subtypes. This study was undertaken to investigate the prognostic impact of abnormal sFLC ratios in mantle cell lymphoma (MCL). two patient cohorts were analysed for sFLC parameters: a preliminary retrospective cohort and a uniformly treated cohort of 20 relapsed/refractory MCL patients, enrolled in a phase II clinical trial of single agent lenalidomide treatment. 52% of patients had an abnormality of one or more sFLC parameter (71% of the first cohort and 40% of the second cohort). In cohort two, a high baseline SFLC ratio correlated with poorer overall survival (OS) compared to a low/normal ratio (median OS: 1·4 months vs. 19 months respectively; P = 0·001). For patients presenting with an elevated sFLC ratio at trial entry a rise of >35% in the sFLC ratio correlated with disease progression and a sFLC ratio of >2× normal at trial entry correlated with aggressive disease. These data are the first to show a clear clinical correlation between sFLC ratios and survival outcomes in a uniformly treated cohort of MCL patients. We suggest that these markers may be useful in managing patients with MCL in the future.

Use of serum free light chain analysis and urine protein electrophoresis for detection of monoclonal gammopathies.

BACKGROUND: Serum free light chain (FLC) analysis is used in the prognostic assessment and monitoring of patients with monoclonal gammopathies (MG). Its use in detection of MG is less widespread despite good sensitivity for diseases poorly detected by serum protein electrophoresis (SPE), e.g., FLC disease and AL amyloidosis. FLC analysis may facilitate earlier diagnosis in these diseases. However, if replacing urine protein electrophoresis (UPE) in an initial screening algorithm, this must be balanced against any loss of detection of Bence Jones proteinuria (BJP). METHODS: We assessed the effect of replacing UPE with FLC. Sensitivity of FLC for BJP was assessed in 126 clinical cases where UPE and FLC analyses were performed. Impact on disease detection was assessed from 753 patient sera tested by SPE and FLC and 128 patients matched associated urine samples. RESULTS: Sensitivity of FLC for BJP was 98%. Use of FLC in routine testing increased the number of MG detected by 7%. CONCLUSIONS: Using FLC alongside or in place of UPE can give clinical benefit through earlier diagnosis and hence treatment earlier in the patients' disease.