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Objective@#To analyze the prognostic value of baseline serum free light chain (sFLC) in immunoglobulin light-chain cardiac amyloidosis (AL-CA) .@*Methods@#Thirty patients diagnosed with AL-CA from January 2012 to December 2016 at Beijing Chaoyang Hospital were included in this study to retrospectively evaluate the clinical data. The cut-off value of dFLC (involved sFLC minus uninvolved sFLC) was determined according to the receiver operator characteristic curve (ROC) and grouped, the prognoses of both groups were evaluated.@*Results@#The onset age of all AL-CA patients was 57 years old. It occurred more commonly in men (21 cases, 70%) and the light chains of immunoglobulin composed mainly of type λ (22 cases, 73.3%) . Renal involvements occurred in 17 cases (56.7%) . The median value of difference between involved and uninvolved serum immunoglobulin free light chain levels (dFLC) was 162.9 (57.9-401.6) mg/L. More subjects in the high dFLC group had higher BNP (P=0.005) , and shorter median survival than those in the low dFLC group (15 months vs 47 months, P<0.001) . Similar results of median survival were observed when the patients were redivided by a new cut-off value of 180 mg/L for dFLC (high dFLC group: 22 months, low dFLC group: 40 months, P=0.001) , or a κ/λ ratio in which patients with κ type sFLC-ratio<3.79 and λ type sFLC-ratio≥0.06 were grouped into the low sFLC-ratio (37 months) , and the reverse the high sFLC-ratio ones (25 months, P=0.021) . In multivariate analysis, dFLC and New York Heart Association (NYHA) classification of cardiac function were two risk factors associated with all-cause mortality in patients, of them the hazard ratio for higher dFLC was 12.13 (95%CI 2.98-49.30, P<0.001) .@*Conclusion@#Measurement of the sFLC level could implicate the prognosis of AL-CA.
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BACKGROUND: Since free light chain (FLC) is metabolized in the kidney, serum FLC concentration and kappa/lambda ratio are increased in patients with decreased renal function, even in the absence of monoclonal protein. In this study, we measured serum FLC levels to investigate the change in kappa/lambda ratios in relation to the severity of renal dysfunction. METHODS: Serum FLC concentrations were measured in 92 archived serum samples from patients diagnosed with chronic kidney disease using the Freelite assay (The Binding Site Group Ltd., UK), and kappa/lambda ratios were calculated. Serum creatinine levels were assayed to calculate estimated glomerular filtration rate (eGFR), and patients were divided into subgroups according to Kidney Disease Improving Global Outcomes (KDIGO) guidelines. We analyzed the difference in serum FLC levels and kappa/lambda ratios between subgroups. RESULTS: Serum FLC levels and kappa/lambda ratios increased depending on the severity of renal dysfunction. When patients were classified by setting cut-off value of eGFR as 60 mL/min/1.73 m2 (group A: eGFR ≥60 mL/min/1.73 m2, group B: < 60 mL/min/1.73 m2), the kappa/lambda ratio of group B was significantly higher than that of group A (group B: 1.60±0.46 vs. group A: 1.35±0.27, P=0.018). Serum FLC kappa/lambda ratios were within the previously determined renal reference interval (0.37–3.1). CONCLUSIONS: When interpreting results of serum FLC kappa/lambda ratio, renal function status should be considered in addition to hematological findings. If renal function deteriorates, a wider renal reference interval is preferred instead of the usual reference interval.
Subject(s)
Humans , Binding Sites , Creatinine , Glomerular Filtration Rate , Kidney , Kidney Diseases , Renal Insufficiency, ChronicABSTRACT
Objective@#To evaluate the prognostic value of serum free light chain ratio (rFLC) and difference (dFLC) in patients with multiple myeloma (MM) .@*Methods@#Clinical data of 479 cases of newly diagnosed MM patients with FLC test records referred to our hospital from January 2012 to March 2016 were collected. rFLC preferred cut-off values were selected as≤14.828,14.828-364.597, ≥364.597 according to the literatures. The dFLC was divided into ≤112.85,112.85-2891.83, ≥2891.83 mg/L three groups. The rFLC and dFLC values among the death, the non-death, the progress and the non-progress groups were compared by t test. The correlation analysis showed that the rFLC and dFLC values were related to the death or progression of the disease. Logistic regression was used to analyze the correlation between each factor and death or progression. Univariate survival analysis (PFS) and total survival (OS) were performed using Kaplan-Meier. Single-variable and multivariate prognostic analysis were performed using Cox model.@*Results@#The cutoff values of rFLC less than 14.828 or dFLC less than or equal to 112.85 mg/L impacted most significant on OS and PFS of the patients (P<0.05) . Different rFLC cut-off values between two groups showed that when rFLC=14.828, OS was significantly better than the other two groups (NR vs 61 & 47 months, P=0.019) ; different dFLC cut-off values between two groups disclosed that PFS and OS were statistically significant when dFLC less than or equal to 112.85 mg/L compared with the other two groups (P<0.05) . The 4-year PFS/OS rates in the initial dFLC≤112.85 mg/L and rFLC≤14.828 groups was significantly higher than of the other two groups.@*Conclusion@#Different cutoff levels of rFLC and dFLC might have obviously effects on the prognoses of patients with newly diagnosed MM. The difference of survival prognosis would be more pronounced when rFLC≤14.828 or dFLC≤112.85 mg/L with lower risk of death and lower risk ratio, which might be ideal cutoff value for determining the prognosis of these patients.
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Objective@#To analyze the significance of serum free light chain (sFLC) for the prognosis of the patients with newly diagnosed multiple myeloma (NDMM). @*Methods@#The clinical data of 621 NDMM patients in Changzheng Hospital from June 2010 to December 2016 was retrospectively analyzed. The serum free light chain levels were measured and the ratios of κ/λ chains were calculated. The significance of serum free light chain ratio (sFLCR) for the prognosis of NDMM patients was analyzed. @*Results@#Among the 621 NDMM patients, 42 patients (6.8%) were in the normal free light chain ratio group (0.26≤sFLCR≤1.65), 247 patients (39.8%) were in the low free light chain ratio group (0.01＜sFLCR＜0.26 or 1.65＜sFLCR＜100), and 332 patients (53.5%) were in the high free light chain ratio group (sFLCR≤0.01 or sFLCR≥100). Compared with normal sFLCR group, the abnormal sFLCR group showed low level of hemoglobin; elevated levels of bone marrow plasma cells, serum creatinine and β 2 -MG, and more patients were in DS stage Ⅲ and ISS stage Ⅲ with high risks of cytogenetics(all P＜0.05). The overall survival (OS) in the normal sFLCR group was significantly better than the abnormol sFLCR groups (not reached vs 58.7 months, P=0.043). Compared with the patients with both high sFLCR and low risks of cytogenetics, the patients with high sFLCR and high risks of cytogenetics showed shorter overall survival time (median OS time was 41.6 months vs 61.4 months, P=0.015). @*Conclusion@#The NDMM patients with significantly abnormal sFLCR may indicate more tumor load and higher aggressive progression. sFLCR should be an independent prognostic indicator for the outcome of multiple myeloma. The patients with high sFLCR and cytogenetic abnormalities, have worse prognosis than the others.
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Renal impairment is common in multiple myeloma .Besides effective chemotherapy , direct removal of se-rum free light chain by plasmapheresis or high cut-off hemodialysis is also important in the treatment of renal im-pairment in multiple myeloma .Based on results of the randomized controlled trials , the role of plasmapheresis in treating renal disease of multiple myeloma is debated .On the other side , high cut-off hemodialysis is novel and re-cently developed .Many studies have shown its potential function to further increase renal response rate when com -bined with chemotherapy .
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Free light chains (FLCs) are tumour markers of monoclonal gammopathies. Detection of urinary FLC or also known as Bence-Jones protein through urinary protein and its immunofixation electrophoreses (UPE and uIFE, respectively) have been considered the gold standard for its biochemical diagnosis. This is mainly due to their superior detection limits compared to their counterpart investigations in serum. However, urinalysis is limited in many ways. The emergence of serum FLC assay with markedly improved detection limit circumvents many of these problems and has gained much importance in biochemical investigations of monoclonal gammopathies. Nevertheless, they are not without limitations. This review discusses the advantages and limitations of serum and urinary FLC assays.
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Abstract The diagnosis of Multiple Myeloma is a challenge to the physician due to the non-specific symptoms (anemia, bone pain and recurrent infections) that are commonplace in the elderly population. However, early diagnosis is associated with less severe disease, including fewer patients presenting with acute renal injury, pathological fractures and severe anemia. Since 2006, the serum free light chain test Freelite® has been included alongside standard laboratory tests (serum and urine protein electrophoresis, and serum and urine immunofixation) as an aid in the identification of monoclonal proteins, which are a cornerstone for the diagnosis of Multiple Myeloma. The serum free light chain assay recognizes the light chain component of the immunoglobulin in its free form with high sensitivity. Other assays that measure light chains in the free and intact immunoglobulin forms are sensitive, but unfortunately, due to the nomenclature used, these assays (total light chains) are sometimes used in place of the free light chain assay. This paper reviews the available literature comparing the two assays and tries to clarify hypothetical limitations of the total assay to detect Multiple Myeloma. Furthermore, we elaborate on our study comparing the two assays used in 11 Light Chain Multiple Myeloma patients at presentation and 103 patients taken through the course of their disease. The aim of this article is to provide a clear discrimination between the two assays and to provide information to physicians and laboratory technicians so that they can utilize the International Myeloma Working Group guidelines.
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Multiple Myeloma , Paraproteinemias , Hematopoietic Stem Cells , Immunoglobulin Light Chains , LymphomaABSTRACT
Objective To analyze the prognostic value of baseline serum free light chain (sFLC) in light-chain (AL) cardiac amyloidosis.Methods Twenty-seven patients with AL cardiac amyloidosis were retrospectively reviewed from January 2014 to January 2015.sFLC was measured by immuoturbidimetric assay.Baseline characteristics,echocardiographic parameters and electrocardiogram data were analyzed.According to the median baseline dFLC (involved sFLC minus uninvolved sFLC),patients were categorized into either the low dFLC(≤307mg/L) or the high dFLC group (＞307mg/L).Results More subjects in the high dFLC group with early/late diastolic mitral velocity ratio (E/A ratio) over 2 (71.4％ vs 30.8％,P =0.035),and subjects in this group had a shorter median survival time than those in the low dFLC group (3 months vs 17 months,P =0.004).A similar phenomenon for median survival time was observed when the subjects were redivided either by a new cut-off value of 180mg/L for dFLC (low dFLC group:17 months;high dFLC group:4 months,P =0.014) or a κ/λ ratio,in which subjects with κ type sFLC-ratio ≤ 19.6 and λ type sFLC-ratio ＞0.065 were in the low sFLC-ratio group (17 months) and those with κ type sFLC-ratio ＞ 19.6 and λ type sFLC-ratio ≤0.065 were in the high sFLC-ratio group (4 months,P=0.023).In multivariate analysis,dFLC and New York Heart Association (NYHA) classification of cardiac function were two risk factors associated with all-cause mortality in patients,among which the hazard ratio for higher dFLC was 4.28 (95％ CI 1.55-11.8,P =0.005).Conclusion The level of sFLC could be a marker for the prognosis of AL cardiac amyloidosis.
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The prognosis of solitary plasmacytoma varies greatly, with some patients recovering after surgical removal or local fractional radiation therapy, and others progressing to multiple myeloma years later. Primary detection of progression to multiple myeloma is important in the treatment of solitary plasmacytoma. There have been several analyses of the risk factors involved in the early progression to multiple myeloma. We describe one case of solitary plasmacytoma of the lumbar vertebra that was treated with surgical decompression with stabilization and additional radiotherapy. The patient had no factors associated with rapid progression to multiple myeloma such as age, size, immunologic results, pathological findings, and serum free light chain ratio at the time of diagnosis. However, his condition progressed to multiple myeloma less than two months after the initial diagnosis of solitary plasmacytoma. We suggest that surgeons should be vigilant in watching for rapid progression to multiple myeloma even in case that the patient with solitary plasmacytoma has no risk factors for rapid progression to multiple myeloma.