The Expression Level and Diagnostic Value of Serum Free Light Chain in B-Cell Non-Hodgkin Lymphoma / 中国实验血液学杂志

OBJECTIVE@#To investigate the expression level and the diagnostic value of serum free light chain in B-cell non-Hodgkin's lymphoma (B-NHL).@*METHODS@#We retrospectively analyzed the results of serum free light chain (sFLC) of 394 newly treated B-NHL patients in our hospital from January 2014 to December 2021 and compared the secretion levels of sFLC among different subtypes of B-NHL. The value of sFLC secretion levels in the diagnosis of WM was evaluated using ROC.@*RESULTS@#Increased proportion of sFLC, abnormal ratio of sFLC (κ / λ) and the secretion levels of sFLC (κ+λ) were different in different B-NHL subtypes, Waldenstrom's macroglobulinemia (WM) had the highest proportion of elevated sFLC(82.68%) and abnormal sFLC(κ/ λ)(87.0%), the proportion of FL(18.0%) and DLBCL patients(12.8%) with elevated sFLC was lower (P<0.05). The expression levels of sFLC can helpful in the diagnosis of WM (AUC=0.874，P<0.001， 95% CI: 0.779-0.970). At the same time, higher sFLC levels and sFLC cloning patterns predicted the possibility of bone marrow infiltration of lymphoma.@*CONCLUSION@#The serum free light chains is common in patients with B-NHL. The elevated level and type of free light chain are associated with the type of lymphoma, and the patients with bone marrow infiltration have higher sFLC（κ+ λ） expression level.

Clinical characteristics and progression risk factors for patients with monoclonal gammopathy of undetermined significance / 中华血液学杂志

Objective: To analyze the clinical presentation and progression risk factors of patients with monoclonal gammopathy of undetermined significance (MGUS) in China. Methods: We retrospectively assessed the clinical features and disease progression of 1 037 patients with monoclonal gammopathy of undetermined significance between January 2004 and January 2022 at Peking Union Medical College Hospital. Results: A total of 1 037 patients were recruited in the study, including 636 males (63.6%) , with a median age of 58 (18-94) years. The median concentration of serum monoclonal protein was 2.7 (0-29.4) g/L. The monoclonal immunoglobulin type was IgG in 380 patients (59.7%) , IgA in 143 patients (22.5%) , IgM in 103 patients (16.2%) , IgD in 4 patients (0.6%) , and light chain in 6 patients (0.9%) . 171 patients (31.9%) had an abnormal serum-free light chain ratio (sFLCr) . According to the Mayo Clinic model for risk of progression, the proportion of patients in the low-risk, medium-low-risk, medium-high risk, and high-risk groups were 254 (59.5%) , 126 (29.5%) , 43 (10.1%) , and 4 (0.9%) , respectively. With a median follow-up of 47 (1-204) months, 34 of 795 patients (4.3%) had disease progression, and 22 (2.8%) died. The overall progression rate was 1.06 (0.99-1.13) /100 person-years. Patients with non-IgM MGUS have a markedly higher disease progression rate per 100 person-years than IgM-MGUS (2.87/100 person-years vs 0.99/100 person-years, P=0.002) . The disease progression rate per 100 person-years in non-IgM-MGUS patients of Mayo classification low-risk, medium-low risk and medium-high risk groups were 0.32 (0.25-0.39) /100 person-years, 1.82 (1.55-2.09) /100 person-years, and2.71 (1.93-3.49) /100 person-years, which had statistically difference (P=0.005) . Conclusion: In comparison to non-IgM-MGUS, IgM-MGUS has a greater risk of disease progression. The Mayo Clinic progression risk model applies to non-IgM-MGUS patients in China.

Una causa olvidada de insuficiencia cardíaca / A forgotten cause of heart failure

Amyloidosis is a low-frequency disease that can cause compromise of different systems. We report a case of heart failure in an 81-year-old woman secondary to amyloidosis, in which the echocardiogram was a valuable diagnostic tool.

A clinical retrospective analysis of newly diagnosed multiple myeloma patients with systemic light chain amyloidosis / 中华血液学杂志

Objective: To analyze the clinical characteristics, treatment response, and prognosis of newly diagnosed symptomatic multiple myeloma (MM) patients with systemic light chain amyloidosis (AL) . Methods: The clinical data of 160 patients with newly diagnosed MM treated at the First Affiliated Hospital of Soochow University from January 1, 2017 to October 31, 2018, were retrospectively analyzed. According to the histopathological biopsy results of bone marrow, skin, and other tissues, the patients were divided into two groups according to whether amyloidosis was combined or not, namely, the MM+AL group and the MM group. The clinical characteristics and treatment responses of the two groups were compared. Results: Among the 160 patients with newly diagnosed MM, there were 42 cases in the MM+AL group and 118 cases in the MM group. In terms of clinical features, the involved light chain and non-involved light chain (dFLC) in the MM+AL group was significantly higher than that in the MM group (P=0.039) . After induction treatment, the MM+AL group had a higher overall response rate (85.7%vs 79.7%, P<0.05) and higher excellent partial response (76.2%vs 55.1%, P<0.05) . After a median follow-up of 26 (0.25-41) months, there was no significant difference in the progression free survival and overall survival (OS) between the two groups (P>0.05) . The OS of patients in autologous hematopoietic stem cell transplantation group was better than that in non transplantation group (P<0.05) .The prognosis of patients with cardiac involvement in the MM+AL group was significantly worse than that in the MM group and MM+AL group without cardiac involvement (P<0.001) , with a median OS of only 13 months. Conclusion: The differential diagnosis between the MM+AL and MM groups requires histopathology, particularly for patients with significantly increased dFLC. The overall remission rate of patients in MM+AL group after 4 courses of induction chemotherapy was higher than that in MM group. The prognosis of patients with cardiac involvement in MM+AL group was poor.

Amiloidosis AL: conceptos actuales / AL amyloidosis: current concepts

Las amiloidosis sistémicas constituyen un grupo de enfermedades con diversas etiologías, caracterizadas por la síntesis de proteínas con plegado defectuoso, capaces de agregarse y depositarse en el medio extracelular de diferentes órganos y tejidos, alterando su estructura y función. Se conocen más de 14 formas de amiloidosis sistémica, de las cuales la más frecuente es la amiloidosis AL, objeto de esta revisión, en la que las proteínas precursoras son cadenas ligeras de inmunoglobulina inestables, secretadas por un clon de células plasmáticas o, con menor frecuencia, por un linfoma linfoplasmocítico o de células del manto. La amiloidosis AL puede llevar a una amplia gama de manifestaciones clínicas y compromiso de órganos, como el corazón y el riñón. El reconocimiento temprano de la enfermedad y el diagnóstico oportuno son determinantes para mejorar la supervivencia de los pacientes. El tratamiento deberá ser individualizado de acuerdo con la condición de cada paciente, lo que hace necesaria una correcta clasificación de los individuos según su pronóstico. La terapia dirigida a la amiloidosis está enfocada esencialmente en disminuir el compromiso orgánico, y por ende, prolongar la supervivencia con mejoría en los síntomas. En esta revisión se discutirán aspectos importantes de la fisiopatología, epidemiología, manifestaciones clínicas, diagnóstico y tratamiento de la amiloidosis AL

Systemic amyloidosis constitutes a group of diseases with diverse etiologies characterized by the synthesis of proteins with defective folding, capable of aggregating and depositing in the extracellular matrix of different organs and tissues, altering their structure and function. More than 14 forms of systemic amyloidosis are known, of which the most frequent is AL amyloidosis, the subject of this review, in which the precursor proteins are unstable immunoglobulin light chains, secreted by a clone of plasma cells or, to a lesser extent, often due to lymphoplasmacytic or mantle cell lymphoma. AL amyloidosis can lead to a wide range of clinical manifestations and organ involvement, such as the heart and kidney. Early recognition of the disease and timely diagnosis are crucial to improve patient survival. Treatment should be individualized according to the condition of each patient, which requires a properly classification of individuals according to their prognosis. Amyloidosis-targeted therapy is essentially focused on reducing organ involvement, and therefore prolonging survival with improvement in symptoms. In this review, important aspects of the pathophysiology, epidemiology, clinical manifestations, diagnosis, and treatment of AL amyloidosis are discussed

Disruptive technologies for hemodialysis: medium and high cutoff membranes. Is the future now? / Tecnologias disruptivas para hemodiálise: membranas de ponto de corte médio e alto. O futuro é agora?

Abstract In the past decade, a new class of hemodialysis (HD) membranes (high retention onset class) became available for clinical use. The high cutoff (HCO) and the medium cutoff (MCO) membranes have wider pores and more uniformity in pore size, allowing an increased clearance of uremic toxins. Owing to the mechanism of backfiltration/internal filtration, middle molecules are dragged by the convective forces, and no substitution solution is needed. The HCO dialyzer is applied in septic patients with acute kidney injury requiring continuous kidney replacement therapy. The immune response is modulated thanks to the removal of inflammatory mediators. Another current application for the HCO dialyzer is in hematology, for patients on HD secondary to myeloma-kidney, since free light chains are more efficiently removed with the HCO membrane, reducing their deleterious effect on the renal tubules. In its turn, the MCO dialyzer is used for maintenance HD patients. A myriad of clinical trials published in the last three years consistently demonstrates the ability of this membrane to remove uremic toxins more efficiently than the high-flux membrane, an evolutionary disruption in the HD standard of care. Safety concerns regarding albumin loss as well as blood contamination from pyrogens in the dialysate have been overcome. In this update article, we explore the rise of new dialysis membranes in the light of the scientific evidence that supports their use in clinical practice.

Resumo Na última década, uma nova classe de membranas de hemodiálise (HD) (classe de início de alta retenção) tornou-se disponível para uso clínico. As membranas de ponto de corte alto (HCO) e ponto de corte médio (MCO) têm poros mais largos e maior uniformidade no tamanho dos poros, permitindo uma maior depuração de toxinas urêmicas. Devido ao mecanismo de retrofiltração/filtração interna, as moléculas médias são arrastadas pelas forças convectivas, não sendo necessária uma solução de substituição. O dialisador de HCO é aplicado em pacientes sépticos com lesão renal aguda que requerem terapia renal substitutiva contínua. A resposta imunológica é modulada graças à remoção de mediadores inflamatórios. Outra aplicação atual para o dialisador de HCO é em hematologia, para pacientes em HD secundária ao rim do mieloma, uma vez que as cadeias leves livres são removidas mais eficientemente com a membrana de HCO, reduzindo seu efeito deletério sobre os túbulos renais. Por sua vez, o dialisador de MCO é utilizado para pacientes em HD de manutenção. Uma miríade de ensaios clínicos publicados nos últimos três anos demonstra consistentemente a capacidade desta membrana de remover toxinas urêmicas de forma mais eficiente do que a membrana de alto fluxo, uma ruptura evolutiva no padrão de cuidado em HD. As preocupações de segurança em relação à perda de albumina, bem como a contaminação do sangue por pirogênios no dialisato foram superadas. Neste artigo de atualização, exploramos o surgimento de novas membranas de diálise à luz das evidências científicas que apoiam seu uso na prática clínica.

Two Serum Free Light Chain Detection Systems in the Diagnosis of Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To investigate the comparability of the Freelite, Binding Site, Beckman and N Latex FLC, Siemens in the detection of serum free light chain (sFLC) .@*METHODS@#Fifty newly diagnosed multiple myeloma (MM) patients in Tianjin Institute of Blood Research from November 2019 to February 2020 were enrolled. The two systems (Freelite, Binding Site, Beckman and N Latex FLC, Siemens) were used to detect the sFLC of the samples. Outlier detection was performed by ESD method, methodological comparison and deviation assessment were performed by Passing-Bablok regression and Bland-Altman regression.@*RESULTS@#Both the systems could quantitatively analyze free kappa light chain serum samples and free lambda light chain samples. Freelite, Binding Site, Beckman and N Latex FLC, Siemens free light chain test showed FLC-κ：36.5 (6.5, 194), 40.5 (6.94, 288), FLC-λ: 30.1 (4.3, 170.5), 35.1 (2.28, 526), rFLC (FLC-κ/ FLC-λ) : 0.82 (0.05, 43.25), 1.03 (0.03, 32.04), dFLC (｜FLC-κ- FLC-λ｜) : -5.8 (-161.97, 183.7), 1.1 (-505.1, 279.01), which existed no outliers. There were systematic differences, and the deviation level was not within the clinically acceptable range.@*CONCLUSION@#Both the systems can meet the needs of clinical diagnosis and treatment, but there is a significant deviation between the two systems, the results are not comparable, and should be analyzed separately. In particular, the same system should be selected for monitoring the prognosis of MM.

Clinical Significance of sFLC/MP Level and Light Chain Escape in Patients with Multiple Myeloma Relapse / 中国实验血液学杂志

OBJECTIVE@#To explore the effects of serum free light chain (sFLC) and monoclonal protein (MP) on the efficacy and prognosis of patients with multiple myeloma relapse, and investigate the clinical value of light chain escape (LCE).@*METHODS@#The relationship between sFLC/MP levels and clinical features and outcomes in 71 patients with multiple myeloma after relapse were retrospective analyzed. The patients were divided into MO group, MLC group and LCE group according to different levels of sFLC/MP after relapse. Then the clinical indicators, efficacy, survival after relapse (SAR) and overall survival (OS) of the patients in each group were compared. Meanwhile a paired sample t test was used to analyze the relevant indicators of the patients before and after relapse in LCE group.@*RESULTS@#There were significant differences in ISS stage, the levels of Hb, PLT, ALB, SFLC/MP and the proportion of myeloplasma cells afte relapse (P<0.05). The initial treatment effect of the patients in MO group was better than those in the other groups, and the LCE group was the worst (P<0.05). Comparison of relevant indicators between the patients before and after relapse in LCE group showed that the levels of MP, Hb and PLT decreased significantly, while sFLC, LDH and Cr increased significantly (P<0.05). Multivariate analysis showed that MO was the independent risk factor affecting SAR, while MO and LCE were the independent risk factors affecting OS (P<0.05) of the patients.The average SAR of the patients in MO, MLC and LCE group was 41, 28.6 and 23.5 months (P=0.002), and the average OS was 79.6, 57.9 and 41 months (P<0.001), respectively. The patients in MO group showed longer SAR and OS, while the LCE group was the shortest.@*CONCLUSION@#After relapse, patients only with elevated MP levels have a better curative effect and prognosis, while only with elevated sFLC levels have poor curative effects and prognosis, which suggesting that sFLC/MP levels can be used as a good indicator for predicting the prognosis of multiple myeloma patients.The appearance of LCE indicates disease progression, poor prognosis and early relapse.

The prognostic value of baseline serum free light chain in immunoglobulin light-chain cardiac amyloidosis / 中华血液学杂志

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.

Effect of Serum Free Light Chain Ratio and Normalization Ratio after Treatment on Diagnosis and Prognosis of Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To evaluate the value of serum free light chain (sFLC) κ/λ ratio (sFLCR) on the diagnosis and prognosis of patients with newly diagnosed multiple myeloma(MM), and explore the effect of sFLCR normalization on the prognosis of patients after 4 courses of induction therapy.@*METHODS@#The clinical data of 43 newly diagnosed MM patients from January 2014 to January 2019 were analyzed retrospectively. Immunoturbidimetry was used to detect the expression levels of sFLC κ and λ. According to the ratio of involved and uninvolved sFLC, using 100 as a boundary, the MM patients were divided into the high ratio group (sFLCR≥100 or ≤0.01) and the low ratio group (0.010.05).@*CONCLUSION@#Patients in the high ratio group at the initial diagnosis have worse renal function, later stage of disease, lower deep remission rate, earlier disease progression, shorter survival time, and worse clinical prognosis.

Cardiac magnetic resonance and amyloidosis: review / Ressonância magnética cardíaca e amiloidose: revisão

Amyloidosis is a disease caused by extracellular deposition of insoluble protein fibrils, that results in changes in tissue architecture and consequently modification of the organ structure. Cardiac involvement is common in amyloidosis. Two major types of systemic amyloidosis affect the myocardium ­ immunoglobulin light chain and transthyretin amyloidosis ­ each leading to different prognosis. Early detection and diagnosis of cardiac amyloidosis are the main objectives in the assessment of the disease. New techniques of magnetic resonance imaging have minimized the need for biopsies for the diagnosis. Late gadolinium enhancement technique, and more recently T1 mapping, have allowed a simplified evaluation of amyloid deposits and extracellular volume. The aim of this review was to describe basic concepts and updates of the use of magnetic resonance imaging for the diagnosis amyloidosis and evaluation of its severity

Evaluation and comparison of prognostic value of serum free light chain ratio/difference in patients with newly diagnosed multiple myeloma / 中华血液学杂志

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.

Effect of Serum Free Light Chain on Renal Function and Prognosis in Patients with Newly Diagnosed Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the effect of serum free light chain (sFLC) on renal function and prognosis in patients with newly diagnosed multiple myeloma (MM).@*METHODS@#The clinical data of 70 newly diagnosed MM patients who received sFLC examination in Fujian Medical University Union Hospital were retrospectively analyzed from April 2012 to November 2016. Univariate analysis was used to analyze the risk factors that associated with renal impairment (RI) and prognosis. Logistic regression and Kaplan-Meier analyze were used to analyze the roles of sFLC in RI and the prognosis.@*RESULTS@#Out of the 70 patients, 20 patients had RI at the initial diagnosis. Compared to normal renal function group, RI group had lower level of hemoglobin, elevated levels of serum uric acid, corrected calcium, serum creatinine, serum β2 microglobulin, and involved sFLC, higher proportion of patients with ISS stage III, involved sFLC≥500 mg/L, hemodialysis (all P＜0.05). Multivariate logistic regression analysis showed that serum uric acid≥430 μmol/L, ISS stage III and a involved sFLC≥500 mg/L were all the independent risk factors for RI in patients with newly diagnosed MM patients (all P＜0.05). Receiver operating characteristic (ROC) curves analysis showed that the involved sFLC was 705.0 mg/L, which was a best cut-off value area under curve (AUC) for prediting RI in patients with MM was 0.727 (P=0.003), sensitivity was 65.0% and specificity was 82.0%). After a median follow-up period of 31 (1-84) months, the median overall survival (OS) of patients with involved sFLC≥500mg/L and involved sFLC＜500 mg/L were 52.0 and 27.0 months, respectively, there was no statistically significant difference (P=0.137). There was also no statistically significant difference in median OS between the high sFLC ratio group (κ/λ＞32 or ＜0.03) and the low sFLC ratio group (0.03≤κ/λ≤32) (27 months vs 40 months, P=0.436).@*CONCLUSION@#The involved sFLC in the RI group is significantly higher than that in the normal renal function group in newly diagnosed MM patients. Serum uric acid≥430 μmol/L, ISS stage III and involved sFLC≥500 mg/L are the independent risk factors for RI. Monitoring sFLC in newly diagnosed MM patients is helpful to the prediction of RI, and the involved sFLC level or sFLC ratio may not affect the prognosis of newly diagnosed MM patients.

Clinical Significance of Serum Free Light Chain and Its κ/λ Ratio in Patients with Multiple Myeloma / 中国实验血液学杂志

OBJECTIVE@#To analyze the clinical significance of serum free light chain (sFLC) and sFLC-κ/λ ratio in patients with newly diagnosed multiple myeloma (MM), so as to provide the theoretical basis for the diagnosis, treatment and prognosis of MM patients.@*METHODS@#A total of 43 patients newly diagnosed as MM in our hospital and 40 cases of other diseases that could cause sFLC increase were selcted. The clinical features of newly diagnosed MM patients were analyzed. On the basis of the type of sFLC, MM patients were divided into sFLC-κ and sFLC-λ group. The correlation of sFLC with clinical index in two groups was analyzed. The difference of sFLC-κ/λ ratio between MM and non-MM patients was analyzed. According to whether the involved/uninvolved sFLC ratio was greater than 100, the MM patients were divided into the low ratio and the high ratio group. The clinical index of these 2 groups were analyzed.@*RESULTS@#Among MM patients, IgG type was the most. In sFLC-κ and -λ groups, the hemoglobin level negatively correlated with sFLC (r=-0.307, r=-0.494, P＜0.05), and the serum β2 microglobulin level positively correlated with sFLC (r=0.453, r=0.689, P＜0.05), and myeloma cells ratio also positively correlated with sFLC (r=0.307, r=0.309, P＜0.05). The concentration of albumin, lactate dehydrogenase and serum calcium did not correlate with sFLC (P＞0.05). The serum creatinine level also did not correlate with sFLC in the sFLC-κ group (P＞0.05), but in the sFLC-λ group they were obviously positive (r=0.697, P＜0.01). The ratio of sFLC-κ/λ ＜0.26 or ＞1.65 in MM patients was higher than that of non-MM patients, and the ratio of involved/uninvolved sFLC≥100 in MM patients was also higher than that of non-MM patients with statistically significant differences (P＜0.01). The levels of serum albumin, creatinine and β2 microglobulin, as well as myeloma cell ratio and ISS international staging of the patients between 2 groups were significantly different (P＜0.05), while the differences in sex, age and levels of hemoglobin, lactate dehydrogenase and blood calcium were not significant between the 2 groups (P＞0.05).@*CONCLUSION@#The light chain type λ in MM patients correlates with renal damage. The abnormalities of sFLC-κ/λ ratio occur mostly in MM patients. The MM patients with involved/uninvolosed sFLC ratio ≥100 show the severe symptoms and poor prognosis.

A Case of Mature B-cell Neoplasm with Light Chain Clonality Confirmed by Cytoplasmic Light Chain Expression Using Flow Cytometry

Surface immunoglobulin light-chain restriction is evidence of clonality in mature B-cell neoplasms. An aberrant pattern of surface light-chain expression can also be considered evidence of clonality. However, because this result could occur due to nonspecific staining or failure to stain, careful interpretation is required for accurate diagnosis. According to a previous study, flow cytometric analysis of the cytoplasmic pattern of light-chain expression in mature B-cell neoplasms is a viable approach to confirming clonality. Herein, we report a case, in which clonality could not be proven by surface light-chain analysis, but was demonstrated by cytoplasmic light-chain analysis. The case was in a patient with B-cell lymphoma showing non-specific surface expression of light-chains. This case support consideration of flow cytometric analysis of cytoplasmic light-chain expression patterns when aberrant surface light chain expression is observed, to confirm clonality of mature B-cell neoplasms.

Renal tubular P-glycoprotein expression is reduced in plasma cell disorders

BACKGROUND: P-glycoprotein (P-gp) transports many chemicals that vary greatly in their structure and function. It is normally expressed in renal proximal tubular cells. We hypothesized that P-gp expression influences light chain excretion. Therefore, we investigated whether renal tubular P-gp expression is altered in patients with plasma cell disorders. METHODS: We evaluated renal biopsy specimens from patients with plasma cell disorders (n = 16) and primary focal segmental glomerulosclerosis (the control group, n = 17). Biopsies were stained with an anti-P-gp antibody. Loss of P-gp expression was determined semi-quantitatively. Groups were compared for loss of P-gp expression, and clinical variables. RESULTS: P-gp expression loss was more severe in patients with plasma cell disorders than it was in those with glomerulonephritis (P = 0.021). In contrast, clinical and histological parameters including serum creatinine, level of urinary protein excretion, and interstitial fibrosis/tubular atrophy grade were not significantly different between the groups. P-gp expression loss increased with age in patients with plasma cell disorders (P = 0.071). This expression loss was not associated with serum creatinine, the level of urinary protein excretion or the interstitial fibrosis/tubular atrophy grade. There was no significant association between the severity of P-gp expression loss with the types and serum levels of light chains, isotypes and serum immunoglobulin levels. CONCLUSION: Renal tubular P-gp expression is significantly down-regulated in patients with plasma cell disorders characterized by nephrotic range proteinuria. Additional studies are needed to determine whether reintroduction of renal tubular P-gp expression would mitigate the proximal tubular injury that is caused by free-light chains.

Sensibilidad diagnóstica de electroforesis de proteínas y cadenas livianas libres séricas en gammapatías monoclonales / Diagnostic accuracy of serum protein electrophoresis and free light chain measurements for monoclonal gammopathies

Background: International guidelines suggest a screening panel for monoclonal gammopathies that contains serum protein electrophoresis (SPE), free light chain (FLC) measurements and immunofixation. This combination provides the possibility of a timely accurate diagnosis. Aim: To evaluate the sensibility of a simple screening panel (SPE + FLC). Material and Methods: We analyzed 191 consecutive serum samples of patients with a suspected monoclonal gammopathy (MG). Results: Seventy five patients were diagnosed with MG. The sensitivity and specificity of the combination of SPE + FLC for the diagnosis of monoclonal gammopathy were 95% (95% confidence intervals 89-99) and 99% (95% confidence intervals 96-100), respectively. Conclusions: We were able to validate the international recommendations on the diagnostic accuracy of this simple combination of two tests in serum for monoclonal gammopathy.

The value of serum heavy/light chain immunoassay to assess therapeutic response in patients with multiple myeloma / 中华血液学杂志

Objective: To assess the value of immunoglobulin heavy/light chain (HLC) immunoassay on therapeutic response in patients with multiple myeloma(MM). Methods: A total of 45 newly diagnosed MM patients were retrospectively enrolled in Peking Union Medical College Hospital from 2013 to 2016, whose 115 serum samples were consecutively collected. HLC was tested to evaluate response and compare with other methods for M protein detection. Results: ①There were 30 males and 15 females in total of whom the monoclonal immunoglobulin was IgG in 27 (IgGκ∶IgGλ 12∶15) and IgA (IgAκ∶IgAλ 9∶9) in 18. The arerage age of the studied population was 59 (range 43-80) . ② In 34 patients with serum sample at diagnosis, 32 (94.1%) had abnormal HLC ratio (rHLC) while 2 patients with IgG had normal rHLC. The percentages of abnormal rHLC was 81.8% (18/22) at partial response、50.0%(9/18) at very good complete response and 16.0%(4/25) at complete response. ③In 25 patients reaching CR, there were 13 with IgG and 12 with IgA. 4 patients equally split of IgG and IgA had abnormal rHLC at complete response. ④By monitoring the rHLC of some patients consecutively, we found that the remission of rHLC was to some extent behind the remission of SPE and IEF, or even rFLC. Conclusion: Immunoglobulin HLC detection is one feasible method for minimal residual disease detection.

Plasma Cell Cheilitis: A Clinicopathological and Immunohistochemical Study of 13 Cases

BACKGROUND: Plasma cell cheilitis is an unusual benign plasma cell proliferative disease of an unknown etiology that typically presents on the lip. OBJECTIVE: The aim of this study was to investigate the clinicopathological characteristics of 13 cases of plasma cell cheilitis. METHODS: The present study investigated the clinical manifestations, treatment modalities, and outcome of 13 patients diagnosed with plasma cell cheilitis from 2011 to 2016 at Kangdong Sacred Heart Hospital and Hallym University Sacred Heart Hospital. Biopsy specimens of the all cases were evaluated using conventional hematoxylin and eosin staining with kappa and lambda immunoglobulin light chain immunohistochemistry. RESULTS: The age of the patients ranged from 39 to 86 years (mean, 64.7 years), with male predominance. Histopathologically, 61.5% and 38.5% of patients showed band-like and pan dermal plasmacytic infiltrates, respectively. Eosinophilic infiltration was noted in 69.2% of patients. All cases showed both kappa and lambda immunoglobulin light chain reactivities, and kappa predominance was confirmed in 9 patients (69.2%). A majority of the patients was treated with local therapy, such as intralesional steroid injection with topical tacrolimus. Among the 13 patients, plasma cell cheilitis completely resolved, partially resolved, and recurred in 3 (23.1%), 5 (38.5%), and 5 patients (38.5%), respectively. CONCLUSION: Plasma cell cheilitis presented as erosive edematous circumscribed patches or plaques affecting mainly the lower lip of elderly male patients. The majority of histopathology cases showed characteristic plasma cell aggregation on the upper dermis that was immunopositive for immunoglobulin light chain, with kappa predominance.

Russell Body Gastritis Disappeared after Helicobacter pylori Eradication

A rare gastric mucosal lesion characterized by Russell body-containing plasma cell infiltration is termed as Russell body gastritis. This lesion is highly suggested to be correlated with Helicobacter pylori-induced chronic gastritis, and often misdiagnosed as mucosa-associated lymphoid tissue lymphoma, signet ring cell carcinoma, plasmacytoma, or xanthoma. However, Russell body gastritis is easily discriminated by its polyclonal immunoreaction to immunoglobulin light chains contrary to monoclonal immunoreaction of neoplastic disease. We report here a case of Russell body gastritis associated with H. pylori infection, which disappeared after H. pylori eradication.