Serum Beta 2-microglobulin Levels Research Articles

Assessment of Serum Beta 2-Microglobulin Levels in Crimean-Congo Hemorrhagic Fever Patients: Implications for Immune Activation and Disease Pathogenesis

Crimean-Congo Hemorrhagic Fever (CCHF) presents a spectrum of clinical manifestations, ranging from asymptomatic cases to severe, life-threatening conditions. Despite extensive research on CCHF pathogenesis, comprehensive understanding remains elusive. Our investigation focused on assessing serum beta 2-microglobulin (β2M) levels in CCHF patients, aiming to elucidate its potential as an immune activation marker and its involvement in disease pathogenesis. The study enrolled 45 CCHF patients and 45 healthy volunteers as a control group. Serum β2M levels were quantified using the immunoturbidimetric analysis method. The patient group was divided into two groups, mild and moderate-severe, using scoring systems. The mean β2M values for the control, mild, and moderate-severe patient groups were 2.27±0.50, 4.37±1.29, and 5.82±2.62 mg/L, respectively (p<0.001). Positive correlations were noted between β2M concentrations and markers such as BUN, creatinine, uric acid, creatine kinase, and aPTT (p<0.001, r=0.684; p<0.001, r=0.602; p=0.003, r=0.439; p=0.008, r=0.392; p=0.019, r=0.348, respectively). Conversely, negative correlations were observed with total protein, albumin, and platelet count (p=0.021, r=-0.342; p=0.003, r=-0.434; p=0.048, r=-0.296, respectively). The findings suggest a prominent inflammatory response in CCHF, indicated by elevated β2M levels, implying its potential role in the molecular mechanisms of the disease

Value of Serum Beta2-Microglobulin Level in Prediction of Acute kidney injury in Critically Ill Neonates.

Value of Serum Beta2-Microglobulin Level in Prediction of Acute kidney injury in Critically Ill Neonates.

Serum beta2-microglobulin acts as a biomarker for severity and prognosis in glioma patients: a preliminary clinical study

BackgroundGliomas are the deadliest malignant tumors of the adult central nervous system. We previously discovered that beta2-microglobulin (B2M) is abnormally upregulated in glioma tissues and that it exerts a range of oncogenic effects. Besides its tissue presence, serum B2M levels serve as biomarkers for various diseases. This study aimed to explore whether serum B2M levels can be used in the diagnosis and prognosis of gliomas.MethodsMedical records from 246 glioma patients were retrospectively analyzed. The relationship between preoperative serum B2M levels and clinicopathological features was examined. Kaplan-Meier analysis, alongside uni- and multivariate Cox regression, assessed the association between B2M levels, systemic inflammatory markers, and glioma patient prognosis. Receiver operating characteristic (ROC) curve analysis evaluated the diagnostic significance of these biomarkers specifically for glioblastoma (GBM).ResultsPatients with malignant gliomas exhibited elevated preoperative serum B2M levels. Glioma patients with high serum B2M levels experienced shorter survival times. Multivariate Cox analysis determined the relationship between B2M levels (hazard ratio = 1.92, 95% confidence interval: 1.05–3.50, P = 0.034) and the overall survival of glioma patients. B2M demonstrated superior discriminatory power in distinguishing between GBM and non-GBM compared to inflammation indicators. Moreover, postoperative serum B2M levels were lower than preoperative levels in the majority of glioma patients.ConclusionsHigh preoperative serum B2M levels correlated with malignant glioma and a poor prognosis. Serum B2M shows promise as a novel biomarker for predicting patient prognosis and reflecting the therapeutic response.

#1372 Association of plasma beta-2-microglobulin with risk of cardiovascular disease in patients with chronic kidney disease

Abstract Background and Aims In patients with chronic kidney disease(CKD), beta 2 microglobulin (B2MG) can be used to assess renal function, and predialysis serum B2MG levels can predict mortality risk. In addition to the kidney, B2MG regulates the expression of interleukin 1 and tumor necrosis factor, participates in the pathogenesis of vascular damage, and is a marker that can detect the formation of amyloid, therefore it is important in the diagnosis of cardiovascular disease (CVD). To assess the correlation of serum B2MG levels with some metabolic and cardiovascular function factors in patients with chronic kidney disease. Method 119 people with chronic kidney disease and 52 healthy control groups were selected as a case-control study and blood samples were analyzed for creatinine, urea, cholesterol, triglycerides, LDL, calcium, phosphorus, albumin, total protein, and B2MG with Cobas 6000 fully automatic analyzer and echocardiography was performed. Renal function was evaluated by CKD EPI crea-cys combined calculation. In the group with CKD, a person with eGFR <90 ml/min/1.73 m² was not included in the study due to the study exclusion criteria. Results The average age of the group with CKD was 54.92, and the average age of the healthy group was 50.66. B2MG has a significantly higher (P < 0.000) statistically significant correlation in the group with CKD compared to the control group. B2MG was significantly associated with creatinine (g = 0.516, P < 0.000), phosphorus (g = 0.342, P < 0.000), cystatin C (g = 0.700, P < 0.000), urea (g = 0.326, P < 0.000), and echocardiography with directly indicators LVMI(g = 0.113, P < 0.000), LVESD (r = 0.265, P < 0.000), thus BMI (g = −0.274, P < 0.000), tTSH (r = −0.516, P < 0.000), calcium ( g = −0.137, P < 0.000), albumin (g = −0.180, P < 0.000), total protein (r = −0.080, P < 0.000), cholesterol (g = −0.215, P < 0.000), BNLP (r = −0.163, P < 0.000), triglycerides (g = −0.142, P < 0.000), and EV of echocardiography (g = −0.292, P < 0.000) have inverse statistical significance. Conclusion B2MG levels have been shown to predict CVD risk and CVD-related mortality in all stages of chronic kidney disease. According to our study, B2MG is directly related to kidney function biomarkers, phosphorus, LVMI, and LVESD indicators of cardiac echocardiography, and inversely correlated with parameters of eGFR, protein, triglycerides, calcium, and cardiac echocardiogram EV indicators, which is similar to studies conducted in other countries. Therefore, B2MG can be used to detect the risk of CVD in people with severe CKD. Figure: Will be uploaded on our poster if accepted.

Comparative assessment of beta-2 microglobulin as predictor of progression of multiple myeloma in asymptomatic and symptomatic multiple myeloma patients in a tertiary care hospital in Eastern India

Background: Multiple myeloma (MM) is a clonal late B-cell disorder in which malignant plasma cells expand and accumulate in the bone marrow and is associated with paraprotein production, bone lesions, anemia, hypercalcemia, susceptibility to infections, and renal impaired. Beta-2 microglobulin (B2M) is a serum marker of tumor burden in lymphoid malignancies, including MM. The purpose of this study was to find whether increased B2M levels can predict the progression of MM from asymptomatic to progressed symptomatic phase, as it is a less invasive and cost-effective method than the more invasive and costly ones to predict the progression of the disease. Aims and Objectives: This study was taken in a medical college, Kolkata, 50 asymptomatic Stage 1 MM patients were taken along with age and gender-matched 50 symptomatic progressed MM patients, blood samples of both groups were evaluated to estimate the difference in serum B2M (SB2M) level in both groups. Moreover, to study the difference in serum albumin, C-reactive protein, creatinine, immunoglobulin (IG), total protein, calcium, hemoglobin, and percentage of plasma cells in both groups and also their correlation with SB2M level in the progressed disease group. As well as to assess if there is increased B2M in the progressed disease group and if the B2M level correlates with the disease severity (i.e. progression of the disease). Materials and Methods: An observational descriptive non-interventional, hospital-based study conducted at central laboratory, medical college, Kolkata, for 6 months. Patients were chosen by systematic random sampling. Fifty asymptomatic MMs were chosen according to the International Myeloma Working Group criteria and out of 50 patients in the progressed disease group, 75% of patients were in Stage III and 25% of patients were in Stage II according to the Salmon and Durie system. Results: More than 80% in the progressed and symptomatic group had β-2M >3.5 mg/L. Whereas in the newly diagnosed group, all the 50 patients had their β-2M level <3.5 mg/L. Moreover, B2M value in the blood of progressed MM patients was found to be positively correlated with percentage of plasma cells from bone marrow, serum creatinine level, serum protein level, serum calcium level, and IgG level and negatively correlated with Hb level and serum albumin level. Hence, in a nutshell, increased B2M level was found in the progressed MM group, and its level positively correlated with the other predictors of the progression of MM. Conclusion: As per this study, SB2M level (which is a less invasive test than bone marrow testing and less costly) can be used as the predictor of progression of MM from asymptomatic to symptomatic. However, small sample size and cross-sectional pattern of the study were the limitations of this study. Bigger sample size and prospective cohort-type study designing method could be a better method to find a stronger correlation between MM staging and SB2M levels.

The Clinical Significance and Prognostic Value of Serum Beta-2 Microglobulin in Adult Lymphoma-Associated Hemophagocytic Lymphohistiocytosis: A Multicenter Analysis of 326 Patients

Introduction: Hemophagocytic lymphohistiocytosis (HLH) is a rare syndrome characterized by an excessive immune response. Beta-2 microglobulin (B2M) forms the light chain section of the major histocompatibility complex (MHC) class Ⅰ antigen. The prognostic role of B2M in lymphoma-associated HLH remains to be determined. This study was to investigate the prognostic role of serum B2M in adult lymphoma-associated hemophagocytic lymphohistiocytosis (HLH). Methods: The clinical and laboratory characteristics of adult patients in a multicenter cohort with lymphoma-associated HLH who had baseline serum B2M levels between August 2009 and June 2023 were retrospectively analyzed. The diagnosis of HLH was established according to the HLH-2004 criteria. Results: A total of 326 cases were included and the median serum B2M level was 5.19 mg/L. The most common subtype of lymphoma was T/NK cell lymphoma (51.8%, 169/326), followed by B-cell non-Hodgkin lymphoma (45.4%, 148/227) and Hodgkin lymphoma 8/326 (2.5). The optimal cut-off value of serum B2M for predicting overall survival was 8.73 mg/L (p < 0.0001). Patients were divided into two subgroups by the optimal cut-off value. The median survival was 21 days for the high level subgroup, and 236 days for the low level subgroup (Figure 1). The 6-month survival rates were 22% and 54%, respectively. The subgroup with B2M level > 8.73 mg/L was older and had a higher proportion of stage IV. Patients with higher levels of B2M showed lower levels of platelets, albumin, and fibrinogen, and high levels of creatinine. A moderate correlation between creatinine and serum B2M was found (Spearman's ρ = 0.417, p < 0.001). The multivariate analysis showed that the high levels of serum B2M (> 8.73 mg/L) and creatinine (≥ 133 μmol/L), decreased fibrinogen (≤ 1.5 g/L), agranulocytosis (< 0.5×10 9/L), severe thrombocytopenia (< 50×10 9/L), and increased Epstein-Barr virus DNA were found to have significant prognostic values in all patients. The high serum B2M level (> 8.73 mg/L), severe thrombocytopenia (< 50×10 9/L), agranulocytosis (< 0.5×10 9/L), and high Epstein-Barr virus DNA copy number were independent prognostic factors in patients with creatinine < 133 μmol/L. Finally, a prognostic scoring system was established based on serum B2M levels as well as five other independent prognostic factors and divided the patients into three groups with significant prognostic differences (median survival: low-risk [score ≤ 1] 428 days vs. intermediate-risk [score = 2] 102 days vs. high-risk [score ≥ 3] 18 days, P < 0.0001) (Figure 2). The 6-month survival rates were 67%, 46% and 14%, respectively. Conclusions: This study confirmed that the serum B2M level could be an independent prognostic factor in lymphoma-associated HLH and established a prognostic scoring system to predict patients' survival.

Clinical Characteristics of Long-Term Survivors Treated with BCMA CAR T Cell

Introduction Anti-BCMA(B-cell maturation antigen) CAR-T therapy, a novel and efficacious method for treating relapsed/refractory multiple myeloma (RRMM), has been approved and applied in clinics. Here, we report the survival analysis and clinical characteristics associated with long-term survivors (complete response at 18 months) after CAR-T cell therapy. Methods Between 1 January 2018 and 1 February 2023, 22 consecutive patients with relapsed/refractory MM were enrolled in a clinical trial of BCMA CAR T cells (registered at www.clinicaltrials.gov as #NCT04500431). This study was approved by the Tongji Hospital of Tongji University Ethics Committee, and written informed consent was provided by each patient. They all were treated with a single infusion of CAR-T cells. FC chemotherapy regimen was administered before transfusion. The median number of CAR-T cells transfused was 5.0 (range 4.0-6.6) ×10 6/kg. Long-term efficacy and related clinical characteristics were evaluated. Results In the 22 patients treated, the overall response rate was 77% (17 of 22). With a median follow-up of 24 months (range, 4-52), the median PFS were 17 months. The adverse events within 30 days after infusion were well tolerated. Toxic hematologic effects were the most common grade ≥3 events, including neutropenia (68%), anemia (54%), and thrombocytopenia (36%).Only 1 patient experienced grade 1 neurologic toxicity.No patients experienced severe infection within 30 days after infusion. Detailed patient baseline characteristics are described in Tables 1. During follow-up after CAR T-cell therapy, the complete response rate was 36.3%(8/22), 40.9(9/22) and 27.2(6/22) at 12 months, 18 months and 24 months, respectively. At 18 months, the patients achieved the highest complete response rate. Baseline characteristics, such as age, sex, isotype, ECOG, high-risk cytogenetics, prior lines of therapy, percentage of plasma blasts in bone marrow, serum monoclonal protein and extramedullary disease in the 9 complete response patients at 18 months were similar to other progressive disease 13 patients. However, the significant differences of International Staging system stage(p=0.034) and Durie-Salm staging system(p=0.002) at baseline were observed between the 9 complete response patients and 13 progressive disease patients at 18 months(Table 1). The International Staging system stage(area under curve 0.80) and Durie-Salm staging system(area under curve 0.86) predicted the outcome of patients at 18 months well. Durie-Salmon Staging system was published in 1975, which used commonly available clinical parameters including calcium, hemoglobin, bone lesions, creatinine level and serum or urine monoclonal protein. The ISS staging system was proposed in 2005 based on baseline serum levels of beta2-microglobulin (β2M) and albumin. And there was no statistically significant difference in the baseline serum levels of beta2-microglobulin, albumin, calcium, bone lesions and creatinine level between the 9 complete response patients and 13 progressive disease patients at 18 months. As figure 1 illustrates, the hemoglobin of 9 complete response patients was higher than that of 13 progressive disease patients with statistical significance at 9 time-points: PreFC(117.6±20.7 vs 94.6±23.6 , p = 0.028), D -4(113.6±15.9 vs 86.0±25.7 , p = 0.016), D -3(107.8±11.8 vs 84.6±23.0 , p = 0.027), D -2(117.6±20.7 vs 94.6±23.6 , p = 0.0009), D -1(111.0±19.9 vs 81.8±19.0 , p = 0.013), D0(107.1±20.4 vs 83.0±22.8 , p = 0.029), D1(107.7±19.1 vs 84.2±24.3 , p = 0.032), D4(104.1±14.9 vs 82.7±19.9 , p = 0.015), D5(103.4±19.1 vs 82.2±18.3 , p = 0.018). In the univariate Cox regression analysis, the hemoglobin at PreFC(hazard ration (HR) = 0.97; 95% confidence interval (CI): 0.95-1; p = 0.029), D -4(HR=0.96 ;95% CI:0.92-1, p = 0.012), D -3 (HR=0.97 ;95% CI:0.94-1, p = 0.029), D -2(HR=0.93 ;95% CI:0.89-1, p = 0.003), D -1(HR=0.97 ;95% CI:0.95-1, p = 0.047), D0(HR=0.97 ;95% CI:0.94-1, p = 0.038), D1(HR=0.97 ;95% CI:0.94-1, p = 0.044), D4(HR=0.95 ;95% CI:0.92-1, p = 0.01) and D5(HR=0.97 ;95% CI:0.94-1, p = 0.027) were relative factors of prognosis. Conclusions These long-term follow-up data in patients after BCMA CAR -T therapy suggest that baseline ISS ,DS staging and hemoglobin at 9 time-points display opposing association with long-term progression-free survival.

Development of a Novel Prognostic Score in Patients with Waldenström Macroglobulinemia Prospectively Enrolled in the Observational NF10 Study of Fondazione Italiana Linfomi

Background. IPSSWM and revised-IPSSWM are the two currently prognostic scores used for survival prediction in symptomatic Waldenström Macroglobulinemia (WM) patients in need of treatment. In addition to age and serum beta-2 microglobulin levels, which are present in both scores, the IPSSWM includes anemia, thrombocytopenia and the concentration of the serum monoclonal component (MC), while revised-IPSSWM includes LDH and serum albumin levels. Both IPSSWM and revised-IPSSWM have been developed in retrospective series and apply only to symptomatic WM patients. Aim. To analyze WM patients prospectively enrolled in the NF10 observational study since 2010 with the aim to define a prognostic score applicable to all WM patients at diagnosis, either symptomatic or asymptomatic. Methods. The progression-free survival (PFS) and overall survival (OS) rate was estimated and plotted using the Kaplan-Meier method, with 95% confidence interval (95% CI), and the effect of covariables on PFS was estimated by means of the Cox proportional hazard (PH) regression. The association with PFS was expressed as hazard ratio (HR) with 95% CI, either in univariable or multivariable regression. All statistical tests were two-sided. The proportionality of risk of the multivariable Cox PH model was checked graphically by means of the scaled Schoenfeld residuals, and the model performance was analyzed using the likelihood displacement method. Starting from a model with 10 variables selected on the basis of clinical and statistical considerations, the final model was selected on considering the Akaike (AIC) and likelihood ratio test. The cut-offs were selected after modelling the covariate with restricted cubic spline in Cox regression. The final model was internally validated using bootstrap techniques to evaluate the discriminant power (C-index), slope shrinkage to check for overfitting, and calibration (comparison between predicted and actual survival). Results. We identified 303 eligible patients from the NF10 study, of whom 185 (60%) needed treatment immediately after diagnosis (42%) or later (18%). These were main patients characteristics: 59% were male, 46% were aged >70 years, 8% had constitutional symptoms, 55% had Hb <12 g/dL, 54% had an absolute lymphocyte count ≥2x10 9/L, 9% had platelets <100x10 9/L, 37% had a serum MC >2 g/dL, 21% had albumin <3.5 g/dL, 23% had LDH > upper limit of normal (ULN), 32% had beta-2 microglobulin >1.5xULN. With a median follow-up of 51 months, 5-year PFS for the entire cohort was 67% (95%CI 60-73%). In univariate analysis, age >70 years (P=0.043), constitutional symptoms (P=0.009), nodal sites (P=0.002), Hb <12 g/dL (P<0.001), absolute lymphocyte count ≥2x10 9/L (P=0.033), serum MC >2 g/dL (P=0.003), high beta-2 microglobulin (P<0.001) and LDH (P=0.001), albumin <3.5 g/dL (P<0.001), C-reactive protein >4 mg/dL (P=0.008) were associated with shorter PFS. In multivariate analysis, age, anemia, hypoalbuminemia and high LDH retained prognostic value and thus entered the final model. Patients were classified into 3 risk groups: low (0-1 factors, 62% of patients), intermediate (2 factors, 24%) or high (3-4 factors, 15%), with a 5-year PFS of 80% (95%CI 70-87%), 49% (95%CI 32-64%) and 25% (95%CI 11-42%), respectively, with C-Harrell=0.744 and robust internal validation and calibration. OS was respectively 96% (95%CI 90-98%), 77% (95%CI 62-87%) and 43% (95%CI 25-60%) for the low, intermediate and high risk group (Figure 1). Conclusions. We developed a prognostic model based on 4 parameters easily attainable in clinical practice, able to predict PFS and OS at diagnosis. This is the first prognostic score for WM developed in a prospective study and applicable to patients presenting either with symptomatic or asymptomatic disease. This prognostic model identifies a subset of high-risk patients with a dismal outcome and a median OS <5 years. External validation in independent cohorts is needed.

LncRNA CRNDE is downregulated and associated with poor prognostic markers in chronic lymphocytic leukemia.

Chronic lymphocytic leukemia (CLL) is characterized by a very heterogeneous clinical outcome. Thus, a plethora of prognostic factors and systems has been identified to place patients into different risk categories and to guide therapy decisions. The classic clinical staging models by Rai and Binet have been the cornerstone of patient management for several years. The greater insight into the molecular biology of CLL facilitated the advent of prognostic genetic biomarkers that are expected to impact clinical practice soon in the future. Therefore, we aimed to investigate the expression of long non-coding RNA (lncRNA) CRNDE in patients with CLL, and to analyze its relationship with the clinicopathological parameters of CLL. In this study, 40 untreated CLL patients and 30 age- and gender-matched controls were enrolled. The analysis of lncRNA CRNDE expression was determined using reverse transcription-quantitative polymerase chain reaction technique. Our result confirmed the downregulated expression of LncRNA CRNDE in CLL patients compared to controls (p < 0.001). The low expression of CRNDE was significantly associated with poor prognostic markers including advanced stage of CLL, high levels of serum beta-2 microglobulin and lactic dehydrogenase, and the presence of del17p (p = 0.029, p = 0.013, p = 0.003, p = 0.028; respectively). Our study demonstrated that LncRNA CRNDE is significantly downregulated and associated with poor prognostic markers in CLL. It provides a rationale to assess its biological and prognostic impact in CLL.

Role of beta 2 microglobulin in chronic kidney disease

The aim: to study the relationship of beta-2-microglobulin (beta-2 MG) with clinical and laboratory manifestations of chronic kidney disease (CKD).Patients and Methods. The results of a comprehensive examination of 284 people (118 males and 166 females) aged 18 to 86 years with various types of socially significant diseases were studied. All patients underwent thorough collection of clinical and anamnestic data, laboratory monitoring with the determination of the level of systolic and diastolic blood pressure (BP), body mass index, red blood, beta-2-microglobulin (B2M), lipid profile and proteinuria. Kidney function was assessed according to the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula using serum creatinine. The main group included 113 patients (55 men and 58 women, mean age 50.9±15.8 years), diagnosed with chronic kidney disease (CKD). The control group consisted of 171 people (63 men and 108 women) with various forms of socially significant diseases, but without signs of CKD. Statistical analysis was carried out using the programs Statistica 10.0 (StatSoft Inc., USA) and Microsoft Office Excel 2010 (Microsoft Corp., USA).Results. In the subgroup of patients with CKD, signs of renal failure were observed in 46 people in 40.7 % of cases. As CKD progressed, the signs of impaired metabolism of B2M were more severe: its serum level was 8.646 (7.892; 12.231) mg/l at C4 and 18.444 (11.225; 23.717) mg/l at C5 stages of CKD, and urinary excretion was 2.502 (0.305; 6.313) mg/l at C4 and 2.614 (1.535; 25.812) mg/l at C5 stages of CKD. Regardless of renal dysfunction, the median serum B2M level was clinically significantly higher in females (p&gt;0.05). Single-factor one-way correlation analysis showed statistically highly significant relationship was between serum B2M and creatinine levels both in the subgroup of patients with CKD (r = 0.905; p = 0.001) and in the total sample (r = 0.749; p = 0.001). There was a strong negative relationship between serum B2M levels and estimated glomerular filtration rate (GFR) (r = -0.717; p = 0.001). In individuals without CKD, an increase in serum creatinine was closely associated with an increase in urinary excretion of B2M (r=0.252; p=0.005). Simultaneously, in this category of patients, there was a close correlation between estimated GFR with serum B2M level (r= -0.433; p=0.002) and its urinary excretion (r= -0.247; p=0.005). A direct relationship between an increase in serum B2M and an increase in diastolic blood pressure (r=0.274; p=0.034) among CKD patients was established. In the total sample, a direct relationship between the value of systolic BP and serum B2M level (r= 0.223; p=0.01) was registered, as well as between diastolic BP (r= 0.268; p=0.01) and urinary excretion of B2M.Conclusion. As a result of the study, metabolism of B2M and its relationship with the clinical and laboratory manifestations of CKD were evaluated. The data obtained show high prognostic potential of changes in metabolism of B2M in the population of patients with various forms of socially significant diseases, as well as CKD, which allows to identify among them groups of patients with high and/or very high renal and cardiovascular risk, in order to take timely targeted therapy.

Comparison of International Prognostic Indices and Validation Study for Patients with Diffuse Large B-Cell Lymphoma in the Rituximab Era

ABSTRACT In diffuse large B-cell lymphoma (DLBCL), patients needing new alternative regimens in first-line treatment should be selected with better risk classification. After International Prognostic Index (IPI), Revised-IPI (R-IPI), National Comprehensive Cancer Network (NCCN)-IPI, and Grupo Español de Linfomas y Trasplante Autólogo de Médula Ósea (GELTAMO)-IPI, have been developed to improve risk predictions. This study compared performances of four prognostic indices concerning differentiation of overall survival (OS), the most critical endpoint. The study was conducted on 116 patients diagnosed with DLBCL. Patients with primary nervous system and testicular DLBCL, and post-transplant lymphoproliferative disorders, were excluded. The fitting of prognostic indices for database and the prediction of patient discrimination were compared using Akaike’s information criterion and concordance index. Of the study cohort, 63.8% were male, the median age was 56 (18-88), and median follow-up term was 45.6 (0.3-75.2) months. All factors, constituting IPI and R-IPI scores, demonstrated a significant difference in OS. Involvements of the extranodal regions specified in NCCN-IPI and elevated serum beta-2 microglobulin levels in GELTAMO-IPI had prognostic significance (p= 0.005 and p= 0.040, respectively). Each of the four prognostic indices, resulted in risk groups with significantly different OS. R-IPI provided the best fit for database, while NCCN-IPI provided the best discrimination between patients with high and low OS. Although NCCN-IPI provides the best discrimination between patients with short and long OS, using original IPI still seems acceptable in the rituximab era. Integration of tumor molecular characteristics into NCCN-IPI may better characterize high-risk group in new treatment approaches. Keywords: International Prognostic Index, National Comprehensive Cancer Network, Validation, Diffuse Large B-Cell Lymphoma, Rituximab

Attempt to assess direct interactions between tumor burden, myeloid-derived suppressor cells and PD-1- and TIM-3-expressing T cells in multiple myeloma patients

The avoidance of immune surveillance by malignant plasma cells (PCs) in multiple myeloma (MM) is mediated by different mechanisms, among which an induction of T cell exhaustion and expansion of myeloid-derived suppressor cells (MDSCs) appear to play substantial roles, but it is still a lack of data on possible MDSC-mediated induction of T cell exhaustion. The aim of the present work was to evaluate possible relationship between frequencies of MM PCs, MDSCs and phenotypically exhausted PD-1+ and TIM-3+ T cells in bone marrow (BM) samples and peripheral blood (PB) of MM patients at various disease stages. Peripheral blood (n = 88) and BM samples (n = 56) were obtained from MM patients (newly diagnosed (n = 6), patients in remission (n = 71) and with progressive disease (n = 11)). Frequencies of T cells expressing checkpoint receptors PD-1 and TIM-3, polymorphonuclear MDSCs (PMN-MDSCs, Lin-CD14-HLA-DR- CD33+CD15+/CD66b+), monocyte MDSCs (M-MDSCs, CD14+HLA-DRlow/-), early MDSCs (E-MDSCs, Lin-HLA-DR-CD33+CD15-/CD66b-), and MM PCs (CD45dimCD38+CD138+CD56+CD19-CD117+CD27- CD81-) were assessed with flow cytometry. Circulating and BM-resident PD-1+/TIM-3+T cell subsets, BM E-MDSCs, as soon as MM PCs and serum beta2-microglobulin (B2-M) levels were gradually increased in patients at different stages. Despite that, there were no associations between the markers of tumor load and the studied cell subsets. In patients in remission, BM PMN-MDSCs negatively correlated with CD4+T cells, CD4+PD-1+ and CD8+TIM-3+T cell subsets; there were positive correlations between BM E-MDSCs and CD4+PD-1+TIM-3+ cells and PB M-MDSCs and CD8+PD-1+ and (as a trend) CD8+TIM-3+T cells. We found no associations for the samples of patients at diagnosis and with progression. We can conclude that a possible mutual influence of malignant PCs, MDSCs and PD-1+/TIM-3+T cells is nonlinear, especially during a manifest tumor growth at diagnosis and progression. The detected negative correlations between resident PMN- MDSCs and T cell subsets might be associated with MDSC suppressive function, affecting both predominantly activated PD-1+ cells and exhausted TIM-3+ subsets. The positive correlations between BM E-MDSCs and CD4+PD-1+TIM-3+ cell subset and circulating M-MDSCs and PD-1+ and TIM-3+ CD8+T cells might confirm an ability of MDSCs to induce T cell exhaustion.

The Prognostic Significance of Serum Beta-2 Microglobulin (sβ2m) Levels in Patients with Hodgkin Lymphoma (HL): Final Analysis on 915 Patients Treated with ABVD or Equivalent (ABVDeq) Chemotherapy or Combined Modality Therapy (CT/CMT) Focusing to the Determination of Optimal Cut-Offs

Objective/Aim: Sβ2m is a well- established prognostic factor for several hematologic malignancies, but its role in HL is still controversial. We aimed to investigate the prognostic significance of sβ2m levels in a large series of homogenously treated HL patients. Methodology: We analyzed 915 patients with HL treated with ABVDeq (1990-2019) and selected solely based on the availability of pretreatment sβ2m levels. Sβ2m levels (upper normal limit 2.4mg/L) were analyzed in relation to other baseline features and the outcome. Freedom From Progression (FFP) was defined as time between treatment initiation and treatment failure (toxic death, primary refractoriness, PR with switch to alternative chemotherapy or relapse); deaths of unrelated causes were censored. Overall Survival (OS) and Disease-Specific Survival (DSS) were measured from treatment initiation to death of any cause or HL-related causes respectively. Sequential cut-offs (1.8-3.5 by 0.1mg/L increments) were used to explore the potential impact of sβ2m on outcomes. Results: The median serum β2m levels were 2.20mg/L (IQR 1.80-3.00, range 0.50-14.40) and 383/915 patients (42%) had elevated levels (>2.4mg/L). Sβ2m correlated strongly with all baseline features. Univariate Analysis: FFP was significantly inferior in patients with higher β2m at all tested cut-offs. At 2.4 mg/L ("normal versus high") the 10-year FFP was 80% vs 70% (p=0.001) after a median follow-up of 81.1 months. However, the best cut-off was 2.0mg/L [10-year FFP 83% vs 70% (p=0.001)]. A dose-response relationship was seen across quartiles Q1-4 with 10-year FFP 84%,78%,73% and 68% (p=0.001). In early stages (IA/IIA), statistically significant results were obtained at cut-offs between 1.8 and 2.1mg/L. The best cut-off was 1.9mg/L [10-year FFP 88% vs 78% (p=0.003)]. In advanced stages, none of the cut-offs yielded statistically significant results (borderline at 2.0mg/L; 10-year FFP 74% vs 64%, p=0.09). Multivariate Analysis: Sβ2m levels remained significant for FFP after adjustment for IPS factors, ESR and B-symptoms at 2.0mg/L [hazard ratio (HR) 1.55, p=0.01) in the whole series of 915 patients; it was not significant at the "normal versus high" comparison at 2.4mg/L. In early stages, sβ2m was a significant predictor of FFP at both cut-offs of 2.0 mg/L and 2.4 mg/L (HR 1.65, p=0.034 and 1.67, p=0.038). In advanced stages, sβ2m was an independent prognostic factor for FFP at 2.0mg/L (HR 1.44, p=0.098 despite the lack of univariate significance), but not at 2.4mg/L. The 10-year OS and DSS was lower in patients with elevated β2m levels (10-year rates 90% vs 77%, p<0.001 and 93% vs 86%, p=0.002). Similar results to FFP were obtained by multivariate analysis of DSS for all 915 and early-stage patients. Conclusion: Higher sβ2m was a significant independent predictor of FFP in HL but the optimal cut-off appears to lie within the normal limits, performing better than a "normal versus high" evaluation (cut-off 2.4 mg/L) and being 2.0mg/L for the whole series and 1.9 mg/L for early-stage patients. The prognostic significance in advanced stages was weaker (best cut-off 2.0 mg/L). Serum β2m was also highly predictive of OS and DSS. An analysis of corrected serum β2m according to renal function is ongoing.

Serum beta2-microglobulin level in systemic lupus erythematosus patients: Relation to disease activity

Aim of the workTo assess the level of β2-microglubulin (β2M) in systemic lupus erythematosus (SLE) patients and its association with disease activity and other disease parameters. Patients and methods40 SLE patients and 22 matched controls were studied. Serum β2M was assessed using enzyme-linked immunosorbent assay (ELISA). SLE Disease Activity Index (SLEDAI) and the damage index were assessed. ResultsThe patients were 36 females and 4 males (F:M 9:1) with a mean age of 28.5 ± 7.9 years and disease duration of 6.7 ± 3.3 years. The SLEDAI was 9.3 ± 5.2 and the damage index 1.83 ± 1.84. The mean level of serum β2M was significantly higher in SLE patients (6.42 ± 2.46 mg/L) than control (2.47 ± 0.4 mg/L) (p < 0.01).The serum level of β2M was significantly higher in patients with nephritis (n = 22) (7.45 ± 2.47 mg/L) compared to those without (n = 18) (5.17 ± 1.82 mg/L)(p = 0.002), And it was similar in those with and without arthritis (7.24 ± 2.3 mg/L vs 5.88 ± 2.4 mg/L (p0.07).The β2M significantly correlated with disease activity (r = 0.86, p 0.001), serum creatinine (r = 0.52, p > 0.001), urea (r = 0.63, p < 0.001), 24 h urinary protein (r = 0.56, p < 0.001), hematuria (r = 0.4, p < 0.01) and pyuria (r = 0.41; p < 0.01), ESR (r = 0.48; p < 0.01) and inversely with hemoglobin level (r = −0.34; p = 0.03). No significant correlation was found with C-reactive protein or with disease damage. Serum (β2M) significantly predicted nephritis and disease activity (sensitivity 63.6 %, specificity 77.8 %; p < 0.001 and 95 %CI: 0.25–0.41; p < 0.001 respectively). ConclusionSerum β2M is significantly associated with disease activity and lupus nephritis, suggesting that serum β2M may serve as a potential biomarker to monitor the disease activity and predicting lupus nephritis. However its association to disease severity needs further longitudinal studies.

MO643: Haemoperfusion Combined with Standard Haemodialysis May Have a Beneficial Effect on Serum Beta-2 Microglobulin Levels in Chronic Haemodialysis Patients

Abstract BACKGROUND AND AIMS Standard haemodialysis (HD) with low-flux membranes does not provide adequate middle molecular weight (MMW) clearance of uraemic toxins [1] and on-line haemodiafiltration (OL-HDF) may not be easily applicable and cost effective in some centres. We investigated whether low-flux conventional HD combined with hemoperfusion (HP) may offer any benefit regarding serum beta-2 microglobulin (β2M) levels as a surrogate of middle molecules in patients haemodialyzed for many years and we compared the method-combination with OL-HDF. METHOD We studied 24 stable anuric patients during 6 months, under standard medical therapy, aged 69 years (46–90), M: F = 20:4, on chronic HD for 84 (65–286) months, who formed three groups: A (GrA), B (GrB) and C (GrC). Each group included 8 age- and HD vintage-matched patients respectively. In GrA patients, a type HA130 cartridge for HP was connected in parallel to the low-flux polysulfone dialyzer and this combination of standard HD with HP (HD + HP) was used once a week for the first month, once every 2 weeks for the second month and once a month for the next 4 months. GrB patients underwent only standard HD treatment with low-flux polysulfone membranes and GrC patients were treated with OL-HDF. In all three groups serum β2M levels were determined at months 0 (M0) and 6 (M6), before (pre-dialysis, preD) and after (post-dialysis, postD) the second weekly session. RESULTS Serum preD β2M levels ​​were similar in GrA and GrB at M0 (44.1 ± 8.6 versus 34.6 ± 16.2 mg/L; P = NS) and at M6 (46.1 ± 7.6 versus 41.1 ± 18.9 mg/L; P = NS). In GrC, preD-β2M values were lower compared with GrA at both M0 (31.1 ± 4.2 mg/L; P = .008) and M6 (33.8 ± 6.82 mg/L; P = .02). In GrC, serum postD-β2M levels ​​decreased significantly at both M0 (7.4 ± 1.9 mg/L; P &amp;lt; .001) and M6 (9.9 ± 3.8 mg/L; P&amp;lt;.001). The postD reduction was maintained, with no difference between M0 and M6. An improvement/decrease in β2M values ​was observed only in GrA between M0 and M6 (−5.8 ± 7.2 versus 1.8 ± 5mg/L; P = .03) but not in GBr. CONCLUSION OL-HDF is obviously the most effective method for elimination of MMW uraemic toxins and in particular β2M [2–3]. Interestingly, the combination HD + HP seems to be more effective than low-flux HD alone [4] and it could be useful for specific patient cases in daily clinical practice in order to prevent or delay the onset and deterioration of symptomatic amyloidosis. Possible result improvement with a more frequent use of HD + HP needs further investigation.

Development of second primary multiple myeloma five years after treatment for limited-stage small cell lung cancer: a rare case report

Introduction. The development of a second primary malignancy (SPM) following small cell lung cancer (SCLC) has been previously reported in the literature. Especially smoking-related malignancy coupling is well known. The development of multiple myeloma (MM) in long-term survivors after treatment for SCLC is unknown. Here, we report the first case in the literature who developed MM 5 years after treatment for limited-stage SCLC. Case report. A 67-year-old male patient was diagnosed with limited-stage SCLC. After he received chemotherapy and radiotherapy, he was followed up without medication. He was admitted to the hospital with back pain and dyspnea 5 years after the diagnosis of small cell lung cancer. MRI revealed osteolytic lesions in the vertebrae. Laboratory testing revealed a markedly elevated serum IgA and an elevated serum beta-2 microglobulin level. Serum immunofixation revealed IgA lambda-type M-protein. Lambda excretion in urine immunofixation electrophoresis was observed. Bone marrow aspiration revealed the frequency of plasma cells to be 80% of all nucleated cells. Hence, the final diagnosis revealed IgA lambda free light chain MM. Treatment was given for multiple myeloma. In the follow-up, the patient experienced increased dyspnea and developed bilateral pleural effusion. The cytology sent from thoracentesis sampling was reported as plasmocyte-rich material. The patient fell into a coma and died in an intensive care unit. Conclusion. We presented the development of MM 5 years after treatment in a patient with SCLC who were treated for one year and then followed up with stable findings. It should be kept in mind that a patient with SCLC who is a long-term survivor and presents with back pain may have developed a primary malignancy originating from bone marrow rather than a bone metastasis. Patients should be advised smoking cessation after the treatment and diagnosis of SCLC. Also, the patients with SCLC who are long-term survivors should be closely monitored for the development of SPM.

Serum levels of Beta-2 microglobulin and interleukin-6 in HIV positive individuals and their correlation with CD-4 cell count

Serum levels of Beta-2 microglobulin and interleukin-6 in HIV positive individuals and their correlation with CD-4 cell count

Beta 2 microglobulin in kidney failure: A review and an algorithm for renal replacement therapy.

For decades, beta 2 microglobulin (B2M) has been a subject of great interest in nephrology and other fields such as multiple myeloma. B2M, a 99 amino acid protein, is associated with amyloid deposits in patients undergoing renal replacement therapy (RRT). The source of information is published articles on B2M in chronic renal failure since 1960. We have reviewed literature published since 1960 to date, highlighting the milestones of the role of B2M in chronic kidney disease (CKD) and B2M serum values in patients treated by various RRTs. B2M deposits associated with the disease include carpal tunnel syndrome, spondyloarthropathy, and arthritis of large joints such as the shoulders. The role of RRT in the removal of B2M in CKD is discussed. Recent reports include factors affecting the process of fibrillation and deposition of B2M in tissues. A comparative report of various modalities of treatment on the serum levels of B2M is provided. The presence of significant residual urine output in continuous ambulatory peritoneal dialysis patients may explain why peritoneal dialysis is a modality that is associated with the lowest level of serum B2M. Patients treated with hemodiafiltration or hemodialysis (HD) using high flux dialyzers have lower levels of B2M than those treated by HD with low flux dialyzers. Finally, based on the literature review, an algorithm for RRT using B2M level monitoring and other variables is proposed and needs evaluation in a controlled trial.

Correlations of serum beta 2-microglobulin level with disease activity and renal involvement in patients with systemic lupus erythematosus

Abstract Objectives To determine correlations of serum beta 2-microglobulin (β2-MG) level with disease activity and renal involvement in patients with systemic lupus erythematosus (SLE). Methods Two hundred eligible SLE patients were assigned into remission and active stage groups according to SLE disease activity index (SLEDAI) scores. They were also assigned into kidney damage and no kidney damage groups. Serum β2-MG, Scr, ALB, BUN, anti-dsDNA, complements C3, C4 and 24-h urinary total protein (UTP) were detected. Estimated glomerular filtration rate (eGFR) was calculated. Correlations of β2-MG level with SLEDAI score and eGFR were subjected to Spearman analysis. Affecting factors were explored by logistic multivariate regression analysis, and predictive values of β2-MG level for SLE, disease activity and renal damage were assessed by ROC curves. Results β2-MG, Scr, ALB, C3, C4, anti-dsDNA and UTP levels, eGFR and SLEDAI score were different between patients with different disease activities, and, except for eGFR, also between patients with different renal damage degrees (p&lt;0.05). Serum β2-MG, Scr, ALB, C3, C4, anti-dsDNA, UTP, eGFR and SLEDAI score were independent factors for disease activity (p&lt;0.05), and β2-MG, ALB, C3, UTP, eGFR and SLEDAI score were factors affecting renal damage (p&lt;0.05). β2-MG level was correlated positively with SLEDAI score (r=0.877, p=0.000) and negatively with eGFR (r=−0.873, p=0.000). This level was highly valuable for predicting SLE, disease activity and renal damage. Conclusions Serum β2-MG levels in SLE patients are correlated positively with disease activity and negatively with renal involvement, being highly sensitive and specific for predicting SLE, disease activity and eGFR.

Potential association between elevated serum human epididymis protein 4 and chronic kidney disease in female patients.

Serum levels of human epididymis protein 4 (HE4) are elevated in a large number of women with chronic kidney disease (CKD). However, it remains unclear whether HE4 can be used as a potential biomarker for the diagnosis of CKD. This study aims to determine whether serum HE4 is a potential biomarker for CKD in Han Chinese female patients. A total of 347 Han Chinese female patients aged 19 to 89 were included in the present study. Among these patients, 154 were healthy control individuals, while 193 were hospitalized patients with CKD. Their demographic characteristics were obtained, and the levels of serum creatinine (Scr), beta2-microglobulin (B2M), and cystatin C (CysC) (to assess renal function) were measured. Serum HE4 concentration was determined by electrochemiluminescence. Serum HE4 levels in patients with CKD were significantly higher than those in the control group (P < 0.001). Meanwhile, there were significant differences in HE4 levels among the four CKD subgroups (P < 0.001) via multiple comparisons. In addition, the diagnostic value of HE4 was significantly higher than other indicators by ROC curve analysis. HE4 may not only serve as a potential biomarker to predict CKD but also have an important reference value for CKD staging.