Serum Beta 2-microglobulin Research Articles

The Utility of Beta 2 Microglobulin (B2M) as an Initial Diagnostic Tool for Oral Squamous Cell Carcinoma (OSCC): Evidence from a Malaysian Scenario

Background: The delay in diagnosis of oral squamous cell carcinoma (OSCC) is a factor in rendering the poor prognosis, and recent research has explored the use of serum tumour markers such Beta 2 Microglobulin (B2M), to aid early diagnosis. However, despite a high incidence of OSCC in Southeast Asia, no studies on the clinical use of B2M in the region were found.
 Objectives: To determine if serum B2M level can serve as an initial diagnostic tool to indicate if a biopsy is warranted, and if so, to propose a local B2M serum reference value to identify OSSC patients.
 Methodology: Twenty-one patients were seen at Hospital Universiti Sains Malaysia (HUSM) for a one-year period, between June 2016 and June 2017, and equal number of healthy controls participated in the study. Apart from patient history, venous blood of approximately 5ml volume was collected from each subject at the pre-treatment stage and analysed by an Abbot ARCHITECT c8000 analyser using the immunoturbidimetry method. The results were analysed using ROC analysis and the Mann Whitney test.
 Results: Serum B2M levels showed a statistically significant increase (p<0.001) in patients compared to controls. The test was shown to have 90.5% sensitivity and 90.5% specificity. It was found to be a sensitive and specific serum tumour marker at a cut off value of 1.57mg/l to differentiate cases from controls.
 Conclusion: B2M is a sensitive and specific tumour marker to differentiate OSCC cases from controls. It is cost effective and minimally invasive, making it a potentially useful adjunct diagnostic tool in a high-risk patient pool.
 Bangladesh Journal of Medical Science Vol.18(4) 2019 p.729-735

The international St-aging system as a prognostic marker in general senior population: Findings from the EPIDOS cohort study

The International Staging System (ISS) -calculated from serum albumin and beta-2 microglobulin (β2m)- is an established prognostic marker in multiple myeloma (MM), which has also been suggested to account for survival among general senior population. Our objective was to examine long-term survival of older women free of MM according to baseline ISS. The study included 230 community-dwelling healthy older women without known MM from the EPIDOS cohort (mean ± SD, 80.4 ± 3.4 years). Serum albumin and β2m were measured at baseline, and used to calculate the ISS a posteriori. Abnormal ISS was defined as ISS = 2 or ISS = 3, although ISS = 1 was considered normal. The vital status was sought after a mean follow-up of 17.6 ± 0.2 years (range, 16.8–18.3). Age, body mass index, mean arterial pressure, diabetes mellitus, hypertension, coronary heart disease, stroke, use corticosteroids, number of drugs daily taken, smoking, physical activity, fall history, bone mineral density, and creatinine clearance were used as potential confounders. All participants died during the 17-year follow-up. Compared to women with normal ISS, those with abnormal ISS (n = 24) had shorter survival time (4.9 ± 4.3 versus 8.7 ± 5.2 years, P = .001) and died earlier (85.6 ± 4.8 versus 89.1 ± 5.6 years old, P = .003). Survival time after blood test correlated with both serum albumin (r = 0.16, P = .015) and β2m (r = −0.27, P < .001). Cox regression revealed that abnormal ISS was associated with mortality (adjusted HR = 3.03, P < .001). Kaplan-Meier distributions showed that participants with abnormal ISS died earlier than those with normal ISS (log-rank P < .001). In conclusion, community-dwelling older women with abnormal ISS had shorter survival time than the others, suggesting that ISS could be considered as a universal prognostic “aging system” rather than a specific MM “staging system”.

Serum beta2-microglobulin levels are highly associated with the risk of acute ischemic stroke

Inflammation is considered an important mechanism of cell death or survival after ischemic stroke. As an important marker of inflammation, the role of β2-microglobulin (β2M) in acute ischemic stroke is unclear. We investigated the relationship between serum β2M and the risk of acute ischemic stroke (AIS). Patients with AIS (202 cases), intracerebral hemorrhage (ICH, 41 cases), and healthy controls (253 cases) were recruited. Clinical and biochemical characteristics were collected. We used three binary logistic regression models to evaluate the correlation of β2M with the risk of AIS. Furthermore, we investigated the relationship between serum β2M and the National Institute of Health Stroke Scale (NIHSS) score, the Trial of ORG 10172 in Acute Stroke Treatment (TOAST) subtypes, and the Essen Stroke Risk Score (ESRS) in patients with AIS. Our results showed that serum β2M levels in patients with AIS were much higher than those in patients with ICH and in the control subjects. Individuals with higher levels of β2M had higher odds of AIS. Moreover, serum β2M levels were significantly and positively correlated with ESRS. In addition, the levels of β2M were varied with different subgroups of AIS (TOAST classification). Serum β2M is highly associated with the risk of AIS.

Incidence and risk factors for acute kidney injury following autologous stem cell transplantation for multiple myeloma.

Acute kidney injury (AKI) is a common complication after allogeneic stem cell transplantation; however, its incidence and outcome in patients transplanted for multiple myeloma (MM) is unknown. We evaluated the incidence, severity, and risk factors for AKI within the first 30 days after autologous stem cell transplantation (ASCT) for MM. We prospectively followed 185 consecutive patients with MM, without chronic renal replacement therapy, who underwent ASCT; 12.5% of patients had MM‐associated amyloidosis. AKI occurred in 19 (10.3%) patients, 8 ± 3 days after ASCT, with 18 patients (9.7%) stage 1 and one patient (0.6%) stage 2 AKI. The development of AKI was not associated with reduced overall survival and recovery of kidney function was evident in 68.4% of patients at 3 months. In Cox regression analysis, preexisting–chronic kidney disease (HR 7.01, CI 95% 2.04‐24.09; P = 0.002), serum beta2 microglobulin (HR 3.05, CI 95% 1.10‐8.44; P = 0.03), and mucositis grade 3/4 (HR 1.29, CI 95% 1.08‐1.53; P = 0.003) were independent risk factors for AKI. Our results suggest that AKI occurs with low incidence and reduced severity after ASCT for MM. Prophylactic measures in patients with preexisting–kidney failure may further reduce this risk.

Frequency of destructive spondyloarthropathy among patients on regular hemodialysis

Objective Musculosk eletal complications occur in patients suffering from chronic kidney diseases. The cause of destructive spondyloarthropathy (DSA) among those patients is not well known. This study aims to study the frequency of DSA among hemodialysis patients. Patients and methods The study was conducted on 75 patients known to be end-stage renal disease patients: they were divided into three groups: chronic kidney disease on regular hemodialysis for more than or equal to 5 years group (n=25), patients on regular hemodialysis for less than 5 years group (n=25), and end-stage renal disease prior to hemodialysis as a control group (n=25). All of them were subjected to: full medical history, clinical examination, and plain radiographs of the whole spine in two views. Serum beta 2-microglobulin (β2-M) levels were determined. Results A comparison of β2-M serum levels in three groups showed a highly significant difference being highest in group I and lowest in group III (P&lt;0.001). There was high statistically significant increase in the frequency of DSA in group I compared with group II and in group II compared with group III (P&lt;0.001). As regards the affected site among positive cases, DSA was observed to affect the cervical region in 82.35% more than the lumbar in 11.76%, and rarely to involve both cervical and lumbar in the same patient in 5.88%, DSA was observed to affect men (58.8%) more than the women (41.2 %). Comparison of age, duration of dialysis, and intact parathyroid hormone levels between positive and negative DSA cases revealed that DSA is significantly more prevalent in older age patients (P&lt;0.05), and those with long dialysis duration (P&lt;0.001), and those having higher intact parathyroid hormone levels (P&lt;0.001). Conclusion DSA is the most serious spinal complication in patients on long-term hemodialysis. Serum β2-M is elevated in patients receiving long-term hemodialysis (&gt;5 years) and is positively correlated with destructive changes (DSA).

Assessment of Red Blood Cell Distribution Width and Multiple Myeloma in a Guangxi Population: a Retrospective Study.

Red blood cell distribution width (RDW) has been reported as a marker for inflammation and tumors. The present study aims to investigate the use of RDW in patients with multiple myeloma (MM). Seventy-three patients with newly diagnosed symptomatic multiple myeloma (SMM), 39 patients with relapsed multiple myeloma (RMM), and 91 healthy individuals were recruited into this study. The demographic and laboratory parameters were reviewed retrospectively, and the correlation between RDW and other parameters among groups were evaluated by Spearman's correlation analysis. The sensitivity and specificity of RDW were determined by receiver operating characteristic (ROC) curve analysis. The RDW values in both SMM and RMM were significantly higher than in the healthy individuals (p < 0.001). In SMM patients with International Staging System (ISS) Stages II and III, the level of RDW was higher than in the patients with ISS Stage I; however, there was no significant difference between each ISS stage in RMM patients. The RDW strongly correlated with platelet distribution width (PDW), cystatin C, serum beta2-microglobulin (Sβ2M), hemoglobin (HGB), hematocrit (HCT), albumin (Alb), and calcium (p < 0.05) in SMM patients, and RDW in RMM patients had a positive or negative correlation with PDW, Sβ2M, globulin, HGB, absolute neutrophil count, platelet count, HCT, and Alb (p < 0.05). The ROC curve analysis showed that RDW > 13.5 had 94.5% sensitivity and 63.7% specificity for SMM, and 92.3% sensitivity and 63.7% specificity for RMM. Elevated RDW in MM patients was associated with the stage of the disease.

Prognostic Value of Serum Beta-2 Microglobulin during and after Completing Chemotherapy in Marginal Zone Lymphoma

Background Baseline serum beta-2 microglobulin (B2M) has been suggested as a prognostic factor for marginal zone lymphoma (MZL). However, there have been no reports on the prognostic value of sequential serum B2M during and after chemotherapy. Herein, we retrospectively reviewed sequential values of serum B2M: baseline (B2Mb), maximum during chemotherapy (B2Mm), end of chemotherapy (B2Me), and the first increased value after completing chemotherapy (B2Mfi).Methods Between January 2000, and June 2018, a total of 94 patients with MZL treated with rituximab, cyclophosphamide, vincristine, and prednisolone (R-CVP) were identified from the database of Asan Medical Center, Seoul, Korea. Respective serum B2Ms less than 2.5 mg/L were considered normal. The cutoff value for differences between serum B2Mb and sequential values of serum B2M were calculated by using the optimal point from the receiver operating characteristic curve.Results Median age of the study population was 55 year-old (range, 10-83) and 54 (57%) patients were male. Fifteen (16%) patients had nodal MZL, 76 (81%) had extranodal MZL and 3 (3%) had splenic MZL. In univariate analysis, serum B2Mb and B2Mfi above 2.5 mg/L were associated with poor prognosis with a hazard ratio (HR) of 2.3 (95% confidence interval (CI): 1.1-4.9; p=0.024) and a HR of 3.3 (95% CI: 1.6-7.0; p=0.001), respectively. In addition, the difference between serum B2Mb and B2Mfi greater than the optimal cutoff value of 0.6 mg/L (area under curve=0.58) was also associated with poor prognosis, with a HR of 4.0 (95% CI: 1.9-8.3; p<0.001). In multivariate analysis, serum B2Mfi above 2.5 mg/L was the only independent adverse prognostic factor in terms of progression-free survival (PFS) with a HR of 4.0 (95% CI: 1.2-14.1; p=0.023). The median time of serum B2Mfi measurement was 5.6 months from the end of chemotherapy (range, 0.5-25.1 months).Conclusion To the best of our knowledge, this is the first report of measuring sequential serum B2M, starting from baseline to its first rise after completing chemotherapy in MZL. In MZL patients treated with R-CVP, the first increased serum B2M above 2.5 mg/L after completing chemotherapy is a powerful prognostic factor for PFS. DisclosuresNo relevant conflicts of interest to declare.

Increased Serum Beta-2 Microglobulin during Induction Chemotherapy Associated with Poor Prognosis in Primary Central Nervous System Lymphoma

Introduction Primary central nervous system lymphoma (PCNSL) is a rare extra-nodal non-Hodgkin lymphoma that exclusively involves the brain, leptomeninges, eyes, or spinal cord. Due to the rare incidence of PCNSL, therapeutic decisions and predictions of outcomes rely on phase 2 clinical trials and retrospective studies. Indeed, it is important to continuously search potential prognostic factors. Serum beta-2 microglobulin (B2MG) is thought to be associated with prognosis in several lymphomas and multiple myeloma. Previous study in our center showed that increased serum B2MG of ≥ 1.8 μg/mL at diagnosis was associated with poor prognosis in PCNSL. In this study, we investigated association of serum B2MG level changes with survival outcomes in PCNSL patients during induction chemotherapy who had elevated serum B2MG level at diagnosis.Methods We retrospectively reviewed prospectively collected PCNSL registry data for patients treated from March 1993 to May 2017 at Asan Medical Center in Seoul, Korea. Patients with serum B2MG of ≥ 1.8 μg/mL at diagnosis who had at least two or more measurement of serum B2MG including at diagnosis, 6 weeks, and 3 months from the initiation of induction chemotherapy were included in the analysis. Two weeks of window period was allowed for measured B2MG at 6 weeks and 3 months from the beginning of treatment. Overall survival (OS) was defined as the time from the initiation of induction treatment to death from any cause, and progression-free survival (PFS) was defined as the time from the initiation of induction treatment to disease progression or death. Univariate analyses were performed to compare survival outcomes using log-rank tests. Multivariate analyses were performed to identify independent prognostic factors for PFS and OS using a Cox proportional hazards model.Results Among 241 patients with diagnosis of PCNSL, 42 patients were included in the study. Median follow-up period was 4.0 years (range, 0.1-9.7). Median OS and PFS was 2.3 years (95% CI 1.9-2.6), and 1.2 years (95% CI 0.6-1.8), respectively. Median age was 67 years old (range, 28-85) and 26 patients (61.9%) were male. All patients received methotrexate-based combination chemotherapy as induction treatment and 31 patients (88.6%) showed complete response or partial response as best responses. Ten patients (23.8%) received consolidation treatment with high-dose chemotherapy followed-by autologous stem cell transplantation. Patients were classified into two groups according to serum B2MG level difference compared to B2MG level at diagnosis with the B2MG level at 6 weeks and 3 months from the initiation of induction treatment. Median B2MG at diagnosis, 6 weeks, and 3 months was 2.4 μg/mL (range, 1.9-11.7), 2.5 μg/mL (range, 1.3-8.7), and 2.6 μg/mL (range, 1.4-8.7), respectively. There was no statistically significant difference in terms of OS between patients with increased B2MG level at 6 weeks (16 patients) and patients with no increment (10 patients) with median OS of 1.4 years (95% CI 0.1-2.8) and 3.0 years (95% CI 1.1-4.9), respectively (P = 0.065). Patients with increased B2MG level at 3 months (23 patients) significantly poor prognosis in terms of OS compared to patients with same or decreased level (13 patients). Median OS was 1.4 years (95% 0.6-2.3) for the increased patients and not reached in patients with no increment (P < 0.001). Multivariate analysis with other factors showed significantly poor outcomes in patients with increased serum B2MG level at 3 months from the initiation of induction treatment in terms of OS with hazard ratio of 14.3 (95% CI 2.1-100.0, P = 0.007).Conclusion Among PCNSL patients who had serum B2MG level of ≥ 1.8 μg/mL at diagnosis, which was associated with poor prognosis in our previous study, patients with no increment of serum B2MG level at 3 months from the initiation of induction chemotherapy was associated with better survival outcomes in terms of OS compared to those with increased level. DisclosuresNo relevant conflicts of interest to declare.

Does Race Impact Survival in Multiple Myeloma?

Purpose:Multiple myeloma (MM), a cancer involving abnormal antibody production from plasma cells, accounts for approximately 1.8% of all new cancer cases in the US. The International Staging System (ISS) for MM classifies patients with serum beta2 microglobulin < 3.5mg/l and serum albumin ≥3.5g/dl as having stage I disease, patients with serum beta2 microglobulin ≥ 5.5 mg/l as having stage III disease, and all others as having stage II disease. The median survival by stage at time of diagnosis is 62 months, 45 months, and 29 months, respectively, for stages I, II, and III.The median age at time of diagnosis of MM is 69 years, with approximately 62% of all patients being at least 65 years old at time of diagnosis. There is a 2-fold increase in MM incidence amongst blacks as compared to whites in both the male and female population. This study was conducted to further characterize our MM patient population and to potentially identify racial and gender impact on mortality.Methods:A retrospective chart review of all patients in our geographic region diagnosed with MM between 2012 and 2017 was conducted using the Louisiana Tumor Registry Board database. Clinical data abstraction included epidemiology, laboratory, and pathologic data at time of diagnosis, and time to autologous stem cell transplant and death, if applicable. We performed chi-square analysis, linear regression, and survival analysis to compare survival outcomes between groups.Results:Chart review data was available for 184 of the 243 patients diagnosed with MM between 2012-2017, including 89 (47.6%) males and 98 females (52.4%), and 90 (48.1%) whites and 88 (47.1%) blacks. Females were significantly older than males (66.1 vs 62.6 years, p=0.037) at time of diagnosis yet whites were not significantly older compared to blacks (65.1 vs. 63.9 years, p=0.498). Among the 108 patients with documented stage of disease, 17 (15.7%) patients were diagnosed with stage I MM compared to 40 patients (37.0%) diagnosed at stage II and 51 (47.2%) diagnosed at stage III. With regards to stage, there was no significant difference between race or sex in our population. When adjusted for gender and age at diagnosis, race was a significant predictor of survival time with survival being 6.45 months shorter for black patients with MM compared to whites with the disease. (95% CI, 1.1 to 11.8; p = 0.019)Conclusion:Our data suggest that race exists as an independent predictor of shorter survival in our black patient population with MM. Additional studies investigating the biologic diversity of this disease are warranted to explain this racial disparity. DisclosuresNo relevant conflicts of interest to declare.

The PRIMA-Prognostic Index (PI) Is Valid in Follicular Lymphoma (FL) Patients with Rituximab Chemo-Free First-Line Treatment

Background: Follicular lymphoma (FL) is a heterogenous disease. The optimal timing, sequence and choice of therapy remain matters of debate and there is no optimal prognostic tool. The FLIPI (Follicular Lymphoma International Prognostic Index) is based on five bio-clinical parameters and is widely used, but not as guide for choice of treatment. Recently a new prognostic score (PRIMA-PI), based solely on two parameters, bone marrow involvement and serum beta2 microglobulin (ß2m) was proposed for patients treated with immunochemotherapy (Bachy E., Blood 2018).The Nordic Lymphoma Group (NLG) performed two randomized trials including patients with symptomatic/progressive indolent CD20+ lymphoma, with rituximab monotherapy or rituximab in combination with interferon (IFN)-α2a as primary treatment, without maintenance (Kimby E., 2008, 2015). The 10 years follow-up of these patients showed a good survival with no major safety issues and no need for later chemotherapy in 38% of FL patients (Lockmer S, JCO 2018).Aim/Purpose: To evaluate two different prognostic systems (the new PRIMA-PI and the FLIPI), for overall survival (OS) and time to treatment failure (TTF) in a cohort of symptomatic/progressive FL patients treated with a rituximab-containing first-line regimen without chemotherapy.Methods: Previously untreated patients with a confirmed FL diagnosis (n=269) or indolent lymphoma not otherwise specified (n=22, most FLs with insufficient material for grading), treated in the NLG randomized trials with two cycles rituximab (375 mg/m2 x 4 weeks), with or without IFN-α2a, were classified into the three PRIMA-PI categories: high-risk: ß2m> 3mg / L, intermediate-risk: ß2m ≤ 3 mg / L with bone marrow involvement and low-risk: ß2m ≤ 3 mg / without bone marrow involvement. The FLIPI scores were also assessed. TTF, defined as the interval between randomization and either initiation of new lymphoma therapy due to relapse or intolerance, or death from any cause, as well as OS were estimated using the Kaplan Meier method. The log-rank test was used for comparison between risk groups.Results: Out of 291 patients, 252 had complete data on PRIMA-PI and FLIPI (at the time of randomization in the original trials) and were available for analyses of TTF and OS. Patient characteristics are shown in Table 1. PRIMA-PI seemed to identify a true high-risk group of 47 patients, 32 of them being high risk also according to FLIPI, while a larger patient group (n=117) was classified as FLIPI high-risk.After a long follow-up time, median 9.9 years (0.4 -18.8) from randomization, median 10.6 years for the 214 patients (74%) still alive, 76 patients (26%) were failure-free and 108 (37%) without need of any chemotherapy, Patients with PRIMA-PI high showed a shorter TTF compared to PRIMA-PI intermediate and low (Fig 1a), whereas the FLIPI risk-groups were not significantly separated (Fig 1b). Evidence of transformation to aggressive disease was seen in 55 patients, with no significant difference in frequency between the PRIMA-PI groups, nor between FLIPI groups.Both PRIMA-PI and FLIPI were of significant value for predicting OS, most evident after a long follow-up time (Fig 1c and d). In 41 patients the cause of death was progressive disease or therapy complications, regarded as lymphoma-related death, whereas 21 died of other causes. The lymphoma-specific survival was related to the PRIMA-PI (log-rank p=0.03), but not to the FLIPI (n.s). Prognosis was worse for the PRIMA-PI high-risk group than the for the low-risk, also when adjusted for sex, high age (>60 years), diagnosis, stage, ECOG and FLIPI risk-group; TTF HR 1.82 (95% CI 1.16-2.85, p=0.01) and OS HR 2.3 (95% CI 1.00-5.38, p=0.05).Conclusion: FL patients included in two NLG trials with complete clinical data and a median follow-up of >10 years after randomization have been assessed for validation of different prognostic indices. In these patients, all with chemo-free first-line therapy, the PRIMA-PI was shown a valid predictor of both TTF and OS and seemed more useful than the FLIPI. The PRIMA-PI high risk identified a group of patients (19% of all) with true poor prognosis. [Display omitted] DisclosuresKimby:Roche: Honoraria; Roche: Honoraria; Janssen: Membership on an entity's Board of Directors or advisory committees; Gilead: Honoraria; AbbVie: Membership on an entity's Board of Directors or advisory committees. Holte:Novartis Pharmaceuticals Corporation: Membership on an entity's Board of Directors or advisory committees; Roche, Norway: Research Funding. Wahlin:Roche: Research Funding; Gilead: Consultancy, Honoraria, Research Funding. Hagberg:Roche: Honoraria.

Dynamic Changes in International Staging System As a Predictor of Survival Outcome in Patients with Advanced Multiple Myeloma

Background: The International Staging System (ISS) based on serum beta-2 microglobulin and serum albumin is a useful tool for risk stratification in patients with multiple myeloma. ISS is usually assessed at the time of diagnosis. Recent studies have suggested that risk stratification should be considered dynamic over the disease course. Our study aimed to describe dynamic changes in ISS over time and their impacts on mortality in patients with advanced multiple myeloma.Methods: This study included 417 patients with multiple myeloma from the Flatiron medical records database (Jan 2011- May 2018) who have received at least two lines of therapy and had data on ISS at the time of diagnosis (TDX) and at the time of initiating the second line of therapy (T2L). ISS stage was either abstracted from medical records or derived from the results of laboratory tests of serum beta-2 microglobulin and serum albumin. Patients were followed up from T2L until the earliest event of the last activity in database or death. We calculated mortality rates by TDX and T2L ISS stages, and generated Cox proportional hazard models to estimate the impact of TDX and T2L ISS stages on mortality. Additionally, in the subgroup of patients in ISS stage III at TDX, we used univariate logistic models to identify the predictors for downward shift to ISS stage I or II at T2L.Results: The study cohort had a median age of 70 (interquartile range: 61 to 77), and 59% were male. Based on ISS at TDX, 30%, 37%, and 33% of the study cohort were classified as stage I, II, and III with the mortality rate of 12, 11, and 24 deaths per 100 person-years, respectively. The hazard ratios were 0.95 (95% confidence interval (CI): 0.57-1.61) for patients in stage II and 1.96 (95% CI: 1.22-3.16) for patients in stage III, compared with patients in stage I. Based on ISS at T2L, 47%, 34%, and 20% were classified as stage I, II, and III, with the mortality rate of 7, 19, and 39 deaths per 100 person-years, respectively. The hazard ratios were 2.62 (95% CI: 1.61-4.25) for patients in stage II and 5.18 (95% CI: 3.10-8.64) for patients in stage III, compared with patients in stage I.Dynamic changes in ISS stages over time and mortality rates were depicted in the Table. Among patients in ISS stage I at TDX, about 25% shifted to higher stages at T2L, and had a higher mortality rate (26 per 100 person-years) than did patients remaining in stage I (8 per 100 person-years). For patients in ISS stage II at TDX, 43% stayed in Stage II at T2L, and 46% moved down to Stage I, with a mortality rate of 20 and 5 per 100 person-years, respectively. Among patients in ISS stage III at TDX, 58% moved down to lower stages at T2L. The mortality rate was 10, 21, and 40 per 100 person-years for patients moving down to Stage I and II at T2L and those remaining in Stage III, respectively. In the subgroup of patients in ISS stage III at TDX, strong predictors for shifting down to lower stages were younger age (odds ratio: 2.65; 95% CI:1.20-5.87 for age <65 vs ≥65 years) and serum creatinine ≤ 2 mg/dL at TDX (odds ratio: 2.26; 95% CI:1.03-4.92 for serum creatinine ≤ 2 vs >2 mg/dL), but not gender, race, or cytogenetic abnormality of del17p, t(4;14), and t(14;16).Conclusion: Large changes in ISS stages were observed in multiple myeloma patients when advancing the line of therapy. Changes in ISS stage were also associated with survival outcome. A downward shift to stage I was associated with substantially improved overall survival; in contrast, patients moving up to or remaining in higher stages had poor outcomes, especially for those remaining in ISS stage III. Our results suggest that re-evaluating ISS stage at the time of change in line of therapy can improve prediction of survival outcomes. [Display omitted] DisclosuresHong:Takeda Pharmaceuticals International Co.: Employment. Crossland:Takeda Pharmaceuticals International Co.: Employment. Galaznik:Takeda Pharmaceuticals International Co.: Employment. Dolin:Shire: Other: PD holds shares in Shire ; GSK: Other: PD holds shares in GSK; Takeda Pharmaceuticals International Co.: Employment.

Pre-Transplant Serum Beta-2 Microglobulin Level Is a Potential Novel Prognostic Marker for Overall Survival after Allogeneic Hematopoietic Stem Cell Transplantation

Abstract Background: Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a curative treatment for hematologic malignancies. In addition to hematopoietic cell transplantation-comorbidity index (HCT-CI) and disease risk index (DRI), age, performance status (PS), conditioning regimen intensity, and donor source are used to assess the transplant outcome in patients. Recently, several serum markers, such as ferritin and albumin, have also been reported as additional useful prognostic markers. Beta-2 microglobulin (BMG) is a component of major histocompatibility complex class 1 molecules in all nucleated cells, and serum BMG levels reflect renal function, tumor burden, and inflammatory conditions. Although elevated serum BMG levels are reportedly markers for poor prognosis of several hematological malignancies, no study has assessed the prognostic significance of pre-transplant serum BMG levels for allo-HSCT. Methods: We retrospectively registered consecutive patients who underwent allo-HSCT from April 2010 to September 2017 with available pre-transplant serum BMG levels at our institute. Cox regression models were used to estimate hazard ratios (HRs) with 95% confidence intervals in the univariate and multivariate analyses. In this study, the variables analyzed were age, sex, disease, HCT-CI, PS, DRI, number of times HSCT was performed, conditioning regimen intensity, donor source, cytomegalovirus (CMV) serostatus, and pre-transplant serum BMG level in each patient. Predictors with borderline significance (p&lt;0.10) in the univariate analysis were subjected to multivariate analysis with both age and sex as mandatory covariates. A p value &lt;0.05 was considered statistically significant. The Kaplan-Meier method was used for calculating overall survival (OS). Gray's test was used to estimate the cumulative incidence of relapse/progression (Rel/Prog) or non-relapse mortality (NRM) and acute/chronic graft versus host disease (GVHD). Rel/Prog and NRM were considered competing events. The Fine-Gray proportional hazard regression model was used for the univariate and multivariate analyses with competing risks. Result: A total of 288 patients were identified during the study period. The median age was 47 (range: 17-48) years. The clinical characteristics are shown in Table 1. The median follow-up period of survivors (192 patients) was 674.5 (range: 15-2642) days. The median pre-transplant BMG level was 2.1 (range: 0.9-11.6) mg/mL. When stratified into quartiles of pre-transplant BMG levels, the 2-year OS rates were 89.2%, 62.8%, 64.3%, and 33.7% in quartiles 1 (0.9-1.6), 2 (1.7-2.0), 3 (2.1-2.9), and 4 (3.0-11.6), respectively. Because quartiles 2 and 3 showed almost the same OS rates, we combined these two groups and assessed the association between major transplant outcomes (OS, Rel/Prog, NRM, acute GVHD, and chronic GVHD) and the following three groups of BMG levels: 0.9-1.6 mg/mL (lower BMG group), 1.7-3.0 mg/mL (intermediate BMG group as the reference), and &gt;3.0 mg/mL (higher BMG group). In the univariate analysis, the lower BMG group was significantly associated with an increased probability of OS (HR: 0.29, p=0.002) and decreased probability of Rel/Prog and NRM (HR: 0.58, p=0.048 and HR: 0.19, p=0.02, respectively) compared with those of the intermediate BMG group. The higher BMG group was significantly associated with a decreased probability of OS (HR: 2.4, p&lt;0.001) and an increasing trend of NRM (HR: 1.7, p=0.09). For OS, age, DRI, HCT-CI, PS, CMV serostatus, donor source, conditioning regimen intensity, and number of times HSCT was performed in each patient were also statistically significant in the univariate analysis. The adjusted OS rates of the three BMG groups by the multivariate analysis are shown in Table 2 and Figure 1. The lower BMG group had favorable OS (HR: 0.31, p=0.005), and the higher BMG group had an unfavorable trend for OS (HR: 1.55, p=0.063) compared with those in the intermediate BMG group. In the multivariate analysis of other transplant outcomes, including Rel/Prog, NRM, and acute/chronic GVHD, pre-transplant serum BMG levels were not statistically significant. Conclusions: The study results suggest that pre-transplant serum BMG level is a potential prognostic marker for survival after allo-HSCT, which is independent of other prognostic factors, including well-known prognostic systems, such as HCT-CI and DRI. Disclosures Nakamae: Otsuka Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding. Hino:Otsuka Pharmaceutical Co., Ltd.: Research Funding; Novartis: Research Funding. Nakamae:Otsuka Pharmaceutical Co., Ltd.: Consultancy, Honoraria, Research Funding.

Serum Beta 2-Microglobulin as a Biomarker of Activity in Ulcerative Colitis

Background: ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease that causes inflammation and ulcers in the innermost layers of the large intestine (colon) and rectum. Assessment of intestinal inflammation in UC is crucial and still remains a difficult challenge for the clinician. Although endoscopic modalities with biopsy sampling seem to be the most reliable method for estimating disease severity, they are invasive and costly. Apart from endoscopic interventions, disease severity can be assessed using both laboratory studies and non-invasive imaging tests. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBCs), acid glycoprotein, platelet count and albumin are in common use but have only modest accuracy in reflecting UC disease activity. Therefore, adjunctive use of additional serum markers that will be more sensitive and specific for determination of disease activity and achieving diagnostic accuracy is strongly needed in daily clinical practice. Aim of the Work: to investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of ulcerative colitis disease. Patients and Methods: a case control study that was conducted at the Gastroenterology Clinic, Internal Medicine Department, Ain Shams University during the period of January to July 2018. 60 patients were recruited for the study. They were divided as follows; Group “A”: 40 patients newly diagnosed as ulcerative colitis based on colonoscopy and biopsy, subdivided as follows; 20 patients with active ulcerative colitis and 20 patients with inactive ulcerative colitis. Group “B”: 20 healthy individuals free from any systemic diseases serving as a control group. Results: in this study, the serum levels of serum B2-microglobulins were highest in patients with active ulcerative colitis compared to those with inactive ulcerative colitis and the control groups. Also B2-microglobulins values become higher with higher number of presenting symptoms and endoscopic activity, which becomes higher in severe disease. Conclusion: our results revealed that serum B2-microglobulin was simple and non-invasive marker that could be helpful for differentiating active UC from inactive disease. Moreover, it was more helpful when used together with serum laboratory inflammatory indices (ESR and CRP).

Serum Beta 2-Microglobulin as a Biomarker of Activity in Ulcerative Colitis

Background: ulcerative colitis (UC) is a chronic, idiopathic, inflammatory bowel disease that causes inflammation and ulcers in the innermost layers of the large intestine (colon) and rectum. Assessment of intestinal inflammation in UC is crucial and still remains a difficult challenge for the clinician. Although endoscopic modalities with biopsy sampling seem to be the most reliable method for estimating disease severity, they are invasive and costly. Apart from endoscopic interventions, disease severity can be assessed using both laboratory studies and non-invasive imaging tests. C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), white blood cells (WBCs), acid glycoprotein, platelet count and albumin are in common use but have only modest accuracy in reflecting UC disease activity. Therefore, adjunctive use of additional serum markers that will be more sensitive and specific for determination of disease activity and achieving diagnostic accuracy is strongly needed in daily clinical practice. Aim of the Work: to investigate the diagnostic utility of beta 2 microglobulin (B2-M) levels and analyze this correlation with the activity of ulcerative colitis disease. Patients and Methods: a case control study that was conducted at the Gastroenterology Clinic, Internal Medicine Department, Ain Shams University during the period of January to July 2018. 60 patients were recruited for the study. They were divided as follows; Group “A”: 40 patients newly diagnosed as ulcerative colitis based on colonoscopy and biopsy, subdivided as follows; 20 patients with active ulcerative colitis and 20 patients with inactive ulcerative colitis. Group “B”: 20 healthy individuals free from any systemic diseases serving as a control group. Results: in this study, the serum levels of serum B2-microglobulins were highest in patients with active ulcerative colitis compared to those with inactive ulcerative colitis and the control groups. Also B2-microglobulins values become higher with higher number of presenting symptoms and endoscopic activity, which becomes higher in severe disease. Conclusion: our results revealed that serum B2-microglobulin was simple and non-invasive marker that could be helpful for differentiating active UC from inactive disease. Moreover, it was more helpful when used together with serum laboratory inflammatory indices (ESR and CRP).

A Rare Case of B-Cell Lymphoma Presenting as a Large Solid Pancreatic Mass: A Case Report

The differential diagnosis of a pancreatic mass is categorized into cystic and solid lesions. Cystic pancreatic lesions include non-neoplastic cysts and pancreatic cystic neoplasms. Possible differential diagnoses for a solid pancreatic mass include primary exocrine pancreatic cancer, pancreatic neuroendocrine tumors, metastatic cancer, focal chronic pancreatitis, and autoimmune pancreatitis. We are presenting a rare case of B cell lymphoma presenting as a large solid pancreatic mass. A 62-year-old female with past medical history of type II diabetes and hypertension presented to University Medical Center (UMC) hospital in Las Vegas emergency room with four days of epigastric abdominal pain associated with jaundice. She reported unintentional weight loss, but no fever or night sweats. She had no history of pancreatic disease or malignancies. She denied smoking or alcohol use. Physical exam was significant for scleral icterus and a palpable epigastric mass. Initial liver function panel showed AST 189, ALT 213, ALP 140, total bilirubin 7.4 with direct bilirubin 6.2, Albumin 2.9 g/dl, Lipase 63, Lactate dehydrogenase 1,008 and CEA 12.6. Autoimmune panel was sent including antinuclear antibodies, antimitochondrial antibodies, anti-LKM antibodies, IgA, IgG and IgM levels. All were found to be unremarkable. CT of the abdomen and pelvis with IV contrast showed a 5.5 x 3.7 x 3.0 cm mass in the pancreatic tail encasing the splenic vein with splenic vein thrombosis in addition to enlarged retroperitoneal lymph nodes (figure 1). Gastroenterology was consulted and an endoscopic ultrasound with fine needle aspiration was subsequently performed. Tissue pathology revealed aggressive B cell lymphoma. A consult was made with oncology for further management. Hematologic malignancies can often manifest in extranodal locations. We present a rare case of aggressive B cell lymphoma presenting as a large pancreatic mass. Rare cases of hematologic malignancies presenting as pancreatic masses have been reported in the past. Early diagnosis is of primary importance so as to avoid unnecessary surgical resection. Clues suggesting the possibility of a primary hematologic malignancy include constitutional symptoms (weight loss, fever, and night sweats), an elevated serum lactate dehydrogenase (LDH) or beta-2 microglobulin level and a normal serum carbohydrate antigen 19-9 (CA 19-9).1429.tif Figure 1: 5.5 x 3.7 x 3.0 cm mass in the pancreatic tail encasing the splenic vein with splenic vein thrombosis in addition to enlarged retroperitoneal lymph nodes

Lower serum beta-2 microglobulin levels are associated with worse survival in incident peritoneal dialysis patients.

There is a general consensus that elevated serum beta-2 microglobulin (B2M) levels measured at a single time-point are significantly associated with mortality in patients on maintenance dialysis. To date, the majority of prior studies that have examined B2M-associated mortality have been conducted in prevalent hemodialysis patients with little residual renal function (RRF). However, studies in incident peritoneal dialysis (PD) patients are lacking. Moreover, changes in serum B2M levels over time have not been considered in this population. We examined the association of time-updated and baseline serum B2M levels with mortality in a 10-year cohort of 725 incident PD patients who were maintained on dialysis between January 2006 and December 2011 using Cox proportional hazards regression analyses. Patients were categorized into tertiles according to B2M levels. During a median follow-up of 38 (interquartile range 23-64) months, 258 (35.4%) deaths occurred, including 106 (14.6%) and 86 (11.9%) deaths from cardiovascular and infectious causes, respectively. The lowest B2M tertile was associated with a higher risk of all-cause and infectious mortality compared with the middle tertile: the hazard ratios (95% confidence interval) for all-cause deaths were 2.12 (1.38-3.26) and 2.20 (0.96-5.05) in time-varying analyses and 1.52 (1.07-2.17) and 2.41 (1.19-4.88) in baseline analyses. Subgroup analyses showed that this association was particularly observed in females, older patients, those with comorbidities such as diabetes, a lower body mass index, lower albumin levels or those with higher RRF (all P for interactions <0.05). In incident PD patients, lower B2M levels were independently associated with overall and infectious mortality. These associations can be potentially modified by malnutrition, inflammation and RRF.

Validation of estimated glomerular filtration rate equations for Japanese children.

The gold standard for evaluation of kidney function is renal inulin clearance (Cin). However, the methodology for Cin is complicated and difficult, especially for younger children and/or patients with bladder dysfunction. Therefore, we developed a simple and easier method for obtaining the estimated glomerular filtration rate (eGFR) using equations and values for several biomarkers, i.e., serum creatinine (Cr), serum cystatin C (cystC), serum beta-2 microglobulin (β2MG), and creatinine clearance (Ccr). The purpose of the present study was to validate these equations with a new data set. To validate each equation, we used data of 140 patients with CKD with clinical need for Cin, using the measured GFR (mGFR). We compared the results for each eGFR equation with the mGFR using mean error (ME), root mean square error (RMSE), P30, and Bland-Altman analysis. The ME of Cr, cystC, β2MG, and Ccr based on eGFR was 15.8 ± 13.0, 17.2 ± 16.5, 15.4 ± 14.3, and 10.6 ± 13.0ml/min/1.73m2, respectively. The RMSE was 29.5, 23.8, 20.9, and 16.7, respectively. The P30 was 79.4, 71.1, 69.5, and 92.9%, respectively. The Bland-Altman bias analysis showed values of 4.0 ± 18.6, 5.3 ± 16.8, 12.7 ± 17.0, and 2.5 ± 17.2ml/min/1.73m2, respectively, for these parameters. The bias of each eGFR equation was not large. Therefore, each eGFR equation could be used.

The prognostic values of beta-2 microglobulin for risks of cardiovascular events and mortality in the elderly patients with isolated systolic hypertension.

Background:The present study aimed to investigate the effects of serum beta-2 microglobulin (B2M) on the risks of major cardiovascular events (MACEs) and all-cause death in Chinese elderly isolated systolic hypertension (ISH) patients without severe renal insufficiency (estimated glomerular filtration rate [eGFR] <30 ml/min/1.73 m2).Materials and Methods:Serum B2M concentration, creatinine-eGFR, and blood pressure variability were evaluated in 460 elderly patients (mean age, 82.6 years; 28 women) with ISH in this observational study. The Cox proportional hazard model was adopted to calculate adjusted hazard ratios (HRs) of risk factors for cardiovascular events and all-cause deaths.Results:During a median follow-up period of 37.6 months, 63 patients (13.7%) died, and 65 patients (14.1%) had MACEs. Multivariable analysis showed that the higher serum B2M concentration (B2M ≥0.28 mg/dl) was an independent predictor of increased risk of MACEs (nonfatal acute myocardial infarction, acute heart failure, ischemic stroke, and cardiovascular deaths) and all-cause death (HR: 2.62, 95% confidence interval [CI]: 1.46–4.69, P = 0.001 and HR: 3.40, 95% CI: 1.78–6.48, P < 0.001, respectively) adjusting for other multiple confounders including creatinine-eGFR and cystatin C. In addition, blood pressure variability derived from ambulatory blood pressure measurement was not associated with incidence of MACEs and all-cause mortality (P > 0.05).Conclusion:Our data suggest that serum B2M concentration may be individually associated with MACEs and all-cause death in elderly ISH patients without severe renal insufficiency even after adjusted for creatinine-eGFR and cystatin C.

A Study on Free Light Chain Assay and Serum Immunofixation Electrophoresis for the Diagnosis of Monoclonal Gammopathies.

Demonstration of monoclonal immunoglobulin molecule in serum forms the mainstay in the diagnosis of monoclonal gammopathies. The major tests that help in this regard are serum protein electrophoresis (SPEP), serum immunofixation electrophoresis (sIFE) and serum free light chain assay (sFLC). Our objectives were to study the accuracy of sFLC and sIFE in the diagnosis of monoclonal gammopathies and also to study the role of combination of SPEP+sIFE+sFLC in the diagnosis of the same. 46 patients who attended the hemato-oncology clinic with signs and symptoms suggestive of monoclonal gammopathy were enrolled in this study. SPEP, sIFE, sFLC and pre-treatment serum beta-2 microglobulin levels were analysed among the study population. Both SPEP and sIFE were performed in the Interlab Genios fully automated machine. Serum beta-2 microglobulin and sFLC were estimated by immunoturbidimetry in Beckman Coulter AU 2700 analyzer. The accuracy of sIFE came to be 80% with respect to sFLC assay. Sensitivity, specificity, positive and negative predictive value of sIFE with respect to sFLC were 81.3, 78.6, 89.7 and 64.7% respectively. It was observed that a combination panel of SPEP+sIFE+sFLC could detect all the cases of myeloma included in this study. Further testing in large samples is required for generalising the findings of this study. The pre-treatment beta-2 microglobulin levels were significantly higher in the group which was positive for myeloma. A combination panel of SPEP+sIFE+sFLC prove to be more useful than individual tests for the detection of myeloma.

Blood biomarkers in adults with lymph node enlargement contribute to diagnostic significance of malignancy.

Lymph node enlargement is a common presentation and has a possibility of malignancy like lymphoma that requires early diagnosis. This study aims to analyze the clinical characteristics of these patients and finds out useful predictors of malignant diseases. We retrospectively investigated 81 patients with lymph node enlargement between July 2, 2014 and May 17, 2016. The characteristics and laboratory findings were evaluated combining with the final diagnosis. The diagnoses were malignancy in 51 patients and benign lymphadenopathy in 30 patients. Increased beta2-microglobulin (B2M) (P = 0.012) was found to be associated with malignant diseases, and level of 3699.5 μg/L was used as a cut-off value to differentiate the malignancies from benign diseases, offering 63.4% sensitivity and 87.0% specificity. Immunoglobulin G (IgG) (P = 0.038) levels were significantly lower in malignant group, whose receiver operating characteristic curve showed that level of 1121.5 mg/dl had sensitivity and specificity as 58.5% and 82.6%. Moreover, through analysis of cytokines, we found interleukin-10 (IL-10) levels were elevated in malignant group compared with benign group. Serum B2M and IgG levels were concluded to be useful parameters for predicting malignancies. Besides, increased IL-10 levels indicated a higher risk of malignancy in some way.