Serum Beta 2M Levels Research Articles

Long-Term Exposure to Pomalidomide-Dexamethasone in Pts with Refractory Myeloma

Background. The IFM2009-02 study was launched in 2009, and randomized 84 patients (pts) with pomalidomide (oral 4 mg daily) and dexamethasone (oral 40 mg weekly) given either 21 days out of 28 or continuous. Whilst the overall median PFS was 4.6 months - this end stage very advanced RRMM population, we observed that 40% of the patients had a prolonged PFS and subsequently OS in the trial.We sought to analyze the characteristics of 58 pts that had more than 3 months of pomalidomide to study the effect of long exposure to Pomalidomide.Method. IFM 2009-02 was a multicentre phase 2 study of pts with RRMM who had at best a stable disease with the last course of bortezomib and of lenalidomide, or who were refractory to bortezomib and lenalidomide (IMWG). This analysis was performed on the ITT population combining data from the 2 study arms. We have analyzed the characteristics of pts according to duration of treatment with pomalidomide and dexamethasone 3 months to one year (<1 year) or more than one year (≥1 year).Results. 60% and 40% of pts were exposed to pomalidomide for <1 year and ≥1 year, respectively. The ORR for the <1 year group was 43%, the median PFS 4.6 months (CI95% 4;6) with only 6% at 12 months, and the median OS 15 months (4;6) and 65% at 12 months, 40% at 18 months. For the ≥1 year group, the response rate and survival were strikingly different, ORR at 83%, PFS 20.7 months, OS not reached (CI95% 40;-) and 100% at 12 months, 91% at 18 months. Of the pts in the <1 year, 87% have died versus 35% in the ≥1 year group. Of note, death of most pts occurred during the follow up period post pomalidomide therapy , however in a far greater extent for the <1 year group, 96% versus 67%, that could suggest it was more difficult to salvage these pts post pomalidomide.We next sought to identify the characteristics of the 2 groups. Interestingly, the median number of prior lines was similar across groups, 5 (range 1-10), with 89% and 79% of the pts exposed to more than 3 lines and 17% and 22% exposed to more than 6 lines, for the <1 year and ≥1 year groups, respectively. 40% and 48% of pts had Bortezomib as last line, 29% and 43% Lenalidomide, 43% and 26% and alkylating agent. Similarly, 80% and 74% of pts were refractory to Bortezomib, 89% versus 87% to Lenalidomide, 65% versus 75% to alkylating agents, 74% and 87% to the last line of therapy, respectively. 74% and 70% were double refractory (Bortezomib and Lenalidomide) and 60% and 70% were triple refractory (double +last line), respectively. The time from diagnosis to IFM 2009-02 study entry was also similar between cohorts, 5.8 and 6.5 years for <1 year and ≥1 year groups; however with 6% versus 26% of pts, entering the study in less than 3 years since diagnosis. There was no difference in terms of patients characteristics between groups, either patients-based such as gender, age, weight, or myeloma-based characteristics.However, serum beta 2m level was higher at diagnosis in the <1 year compared to the ≥1 year, 54% versus 35%, with a slightly more adverse cytogenetic profile 35% versus 12%, with the limitation that this was not available for all the patients. Presence of plasmacytoma/EMD was also greater in the former group, 20% versus 4%, respectively. It seems that the <1 year had more intrinsic adverse features of the tumor cells compared to the ≥1 year group.There was no clear difference in terms of safety management of pomalidomide and/or dexamethasone, with respect to the daily dose intensity of Pomalidomide (median, 3.0 and 2.9 mg/day), and the relative dose intensity of pomalidomide that was 89% and 84%, respectively; similar to the rate of dose reduction and dose interruption.Conclusion. Pomalidomide and dexamethasone is effective and well tolerated in these heavily pre-treated MM pts refractory to Bortezomib and Lenalidomide, with approximately 40% of the patients having a prolonged exposure to treatment, which translated into a significantly prolonged OS. Our study suggests that patients with more intrinsic adverse features of Myeloma tumor cells could not have prolonged exposure to pomalidomide as they progressed within a year from start of pomalidomide. Future studies should examine optimizing pomalidomide therapy in those patients, such as using multidrug pomalidomide-based combined regimens to prolong exposure to pomalidomide and improve the survival of these patients. DisclosuresKarlin:Janssen: Honoraria; celgene: Consultancy, Honoraria; Sandoz: Consultancy. Stoppa:Celgene Jansen: Honoraria.

Higher serum beta2-microglobulin levels are associated with better survival in chronic hemodialysis patients: a reverse epidemiology

beta2-Microglobulin (beta2-M) has been considered a surrogate marker of putative mid-molecular weight (MW) uremic toxins, compounds difficult to dialyze by low-flux dialysis membranes. This study was performed to evaluate the relationship between serum beta2-M and survival of chronic hemodialysis (CHD) patients and the association of beta2-M levels and factors associated with mortality. Part I of this study is a retrospective cohort evaluation that determined the relationship between beta2-M and mortality, and Part II is a cross-sectional study that evaluated the relationship between beta2-M and factors associated with mortality. Laboratory parameters, including beta2-M, albumin, prealbumin, creatinine, blood urea nitrogen (BUN), high-sensitivity C-reactive protein (hs-CRP), lipid battery, KT/V, and normalized protein nitrogen appearance (nPNA), were reviewed in Part I and measured in Part II. Clinical and demographic data, including age, sex, duration of hemodialysis, presence of cardiovascular disease, and presence of diabetes mellitus, were also recorded. Part I: During the follow-up period of 5 years, there were 95 all-cause deaths among the 289 patients. Comparison of survivors and non-survivors indicated that serum beta2-M was higher in survivors (36.8 ± 12.3 vs. 32.6 ± 13.2 µg/ml, p = 0.009). Kaplan-Meier analysis indicated that all-cause mortality in the lower beta2-M group was significantly higher compared to the higher beta2-M group (p < 0.0001). Multivariate Cox regression analyses indicated elevated beta2-M levels were significantly associated with lower mortality rate (relative risk: 0.608; 95% CI: 0.37 to 0.99; p = 0.046). Part II: The mean serum beta2-M concentration was 37.1 ± 14.4 µg/ml. Univariate analysis indicated that beta2-M was positively correlated with nPNA, duration of HD, BMI, and the concentrations of creatinine, albumin, BUN, and hs-CRP, but was negatively correlated with HDL-C concentration. Multiple regression analysis indicated that levels of nPNA (p < 0.001), duration of hemodialysis (p < 0.001), creatinine (p < 0.001), albumin (p = 0.006), BUN (p = 0.011), and HDL-C (p = 0.038) were independently associated with serum beta2-M concentration. Our results showed that higher serum beta2-M levels are associated with better survival in CHD patients and that nutritional status might be an independent predictor of serum beta2-M concentration in these patients.

Role of Residual Kidney Function and Convective Volume on Change in β2-Microglobulin Levels in Hemodiafiltration Patients

Removal of beta2-microglobulin (beta2M) can be increased by adding convective transport to hemodialysis (HD). The aim of this study was to investigate the change in beta2M levels after 6-mo treatment with hemodiafiltration (HDF) and to evaluate the role of residual kidney function (RKF) and the amount of convective volume with this change. Predialysis serum beta2M levels were evaluated in 230 patients with and 176 patients without RKF from the CONvective TRAnsport STudy (CONTRAST) at baseline and 6 mo after randomization for online HDF or low-flux HD. In HDF patients, potential determinants of change in beta2M were analyzed using multivariable linear regression models. Mean serum beta2M levels decreased from 29.5 +/- 0.8 (+/-SEM) at baseline to 24.3 +/- 0.6 mg/L after 6 mo in HDF patients and increased from 31.9 +/- 0.9 to 34.4 +/- 1.0 mg/L in HD patients, with the difference of change between treatment groups being statistically significant (regression coefficient -7.7 mg/L, 95% confidence interval -9.5 to -5.6, P < 0.001). This difference was more pronounced in patients without RKF as compared with patients with RKF. In HDF patients, beta2M levels remained unchanged in patients with GFR >4.2 ml/min/1.73 m2. The beta2M decrease was not related to convective volume. This study demonstrated effective lowering of beta2M levels by HDF, especially in patients without RKF. The role of the amount of convective volume on beta2M decrease appears limited, possibly because of resistance to beta2M transfer between body compartments.

Clinical relevance of soluble HLA class I molecules in Waldenstrom Macroglobulinemia

Waldenstrom Macroglobulinemia (WM) is a B-cell neoplasm characterised by secretion of IgM by lymphoplasmacytic bone marrow cells and by cytopenias and hypogammaglobulinemia in a subset of patients. Beta-2 microglobulin (b2m) is a major prognostic factor in WM and the heavy chain of HLA class I molecules, which are known to have immunosuppressive properties and have been implicated in the pathogeny of several malignancies. We assessed the serum levels of the total soluble HLA-I molecules and the HLA-Gs molecules in 105 patients with IgM-related disorders [WM (n = 42) and IgM MGUS (n = 63)], and compared the results to 41 healthy subjects. We found higher levels of HLA-Is in WM, compared to IgM MGUS and healthy donors. HLA-Gs levels were similar in WM and in IgM MGUS, but higher than in healthy donors. The association between HLA-Is at the cut-off of 1.8 microg/mL and known markers of poor prognosis was then evaluated among WM patients using univariate and multivariate methods. Based on this, high HLA-Is level was strongly associated with high serum beta2M level >3 mg/L [OR = 2, (CI 95% 1.1-5.7); P = 0.04], age > 65 yrs [OR = 1.5, (CI 95% 0.5-4.1), P = 0.06] and haemoglobin < or =11.5 g/dL [OR = 3.3, (CI 95% 1.2-9.7); P = 0.03]. High levels of serum HLA-Is were also found in patients with cryoglobulinemia, however irrespectively of WM or IgM-MGUS status. Together our results suggest a possible role for soluble MHC class I molecules in WM disease. Further investigations are necessary to further demonstrate the prognostic impact of soluble MHC class I molecules in Waldenstrom Macroglobulinemia.

Serum and Tissue Beta-2 Microglobulin Levels in Patients with Helicobacter pylori Infection

Beta-2 microglobulin (beta2-m) is a minor plasma protein, secreted from the plasma membranes as a result of the continuous regeneration of membrane proteins in the cell surface of all nucleated cells. The relationship between Helicobacter pylori and beta2-m has not been adequately established in studies. In this study, we aimed to compare the levels of serum and tissue beta2-m in patients with and without H. pylori infection, and to examine the relationship between levels of serum and tissue beta2-m. About 30 patients with H. pylori gastritis and 22 healthy persons were enrolled in this study. Gastric biopsies were histologically analyzed and compared according to tissue and serum beta2-m levels. Serum beta2-m levels were comparable in H. pylori and control groups. There was no significant link between tissue H. pylori grade and serum beta2-m levels. Subendothelial beta2-m was detected in 19 (63.3%) cases with H. pylori and none of the control group with immunohistochemical staining (P < 0.001). There was no correlation between serum and tissue levels of beta2-m. beta2-m accumulates in the majority of gastric tissues of patients with active chronic gastritis who were H. pylori (+), whereas no accumulation was found in H. pylori (-) control subjects.

Prospective validation of serum CYFRA 21-1, beta-2-microglobulin, and ferritin levels as prognostic markers in patients with nonmetastatic nasopharyngeal carcinoma undergoing radiotherapy.

Patients with undifferentiated nasopharyngeal carcinoma (NPC) have elevated serum levels of CYFRA 21-1 (CYFRA), ferritin, and beta-2-microglobulin (beta2M) compared with healthy control individuals. The prognostic value of these markers has never been validated prospectively. Paired serum samples from 160 patients with newly diagnosed, nonmetastatic, undifferentiated NPC were collected before radiotherapy (RT) and at 4-6 weeks after the completion of RT. Pre-RT and post-RT levels of serum CYFRA, ferritin, and beta2M were analyzed and correlated with overall survival (OS), progression-free survival (PFS), time to locoregional recurrence, (TLR) and time to distant recurrence (TDR). The results of pre-RT and post-RT plasma Epstein-Barr virus (EBV) DNA levels available from a previous study were included in a Cox regression model together with age, tumor (T) classification, and lymph node (N) classification. Sixty percent of patients had International Union Against Cancer Stage III-IV disease. At a median follow-up of 116 weeks (range, 37-239 weeks), 38 patients had disease progression. On multivariate analysis, pre-RT CYFRA and post-RT EBV DNA levels were independent predictors of poor OS, post-RT EBV DNA level and N classification predicted poor PFS and TDR; and only T classification predicted TLR. Patients who had pre-RT CYFRA levels > or = 1.5 U/mL were more likely to die (hazard ratio, 1.18; 95% confidence interval, 1.10-1.26) compared with patients who had pre-RT CYFRA levels < 1.5 U/mL. There were no associations between age, post-RT CYFRA levels and pre-RT or post-RT serum ferritin and beta2M levels, and the survival and recurrence rates on multivariate analysis. Serum CYFRA levels taken before RT predicted reduced survival in patients with nonmetastatic, undifferentiated NPC who underwent RT.

Evolution of serum beta2-microglobulin concentrations during treatment of tuberculosis patients.

A total of 36 human immunodeficiency virus-seronegative patients were studied in order to evaluate serum beta2-M levels in immunocompetent patients with tuberculosis who were receiving treatment. Six measurements of several clinical and laboratory parameters were carried out at different intervals during the 6 months of treatment. The mean serum beta2-M at presentation was 149 nmol/l and 4 patients had values above the upper normal limit. Significant decreases in the mean serum beta2-M concentration were observed in the follow-up determinations in the patients as a whole (p = 0.002), in the patients with normal (p = 0.039) and in the patients with increased beta2-M at presentation (p = 0.037). beta2-M significantly correlated with erythrocyte sedimentation rate (p = 0.002). The statistically significant decrease observed in patients with both normal and increased beta2-M values at presentation, suggests that the immunological dysfunction responsible for the increase in beta2-M involves most, if not all, patients with tuberculosis. The measurement of beta2-M in conjunction with other clinical and laboratory parameters could be helpful in evaluating the response to therapy, particularly in those patients with increased beta2-M at presentation.

The prognostic value of soluble interleukin-6 receptor in patients with multiple myeloma

The effect of interleukin-6 (IL-6), the major growth factor for myeloma cells, may be enhanced by soluble IL-6 receptor (sIL-6R). Therefore, the current study investigated the clinical significance of serum sIL-6R in patients with multiple myeloma (MM). Serum levels of sIL-6R were determined by enzyme-linked immunoassay in 55 normal controls, 81 individuals with monoclonal gammopathy of undetermined significance (MGUS), and 164 patients with MM in various phases of the disease. sIL-6R concentrations were higher in MM patients (162.0 +/- 134.6 ng/mL) than in individuals with MGUS (58.9 +/- 36.7 ng/mL) or in controls (45.6 +/- 22.3 ng/mL) (P = 0.0000). sIL-6R was not found to have a significant linear correlation with any other parameter, including IL-6, beta2-microglobulin (beta2-m), and neopterin, either in newly diagnosed cases or during the course of the disease. In addition, there were no statistically significant differences in sIL-6R concentrations between the clinical stages at the time of diagnosis. In univariate logistic regression analysis sIL-6R was a significant but weak prognostic indicator (P = 0.000000). Kaplan-Meier analysis showed that elevated levels of sIL-6R were associated with shorter survival (P = 0.00282). Patients also were stratified according to their serum beta2-m and sIL-6R levels. Patients with low levels of both parameters had a clear survival benefit over the other groups (P = 0.000000). The correlation between sIL-6R levels and survival is significant but weak, making it unlikely to be of much value in predicting the outcome of patients with MM alone. The results of the current study support the role of sIL-6R levels in improving the prognostic value of beta2-m and in discriminating patients with MM from individuals with MGUS.

CD8+,CD38+ lymphocyte percent: a useful immunological marker for monitoring HIV-1-infected patients.

We investigated the relationship between three prognostic markers, CD4 lymphocyte count, serum beta2-microglobulin (beta2M) levels, and CD8+,CD38+ lymphocyte percent, and the association with the rate of development of AIDS. The markers were measured regularly throughout follow-up in 224 patients. The risk of developing AIDS during follow-up was investigated using Cox proportional hazards models. Time-updated values of the prognostic markers were used, which modelled the risk of AIDS according to the latest measurement of the marker rather than using a single value of the marker at baseline. During a median follow-up period of 13.6 months (range 0.5-31.9 months), 34 cases of AIDS occurred. In a univariate analysis, all three markers predicted the development of AIDS; a 10% increase in the percentage of CD8+ T cells expressing CD38+ resulted in an 88% increase in the risk of AIDS (95% confidence interval: 53-130%; p < 0.0001). After adjustment for the current CD4 count and beta2M, a 10% increase in the CD8+,CD38+ population was associated with a 37% increase in the risk of AIDS (95% confidence interval: 4-81%; p = 0.02). Thus, the percentage CD8+,CD38+ level predicts the development of AIDS independently of the latest CD4 count and beta2M. This assay is therefore potentially useful in conjunction with blood CD4 counts and serum beta2M levels in patient management and clinical trial design.

Correlation between tumour and serum beta 2m expression in patients with breast cancer.

HLA class I antigens are composed of a major histocompatibility complex (MHC) encoded heavy chain that is associated non-covalently with a light chain beta-2 microglobulin (beta-2m). When the HLA complex is metabolized, beta-2m is shed into the serum. A large variety of human and experimental tumours have altered MHC class I expression. In a previous study we observed elevated mean beta-2m serum levels in breast cancer patients, as compared to controls. To study the relationship between tumour expression and serum levels, we examined 54 patients with breast cancer. Tumour beta-2m was determined by immunohistochemistry and serum levels by the ELISA technique. Of the 54 patients, 38 had low and 16 had high beta-2m expression on the tumour. There was a significant correlation between tumour beta-2m and serum beta-2m levels (P = 0.02), with patients whose tumours expressed high beta-2m having high serum beta-2m levels. There was an inverse correlation between tumour grade and tumour beta-2m expression which approached statistical significance (P = 0.06). These findings suggest that in a substantial number of patients the high serum levels derive from shedding of beta-2m from tumour cells. These levels may have implications for tumour growth and metastases due to influences on immunological responses.

Relationship between serum &lt;italic&gt;β&lt;/italic&gt;&lt;sub&gt;2&lt;/sub&gt;-microglobulin bone histology, and dialysis membranes in uraemic patients

beta 2-Microglobulin (beta 2M) is the main constituent of osteoarticular amyloid deposits in haemodialysis patients. When dialysed with cellulosic (C) membrane such patients present a higher incidence of beta 2M-related amyloid arthropathy than with synthetic high-flux (SHF) membrane, and they have higher serum levels of beta 2M. This could favour beta 2M deposition as amyloid fibrils and/or modify bone and cartilage metabolism. We examined 56 uraemic patients dialysed in the same centre for 7.5 +/- 4.8 years (mean +/- SD). Based on bone histomorphometry criteria they were classified into either high-turnover bone disease (HTBD, 45 patients) or normal/low-turnover bone disease (N/LTBD, 11 patients). A subgroup of 30 patients had been dialysed with the same dialysis membrane for at least 18 months prior to study, 8 on C and 22 on SHF membrane. Serum intact parathyroid hormone levels were not different between the two patient subgroups. In contrast, serum beta 2M levels were higher in patients on C than on SHF membrane: 59.8 +/- 14.1 versus 32.8 +/- 8.7 mg/l, and so were serum total alkaline phosphatase and osteocalcin levels: 323 +/- 167 versus 173 +/- 50 IU/l, and 656 +/- 395 versus 288 +/- 263 ng/ml respectively. The increase of these serum markers of bone formation was associated with a higher bone cell number: osteoblast surface, 21.7 +/- 5.1 versus 9.8 +/- 11%; osteoclast surface, 4.27 +/- 1.86 versus 1.96 +/- 1.34%; and osteoclast number/mm2, 2.85 +/- 1.26 versus 1.27 +/- 0.88 respectively. Serum beta 2M was positively correlated with serum osteocalcin (r = 0.58, P < 0.001), bone-specific alkaline phosphatase (bAP) (r = 0.46, P < 0.008), and free pyridinoline (PYD) (r = 0.62, P < 0.002), and negatively correlated, only for HTBD, with osteoid volume: r = -0.40, P < 0.006. Serum beta 2M was higher in patients with HTBD than N/LTBD: The bone metabolism of chronic haemodialysis patients may be influenced by dialysis membrane biocompatibility. Moreover, the association of high serum beta 2M with increased bone cell number and serum markers of bone turnover suggests that beta 2M is either another marker of bone cell activity or an activator of bone cells.

Serum and urine beta-2-microglobulin in hemophagocytic syndrome.

Previous reports suggesting a correlation between lymphoproliferative disease and serum levels of beta-2-microglobulin (beta-2M) and in vitro data indicating a role of cytokines in the production of beta-2M prompted a study of serum and urine beta-2M concentration in patients with hemophagocytic syndrome (HPS), because no data were previously available for HPS, a pathologic state associated with excessive cytokines secreted from activated reactive/malignant lymphocytes and histiocytes. Serum and urine beta-2M levels were measured in six children with HPS during active and convalescent phase and in other diseases. Serum and urine beta-2M levels during active phase HPS were significantly high not only in serum (median, 7.5 mg/l; range, 2.3-16.0 mg/l; P < 0.01), but also in urine (median, > 31,650 micrograms/gram Creatinine (gCr); range, 8179-236,333 micrograms/gCr; P < 0.01), compared with levels during convalescent phase HPS (median, 2.0 mg/l; range, 0.9-2.5 mg/l in serum and median, 338 micrograms/gCr; range, 223-585 micrograms/gCr in urine) and in control subjects with diseases such as acute lymphocytic leukemia (median, 2.3 mg/l; range, 1.0-2.8 mg/l in serum and median, 327 micrograms/gCr; range, 48-2684 micrograms/gCr in urine), infectious mononucleosis (median, 2.9 mg/l; range, 2.5-5.5 mg/l in serum and median, 348 micrograms/gCr; range, 80-1325 micrograms/gCr in urine), and Kawasaki disease (median, 2.8 mg/l; range, 1.5-3.3 mg/l in serum and median, 1016 micrograms/gCr; range, 214-4500 micrograms/gCr in urine). Noteworthy was the observation that urine beta-2M levels correlated closely with HPS disease activity. Urine beta-2M appears to be a useful marker for assessing disease activity in patients with HPS.

Laboratory markers and the risk of developing HIV-1 disease among injecting drug users

To characterize the progression to HIV-1 disease among injecting drug users (IDU) according to laboratory markers. Prospective study of cohort of HIV-1-seroprevalent IDU, with case-comparison component. Different laboratory markers were examined as predictors of progression to HIV-1-associated diseases including AIDS in a cohort of 318 HIV-1-infected IDU. The cohort was enrolled from a methadone treatment program in the Bronx, New York, USA. The independent utility of non-CD4 cell markers was evaluated after adjustment for the association of low CD4 lymphocyte count with AIDS risk. Clinical events in the natural history of HIV-1 were related to changes in levels of two variables related to duration of infection, CD4 lymphocyte count and serum beta 2-microglobulin (beta 2M) concentration. On univariate analysis, AIDS incidence measured from baseline increased with declining CD4 lymphocyte number and percentage, increasing serum beta 2M level, low platelet count, low leukocyte count and p24 antigenemia. Among HIV-1-related outcomes prior to any AIDS diagnosis, the relative risk of pyogenic bacterial infections conferred by these markers was similar to the relative risk of AIDS. For all HIV-1 outcomes, the elevated risk encountered at CD4 lymphocyte number < or = 200 x 10(6)/l was entirely due to the high risk at < or = 150 x 10(6)/l. On multivariate analysis, control for CD4 lymphocyte count eliminated the association of any other marker with increased AIDS hazard. HIV-1-related outcomes tended to occur in this order: multiple constitutional symptoms, oral candidiasis, pyogenic bacterial infections and AIDS. In HIV-1-infected IDU, several laboratory markers may predict AIDS when analyzed individually. These are not, however, independently related to increased AIDS risk after adjustment for low CD4 lymphocyte count. A CD4 count < or = 150 x 10(6)/l is more strongly related to immediate risk of adverse outcome than a count of 200 x 10(6)/l. A progressive series of clinical events is associated with markers of duration of HIV-1 infection, prior to and including AIDS diagnosis.

Prognostic role of serum beta 2-microglobulin in Hodgkin's disease.

To evaluate the role of serum beta 2-microglobulin (beta 2M) in the prognosis of patients with Hodgkin's disease. One hundred sixty previously untreated patients with Hodgkin's disease had serum beta 2M levels determined before initiation of treatment. Serum beta 2M was tested for its correlation with known prognostic factors for patients with Hodgkin's disease. These variables, including beta 2M, were correlated with complete remission (CR) rate and time to treatment failure (TTF). Univariate and multivariate analyses were performed. Serum beta 2M levels greater than 2.5 mg/L were found in 29% of patients. Such elevation was more common in patients with more advanced-stage disease. Elevated serum beta 2M was an independent and powerful factor in the prediction of lower response rate and shorter TTF. Its impact appeared to be more significant in patients with advanced disease. Serum beta 2M appears to correlate with tumor stage in patients with Hodgkin's disease and elevated serum levels of this polypeptide predict a less favorable prognosis.

Clinical Evaluation of a New Dialyzer, FLX‐12 GW, with a Polyester‐Polymer Alloy Membrane

The performance of a membrane in renal failure therapy is determined by its structure, its overall mass transfer properties, and its blood compatibility. In this regard, removal of beta 2-microglobulin (beta 2M) has become a major objective of dialysis therapy. In the present study, a newly developed high-flux membrane composed of a polyester-polymer alloy (PEPA) with the components of polyarylate and polyethersulfone (dialyzer FLX-12 GW; Nikkiso Co., Japan) has been evaluated with regard to both biocompatibility and elimination capacity for beta 2M during hemodialysis of 8 stable chronic uremic patients. The clearance values of low molecular weight solutes were in the same range as those reported for high-flux dialyzers of comparable surface area. There was no drop in leukocyte counts and only a minimal fall in platelet counts nearly in the same range as has been observed by other investigators using polyamide membrane. C3a Des Arg generation was low, and C5a Des Arg formation was not significantly influenced. There was a sharp drop in the serum beta 2M level (-35%) during dialysis with a clearance between 59.7 +/- 5.6 ml/min (QB 200 ml/min) and 70.1 +/- 9.7 ml/min (QB 300 ml/min), respectively. Accordingly, the sieving coefficient was calculated to be 0.2 at 30 min after start of dialysis and 0.6 1 h later. The membrane was able to remove 184.0 +/- 22.3 mg/4 h due to an apparent rate of adsorption during the first hour of treatment in combination with high transmembrane transfer in the following time.

Elevated serum levels of neopterin but not beta 2-microglobulin in HIV-1-seronegative injecting drug users.

To determine whether injecting drug use is associated with cellular immune activation in the absence of HIV-1 infection. Serum levels of neopterin and beta 2-microglobulin (beta 2M) were measured cross-sectionally in injecting drug users (IDU) enrolled in a prospective study. Two hundred and nineteen HIV-1-seronegative, healthy heterosexual black male IDU aged 21-49 years were selected from the Baltimore-based AIDS Linked to Intravenous Experiences (ALIVE) study. The possibility of including subjects in the process of seroconverting to HIV-1 was minimized by restricting the study to individuals who remained seronegative 6 months after the specimens used for analysis were collected. Mean serum beta 2M levels were not statistically different among groups of IDU whose usual pattern of injection was at least once a day for up to 3 consecutive days (daily users; n = 65), less than once per day (less-than-daily users; n = 75), or not at all for at least 2 weeks (non-recent users; n = 79). In contrast, the mean neopterin level was significantly (P = 0.039) greater in daily users (6.17 nmol/l) than in the other two groups (5.07 and 5.19 nmol/l, respectively, which were not statistically different). These results were not affected, by the frequency of using borrowed non-sterile works or by other demographic and risk factor variables. Frequent injecting drug use may be independently associated with a small elevation of serum neopterin levels, but not beta 2M levels. Although the occurrence of a type I error in this sample cannot be completely excluded, serum neopterin may be more sensitive than serum beta 2M in detecting activation of immunocompetent cells associated with frequent injecting drug use in this population.

β2-Microglobulin Elimination in End-Stage Renal Disease Patients on Renal Replacement Therapy

beta 2-microglobulin (beta 2M) is a small molecular mass protein associated with dialysis amyloidosis. We have studied beta 2M elimination in end-stage renal disease (ESRD) patients treated by peritoneal dialysis. In 12 patients on continuous ambulatory peritoneal dialysis (CAPD) and 7 patients on intermittent peritoneal dialysis (IPD) 30.4 +/- 4.2 mg/day and 21.3 +/- 1.8 mg/12 hour of beta 2M, respectively, were removed by dialysis fluid. Approximately the same amount of beta 2M was removed by each of four 2-L exchanges in CAPD; however, the most efficient removal of beta 2M was in the first IPD exchange. Serum beta 2M levels in these patients were 25.7 +/- 4.4 and 31.4 +/- 5.2 mg/L, respectively. In 24 patients on hemodialysis using cuprophan membrane the serum level of beta 2M was 55.1 +/- 4.1 mg/L. After a 3-month dialysis on polyacrylonitrile (PAN) membrane, the serum beta 2M level decreased to 45.0 +/- 2.3 mg/L. A substantial amount of beta 2M was removed by urine, 14.6 +/- 2.3 mg/L, and saliva, 2.3 +/- 0.4 mg/L. This study has shown markedly increased beta 2M levels in patients on conventional hemodialysis treatment, predisposing to beta 2M-related amyloidosis. A significant amount of beta 2M was removed during both CAPD and IPD treatment.

Differences in laboratory values in HIV infection by sex, race, and risk group.

To determine differences in CD4+ and CD8+ lymphocyte values, beta 2-microglobulin (beta 2M), and HIV p24 antigenemia by sex and race among HIV-seropositive and HIV-seronegative injecting drug users (IDU), and to compare these values with those in homosexual men of equivalent status. Baseline values from a cohort of 206 HIV-seropositive and 173 HIV-seronegative IDU were compared with values from a cohort of 288 HIV-seropositive homosexual men and 176 HIV-seronegative controls, who were prospectively followed at 6-month intervals, to examine differences in laboratory values in HIV-infected individuals by sex, race, and risk group. Among HIV-seropositives, we compared white and black IDU only (n = 167), and white male IDU (n = 38) with white homosexual men (n = 256). Laboratory values from the cohort of homosexual men at 24, 36 and 48 months of follow-up were compared with IDU values. HIV-infected female IDU had significantly higher CD4+ lymphocyte counts (P < 0.03) and percentages of CD4+ lymphocytes (P < 0.004) than male IDU, resulting in higher CD4:CD8 ratios (P < 0.002). White IDU had significantly higher serum beta 2M levels than black IDU (P < 0.02). Black female IDU were much less likely to be HIV p24-antigenemic (1%) than all other groups (P < 0.005). Compared with homosexual men, male IDU had significantly elevated beta 2M levels (0.58 mg/l higher). When controlled for CD4+ lymphocyte values as a surrogate for length of time HIV-infected, beta 2M and HIV p24 antigenemia differences persisted. These differences should be considered when HIV p24 antigen, CD4+ lymphocyte counts and beta 2M levels are used as surrogate markers in clinical trials and management of HIV disease.

The Effect of Zidovudine Treatment on Serum Neopterin and ??2-Microglobulin Levels in Mildly Symptomatic, HIV Type 1 Seropositive Individuals

Sixty-one subjects with mildly symptomatic human immunodeficiency virus (HIV) infection were included in a double-blind, randomized, placebo-controlled trial of zidovudine (part of AIDS Clinical Trials Group protocol 016, ACTG 016) to evaluate changes in the serum immune activation markers neopterin and beta 2-microglobulin (beta 2M) as early markers of the antiviral effect of zidovudine on HIV type 1 (HIV-1) infection. The mean values of serum neopterin and beta 2M levels in 27 placebo-treated subjects tended to increase with time. The mean value of neopterin in 34 subjects receiving zidovudine decreased at 4 weeks (15.76 nmol/L before treatment to 12.73 nmol/L, p = 0.001). The maximum reduction was seen at 8 weeks of treatment (10.78 nmol/L, p less than 0.0001). Subsequently, the mean value of serum neopterin increased but remained below the pretreatment value for more than a year. Serum beta 2M levels decreased (from 3.01 to 2.69 mg/L at 4 weeks, p = 0.01) and reached the lowest level at 8 weeks (2.45 mg/L, p = 0.0002) in zidovudine recipients. The mean beta 2M level returned to pretreatment value at approximately 24 weeks of the treatment. There was a close correlation between changes from baseline in serum neopterin and beta 2M during the first 16 weeks of the zidovudine therapy, but not later. Subjects with greater reductions of serum neopterin or beta 2M tended to maintain lower levels of these markers with continued zidovudine administration.(ABSTRACT TRUNCATED AT 250 WORDS)

Prognostic Value of Serum β-2 Microglobulin in Low-Grade Lymphoma

To evaluate serum beta-2 microglobulin (beta-2M) and other prognostic indicators in previously untreated low-grade lymphoma. Cohort study of 80 patients with uniformly treated low-grade lymphoma, followed for a median of 21 months. These 80 patients, all of whom had serum beta-2M drawn within 2 weeks before starting therapy, were derived from a cohort of 119 previously untreated patients entered into one of three clinical trials. Tertiary referral cancer center. Eighty previously untreated stage I to IV patients (mean age, 55 years). Treatment was given according to Ann Arbor stage: Patients in stage IV were treated with CHOP-bleomycin and maintained on interferon therapy; those in stage III received CHOP-bleomycin and radiotherapy; and those in stages I and II received COP-bleomycin and radiotherapy. Outcome was determined by assessing complete remission rate and time to treatment failure. Univariate and multivariate analyses were used. The complete remission rate for patients with a beta-2M level of 3.0 mg/L or greater was 36% compared with 71% for those with a level of less than 3.0 mg/L. Using multivariate analysis that tested beta-2M as a continuous variable, it was selected as the most significant factor for complete response. The adjusted odds ratio was 0.285 (95% CI, 0.101 to 0.809). The Ann Arbor stage had marginal significance (adjusted odds ratio, 0.435; CI, 0.150 to 1.263). For time to treatment failure, beta-2M was the only variable retained in the multivariate model. At 42 months, no patient with a beta-2M level of 3.0 mg/L or greater was projected to be in remission as compared with 85% of patients with a beta-2M level of less than 3.0 mg/L. The serum beta-2M level is a good predictor of complete response and time to treatment failure. A larger number of patients should be studied to clarify the role of other potentially independent variables such as stage and age.