Serum β2M Levels Research Articles

Evaluation of the Revised International Staging System (R-ISS) in an Independent Cohort of Unselected Patients with Multiple Myeloma

The International Staging System (ISS), which is based on beta2-microblobulin (β2M) and serum albumin, has been widely used for the risk stratification of multiple myeloma (MM) patients, since 2003. Chromosomal abnormalities (CA) detected by iFISH have been also recognized as strong prognostic factors, while elevated serum lactate dehydrogenase (LDH) has been consistently associated with poor prognosis. In order to improve the prognostic power of ISS, IMWG has revised ISS (R-ISS) by adding high risk cytogenetics by iFISH and serum LDH: R-ISS-1 includes patients with ISS-1 (serum β2M level <3.5 mg/L and serum albumin level ≥3.5 g/dL), no high-risk CA [del(17p) and/or t(4;14) and/or t(14;16)] and normal LDH levels (below the upper limit of normal (UNL)); R-ISS-3 includes patients with ISS-3 (serum β2M level >5.5 mg/L) and either high-risk CA or high LDH level; and R-ISS-2 includes all the other possible combinations. R-ISS was based on the data of 3,060 patients who had participated in clinical trials. However, it has not been validated in an independent cohort of unselected patients. Our aim was to evaluate R-ISS in consecutive, unselected patients, treated in a single center.Our study included 475 patients with available data for cytogenetics [t(4;14) and del17p by iFISH], LDH and ISS. Median age was 67 years (range 27-91); 53% were >65 years and 25% >75 years of age. Only 8.6% did not receive new drugs as primary therapy; 42% received IMiDs (19% thalidomide-based, 23% lenalidomide-based) and 49% bortezomib-based primary therapy, while 36% received ASCT. In the IMWG cohort, 65% had received ASCT, 6% no new drugs, 44% proteasome inhibitors and 66% IMiDs. Per ISS, 24% were ISS-1, 34% ISS-2 and 42% ISS-3. High risk cytogenetics (either t(4;14) or del17p) were present in 23.5% and elevated LDH in 15%. In the IMWG cohort used for the formulation of R-ISS, 38% were ISS-1, 38% ISS-2 and 24% ISS-3; thus, our patients had more often ISS-3 and less often ISS-1 disease. High risk CAs and elevated LDH were not different compared to our cohort of patients (24% and 13%, respectively). The difference in ISS disposition between the two cohorts probably reflects the unselected nature of our population, which also included patients with severe renal impairment who often are excluded from clinical trials.Per R-ISS, 85 (18%) patients had R-ISS-1, 83 (17.5%) had R-ISS-3 and 306 (64.5%) had R-ISS-2. The disposition in the original cohort was 28% for R-ISS-1, 62% for R-ISS-2 and 10% for R-ISS-3. This difference was due to the higher proportion of patients with ISS-3 disease in our cohort. The R-ISS disposition in those ≤65 years, was 21%, 60% and 19% for R-ISS-1, -2 and -3; among patients 66-75 years it was 19%, 63% and 18%, and among those >75 years it was 11%, 74% and 15%, respectively (p=0.128). The median follow up was 40 months; 57% of patients progressed or died and 63% have remained alive. Median PFS was 27 months and estimated median OS was 63 months. Median PFS for R-ISS-1, -2 and -3 was 34, 28 and 17 months, respectively (p<0.001). According to R-ISS, the probability of 3-year OS was 83%, 69% and 45% and of 5-year OS 77%, 53% and 19% for R-ISS-1, -2 and -3, respectively (p<0.001). In patients treated with ASCT, the probability for 5-year OS per R-ISS stage was 93%, 77% and 32%, respectively (p<0.001), while for patients not treated with HDM it was 64%, 41% and 13% (p<0.001). The probability for 5-year OS for patients treated with bortezomib was 95%, 69% and 18% for R-ISS-1, -2 and -3 (p<0.001) and for those treated with IMiDs, it was 68%, 41% and 23%, respectively (p=0.002).We evaluated the performance of R-ISS in patients ≤65, 66-75 and >75 years. In patients ≤65 years, the probability for 5-year OS was 84%, 71% and 29%, for R-ISS-1, -2 and -3 (p<0.001); for patients 66-75 years, it was 73%, 43% and 18% (p=0.001), while in patients >75 years, the median OS was >5 years, 35 and 29 month, respectively (p=0.122). Thus, R-ISS identified a group of patients >75 with favorable prognosis, although there was no significant difference in the OS for R-ISS-2 vs -3, probably due to the impact of other comorbidities and performance status of the very elderly.In conclusion, our data in consecutive, unselected patients, with differences in the characteristics and treatment approaches compared to the original IMWG cohort, verified that R-ISS provides significant prognostic information and it allows the identification of three different patient groups with clearly different outcome. DisclosuresTerpos:Novartis: Honoraria; Celgene: Honoraria, Other: travel expenses; Janssen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: travel expenses; Amgen: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding. Dimopoulos:Novartis: Honoraria; Celgene: Honoraria; Genesis: Honoraria; Janssen: Honoraria; Onyx: Honoraria; Janssen-Cilag: Honoraria; Amgen: Honoraria.

Serum Beta-2 Microglobulin: a Possible Marker for Disease Progression in Egyptian Patients with Chronic HCV Related Liver Diseases.

Egypt has the highest prevalence of HCV infection in the world (~14.7%). Around 10-15% of HCV-infected persons will advance to cirrhosis within the first 20 years. The incidence of HCC is expected to grow in the next two decades, largely due to HCV related cirrhosis, and detection of HCC at an early stage is critical for a favorable clinical outcome. No simple reliable non-invasive marker has been available till now. B2M, a non-glycosylated polypeptide composed of 99 amino acids, is one of the components of HLA class I molecules on the surfaces of all nucleated cells. It has been reported that the level of serum B2M is elevated in patients with chronic hepatitis C and HCV-related HCC when compared to HCV-negative patients or healthy donors. Determining the clinical utility of serum β2M as a marker for disease progression in Egyptian patients with HCV related chronic hepatitis, cirrhosis and hepatocellular carcinoma was the aim of the present study. In this analytical cross sectional study 92 participants were included in 4 equal groups: Group (1) non cirrhotic chronic HCV; Group (2) HCV related liver cirrhosis; Group (3) HCC on top of HCV,; and Group (4) healthy controls. History taking, clinical examination, routine labs and abdominal ultrasound were conducted for all patients, PCR and Metavir scores for group (1) patients, and triphasic CT abdomen and AFP for Group (3) patients. β2M levels were measured in serum with a fully-automated IMX system. The mean serum B2M level of Group (1) was 4.25 ± 1.48 μg/ml., Group (2) was 7.48 ± 3.04, Group (3) was 6.62 ± 2.49 and Group (4) was 1.62 ± 0.63. Serum B2M levels were significantly higher in diseased than control group (p<0.01) being significantly higher in cirrhosis (7.48 ± 3.04) and HCC groups (6.62 ± 2.49) than the HCV group (4.25 ± 1.48) (p<0.01). There was a significant correlation between B2M Level and ALK, total and direct bilirubin and INR (p<0.05), and a significant inverse correlation between B2M level and albumin, total proteins, HB and WBCS values (p<0.05). There was no significant correlation between B2M level and viral load or Metavir score, largest tumour size or AFP (p>0.05). The best B2M cut-off for HCV diagnosis was 2.6 with a sensitivity of 100%, a specificity of 92%, a positive predictive value (PPV) of 97% and a negative predictive value (NPV) of 100%. The best B2M cut-off for HCC diagnosis was 4.55 which yielded sensitivity, specificity, positive predictive value, negative predictive values of 74%, 62%, 39.5, 87.8% respectively (p-value <0.01) while best cut-off for cirrhosis was 4.9, with sensitivity 74 % and specificity 74%. The sensitivity for HCC diagnosis increased upon B2M and AFP combined estimation to 91%, specificity to 79%, NPV to 95% and accuracy to 83%. Serum B2M level is elevated in HCV related chronic liver diseases and may be used as a marker for HCV disease progression towards cirrhosis and carcinoma.

Serum Albumin and Peripheral Blood Lymphocyte/Monocyte Ratio at Diagnosis May Provide Additional Prognostic Information in R-IPI Good Risk Diffuse Large-B-Cell Lymphoma Patients Treated with R-CHOP

Background and Aim: Diffuse large B-cell lymphoma (DLBCL) is the most common type of non-Hodgkin lymphoma. Currently, the standard of care in DLBCL patients (pts) is rituximab-CHOP immunochemotherapy (R-CHOP) and the prognostic stratification is performed by the Revised International Prognostic Index (R-IPI), identifying 3 distinct prognostic groups with a very good, good and poor outcome. A lot of new prognostic markers have been introduced into the clinical practice to perform better pts' stratification. Particular prognostic relevance has been attributed to serum albumin (SA), β2-microglobulin (B2M), peripheral blood lymphocyte/ monocyte ratio (LMR), neutrophil/lymphocyte ratio (NLR) etc. However the data of these prognostic factors across the different R-IPI prognostic groups are limited. Therefore, we decided to access whether SA, B2M, LMR and NLR were predictors of overallsurvival (OS) across the different R-IPI groups of R-CHOP treated DLBCL pts.Patients and Methods: We retrospectively reviewed the clinical outcome of 281 R-CHOP treated DLBCL pts with median age 58 years and 51.8 % male. According to the R-IPI score, the pts in very good, good and poor risk were 24.2%, 54.8% and 21%, respectively. Laboratory levels of albumin, absolute lymphocyte, monocyte and neutrophil count were recorded, and LMR and NLR - calculated. Serum B2M levels were measured by radioimmunoassay. A receiver operating characteristic (ROC) curve analysis was used to illustrate in our data set the best cut off values of SA, B2M, LMR and NLR to predict OS by Kaplan-Meier method. Univariate analysis to evaluate differences between variables was performed by the log rank. A multivariate analysis was performed by Cox proportional-hazards models.Results: The estimated 5-year OS was 87.1%, 74% and 31% for R-IPI very good, good and poor-risk patients, respectively. The median values of SA, B2M, LMR and NLR were 40.7 g/L, 2.9 mg/L, 2.95 and 2.86, respectively. Our data showed that on univariate analysis inferior OS was associated with decreased SA (≤39.4 g/L; 95% confidence interval (CI) 0.70-0.82, p=<0.001), elevated B2M (>2.6 mg/L; 95% CI 0.68-0.80, p=<0.001), reduced LMR (≤2.16; 95% CI 0.71-0.81, p=<0.001) and increased NLR (>2.61; 95% CI 0.66-0.77, p=<0.001), presented as dichotomized variables. On multivariate analysis the independent prognostic significance was confirmed only for SA and LMR, with hazard ratios of 0.23 (95% CI 0.11-0.49, p<0.001) and 0.41 (95% CI 0.21-0.81, p=0.011), respectively.Based on the dichotomized SA and LMR values a SA/LMR prognostic index (PI) was created stratifying patients into 3 risk groups: very good (SA >39.4 g/L and LMR >2.16; n=75), good (SA ≤39.4 g/L or LMR ≤2.16; n=52) and poor-risk (SA ≤39.4 g/L and LMR ≤2.16; n=41) populations. The estimated 5-year OS was 88.7% for very good, 51.7% for good, and 8.8% for poor SA/LMR PI group (p<0.001). Median OS for poor-risk patients was 1.1 years (95% CI 1.03-1.72 years) and not reached for both the very good and good-risk groups.We sought to determine whether the SA/LMR PI may provide additional prognostic information within the R-IPI risk groups. Due to low number of deaths - 4.4% (3/68), no statistics could be calculated in very good R-IPI risk group. Within the R-IPI good risk patients SA/LMR PI allowed us to discriminate 3 subgroups, characterized by significant differences in 3-year and median OS (Figure 1): a SA/LMR PI poor risk subgroup (n=18) with 10.4% 3-years OS and 1.13 years (95% CI 0.82-1.44 years) median OS; a SA/LMR PI good risk subgroup (n=32) with 59.5% 3-years OS and median not reached; and a SA/LMR PI very good risk subgroup (n=50) with not reached median OS and 91.3% 3-years OS comparable to the OS in R-IPI very good patients (p=0.229). Only SA retained its independent prognostic significance in R-IPI poor risk group.Conclusion: SA and LMR are independent prognostic markers to predict survival in DLBCL pts. Adding these variables to prognostic models such as the R-IPI score might improve their predictive ability, providing particularly relevant information within the R-IPI good risk group. A subgroup of R-IPI good risk pts with a very good SA/LMR PI was identified, comparable to the R-IPI very good risk category in terms of OS. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Genomic Alterations Important for the Prognosis in Patients with Follicular Lymphoma Treated on SWOG Study S0016

Background: FL is a common, indolent, yet typically incurable disease characterized by clinical and genetic heterogeneity. Recent studies suggested that TNFRSF14 mutation and 1p36 deletion were associated with worse outcome in FL and that TNFAIP3 mutation on 6q occurred at FL transformation. However, no genomic biomarkers are currently in clinical use for prognostic and therapeutic decisions. We aimed to identify novel genomic aberrations associated with prognosis of patients with FL in the context of a randomized cooperative group trial (Press 2013 JCO).Patients and Methods: We employed a comprehensive genomic array testing strategy to assess the common genomic abnormalities, including copy number aberrations (CNAs), copy-neutral loss-of-heterozygosity (cnLOH), and common cancer gene mutations. Our study set includes all patients enrolled in the SWOG FL study S0016 with available pre-treatment tissue specimens (n=250). To date, chromosome genomic array testing (CGAT) has been performed on archived formalin-fixed, paraffin embedded (FFPE) lymphoma tissue specimens from 158 patients. A SWOG pathologist reviewed all tissues prior to CGAT to ensure that each sample met the diagnostic criteria for FL and had at least 30% tumor content. The OncoScan platform was used for CGAT with data analysis performed by Nexus Express. Statistical analysis was performed using the Cox-proportional hazard regression model. Hazard ratio (HR) and 95% confidence interval (CI) were estimated from the multivariate model. For this exploratory analysis, statistical significance was determined at an alpha-level of 0.05 without adjustment for multiple comparisons.Results: Most samples (>90%) showed multiple chromosome abnormalities (median 10, range 1-65). The most frequently affected chromosome arms were: 1p (49.3%), 6q (41.7%), 6p (40.5%), 1q (38.6%), 16p or 22q (36%), and 18q (35.4%). Specific common CNAs were deletions of 1p, 6q, and 10q, gains of X, 1q, 2p, 7, 8q, 12q, 17q, and 18, and cnLOH of 1p, 6p, and 16p. Point mutations were not identified. Univariate analysis for progression free survival (PFS) identified several aberrations (of the 94 aberrations assessed) significantly associated with prognosis at unadjusted .05 level; these include gain of 12p, 17q, 18q, and Yp, deletions of 2q, 6q, 8q, 9p, and Yq, and deletion or cnLOH of 9p and 10q. Multivariate analysis adjusting for FLIPI risk, bulky disease, and combined serum β2M and LDH levels demonstrated that selected markers, including deletion or cnLOH of 9p and 10q and gain of 12p and 17q, remained significant for PFS (HR 2.0 for 9p, 0.5 for 10q, 2.8 for 12p, and 2.0 for 17q), while FLIPI risk and serum β2M/LDH levels were no longer significant. In particular, estimated two-year PFS was lower in patients with 9p deletion or cnLOH (60% vs 77%), gain of 12p (62% vs 78%), and gain of 17q (59% vs 80%) compared with those without.Conclusion: We confirmed the frequent 1p and 6q deletions in FL reported in literature. In addition, we identified several genomic aberrations that may be prognostic of FL patients. Among these, deletions and cnLOH of CDKN2A (9p), PTEN (10q) and CREBBP (16p) are of significant interest for their known tumor suppressor functions. Gain of 12p, 17q, and 18q may also help identify oncogenes and other activating tumorigenic processes relevant to disease progression and survival. Multivariate analysis suggested that the genomic aberrations might add to currently utilized clinical risk stratification as a means to identify high risk patients at diagnosis of follicular lymphoma.Support: This work was supported by Affymetrix Inc., NIH/NCI National Clinical Trials Network (NCTN) grants CA180888 and CA180819, and in part by GlaxoSmithKline. DisclosuresHsi:Abbvie: Research Funding; Cellerent Therapeutics: Research Funding; Eli Lilly: Research Funding; Onyx: Honoraria; Seattle Genetics: Honoraria. Smith:Pharmacyclics: Consultancy; Celgene: Consultancy. Fang:Affymetrix: Research Funding.

The Relationship Between Serum Zinc Levels and Tumor Markers in Hemodialysis Patients

The incidence of neoplasia is increased in end-stage renal disease (ESRD) patients. Zinc (Zn) deficiency is associated with neoplasia and also commonly seen in ESRD patients. However, the data regarding the relationship between Zn levels and tumor markers is scant in this population. We aimed to investigate the relationship between Zn levels and tumor markers in hemodialysis patients. Twenty-six hemodialysis patients (11 male, 15 female, mean age 41.6±14.3 years) and 11 healthy subjects (6 male and 5 female, mean age 38.7±7.2 years) were included. Serum Alpha fetoprotein (AFP), carcinoembriyonic antigen (CEA), CA 19-9, CA 15-5, CA 125, beta subunit of human corionic gonadotrophin (β-HCG) and beta-2 microglobulin (β2M) and Zn levels were measured. Data were analysed by Student’s t test. Serum Zinc levels were significantly lower in ESRD patients (group 1) compared to healthy subjects (group 2) (p<0.0001, for all). Serum CEA and β2M levels were also significantly higher in group 1 patients compared to group 2 subjects (p<0.005, p<0.0001, respectively). Serum Ca15-3 and CA-125 levels were found to be significantly lower in group 1 patients compared to group 2 subjects (p<0.005, p<0.001, respectively). There were no statistically significant difference in terms of serum CA 19-9, β-HCG and AFP between group 1 and group 2 patients. In group 1 patients, there was a negative correlation between serum Zn levels and AFP, while a positive correlation was obsorved between serum Zn levels and CA15-3. The measurement of AFP may be beneficial in HD patients. Further studies are needed.

Sonographic features suggestive of amyloidosis in hemodialysis patients: Relations to serum beta2-microglobulin

Aim of the workTo determine sonographic features suggestive of amyloidosis in hemodialysis patients complaining of shoulder pain, and to study their relations to serum beta2-microglobulin (β2M). Patients and methodsClinical examination, skeletal survey, musculoskeletal ultrasonography of the shoulder joints, and serum β2M were done for 32 patients with end stage renal disease, who were regular on hemodialysis. ResultsSerum β2M levels were markedly raised in all patients, and increased with increasing duration of dialysis (r=0.91, p<0.001). Twenty-five patients had a non homogeneous thickening of the supraspinatus tendon >7mm, and thickening of the biceps tendon >4mm, 30 had synovial deposits, 27 had subdeltoid bursa effusion, 25 had thickened subacromial bursa, 7 had supraspinatus tendon tear, and 17 had bony erosions. Serum β2M levels significantly correlated with thickened supraspinatus tendon (>7mm) and supraspinatus tendon tear (r=0.41, p=0.03 and r=0.42, p=0.01 respectively). Long time on hemodialysis was the significant independent determinant for supraspinatus tendon tear and humeral head erosions (p=0.001 for each). ConclusionElevated serum β2M levels and sonographic features suggestive of dialysis-related amyloidosis (DRA) were found in all hemodialyzed patients complaining of shoulder pain either with or without clinical and/or radiological features suggestive of DRA. So, for diagnosis of DRA, sonographic features should correspond to the presence of clinically or radiologically evident β2M amyloid, and we should exclude other causes of non-amyloid changes.

Clinical Monoclonal B Lymphocytosis (cMBL), Chronic Lymphocytic Leukemia (CLL) and Small Lymphocytic Lymphoma (SLL): Diagnostic Criteria, Features At Diagnosis and Natural History

IntroductionCLL, SLL and cMBL are considered to be part of the same spectrum of clonal expansions of CD5+ B cells. Clinically, the transition from one to another of these forms over time is a well recognized event. Diagnostic criteria to separate these disorders have been proposed (IWCLL, 2008; WHO, 2008). AimTo compare presenting and evolving features of three groups of patients with cMBL, Rai 0 CLL or SLL and to ascertain the usefulness of current diagnostic criteria for these disorders. Patients and MethodsRetrospective study of clinical, biologic and evolving characteristics of patients diagnosed with cMBL, Rai 0 CLL or SLL according to current criteria (CLL: ≥5x109 clonal B cells/L in peripheral blood; SLL <5x109/L clonal B cells with lymphadenopathy, organomegaly, cytopenia or disease-related symptoms; cMBL <5x109 clonal B cells with no signs or symptoms). ResultsBaseline characteristics of the patients are shown in the Table. Median age was 68 years (range, 24-94) and 57% of patients were males. Out of 1,093 patients, 79 had cMBL (7.2%), 522 Rai 0 CLL (48%) and 94 SLL (8.6%).CharacteristicscMBLRai 0-CLLSLLP valueAll patients (N=695)7952294Age, median (years)70 (34-90)66 (31-92)66 (24-94)NSGender, male42/79 (53%)270/522 (51%)56/94 (59%)NSWBC median (x109/L)9.4 (4-14)24 (4-170)8.1 (3-19)< 0.001Hb, median (g/dL)13.7 (10-17)13.9 (11-18)13.5 (10-18)NSPlatelets, median (x109/L)208 (11-573)211 (96-791)194 (52-390)NSLDH > 450 u/L7/78(9%)25/481 (5%)18/91 (20%)< 0.001B2M ≥ 2.4 mg/dl22/62 (36%)130/356 (37%)49/77 (64%)< 0.001ZAP70 ≥ 2011/57 (19%)104/361 (29%)34/54 (63%)< 0.001CD38≥ 3010/52 (19%)78/323(24%)36/51 (71%)< 0.001IGHV genemut.24/27 (89%)139/217 (64%)17/37 (46%)0.002NOTCH1 genemut.1/44 (2%)35/250 (14%)6/42 (14%)NSSF3B1 genemut.0/14 (0%)5/157 (3%)3/24 (12%)NSFISHNormal98/339 (29%)15/60 (25%)17/53 (33%)NS13q- (isolated)22/52 (42%)146/339 (43%)13/60 (22%)NS+ 1211/52 (23%)39/325 (12%)14/60 (34%)0.01611q-0/50 (0%)19/339 (6%)8/60 (13%)0.0117p-2/52 (4%)37/339 (11%)10/60 (17%)NSOverall, adverse biomarkers such as high LDH (p<0.001), high B2M (p<0.001), increased ZAP70 (p<0.001), high CD38 (p<0.001), unmutated IGHV status (p=0.002), +12 (p=0.02) and 11q- (p=0.01) were significantly more frequent in SLL.In subgroup analyses, the only difference between cMBL and Rai 0 CLL was a higher proportion of cases with mutated IGHV in cMBL (p=0.008). Furthermore, when SLL was compared to Rai I to IV CLL no differences were observed (data not shown). The actuarial risk for transformation from cMBL or SLL to CLL was 4.2% and 4.4 % per year (p=0.5), respectively. Median TTFT was significantly shorter in the SLL group (12 m.) than in Rai 0 CLL (174 m.) or cMBL (244 m.) (p<0.001). Median overall survival was also significantly shorter for SLL (94 m.) compared with Rai 0 CLL and cMBL (153 and 157 m., respectively) (p=0.028). Multivariate analysis of 695 patients (cMBL/Rai 0-CLL/SLL) revealed four variables independently correlated with shorter TTFT: diagnosis of SLL vs. Rai 0 CLL vs. cMBL (HR 2.28; p=0.008), high ZAP70 (HR 4.08; p<0.001), high CD38 (HR 4.68; p=0.001) and increased serum B2M levels (HR 1.54; p = 0.031). Importantly, however, when the multivariate analysis was restricted to patients with cMBL and Rai 0 CLL, variables correlated with TTFT were the clonal B-cell count (HR 3.76; p=0.01), ZAP70 (HR 3.31; p<0.001), and CD38 (HR 4.61; p=0.02). FISH cytogenetics, IGHV mutational status,NOTCH1 or SF3B1 mutations were not included in the analysis because of missing data. ConclusionsDisparities in biologic and clinical features of cMBL, CLL and SLL mainly reflect the different tumor burden in this spectrum of CD5+ monoclonal B cell disorders. In this study, the transformation rate from either cMBL or SLL to CLL was around 4% per year. As a result of differences in tumor mass, the need for therapy was shorter in SLL than in Rai 0 CLL and cMBL, and the overall survival poorer. Biologically, the only consistent difference between cMBL and Rai O CLL was a higher proportion of mutated IGHV in cMBL. Clinically, however, no differences in median survival were observed. Moreover, the clonal B cell count was the most reliable predictor of disease outcome in both cMBL and Rai 0 CLL. Therefore, the distinction between cMBL and Rai 0 CLL seems hardly justified. Disclosures:No relevant conflicts of interest to declare.

Predicting long-term outcome in renal transplantation

Long-term outcome in renal transplantation is heterogeneous, and predicting success is challenging. Astor and colleagues report that serum β2M levels measured on discharge after transplantation correlate closely with long-term patient and graft survival, and may serve as a biomarker of clinical risk. β2M may provide a more precise measurement of glomerular filtration, combined with an index of inflammatory burden related to rejection or systemic vascular disease. Association must not be confused with prediction, however, and the role of β2M must be tested in a validation cohort to define sensitivity, specificity and predictive performance at the individual, rather than the population, level.

Serum β-2 microglobulin predicts mortality in people with diabetes

Serum β-2 microglobulin (B2M) level predicts mortality in chronic kidney disease. Glycation of B2M is cytotoxic and may contribute to the risk of mortality in diabetic patients. Our objective was to evaluate the relationship between B2M and mortality in diabetic patients. In this prospective study, 896 participants of the Third National Health and Nutrition Examination Survey with diabetes were included in the analysis. Serum B2M level was used in multivariate Cox regression analysis to predict all-cause and diabetes-related mortality. During a median follow-up of 11.8 years (range 0.1-18.2 years) and 9220.5 person/years, 541 (42.4%) and 207 (16.8%) participants died from all causes and diabetes-related causes respectively. One natural-log unit of B2M was significantly associated with all-cause (hazard ratio (HR)=6.53, 95% CI 2.07-20.6) and diabetes mortality (HR=7.35, 95% CI 1.01-53.38) after multivariable adjustment. Similar results were obtained when B2M was analyzed as tertiles or in the threshold model (T1+T2 vs. T3). Examination of regression splines suggests a linear increase in hazard for mortality with increasing B2M levels. Serum B2M level is a novel predictor of all-cause and diabetes-related mortality in people with diabetes regardless of renal function.

Within-Person Variability in Kidney Measures

Our objective was to quantify short-term total within-person variability in standard and nontraditional kidney measures using national data. Repeated examination study of serum and urine kidney measures. Participants 18 years or older in the Third National Health and Nutrition Examination Survey (NHANES III) who had repeated blood and urine samples collected during visits occurring approximately 18 days apart. Standardized serum creatinine, standardized cystatin C, β-trace protein (BTP), β(2)-microglobulin (B2M), and urine albumin and creatinine. We calculated the within-person coefficient of variation (CV(w)), which includes both biological and analytical variability. We also evaluated the impact of variability on estimates of the prevalence of reduced estimated glomerular filtration rate and albuminuria. Serum cystatin C level demonstrated the lowest short-term within-person variability (CV(w) = 6.8%). Serum creatinine and B2M levels (CV(w) = 7.6% and 8.4%, respectively) also had low variability. BTP level had the most variability of the serum markers (CV(w) = 11.6%). As expected, urine albumin and urine creatinine measurements showed high variability (CV(w) >30% for both); however, albumin-creatinine ratio performed much better than either measure alone, with CV(w) of 11.3%. The effect of short-term variability on the prevalence of reduced estimated glomerular filtration rate was moderate, with an ~20% lower prevalence when defined based on single measurements compared to repeated application of the same test approximately 18 days apart. Repeated testing for albuminuria had a larger effect, showing a 33% lower prevalence of albuminuria when repeated testing was applied. Only 2 measurements available. General population with low prevalence of kidney disease. Our results suggest that creatinine, cystatin C, and B2M levels have similarly low short-term variability. BTP level was more variable compared with the other serum filtration markers. Urine albumin and creatinine levels were highly variable and may benefit from repeated assessments to reduce the misclassification of albuminuria.

Is Chronic Lymphocytic Leukemia Still Incurable?

AbstractAbstract 3929 IntroductionUp until now, Chronic Lymphocytic Leukemia (CLL) has been considered incurable except with an allogeneic stem cell transplant. In the last 10 years, evidence has demonstrated that chemo-immuotherapy with fludarabine, cyclophosphamide, and rituximab, (FCR) has significantly improved CR rates, overall survival (OS), and progression free survival 1. Long term follow up data for FCR at MDACC demonstrated that a significant proportion of patients (pts.) were free at 8 years2 raising the question of whether pts. are potentially cured.Definition of cure in a chronic disease such as CLL has not been addressed. To investigate this possibility we evaluated the outcome characteristics of 222 of the 300 patients (who commenced FCR more than 10 years ago) in our previously reported study of initial therapy with FCR in CLL2.Seventy eight (35%) pts were free of relapse and 127 (58%) were alive at 10 years (Fig. 1). Thirty three patients died in CR/PR of infection (5), second malignancies (8), Richter's transformation (8). MDS (9), and other causes (3). One hundred and sixty three pts. (73%) achieved CR, 22 pts. (10%) a nodular PR (nPR), 27 pts. (12%) a PR, and 10 (5%) failed treatment. The 10 year PFS correlates strongly with response, CR (41%), nPR+PR (15%) (Fig. 2). None of these patients were transplanted in remission.FISH analysis was not available at the time of this study. Conventional karyotyping demonstrated +12 (24 pts), del 11q (15), del 17p (4), other abnormalities (15), diploid (105), and in 59 patients the test was not done or had no metaphases. The worst outcomes were del 17p and del 11q each significantly inferior to diploid (+12) patients had the best time-to-treatment failure (TTF) with P<.09 compared to diploid.The 10-year TTF was significantly higher for Rai <3 versus 3 – 4 (P=.02), serum beta-2-microglobulin (β2M) value of ≤ 4 mg/L (p<.001), mutation status of IgVh (P<.001) and number of courses of FCR received. (Table 1) The causes for receiving <6 courses of FCR were persistent cytopenia (15), infections (6), resistance (5), Richter’s transformation and other malignancies (9), autoimmune hemolysis (5), and other causes and lost to follow-up (16).Table 110 yr TTF10 yr OSCharacteristicValuePts.CR (%)Χ2TTF (%)p-valueOS (%)p-valueRai Stage<3/3-4145/7778/50.0438/22.0264/50<.01Serum b2M<4/>4129/9583/58<.00144/22<.00174/40<.001IgVh MutationMut/Unmut.47/8283/77ns49/11<.00176/46<.01# Courses<6/657/16551/81<.00116/38.00270/31<.001Of the 77 patients who are still in remission at 10 years, two have relapsed and one developed Richter's transformation. Four of 21 patients checked had no residual disease in their blood at 10 years by 4-parameter flow cytometry. All other 10 yr. TTF patients are being contacted to provide blood for 4-parameter flow residual disease. ConclusionThe present data suggest that one-third of patients treated with chemoimmunotherapy are potentially cured of CLL. The characteristics most strongly associated with 10 yr. TTF were Rai stage, serum β2M level, mutation status, and tolerance of chemotherapy. Second malignancies and transformations are emerging as significantly impairing the likelihood of cure. [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

Serum beta2-microglobin is a predictor of prognosis in patients with upper aerodigestive tract NK/T-cell lymphoma

Upper aerodigestive tract natural killer (NK)/T-cell lymphoma (UNKTL) is the most common type of extranodal NK/T-cell lymphoma, nasal type. Serum beta2-microglobulin (β2-M) was found to be a predictor in some subtypes of B-cell lymphoma. However, its prognostic significance in NK/T-cell lymphoma has never been explored. We retrospectively analyzed 82 patients newly diagnosed as UNKTL. Serum β2-M was detected prior to treatment in this series. Various statistical analyses were performed to evaluate the significance of the relevant clinical parameters. High serum β2-M level was calculated as ≥2.5 mg/L by the median value. The number of patients with serum β2-M ≥2.5 mg/L at diagnosis was 39 (47.6%) and 43 patients (52.4%) with β2-M <2.5 mg/L. Patients with high serum β2-M level at diagnosis seemed to have more adverse clinical features: B symptoms (p=0.007) and elevated LDH level (p<0.001), and high KPI score (p=0.002). Serum β2-M ≥2.5 mg/L was significantly associated with poor overall survival (5-year OS, 35.2% vs 73.6%; p=0.001) and progression-free survival (5-year PFS, 27.5% vs 55.9%; p=0.028). For patients with early stage, serum β2-M at diagnosis could also help to distinguish those with favorable outcomes from those with poor outcomes. In multivariate analysis, high serum β2-M level remained its prognostic impact on survival (OS: p=0.002; PFS: p=0.039), independent of the International Prognostic Index score. Our study suggested high serum β2-M was a novel predictor of prognosis in patients with UNKTL. A simply and regular way might be established to identify UNKTL patients of different risks at diagnosis.

Comparison Of Immunonephelometric And Immunoturbidimetric Methods for Measuring Beta 2-Microglobulin: Fit for Purpose in Routine Clinical Laboratories

Serum free beta 2-microglobulin (b2M) level has been regarded as an independent biomarker in several cancers, and has traditionally been analyzed using methods such as Immunonephelometry on specialized analyzers. It is now possible to perform this test on clinical chemistry analyzers, using immunoturbidimetry. The aim of this study was to compare these two methods, for measuring serum b2M level. Fourty three samples which were randomly chosen from sera of patients with various malignant conditions were analyzed for serum b2M level, both by immunonephelometric method in Beckman Immage 800 (Beckman Coulter Inc., CA, USA) nephelometer, and by immunoturbidimetric method in Beckman UniCel DXC 800 Synchron (Beckman Coulter Inc., CA, USA) auto-analyzer. Method comparison demonstrated good agreement between the immunonephelometric and immunoturbidimetric b2M testing, in which we found good correlation (r=0.973) and high accuracy (slope=1.009). As a conclusion, Beckman UniCel DXC 800 Synchron immunoturbidimetric b2M assay is suitable for routine use, and correlates well with representative immunonephelometric assays on the Beckman Immage 800 analyzer. The ability to perform specific protein analyses such as b2M on an integrated clinical chemistry/immunoassay system, can allow consolidation of testing on a single platform and results in improved laboratory operations efficiency. It is thought that immunoturbidimetric method can be used safely in the routine screening of serum b2M level, for different types of malignancies

Serum β2—Microglobulin Levels in Patients with Various Solid Cancer

Background: The level of β2-M has become one of the most important prognostic factors and predictors of survival in patients with certain caner. The aim of this study was to investigate the serum levels of β2-M in patients with various solid cancers, to find the prognostic and predictive value of serum β2-M level elevating in patients with solid cancer. Methods: A total of 1158 serum from 774 patients with various solid cancer and 384 patients with various solid benign tumor patients were analyzed by β2-microglobulin ELISA kit, the data were analyzed by using statistical 36 packages for sciences (spss11.0) software. Results: In patients with thyroid cancer, patients with breast cancer and that with liver cancer the mean β2-microglobulin levels and positive rate were significantly higher than that in controls (p 0.05), and the positive rats were not significantly different compared with that in controls (p>0.05) except the patients with esophagus cancer in which the positive rate was significantly different compared with that in controls (p < 0.01). In female breast cancer patients the mean β2- microglobulin levels and the positive rate were significantly higher than that in breast benign tumor patients (p<0.05: p<0.05), no significant difference stages and clinical stages. In thyroid cancer patients the mean β2-microglobulin levels and the positive rate were significantly higher than that in thyroid benign tumor patients (p< 0.05, p< 0.01), no significant difference in sex, ages, clinical stages, but the mean β2-microglobulin levels and the positive rate were significantly higher in patients with follicular thyroid cancer than that in patients with mamillary thyroid 54 cancer patients. Conclusion: β2-M is an important tumor marker in breast, thyroid and liver cancer that would be one of assistantly diagnostic factors in patients with these cancers.

G-CSF therapy and catheter-related Gram-positive sepsis increase serum IL-2 receptor α level and may falsely suggest a relapse in children with soft tissue sarcomas unless serum beta2-microglobulin, lactate dehydrogenase and C-reactive protein levels are determined concomitantly

Many components of oncologic treatment increase serum sIL-2Rα level, which may falsely suggest a relapse. We tried to establish whether granulocyte colony stimulating factor (G-CSF) and central vein catheter (CVC)-related sepsis increase serum sIL-2Rα level to values on relapse of childhood soft tissue sarcomas (STS) and how to distinguish real relapse from a “false” one. Serum sIL-2Rα, B2-M, LDH, CRP and ESR levels and rates of markers’ elevated values were determined prospectively in 18 STS children: pre-treatmently (ST1), in complete remission (CR; ST2), in CR during G-CSF therapy (ST3), in CR during CVC-related sepsis (ST4), on relapse (ST5) and after treatment (ST6) and once in 50 healthy pediatric controls. It appeared that pre-treatment serum sIL-2Rα, LDH, CRP and ESR but not B2-M declined significantly with remission (ST2) achievement. At ST5 sIL-2Rα, B2-M, LDH and CRP increased from ST2 to ST1 values. SIL-2Rα levels at ST3 and ST4 rose significantly in all patients from ST2 to ST1 and ST5 values. At ST3 also serum LDH and B2-M increased to values at ST1 and ST5 and exceeded significantly those at ST2 and ST4. At ST4 CRP but not B2-M and LDH, rose significantly in most patients to values at ST1 and ST5. Thus, serum sIL-2Rα monitoring in pediatric STS reflects well response to chemotherapy unless samples are collected during G-CSF therapy or CVC-related sepsis. Determination of serum B2-M, LDH and CRP together with sIL-2Rα may help to distinguish between “real” relapse and “false” sIL-2Rα increase due to G-CSF administration or CVC-related sepsis.

294 Prognostic significance of beta 2 microglobulin in survival and transformation to acute myelogenous leukemia in patients with myelodysplastic syndrome

s of the 11th International Symposium on Myelodysplastic Syndromes (MDS) 18 May 2011 21 May 2011 S116 Posters / Leukemia Research 35 (2011) S27–S142 294 Prognostic significance of beta 2 microglobulin in survival and transformation to acute myelogenous leukemia in patients with myelodysplastic syndrome A. Galanopoulos, A. Aggelidis, D. Gogos, A. Megalakaki, I. Kotsianidis, M. Dimou, P. Panagiotidis, N. Zoumbos, N.I. Anagnostopoulos, M. Voulgarelis, H. Papadaki, A. Symeonidis. Clinical Hematology, G. Gennimatas General Hospital, Athens, Clinical Hematology, Metaxas Hospital, Piraeus, Clinical Hematology, Dimokritio University of Thraki, Alexandroupolis, Clinical Hematology, Laikon General Hospital/National and Kapodistrian University of Athens, Athens, Clinical Hematology, University of Patras, Medical School, Patras, Clinical Hematology, University of Crete School of Medicine, Heraklion, Greece Background: Beta 2 microglobulin (b2M) is a 12 kDa light chain protein that binds to the a chain of class I MHC (MHC1) molecule. Serum b2M levels are known to reflect renal function and membrane turnover, which is associated with tumor mass and growth rate. Elevated serum levels of b2M are reported to predict poor survival in several hematologic malignancies. Purpose: To investigate the prognostic relevance of b2M with regard to survival and the risk of transformation into acute myelogenous leukemia (AML) in patients with myelodysplastic syndrome (MDS). Material and Methods: We evaluated serum b2M levels in 407 MDS patients from the Hellenic MDS Study Group. From these 152 patients were excluded from further analysis for various reasons such as serum creatinine levels greater than 1.5mg/dl, treatment with intensive therapy and blood stem cell transplantation or insufficient data. B2M and karyotype were recorded along with other hematologic, biochemical and clinical covariates. Serum b2M levels were quantified by a radioimmunoassay. The log rank test was used to compare overall survival and AML transformation. Multivariate analysis was conducted utilizing the Cox proportional hazards regression model with a stepwise backward selection. Results: Thirty patients had refractory anemia (RA), 64 refractroy anemia with excess of blasts-1(RAEB-1), 34 refractory anemia-2 (RAEB-2), 24 refractory anemia with ringed sideroblasts (RARS), 69 refractory cytopenia with multilineage dysplasia (RCMD), 13 refractory cytopenia with multilineage dysplasia with ringed sideroblasts (RCMD-RS) and 11 5q− syndrome. The median value for b2M was 2.67(±1.53). The univariate analysis revealed that patients with b2M below 3mg/dl had a higher overall survival compared to patients with b2M above 3mg/dl (log-rank=7.42; p = 0.006). Other factors that exerted a statistically significant effect on overall survival were the medullary blasts (log-rank =13.5; p 15%. MDS with del(5q) was identified in 135 (6.6%) of the cases, RARS-T in 76 patients (3.7%). There were 122 (6%) cases with MDS unclassifiable, including 95 (4.7%) with 1% peripheral blasts, 26 (1.3%) with pancytopenia, and only one patient without signs of dysplasia despite chromosomal abnormalities. Survival data (months) and AML progression rates (%) at 2 and 5 years are shown in the tables. Types with unilineage Dysplasia WHO 2008 Hb g/dl PLT/ nl ANC/ ml Abnormal karyotype in % Complex karyotype in % IPSS low/ int 1/int 2 median survival in month AML progression in % after 2 years AML progression in % after 5 years RCUDbi 10.3 116 2000 50 19 30/57/13 64 9 14 RA 8.5 248 3900 40 14 91/9/0 48 2 2 RT 11.7 56 2650 57 0 80/20/0 not reached 0 11 RN 11.9 137 1300 8 0 92/8/0 141 10 10 RARS 9.5 267 3150 28 6 73/24/2 63 4 4 MDS-U-PAN 8.5 44 750 33 0 0/100/0 30 0 18 Types with multilineage Dysplasia WHO 2008 HB g/dl PLT/ nl ANC/ ml Abnormal karyotype in % Complex karyotype in % IPSS low/ int 1/ int 2 median survival in month AML progression in % after 2 years AML progression in % after 5 years RCMD 9.3 134 2030 49 19 40/51/9 36 11 17 RCMD-RS 8.8 185 2200 55 24 45/41/14 31 10 17 RARS-T 9.1 584 4750 41 18 67/33/0 55 3 8 MDS del (5q) 9.3 255 2300 100 0 73/27/0 91 4 14 MDS-U-PB 9.4 118 2300 47 20 41/52/7 35 10 13 Conclusions: 1. While RCUD carries a relatively good prognosis, pancytopenic patients (MDS-U-Pan) have a shorter survival, similar to RCMD. The separation of MDS-U-Pan therefore seems to be is justified. 2. RCUD with bicytopenia accounts for a considerable fraction (52.3%) of RCUD. The prognosis of RCUDbi is intermediate between RCUD with unilineage cytopenia and MDS-U-Pan. 3. The prognostic impact of blast cells in the peripheral blood is similar to that of pancytopenia. 4. Survival rates are not substantially different for RCMD and RCMDRS. 5. RARS-T and MDS with del5q usually present with multilineage dysplasia. From a prognostic point of view, they are similar to RCUD, but their specific pathogenetic features justify their existence as distinct subtypes in the WHO classification.

Beta-2 microglobulin as an immunological marker to assess the progression of human immunodeficiency virus infected patients on highly active antiretroviral therapy

BackgroundAcquired immune deficiency syndrome (AIDS) defines the end stage of Human immunodeficiency viral (HIV) infection before the introduction of highly active antiretroviral therapy (HAART). This study was carried out to assess the serum β-2 microglobulin (B2M) as a marker for progression of HIV infected patients undergoing HAART. MethodsBlood samples were collected from 50 subjects of HIV infected patients residing at semi urban area undergoing treatment at Chellam Hospital, Salem, India. Twenty five age-matched healthy subjects were taken as control group. Serum B2M level was measured by using enzyme immunoassay, absolute CD4 and CD8 counts were carried out by single platform (SP) technology using a flow cytometer. Viral RNA was measured by real time PCR. The serum LDH level and total WBC count were also measured. ResultsOur result showed a statistically high significant increase in B2M in HIV patients on HAART non complaint group whereas absolute CD4, CD8 count, CD4/CD8 ratio and WBC count were decreased significantly when compared to control and HAART complaint group. Statistically a significant negative correlation was observed between B2M and absolute CD4, CD8 count, CD4/CD8 ratio and WBC count. B2M showed a significantly positive correlation with viral RNA and LDH values. ConclusionsThe increase of B2M and reduced absolute CD4, CD8 count, CD4/CD8 ratio and WBC count in HIV patients on HAART non complaint group may have a contributory role in the immune progression of HIV with interruption of HAART. B2M plays an important role in the diagnosis of HIV and might indicate HIV progression.

The Impact of β2-Microglobulin Clearance on the Risk Factors of Cardiovascular Disease in Hemodialysis Patients

beta2-Microglobulin (beta2M) is an independent predictor of outcome for hemodialysis (HD) patients and a representative substance of middle molecules. We tested the relationship among serum beta2M levels and cardiovascular disease (CVD) risk factors in HD patients. A total of 132 HD patients were divided according to the dialysis membrane used [property; cellulose and synthetic or beta2M clearance; low filtration (LF), middle filtration (MF), and high filtration (HF)]. There was no significant difference in CVD risk factors between cellulose and synthetic groups. On the other hand, serum beta2M, highly-sensitive C-reactive protein (hCRP), troponin-T (TnT), and myeloperoxidase (MPO) levels of LF were significantly higher and those of prealbumin (PA) were lower than the MF and HF. Serum beta2M level was positively correlated with hCRP, interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), MPO, TnT, N-terminal pro-B-type natriuretic peptide (NT-proBNP) and inversely correlated with PA and ankle-brachial index (ABI). There was a significant correlation between serum beta2M levels and various CVD risk factors in HD. Cardiovascular disease risk factors in HD patients were dependent on the beta2M clearance but not membrane property.

Combination of Bortezomib and Dexamethasone (VD) or Bortezomib, Adriamycine and Dexamethasone (PAD) Followed by High Dose Therapy and Peripheral Blood Stem Cell Transplantation in First-Line Treatment of T(4;14) Multiple Myeloma : a Prospective Study of the MAG Group.

Abstract 3408Poster Board III-296The t(4;14)(p16.3;q32), leading to the ectopic expression of two potential oncogenes, the Multiple Myeloma Set Gene (MMSET) and the Fibroblast Growth Factor 3 (FGFR3), is found in 15% of patients with multiple myeloma (MM) and is associated with a very poor prognosis. We previously shown in patients under 65 years of age that High Dose Therapy followed by Peripheral Blood Stem Cell Transplantation (HDT-PBSCT) provides a high response rate (RR) but a very short median relapse-free survival of only 11 months. In addition, relapses are often aggressive and chemoresistant. Thus, more effective regimen is urgently needed. We prospectively studied 23 t(4;14) MM patients treated with 3 or 4 cycles of a combination of Bortezomib and Dexamethasone (VD) (n=4) or of Bortezomib, Adriamycine and Dexamethasone (PAD) (n=19) as induction treatment before HDT-PBSCT (Melphalan 200 mg/m2). T(4;14) was detected using real time quantitative PCR searching for IGH/MMSET and FGFR3 transcripts. RR, event-free survival (EFS) and overall survival (OS) were evaluated. Median age at diagnosis was 51 years (range, 33-64). Isotype was IgA in 12 (52%) patients. All patients had stage II or III MM. An elevated serum β2m level (>3.5 mg/L) was found in 14 (61%) patients, and a low haemoglobin (Hb) level (<10 g/dL) in 10. Four presented with renal failure and 5 with hypercalcemia. Three (16%) of 19 patients had a t(4;14) without expression of FGFR3. After induction treatment with VD or PAD, PBSC were successfully harvested with granulocyte-colony stimulating factor only (n=15) or following a cycle of high-dose cyclophosphamide (n= 7). RR after induction treatment was complete response (CR) in 6 (26%) patients, very good partial response (VGPR) in 9 (39%), partial response (PR) in 3. Five patients had refractory or progressive disease (PD), including 1 who died before stem cell mobilization. RR after HDT was CR in 11 (48%), VGPR in 4 (17%) and PR in 4 (overall RR of 82%). Three had PD. With a median follow-up of 18 months (range, 3-32), 9 (39%) patients are alive without relapse, including 4 with a 19, 27, 30 and 32 months follow-up respectively. Twelve (52%) patients relapsed. Two patients died in the first month post HDT from PD. We found a median EFS and OS from initiation of therapy of 14.7 and 30.9 months respectively. EFS was not influenced by Hb and/or serum β2m level. However, we found a significantly longer OS in patients with low β2m (median non reached) as compared to patients with high β2m (median=23.1 months, p=0.04). These preliminary results illustrate the heterogeneity of this disease and indicate that some t(4;14) MM patients seem to benefit from bortezomib containing regimen as induction treatment before HDT in term of EFS and OS. A larger series with a longer median time of follow up will be presented. Disclosures:No relevant conflicts of interest to declare.

Prognostic Significance of Beta-2 Microglobulin (B2M) in Adult Acute Lymphoblastic Leukemia (ALL).

Abstract 4679▪▪This icon denotes an abstract that is clinically relevant.Beta-2 microglobulin (B2M) is 12-kDa light chain protein that binds to the alpha chain of class 1 MHC molecules, dissociated into extracellular fluids after degradation of HLA. Elevated levels of serum B2M have historically been associated with a poor prognosis in several lymphoproliferative disorders. The prognostic relevance of B2M in myeloid disorders such as acute myelogenous leukemia and myelodysplastic syndrome has also been noted, in some cases providing further refinement of existing prognostic models. The significance of pretreatment serum B2M levels has not been extensively studied in adult ALL. In our historical experience with the conventional VAD (vincristine, doxorubicin, dexamethasone) regimen, elevated levels of B2M were associated with a lower complete remission (CR) rate, worse survival (OS), and higher propensity for development of CNS leukemia, after adjusting for renal dysfunction and older age [Kantarjian, Am J Med 93:599, 1992]. The analysis was somewhat limited by the strong negative impact of the mature B-cell ALL subset were the significantly high levels of B2M were associated with poor prognosis in the era prior to intensive multi-agent chemotherapy regimens. We assessed the associations of pretreatment B2M levels with outcome in 320 adolescents and adults with de novo ALL (Burkitt leukemia/lymphoma, Philadelphia chromosome positive ALL, and lymphoblastic lymphoma subtypes were excluded from the analysis) treated with the more intensive hyper-CVAD regimen (fractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone alternating with methotrexate and cytarabine) and its variants (modified hyper-CVAD with or without anthracycline intensification and with or without rituximab). Median serum B2M level was 3 mg/L (range 0-14.7). As observed previously, the CR rate was lower for patients (pts) with elevated levels of B2M, an effect which persisted after excluding the elderly subset and accounting for renal dysfunction (93% versus 98%, p=.02). The 3-yr rates for CRD and OS were also worse if B2M was elevated above the median, 55% vs 70% (p=0.09) and 60% vs 70% (p=.01), respectively. These findings confirm the prior observations in a larger more homogenous population of de novo ALL treated with intensive chemotherapy. A limited multivariate analysis identified the independent prognostic influence of B2M on survival. Additional analyses will be conducted to determine how these observations can be best incorporated into clinical practice. Disclosures:No relevant conflicts of interest to declare.