Serum Β2-microglobulin Levels Research Articles

The Relative Risk of Prognostic Factors of Age Stratified Multiple Myeloma

Background: Age is a pivotal prognostic factor for multiple myeloma (MM). The risk of evolving from MGUS and SMM to symptomatic MM steadily increases with age. And there are nuances in clinical manifestations and cytogenetic characteristics between young and old patients. The aim of this study is to delineate the clinical and laboratory features and determine the relative contribution of ISS, performance status and cytogenetic abnormalities in each age MM patients. Methods: In this study, 778 MM patients were enrolled in the prospective, non-randomized BDH2008/02 clinical trial between January, 2008 and December, 2016. Briefly, the patients accepted bortezomib or thalidomide-based induction therapy. Transplantation eligible patients accepted ASCT, otherwise they accepted the original regimen consolidation therapy. Subsequently, unless intolerance, patients received either thalidomide-based or lenalidomide-based maintenance therapy for two years. Conventional FISH panel included del(13q), del(17p), gain(1q), t(11;14), t(4;14), t(14;16), and t(14;20). The positive cut-off value for chromosome deletion or gain was 20%, and for chromosome translocation was 10%. A multivariate Cox proportional-hazards model was developed to assess the variables with significant effects on PFS and OS. Explained variation of variables was quantified by RD2. Statistical analysis was conducted by Stata/MP 16.0 (Stata Corp., TX, USA) and SPSS 26.0 (IBM Corp., Chicago, Illinois, USA). Results: Among 778 patients with complete data, 59.5% (463/778) were younger than 60 years old, 31.4% (244/778) were 61-70 years old, and only 9.1% (71/778) were over 71 years old. The median PFS of patients≤60, 61-70 and ≥71 years of age was 36.3, 32.6 and 23.1 months, respectively (P<0.001). The median OS in each age group was 86.2, 60.7 and 34.9 months, respectively (P<0.001) (Figure A-D). The median evaluated glomerular filtration rate of the three groups was 89.1, 74.0 and 66.4 ml/min (P<0.001), respectively. The serum β2-microglobulin level gradually increased with age (P<0.001), along with the proportion of patients with ISS 3 stage. Patients ≥71 years old had a higher proportion of ECOG performance status score 3-4, twice than that of patients ≤60 years old. The incidence of high-risk IgH translocation decreased with age, and was 25.4%, 21.3% and 14.3% across age groups. The incidence of gain(1q) increased with age, and was 43.9%, 47.1% and 54.8%, respectively. The incidence of del(17p) and del(13q) seldom changed with age (Figure E). With age, the risk of high-risk cytogenetic abnormalities did not change significantly, accounting for about 50% in each age group. The risk of ISS gradually decreased, accounting for 36%, 27%, and 14% in ≤60, 61-70 and ≥71 year subgroups, respectively. The risk of the ECOG performance status gradually increased with age, accounting for 10%, 17%, and 36% in the three subgroups (Figure F). The overall response rate of induction treatment gradually decreased with age, and were 90.2%, 81.9%, and 69.2%, respectively (P<0.001). Elderly patients with impaired renal function or more than one high-risk cytogenetic abnormalities might benefit more from bortezomib based treatment than younger patients (Figure G). Conclusion: Age is an important prognostic factor in MM. With age, the risk of MM progression or death steadily grows. Cytogenetic abnormalities are equally important in every age group. The risk of poor performance status increases in elderly patients with a reduction risk in ISS. Elderly patients should focus on the status of frailty and molecular events to determine treatment. Figure Disclosures No relevant conflicts of interest to declare.

Hypercalcemia caused by humoral effects and bone damage indicate poor outcomes in newly diagnosed multiple myeloma patients.

BackgroundHypercalcemia of malignancy (HCM) is a serious metabolic complication, and the highest rates are in multiple myeloma (MM). The cause of hypercalcemia in newly diagnosed multiple myeloma (NDMM) remains unknown. We sought to evaluate the prognostic impact and mechanism of hypercalcemia in patients with symptomatic NDMM.MethodsWe studied all consecutive MM patients who were initially diagnosed and followed up at Beijing Jishuitan Hospital between February 2013 and December 2019; 357 patients were included in the retrospective analysis.ResultsA total of 16.8% of MM patients presented with hypercalcemia at the time of MM diagnosis. The presence of hypercalcemia was associated with higher serum levels of β2 microglobulin, creatinine, phosphorus, uric acid, procollagen I N‐terminal peptide, β‐carboxy‐terminal cross‐linking telopeptide of type I collagen and osteocalcin, lower serum levels of hemoglobin, parathyroid hormone (PTH), and advanced ISS and R‐ISS stages. Multivariate analysis showed that serum PTH, hemoglobin, creatinine, and uric acid levels were the main factors affecting hypercalcemia. The presence of hypercalcemia was associated with significantly inferior survival (40 months vs 57 months, p < 0.05) based on univariate analysis, and it remained an independent poor prognostic factor (HR: 1.854, 95% CI: 1.006‐3.415, adjusted p = 0.048) in a multivariate model that included age and R‐ISS stage.ConclusionThis study shows that hypercalcemia is associated with poor survival and is caused by manifold factors with humoral effects and local bone destruction.

Saponins from Panax japonicus ameliorate age-related renal fibrosis by inhibition of inflammation mediated by NF-κB and TGF-β1/Smad signaling and suppression of oxidative stress via activation of Nrf2-ARE signaling

BackgroundThe decreased renal function is known to be associated with biological aging, of which the main pathological features are chronic inflammation and renal interstitial fibrosis. In previous studies, we reported that total saponins from Panax japonicus (SPJs) can availably protect acute myocardial ischemia. We proposed that SPJs might have similar protective effects for aging-associated renal interstitial fibrosis. Thus, in the present study, we evaluated the overall effect of SPJs on renal fibrosis. MethodsSprague-Dawley (SD) aging rats were given SPJs by gavage beginning from 18 months old, at 10 mg/kg/d and 60 mg/kg/d, up to 24 months old. After the experiment, changes in morphology, function and fibrosis of their kidneys were detected. The levels of serum uric acid (UA), β2-microglobulin (β2-MG) and cystatin C (Cys C) were assayed with ELISA kits. The levels of extracellular matrix (ECM), matrix metalloproteinases (MMPs), tissue inhibitors of metalloproteinases (TIMPs), inflammatory factors and changes of oxidative stress parameters were examined. ResultsAfter SPJs treatment, SD rats showed significantly histopathological changes in kidneys accompanied by decreased renal fibrosis and increased renal function; As compared with those in 3-month group, the levels of serum UA, Cys C and β2-MG in 24-month group were significantly increased (p < 0.05). Compared with those in the 24-month group, the levels of serum UA, Cys C and β2-MG in the SPJ-H group were significantly decreased. While ECM was reduced and the levels of MMP-2 and MMP-9 were increased, the levels of TIMP-1, TIMP-2 and transforming growth factor-β1 (TGF-β1)/Smad signaling were decreased; the expression level of phosphorylated nuclear factor kappa-B (NF-κB) was down-regulated with reduced inflammatory factors; meanwhile, the expression of nuclear factor erythroid 2-related factor 2-antioxidant response element (Nrf2-ARE) signaling was aggrandized. ConclusionThese results suggest that SPJs treatment can improve age-associated renal fibrosis by inhibiting TGF-β1/Smad, NFκB signaling pathways and activating Nrf2-ARE signaling pathways and that SPJs can be a potentially valuable anti-renal fibrosis drug.

Global Dialysis Perspective: Vietnam.

Vietnam is one of the most populated Southeast Asian countries, with a population of around 97 million people in 2018 (1). Three kinds of RRT, including hemodialysis (HD), peritoneal dialysis (PD), and kidney transplantation, are currently available in Vietnam; they service a total of about 36,000 patients, but this only accounts for about one third of the estimated ESKD population in need of dialysis across the country. The purpose of this article is to give a broad overview of some key aspects of RRT and nephrology in Vietnam. HD has been available in Vietnam since 1968. Initially, it was only used to treat acute kidney failure. During that period, only the Travenol Drake-Willock machine was used. Starting from 1996, with the initiation of the national insurance reimbursement system, a remarkable development in dialysis was seen throughout the country, with the number of patients on maintenance hemodialysis (MHD) steeply increasing. MHD has become the most common type of dialysis and has been available in many Vietnamese cities and provinces since then (2). Although little is known about the actual number of patients with ESKD in need of dialysis in the general population, it is estimated to be >100,000 persons. However, only about one third of them (approximately 30,000 patients) are actually on MHD all over the country. Although this proportion is still very low compared with the estimated demand, all dialysis facilities are frequently overwhelmed and have to operate up to four 4-hour shifts per day; home dialysis is not available yet in Vietnam. All dialyzers are capillary type, mainly low flux, and they are reused six times in total to compensate for the low reimbursement of only $25 per session. We import all dialysis machines and dialyzers from various foreign brands, such as Nipro (Japan), B. Braun, and Fresenius (Germany), …

Real-world data on the survival outcome of patients with newly diagnosed Waldenström macroglobulinemia.

Background/AimsWaldenström macroglobulinemia (WM) is a rare lymphoproliferative disorder that usually follows an indolent clinical course. However, some patients show an aggressive clinical course leading to death. We explored the risk factors predicting poor prognosis in WM patients.MethodsWe retrospectively analyzed 47 patients diagnosed with WM between 2000 and 2018 to explore risk factors predicting poor prognosis using various clinical and laboratory parameters and risk models including the International Prognostic Staging System for WM (IPSS-WM).ResultsOver a median follow-up duration of 80.4 months, 29 patients died. The main causes of death were disease progression, organ failure related to amyloidosis, and infection. The median overall survival (OS) was 55.1 months, and 14 patients, including three with amyloidosis, died within 2 years. Serum β2-microglobulin level higher than 4 mg/dL was significantly associated with poor OS. Accordingly, the IPSS-WM showed a significant association with poor prognosis compared with other risk models, and the low-risk group had better OS than intermediate- and high-risk groups. In the retrospective analysis using the results of targeted sequencing in two cases representing good and bad prognosis, different patterns of mutation profiles were observed, including mutations of MYD88, TP53, ARID1A, and JAK2 in a refractory case.ConclusionsSerum β2-microglobulin could be a single biomarker strongly predictive of poor survival of WM patients, and the low-risk group of the IPSS-WM risk model including serum β2-microglobulin has better prognostic value than other risk models. Mutation analysis also might provide additional information to predict high-risk patients.

Β2-Microglobulin Post Kidney Transplantation as A Predictor of Subsequent Kidney Allograph Dysfunction

Background: Long-term outcome in renal transplantation is heterogeneous, and predicting success is challenging. Serum β2-microglobulin (β2MG), a novel marker of kidney function, predicts mortality and kidney failure in the general population, and its elevation following transplantation is a marker of acute rejection. Objective: To determine whether serum beta-2-micro-globulin one three-year post-transplant period could predict the decline in GFR over a follow-up period of six months. Patients and methods: This study was carried out at the National Institute of Nephrology and Urology, Cairo, Egypt. The patients were subjected to different demographic, clinical, biochemical, ultrasonographic, and endoscopic findings. In this study, 42 primary kidney transplant recipients were included. Results: The results showed a significant increase in serum β2-microglobulin level between renal transplant recipients with unstable kidney functions in comparison to renal transplant recipients with stable kidney function. The results showed serum β2-microglobulin level could be a good predictor of renal graft outcomes. Measurements of serum levels of beta 2 micro-globulin could be more sensitive and more specific than serum creatinine as renal function tests for early prediction of graft dysfunction. Conclusion: In this study, we found an association between serum level of β2MG in the late post-transplant period and a subsequent decline in kidney allograft function within a short time-frame. The overall results show that a higher serum level of β2MG after a single measurement at different intervals of the late post-transplant period independently predicts the lower eGFR. Thus, higher serum β2MG is a risk factor for graft function, particularly with longer follow-up.

Clinical characteristics and outcomes of patients with diffuse large B cell lymphoma treated with R-CHOP-like or CHOP-like regimens: an 8-year experience from a single center.

The CHOP regimen comprising cyclophosphamide, doxorubicin, vincristine, and prednisone is a basic chemotherapeutic regimen for diffuse large B cell lymphoma (DLBCL). Addition of rituximab (R) to chemotherapy has led to better efficacy than other regimens in clinical trials. However, data of clinical characteristics and outcomes of patients with DLBCL are scarce. Therefore, this study reports the clinical characteristics, treatment, and outcomes of patients with DLBCL in our hospital. We conducted a retrospective analysis of newly diagnosed DLBCL patients treated with CHOP-like or R-CHOP-like regimens at our hospital between 2011 and 2018. We analyzed the data on demography, clinical characteristics, treatment, treatment response, and survival time. Both univariate and multivariate analyses were applied. In total, 570 newly diagnosed DLBCL patients were included, of which 133 were treated with CHOP-like regimens and 437 with R-CHOP-like regimens. The overall response rate was 83.3%. Germinal center B-cell-like (GCB) subtype, R-CHOP-like treatment, Ann Arbor stage I-II, not more than 1 extranodal disease site, Eastern Cooperative Oncology Group (ECOG) score ≤1, normal serum lactate dehydrogenase (LDH) level, normal serum β2 microglobulin (β2-MG) level, absence of B symptoms, and lower International Prognostic Index (IPI) or National Comprehensive Cancer Network-International Prognostic Index (NCCN-IPI) scores were associated with longer overall survival (OS) and progressionfree survival (PFS), and were favorable prognostic factors for OS and PFS. Only GCB subtype, R-CHOPlike treatment, absence of B symptoms, and lower IPI or NCCN-IPI scores were independent favorable prognostic factors for OS and/or PFS. Neither IPI nor NCCN-IPI could accurately and precisely predict the prognosis of high-risk DLBCL patients. This analysis of newly diagnosed DLBCL patients indicates that patients treated with R-CHOP-like regimens or with GCB subtype exhibited better outcomes. Further, IPI and NCCN-IPI have limited prognostic values in high-risk DLBCL patients.

P1228IMPROVEMENT OF BODY WEIGHT MANAGEMENT, BETA2-MICROGLOBULIN LEVEL AND RESISTANCE TO ERYTHROPOIESIS-STIMULATING AGENTS BY HYBRID PERITONEAL DIALYSIS PLUS HEMODIALYSIS THERAPY

Abstract Background and Aims Peritoneal dialysis (PD) has the advantages of not causing rapid changes in the body fluid levels or solute contents in the blood due to the continuous treatment on all days of the week, and of not needing the patients to visit the hospital 3 times a week or lie on a bed for 4 hours to receive treatment. PD alone can, however, not adequately remove all the uremic toxins and excess water, and the patients are likely to be resistant to erythropoiesis-stimulating agents (ESA). These drawbacks could be potentially improved if PD and hemodialysis (HD) were used together. The aims of the present study were to clarify the changes in the body weight, serum β2-microglobulin (β2MG) level, and resistance to ESA in PD patients switched from PD alone to PD-HD hybrid therapy (hybrid therapy). Methods The data of seven patients who were switched from PD alone to PD-HD hybrid therapy at our hospital were retrospectively analyzed to determine the changes in the body weight, serum β2MG level, dose of ESA (Darbepoetin Alfa) and the hemoglobin level before and at 3 months after the switch to hybrid therapy; in hybrid therapy, the patient received HD once a week and did not receive PD on that day. We also carried out a questionnaire survey to determine the changes in the feeling of well-being and quality of life of the patients after the switch to hybrid therapy. Results and Discussion The body weight decreased significantly from 67.4 ± 11.8 kg to 63.7 ± 8.7kg (p = 0.0345) after the switch from PD alone to PD-HD hybrid therapy, indicating that the control of the body fluids was much easier with hybrid therapy than with PD alone. The mean serum β2MG level in the patients decreased from 37.3 ± 11.6 μg/mL to 32.6 ± 5.9 μg/mL (p = 0.1607, not significant), ; in particular, in those patients in whom the serum β2MG levels were over 30 μg/mL, the level decreased significantly from 42.5 ± 8.7 μg / mL to 34.4 ± 6.1 μg / mL (p = 0.0337). The dose of ESA decreased significantly in all patients from 193 ± 74 μg/month to 69 ± 38 μg/month (p = 0.006), while the hemoglobin level remained unchanged (from 10.2 ± 1.7 g/dL to 11.2 ± 1.2 g/dL, p = 0.1406). In the questionnaire survey, almost all the patients expressed positive feelings about the switch of the treatment modality, such as “it became easier to go up the stairs,” “improved working efficiency,” and “comfortable feeling.” Since the peritoneum was allowed to rest once in a week, on the day of the HD, it could also preserve peritoneal functions. Therefore, hybrid therapy was also considered to be effective from the viewpoint of performing PD over the long term. Conclusion We can expect easier management of the body fluid, efficient β2MG removal, and improvement of ESA resistance by switching the dialysis treatment modality from PD alone to HD-PD hybrid therapy.

Tumor load in patients with multiple myeloma: β₂-microglobulin levels versus low-dose whole-body CT.

Beta-2-microglobulin is a serum marker of tumor burden in multiple myeloma (MM). Our aim was to correlate serum β₂-microglobulin levels in patients with MM to tumor burden determined by low-dose whole-body CT (LDWBCT). A total of 52 patients with newly diagnosed, untreated MM who underwent LDWBCT were included. LDWBCT scans were assessed by two musculoskeletal radiologists in consensus for focal lesions. The Durie and Salmon PLUS staging system was used for staging patients in stages I-III. β₂-microglobulin was also subdivided into stages I-III on the basis of the multiple myeloma International Staging System (ISS). Using the Durie and Salmon PLUS staging system criteria for image evaluation, we were able to identify stage I MM in 17 patients, stage II MM in nine patients, and stage III MM in 26 patients. Eight of nine patients with stage II MM and 16 of 26 patients with stage III MM had normal β₂-microglobulin levels. Thus, 24 of 35 patients (68.6%) had 5 or more focal lesions and false-negative β₂-microglobulin levels. Serum β₂-microglobulin levels alone may not indicate the full extent of tumor burden in a significant subset of myeloma patients.

Immunological microenvironment gene expression in patients with diffuse large B cell non Hodgkin lymphoma

BackgroundNon Hodgkin lymphoma (NHL) is one of the immune system cancers. The occurrence and progression of malignant lymphomas depends on cellular pathways deregulation. Understanding the relationship between the immune system at the genetic level and malignant transformation is critical to reach its etiology. ObjectiveThe aim of this work is to evaluate the expression of five immune related genes (PD-1, FOXP3, GrA, GrB and CD11c) in patients with diffuse large B cell non Hodgkin lymphoma (DLBCL). Materials and methodsThis study was conducted on fifty patients with DLBCL and fifty sex and age matched apparently healthy subjects. The participants were subjected to these laboratory investigations: complete blood count, serum lactate dehydrogenase and β2microglobulin (β2M) levels and determination of PD-1, FOXP3, GrA, GrB and CD11c gene expressions. ResultsThe results of this study revealed that PD-1, FOXP3, GrA, GrB and CD11c gene expressions were significantly increased in DLBCL patients. ConclusionPatients with DLBCL have variablePD-1, FOXP3,GrA, GrB and CD11cgene expressions levels, which are correlated with the overall survival (OS) indicating that they can be good predictors of outcome in these patients.

CXCR4 mutational status does not impact outcomes in patients with Waldenström macroglobulinemia treated with proteasome inhibitors.

CXCR4 mutational status does not impact outcomes in patients with Waldenström macroglobulinemia treated with proteasome inhibitors.

Prognostic factors of patients with mycosis fungoides.

IntroductionMycosis fungoides (MF) is the most common type of primary cutaneous T-cell lymphoma. Prognostic factors may help to evaluate the course of the disease and may also be useful in selecting appropriate treatment plans for patients.AimTo investigate the potential prognostic factors of MF and their correlations with MF stage.Material and methodsWe evaluated the records of patients with MF who were followed in our lymphoma clinic between 1998 and 2015. Age, sex, disease stage, peripheral blood eosinophilia, eosinophil cationic protein, serum total IgE, lactate dehydrogenase (LDH), and β2-microglobulin levels were investigated and recorded at the time of diagnosis.ResultsThere was a statistically significant positive correlation between high β2-microglobulin levels and the advanced stage of disease (p < 0.001). The older group of patients had statistically significantly higher levels of β2-microglobulin compared to the younger group (p = 0.001). We found strong, significantly positive correlations between disease stage and β2-microglobulin, LDH, and total IgE levels (p < 0.001, rho = 0.335; p = 0.001, r = 0.302; p = 0.001, r = 0.311, respectively). Additionally, there were significantly positive correlations between LDH levels and β2-microglobulin, total IgE levels (p < 0.001, rho = 0.484; p = 0.001, r = 0.212, respectively). Study limitations: A limited number of patients and the retrospective nature of the study.ConclusionsWe found that β2-microglobulin was a significant prognostic factor in our study population of MF patients. Also, elevated LDH, β2-microglobulin, and total IgE levels were correlated with advanced disease. Thus, these parameters can be used together to identify patients who have progressed to the later stages of the disease and who require more aggressive treatment.

Multiple myeloma with 1q21 amplification is highly sensitive to MCL-1 targeting

AbstractProsurvival BCL-2 family proteins are potent inhibitors of apoptosis and often overexpressed in lymphoid malignancies. In multiple myeloma (MM), MCL-1 expression contributes to survival of malignant plasma cells, and overexpression correlates with poor prognosis. In this study, we investigated whether sensitivity to the novel MCL-1 inhibitor S63845 could be predicted using cytogenetics, focusing on amplification of 1q21, the chromosomal region that contains the MCL1 locus. In addition, we studied the relation of MCL-1 inhibitor sensitivity with other diagnostic characteristics and BCL-2 family protein expression. In 31 human myeloma cell lines and in bone marrow aspirates from 47 newly diagnosed MM patients, we measured the effect of S63845 alone, or combined with BCL-2 inhibitor ABT-199 (venetoclax), and BCL-XL inhibitor A-1155463 or A-1331852 on cell viability. We demonstrated for the first time that MM cells from patients with 1q21 amplification are significantly more sensitive to inhibition of MCL-1. We suggest that this increased sensitivity results from high relative MCL1 expression resulting from amplification of 1q21. Additionally, and partially independent from 1q21 status, high serum β2 microglobulin level and presence of renal insufficiency correlated with increased sensitivity to MCL-1 inhibitor treatment. Combining S63845 with other BH3 mimetics synergistically enhanced apoptosis compared with single inhibitors, and sensitivity to inhibitor combinations was found in a large proportion of MM insensitive to MCL-1 inhibition alone. Collectively, our data indicate that amplification of 1q21 identifies an MM subset highly sensitive to MCL-1 inhibitor treatment and can be used as a predictive marker to guide selection of therapy.

CXCR4 Mutational Status Does Not Impact Outcomes in Patients with Waldenstrom Macroglobulinemia Treated with Proteasome Inhibitors

Introduction: Approximately 40% of patients with Waldenström macroglobulinemia (WM) have an activating somatic mutation in CXCR4, including both nonsense and frameshift variants. There are limited data on the impact of CXCR4 mutations on the outcomes to therapy in WM patients. Mounting evidence suggests that CXCR4 mutations adversely affect depth of response and progression-free survival (PFS) to ibrutinib in patients with WM. Methods: We performed a pooled analysis evaluating the impact of CXCR4 mutations and CXCR4 mutation subtypes on response, PFS and survival after frontline treatment initiation (SAFTI) on 76 WM patients who received proteasome inhibitor-based primary therapy. All patients were participants on three prospective clinical trials evaluating the combinations of bortezomib, dexamethasone and rituximab (BDR; ClinicalTrials.Gov ID NCT00250926), carfilzomib, dexamethasone and rituximab (CaRD; ClinicalTrials.Gov ID NCT01470196), and ixazomib, dexamethasone and rituximab (IDR; ClinicalTrials.Gov ID NCT02400437) in previously untreated patients with WM, and were treated at the Bing Center for WM. All patients met criteria for a clinicopathological diagnosis of WM and for treatment initiation, according to the guidelines established by the 2nd International Workshop for WM (IWWM). CXCR4 mutations were divided in nonsense and frameshift mutations, as previously described. Response to therapy was assessed using response criteria by the 3rdIWWM. We fitted univariate and multivariate logistic regression and proportional-hazard Cox regression models for major response and PFS and SAFTI, respectively. P-values &lt;0.05 were considered statistically significant. Results: A total of 76 patients were included in this analysis, of which 19 (25%) received BDR, 31 (41%) received CaRD and 26 (34%) received IDR. Thirty-six patients (55%) did not have CXCR4 mutations and 29 (45%) had a CXCR4 mutation, of which 16 had nonsenseand 13 had frameshift CXCR4 mutations. In 11 patients, the CXCR4 mutational status was not determined. The median age at treatment initiation was 63 years (range 46-83 years), median hemoglobin level was 10.3 g/dl (range 6.9-17.1 g/dl), median platelet count was 245 K/uL (range 68-584 K/uL), median serum IgM level was 4,048 mg/dl (range 345-9,550 mg/dl), median serum β2-microglobulin level was 3.5 mg/l (range 1.0-10.8 mg/l), serum albumin was 3.7 g/dl (range 2.4-4.8 g/dl) and median bone marrow involvement was 55% (range 5-95%). There was a higher proportion of serum IgM levels ≥4,000 mg/dl (62% vs. 39%) and lower proportion of serum albumin levels ≤3.5 g/dl (21% vs. 47%) in patients with than in patients without CXCR4 mutations. Our study showed no detectable differences in major response rate at 6 months (OR 0.77, 95% CI 0.27-2.22; p=0.63) and 12 months (OR 0.76, 95% CI 0.18-3.23; p=0.71) between patients with and without CXCR4 mutations. The median PFS for patients without CXCR4 mutations was 3.6 years (95% CI 1.7-5.9 years) versus 6.5 years (95% CI 2.7-not reached) for patients with CXCR4 mutations, which was not statistically significantly different (HR 0.59, 95% CI 0.29-1.17; p=0.13). Frameshift CXCR4 mutations were associated with better PFS than nonsense CXCR4 mutations in a multivariate Cox regression model (HR 0.22, 95% CI 0.06-0.80; p=0.02). Patients with CXCR4 mutations had a 10-year SAFTI rate of 75% (95% CI 13-96%) versus 83% (95% CI 27-97%) in patients without CXCR4 mutations, which was not statistically significantly different (HR 3.01, 95% CI 0.17-52.6; p=0.45). Conclusions: We conclude that there is no evidence that CXCR4 mutations adversely impact response, PFS and SAFTI in WM patients receiving proteasome inhibitor-based primary therapy. Figure Disclosures Castillo: Janssen: Consultancy, Research Funding; Abbvie: Research Funding; TG Therapeutics: Research Funding; Pharmacyclics: Consultancy, Research Funding; Beigene: Consultancy, Research Funding. Hunter:Janssen: Consultancy. Treon:BMS: Research Funding; Janssen: Consultancy; Pharmacyclics: Research Funding.

Effect factors related to a high probability of hemodialysis independence in newly diagnosed multiple myeloma patients requiring hemodialysis.

BackgroundRenal failure is a severe complication of symptomatic myeloma, related to higher mortality. Recovery from dialysis dependence can lead to enormous survival benefits. We investigated the effect factors for probability of dialysis independence.MethodsRetrospective data on 45 newly diagnosed MM (NDMM) patients with serious renal impairment and requiring hemodialysis were analyzed. The statistical methods including logistic regression analysis, Kaplan‐Meier survival curves, the log‐rank test and the Cox proportional hazards model for survival analysis were used in our study.ResultsTwenty‐two of the 45 patients, who were on hemodialysis at diagnosis, became dialysis independence. In the logistic regression analysis, serum level of β2‐microglobulin, kidney disease history, involved free light chain, and achieving at least VGPR were significantly associated with reversibility from dialysis dependence. In addition, achieving hemodialysis discontinuation was related to better survival. The multivariate analyses demonstrated that reversibility from dialysis dependence, proteinuria < 3.5 g/24 h, and achieving at least VGPR were significantly associated with OS among NDMM patients requiring hemodialysis.ConclusionLower serum level of β2‐microglobulin and lower level of free light chain at diagnosis, achieving at least VGPR, and shorter kidney disease history are related to a high probability of dialysis independence in NDMM patients with serious renal failure requiring dialysis.

Clinical Significance of Serum Free Light Chain and Its κ/λ Ratio in Patients with Multiple Myeloma

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

Frequency and prognostic impact of KIT and other genetic variants in indolent systemic mastocytosis

AbstractIndolent systemic mastocytosis (ISM) patients have a normal life expectancy, except in the 5% to 10% of cases that progress to more advanced SM (advSM), which has a significantly poorer outcome. Mutations in genes other than KIT frequently found in myeloid neoplasms have been associated with a poorer outcome among advSM, whereas limited information exists about their frequency and prognostic impact in ISM. We investigated the frequency and prognostic impact of variants in 18 genes, found to be altered in advSM, in 322 ISM patients (median follow-up, 5.7 years) divided into discovery (n = 200) and validation (n = 122) cohorts. Overall, 71 genetic variants were detected in 55 of 322 (17%) patients. Mutated ISM cases, particularly those carrying ASXL1, RUNX1, and/or DNMT3A (A/R/D) pathogenic variant allele frequencies (VAFs) ≥ 30%, exhibited significantly shortened (P < .001) progression-free survival (PFS) and overall survival (OS). Multivariate analysis showed that serum β2-microglobulin (sβ2M) levels > 2.5 µg/mL (hazard ratio [HR], 9.8; P = .001), together with a KIT D816V VAF ≥ 1% in bone marrow (BM) (HR, 10.1; P = .02) and pathogenic variants of A/R/D VAFs ≥ 30% (HR, 4.2; P = .02), were the best combination of independent predictors for PFS. In turn, A/R/D gene pathogenic VAF ≥ 30% was the only independent predictor for OS (HR, 51.8; P < .001). Based on these variables, 2 scoring systems were constructed for risk stratification of ISM at diagnosis with significantly different 10-year PFS (100%, 91%, 0% for scores of 0, 1, ≥2, respectively) and OS (100% and 50% for scores of 0 and 1) rates.

Diagnostics of contrastinduated nephropathy after percutaneous coronary intervention

The present study is devoted to search for the opportunities of early diagnosis of the development of contrastinduced nephropathy when performing coronary angiography and percutaneous coronary intervention in patients with a chronic ischemic heart disease. The predicative ability of modern biomarkers was studied in comparison with serum creatinine. Baseline serum β2-microglobulin levels &gt;1.1 mg/l can be attributed to patients at a high risk of developing complications. Increasing the level of cystatin C in the blood by 25 % from baseline after 24 hours or &gt;1.064 mg/l, increasing the level of β2-microglobulin in blood after 24 hours &gt; 1.42 mg/l allows you to diagnose acute kidney damage, before the creatinine dynamics and can be used in routine clinical practice. The determination of neutrophil lipocalin in the urine improves the accuracy of diagnosis, but is difficult in routine practice.

Clinical Characteristics and Karyotype Analysis of Myelodysplastic Syndrome Patients with TP53 mutation

To investigate the clinical characteristics of myelodysplastic syndrome (MDS) with TP53 mutant and the relationship between TP53 mutation and monosomal karyotype in MDS patients. The TP53 mutations in 102 patients with de nove MDS were retrospectively analyzed, and the clinical features of the TP53 mutation group and the non-mutation group were compared. The relationship between TP53 mutation and karyotype, especially monosomal karyotype was analyzed. Fifty-two out of the 102 MDS patients were male and 50 were female, the median age was 59.5 (23-83) years old. The mutational frequency of TP53 was 12.7%, which mostly occurred in patients with MDS-EB. As compared with non-mutation group, the hemoglobin level and platelet count were lower (P=0.001, P=0.033), the LDH level and bone marrow blast ratio were higher in TP53 mutation group (P=0.002, P＜0.001), but the statistical difference of alsolute count of neutrophils and levels of serum ferritin and β2-microglobulin between 2 groups was not found. The karyotype abnormality frequency of patients with TP53 mutation was 90.9%, among them 72.7% was monosomal karyotype. The incidence of monosomal karyotype in the TP53 mutation group was very significantly higher than that in the non-mutation group (P＜0.001). MDS with TP53 mutation and monosomal karyotype appeared in the groups with high and very high IPSS-R risk. MDS patients with TP53 mutation have unique clinical features and high incidence of monosomal karyotype, and their overall prognosis is poor.

Serum B-cell maturation antigen as a prognostic marker for untreated chronic lymphocytic leukemia.

7525 Background: New prognostic markers in chronic lymphocytic leukemia (CLL) are in demand. Different groups have developed models which combine multiple prognostic markers into a single index to classify CLL patients (pts). The CLL-International Prognostic Index (CLL-IPI) combines five parameters: age, clinical stage, TP53 status, IGHV mutational status, and serum β2 microglobulin levels. B-cell maturation antigen (BCMA) is a cell membrane receptor expressed exclusively on late stage B-cells and plasma cells with elevated serum (s) levels found in B-cell malignancies, such as multiple myeloma (MM). In MM, sBCMA levels can be used to monitor disease status and predict overall survival (OS). To further evaluate this biomarker in other hematologic malignancies, we studied it in CLL. Methods: Untreated (UNTX) CLL pts seen and consented at Mayo Clinic were identified. sBCMA levels were measured on stored sera of 331 UNTX CLL pts using an ELISA-based assay with a polyclonal anti-BCMA antibody from R&amp;D Systems (Minneapolis, MN). The Mann-Whitney analysis was used to assess differences between CLL pts and healthy controls. The relationships between sBCMA and both time to first treatment (TFT) and OS were also assessed using Cox Regression models with an optimal sBCMA cutoff of 40.9 ng/mL. Results: The median age of pts was 61 years, and 71% were male. The distribution of CLL-IPI risk groups was as follows: 135 (41%) Low; 114 (34%) Intermediate; 67 (20%) High; 15 (5%) Very High. The median level of sBCMA in CLL pts (48.6 ng/mL) was higher (P &lt;0.0001) than those of healthy controls (n = 104; 36.03 ng/mL). In CLL pts, sBCMA is significant in univariable analyses of TFT (HR 2.9 (95%CI, 2.0-4.2); P &lt; 0.0001) and OS (HR 2.5 (95%CI, 1.5-4.0); P &lt; 0.0003), and remains significant when adjusting for sex and CLL-IPI factors (HR 2.3 (95%CI, 1.6-3.3), P &lt; 0.0001; HR 1.9 (95%CI 1.1-3.1), P = 0.01, respectively). Conclusions: sBCMA is elevated in CLL pts compared to healthy controls. After adjusting for CLL-IPI and sex, sBCMA levels provided independent prognostic value in predicting TFT and OS in this cohort. Measuring sBCMA with a readily accessible ELISA-based test, provides incremental value over the current CLL-IPI model in predicting prognosis of CLL.