Secondary Monoclonal Gammopathy Of Undetermined Significance Is Frequently Associated With High Response Rate and Superior Survival In Patients With Plasma Cell Dyscrasias

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5537-5537
Author(s):  
Dehui Zou ◽  
Gang An ◽  
Guoqing Zhu ◽  
Yan Xu ◽  
Weiwei Sui ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Clinical Parameters ◽  
Number Of Patients ◽  
Immunofixation Electrophoresis ◽  
Plasma Cell Dyscrasias ◽  
Undetermined Significance

Abstract Background Secondary monoclonal gammopathy of undetermined significance (MGUS) is a special phenomenon during the treatment of multiple myeloma (MM). The incidence, biological characteristics and prognostic value of secondary MGUS in patients with MM remain undefined. Materials and Methods Serum immunofixation electrophoresis (IFE) was retrospectively analyzed in 438 cases of patients with plasma cell dyscrasias, including 409 cases of newly diagnosed MM and 29 cases of primary plasma cell leukemia (pPCL). Patients who developed a secondary MGUS were identified through a retrospective analysis of serum immunofixation electrophoresis (IFE). IFE test was performed with Sebia Hydragel kits on the Sebia Hydrasys electrophoresis system (Sebia, Norcross, GA) using agarose gels. The identification of secondary MGUS required the detection of at least one new monoclonal (M) protein with heavy and/or light chain immunoglobulin different from the initially diagnosed MM Results Secondary MGUS was more common in patients with myeloma who had undergone SCT than in those who had not (17 [29.8%] out of 57 versus 5 [1.4%] out of 352, P < 0.001). The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS were comparable. The overall CR rates in patients with or without secondary MGUS were 81.8% and 21.8% respectively (p<0.01). The median PFS and OS of the entire cohort with MM was 25.0 months (95% CI: 19.9-30.0) and 36.0 months (95% CI: 29.4-42.6), respectively. Despite the small number of patients with secondary MGUS, these patients had a clearly better disease outcome as compared with those without secondary MGUS. The median PFS was 52.0 months (95% CI: 41.1-62.9) in patients with secondary MGUS versus 22.5 months (95% CI: 19.6-25.4) for the rest of the cohort (P = 0.002). Patients with secondary MGUS also had much longer OS, and the median OS was not reached versus 35.0 months (95% CI: 29.4-40.6) for the patients without secondary MGUS (P < 0.001). Univariate analysis performed on the whole group of 409 patients identified several prognostic factors that had significant negative effect on OS. These factors included advanced International Staging System stage (P<0.001), 17p deletion (P<0.001), 13q deletion (P=0.009), t(4;14) (P=0.042), 1q gains(P=0.006), absence of secondary MGUS (P<0.001). A multivariate Cox regression model including ISS stage, chromosome aberration determined by FISH and secondary MGUS was applied. The presence of secondary MGUS retained independent prognostic values for OS (HR 0.128 [95% CI 0.018-0.922], p=0.041). A similar analysis for prediction of PFS did not identify presence of sMGUS as independent prognostic factor. Survival was then analyzed in patients undergoing stem cell transplantation. Patients with secondary MGUS seemed to have a longer median PFS, but the difference was not statistically significant (52 months versus 41.0 months; p=0.126). Median OS was not reached in both group and no statistical difference was found (p=0.220) Conclusion We observe that secondary MGUS is frequently observed in MM patients after transplantation, and associated with a more favorable prognosis. The clinical parameters and cytogenetic characteristics in patients with or without secondary MGUS are comparable. The favorable survival could be explained by the higher depth of response especially after myeloablative therapy. Disclosures: No relevant conflicts of interest to declare.

High Resolution Array-CGH Provides New Insights Into the Prognosis of Chronic Lymphocytic Leukemia (CLL): Is 8p Loss Worse Than 17p Loss?.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2339-2339
Author(s):  
Andrea Rinaldi ◽  
Michael Mian ◽  
Davide Rossi ◽  
Francesco Forconi ◽  
Clara Deambrogi ◽  
...  
Keyword(s):  
Cox Regression ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Lymphocytic Leukemia ◽  
Rank Test ◽  
Western World ◽  
Clinical Parameters ◽  
Log Rank Test ◽  
The Impact

Abstract Abstract 2339 Poster Board II-316 BACKGROUND: CLL, the most common adult-onset leukemia in the Western world, has a heterogeneous clinical course. Many advances have led to a better understanding of its pathogenesis and to improvements in treatment strategies, but striking solutions are still missing. We conducted a study to evaluate the impact of genomic aberrations on the clinical course. METHODS: From January 1980 to May 2008, 395 frozen samples of CLL patients, were prospectively collected in four centers. Extracted DNA was analyzed with Affymetrix Human Mapping 6.0 arrays. Normal matched DNA was analyzed for one fourth of the cases. Correlations between minimal common regions (MCR) and clinical parameters were evaluated with the Fisherôs-exact test and their impact on OS with the log-rank test. A p-value after Bonferroni multiple test correction (MTC) (p-adj.) <0.05 was considered as statistically significant. Up to now 266 samples have been analyzed. RESULTS: Analysis of the clinical parameters (CPs) and known risk factors (Rai/Binet, age, doubling time, LDH, beta2, IGVH status, p53 mutations, telomere length, CD38, 11q, 17p) was consistent to previous published series. ZAP70 did not affect the clinical course, likely due inter-laboratories variability. After a median follow up of 53 months, 143/239 (60%) of the patients have started therapy and 63/261 (24%) died. 5-yr OS was 82%. Fisher test between the MCRs and CPs revealed an inverse relation between the presence of trisomy 12 by FISH and del13q14.3, an association between del17p and losses of 8p regions and between CD38 and 12q gain. Before MTC, 46 MCRs had a significant impact on OS and 67. After MTC, 3 regions maintained their role: 8p22 loss (38/248, 15%, p-adj.=0.002, median OS: 26 months vs. 48), 17p13.3-11.2 loss (20/248, 8%, p-adj.=0.001; median OS: 10 months vs. 48). In univariate analysis, the log-rank test among pts with 8p-/17p- (8/248, 3%), 8p- (30/248, 12%), 17p- (12/248, 5%), wild type (198/248, 80%) was statistically significant (p<0.001; see figure). Importantly, none of the analyzed clinical and biological parameters was associated with this aberration. CONCLUSIONS: Loss of 8p22 designated a CLL subgroup with a worse outcome among all patients and in the subset with 17p loss. Our data suggested that this aberration might constitute an independent prognostic factor to be evaluated in independent studies. Results, including a Cox regression model, will be presented on all 395 cases. Disclosures: No relevant conflicts of interest to declare.

FLC Assay and Multiparameter Flowcytometry Based Clonal Plasma Cell Measurement Are Independent but Complementary in Assessing the Treatment Response in Multiple Myeloma.

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 2969-2969
Author(s):  
Hiroki Sugihara ◽  
Kenji Tsuda ◽  
Tomotaka Ugai ◽  
Yuki Nishida ◽  
Masayuki Yamakura ◽  
...  
Keyword(s):  
Prognostic Factor ◽  
Partial Response ◽  
Plasma Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Response To Treatment ◽  
Rank Test ◽  
Multiparameter Flow Cytometry ◽  
Prognostic Impact

Abstract Abstract 2969 Purpose: Although stringent complete response (sCR) defined by paraprotein negativity on immunofixation and serum free light chain (sFLC) ratio normalization are considered deeper responses in the IMWG criteria, recent report indicated that Multiparameter flow cytometry (MFC)-dased immunophenotypic response (IR) is a more relevant prognostic factor in MM patients. However, data on the prognostic impact of IR and sFLC ratio (sFLCκ/λ) normalization are still scarce. We investigated the prognostic impact of IR and sFLCκ/λ normalization in MM patients treated with novel agents. Patients and Methods: A total of 124 consecutive patients (M:F=68:56; median age, 71 yr) were treated by chemotherapy regimens containing at least one novel agent (thalidomide, bortezomib, lenalidomide)from April 2005 to May 2012. Treatment responses were assessed using the IMWG criteria, and the best response to treatment during the clinical course was assessed by simultaneous serum immunofixation, sFLC measurements, and MFC analysis of bone marrow (BM) plasma cells. Normalization of sFLCκ/λ was defined 2 consecutive normal sFLCκ/λ apart from at least 4 weeks. MFC-defined minimal residual disease (MRD) was evaluated by single-tube 6-color MFC, CD45-CD38 gating strategy, and combination CD19, CD56, and cytoplasmic κ-λ analysis. Clonal plasma cell (PC) negativity by MFC (MFC-negative) was defined as <10−4 neoplastic PCs in BM samples on MFC. Overall survival (OS) and progression-free survival (PFS) were analyzed by the Kaplan–Meier (K-M) method and differences between curves were calculated by two-sided log-rank test. Univariate analysis was used to assess the impacts of factors on sFLCκ/λ normalization and MFC negativity (age, Durie–Salmon stage, ISS stage, LDH, hemoglobin, serum albumin, serum creatinine, FISH at diagnosis). The Cox regression proportional hazard model (stepwise regression) was used to explore the independent effects of these variables on PFS and OS. Results: At a median follow-up of 25.8 months, 3- and 5-year OS of all patients were 61.0% and 42.4%, respectively. CR was obtained in 25% (31/124), very good partial response (VGPR) in 33.5% (41/124), partial response (PR) in 30.5% (38/124), and stable disease or less (SD) in 11% (14/124). Normal sFLCκ/λ was achieved in 81% of CR, 56% of VGPR, 13% of PR, and 0% of SD or less response of patients. K-M estimated 3- and 5-year OS were 100% in CR patients; these were significantly better than in VGPR (75.8% and 43.2%, respectively) and PR patients (63% and 26.7.%, respectively). There were no significant differences in 3- or 5-year OS between VGPR and PR patients. Normal sFLCκ/λ and MFC negativity were achieved in 25 (81%) and 18 (58%) of 31 CR patients, respectively. Among 25 CR patients with normal sFLCκ/λ (stringent CR), 15 (60%) were MFC-negative and 10 (40%) were MFC-positive; three of 6 CR patients (50%)without normal sFLCκ/λ were MFC-positive. Twenty-three of 41 VGPR patients (56%) obtained normal sFLCκ/λ, while only 5 (12%) became MFC-negative; all 5 MFC-negative patients also obtained normal sFLCκ/λ. Among 52 patients with less than PR, only 5 (9.6%) obtained normal sFLCκ/λ and none achieved MFC negativity. Patients with MFC-negative CR showed significantly better PFS than patients with MFC-positive CR (p<0.05). Although patients in stringent CR with MFC-negative showed slightly better PFS compared to patients in stringent CR with MFC-positive, difference between the curves were not significant. Within the group of VGPR, PFS and OS were significantly longer in normal sFLCκ/λ patients than abnormal sFLCκ/λ(P<0.001). Univariate analysis showed that hemoglobin 10.0 g/dl>, age >70 yr, and abnormal LDH had negative prognostic impacts on attaining normal sFLCκ/λ, but none of these factors remained significant on multivariate analysis. Cox analysis showed that sFLCκ/λ normalization was an independent prognostic factor for longer PFS and OS in patients with CR, VGPR and PR (P=0.001). Conclusions: This study confirmed that magnitude of CR and VGPR response defined by IMWG criteria was heterogeneous in terms of sFLCκ/λ normalization and MFC negativity. Although MFC and sFLC analysis frequently gave discrepant results among patients with CR and VGPR, both analyses appeared to give important complementary information for assessing the depth of CR and VGPR category. Disclosures: No relevant conflicts of interest to declare.

Prognostic Impact Of Comorbidity In Multiple Myeloma

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 5340-5340 ◽  
Author(s):  
Rafael Ríos Tamayo ◽  
Joaquín Martínez López ◽  
Manuel Jurado ◽  
María Esther Clavero Sánchez ◽  
Fátima López Jiménez ◽  
...  
Keyword(s):  
Multiple Myeloma ◽  
Prognostic Factors ◽  
Liver Disease ◽  
Plasma Cell ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Statistical Significance ◽  
Univariate Analysis ◽  
Prognostic Impact ◽  
Alcoholic Fatty Liver

Abstract Multiple myeloma (MM) is a heterogeneous disease. Evaluation of prognostic factors and risk stratification at diagnosis is necessary to compare outcome. Attempts have been made to apply a comorbidity score in the clinical sitting, but a standardized general approach is still lacking. We hypothesized that a comprehensive examination of every associated disease in a large cohort of patients could better highlight the prognostic impact of comorbidity in MM. All consecutive patients diagnosed in our institution, from 1993 to 2013, with symptomatic MM according to IMWG criteria were included in our population-based MM registry. Patients with plasma cell leukemia or with palliative management were excluded. Clinical variables analyzed were: age, sex, Durie-Salmon, International Scoring System (ISS), percentage of plasma cell in bone marrow by morphology (PC), serum creatinine (Cr) and estimated glomerular filtration rate according with Modification of Diet in Renal Disease (eGFR-MDRD). The following comorbodities were analysed: hypertension (HTA), diabetes (DM), obesity (OB) (body mass index > 30 Kg/m2), hyperlipaemia (HL), prior malignancy (PM), hepatitis B virus (HBV), hepatitis C virus (HCV), human immunodeficiency virus (HIV), peptic ulcer (PU), thromboembolism (TE), renal transplant (RT), splenectomy (S), cutaneous disease (CD), amyloidosis (AM), heart disease (HD) (arrhythmia, congestive heart failure, coronary artery disease, other), lung disease (LD) (chronic obstructive pulmonary disease, asthma, other), liver disease (HE) (cirrhosis, non-alcoholic fatty liver disease, other), neurological disorder (ND), psychiatric disorder (PD) and rheumatologic disorder (RD). Kaplan-Meier method was used to estimate OS curves. Cox regression was used to determine the prognostic impact of each comorbidity in a univariate and multivariate model. 311 patients were eligible. Median age was 66 years (12-91), 148 men (47.6 %) and 163 women. Percentage of comorbidities was: HTA 45; OB 32.5; DM 20.4; HD 20.4; LD 15.2; PU 10; HL 9.7; ND 8; PM 7.8; PD 6.5; HBV 3.9; HE 3.9; TE 3.6; RD 3,5; AM 2.3; HCV 1.9; CD 1.6; S 1; RT 0.6; HIV 0.3. 63 patients (20.4 %) showed no comorbidities. Univariate analysis (table 1) demonstrated that AM (P=0.022), HCV (0.038), HIV (0.022), PD (0.015) and ND (0.05) were significantly associated with shorter OS. The variables associated with mortality in the multivariate analysis were age (p=0.002), ISS (III vs I: p=0.01), PC (p=0.05) and Cr (p=0.02). Results will be validated in another MM series and presented during the meeting. The overall prognosis of MM depends on a variety of host and disease-related characteristics. We confirm age, ISS, PC and Cr as robust and independent prognostic factors. Adjusting for these factors, no isolated comorbidity reach statistical significance; however, comorbidity seems to have a role in MM prognosis. More studies are warranted to define the prognostic impact of comorbidities in MM. Disclosures: No relevant conflicts of interest to declare.

Estimating the Risk of Progression of Monoclonal Gammopathy of Undetermined Significance into Lymphoplasmacytic Malignancies in the United States: Determining Demographic Differences Using a National Dataset

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 843-843 ◽  
Author(s):  
Ronald S. Go ◽  
Herbert C Heien ◽  
Lindsey R Sangaralingham ◽  
Elizabeth B Habermann ◽  
Nilay D Shah
Keyword(s):  
United States ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
The United States ◽  
First Year ◽  
Administrative Claims ◽  
Number Of Patients ◽  
Risk Of Progression ◽  
Undetermined Significance

Abstract Background: Prior studies on the risk of progression of monoclonal gammopathy of undetermined significance (MGUS) into lymphoplasmacytic malignancies (LPMs) were almost exclusively in the White populations, comprised of limited number of patients residing in relatively small geographic areas, or included patients mostly detected by serologic screening as part of clinical study (as opposed to detected clinically during evaluation of symptoms suspicious for LPMs). Similar epidemiologic studies in a large, racially diverse population are lacking. Methods: We conducted a retrospective analysis of incident MGUS patients diagnosed from 2006-2013 using theOptum Labs Data Warehouse, a large database including administrative claims information on >110 million privately insured and Medicare Advantage enrollees throughout the United States. We identified patients with a diagnosis of MGUS (ICD9: 273.1) with 1-5 years of continuous enrollment. Each enrollment cohort based on the duration of follow-up (1-, 2-, 3-, 4-, or 5-year) was analyzed individually to help estimate the progression to cancer. We excluded patients who were diagnosed with LPMs within three months of MGUS diagnosis. We calculated the rate of progression into LPMs (chronic lymphocytic leukemia [CLL], light chain amyloidosis [AL], multiple myeloma [MM], non-Hodgkin lymphoma [NHL], and Waldenström macroglobulinemia [WM]) expressed as number per 100 person-years. Results: There were 14,728 MGUS patients for a total of 21,288 person-years of follow-up. The distributions of the number of patients and events according to the cohorts classified by duration of follow-up were: 1-year (14,728 patients; 243 events), 2-year (10,644 patients; 307 events), 3-year (7,333 patients; 299 events), 4-year (4,497 patients; 237 events), and 5-year (2,960 patients; 191 events). The rates of progression to LPMs were consistently highest during the first year after MGUS diagnosis (~2.00), generally declined by half during the second year and remained fairly stable thereafter (~1.00; Table 1). The rates of progression into LPMs overall as well as by demographics are shown in Table 2. The risk of progression was significantly higher among men (P < 0.01) and older patients (>50 years; P = 0.03) compared to their counterparts but similar among races (P = 0.15). Of the 243 patients who progressed, the distribution of LPMs was MM (70.0%), NHL (13.2%), WM (12.3%), AL (4.1%), and CLL (0.4%). Conclusions: Among patients withMGUS, the risk of transformation into LPMs is continuous although twice as high during the first year after MGUS diagnosis compared to subsequent years. The risk of transformation was higher among men and those who were older but did not differ among the racial subgroups. Our findings can be used to develop an optimal risk-based MGUS follow-up strategy that incorporates not only serum biomarkers but also demographic factors. Disclosures No relevant conflicts of interest to declare.

Differential Diagnosis of Monoclonal Gammopathies

1999 ◽  
Vol 123 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Raymond Alexanian ◽  
Donna Weber ◽  
Frank Liu
Keyword(s):  
Multiple Myeloma ◽  
Differential Diagnosis ◽  
Clinical Features ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Monoclonal Immunoglobulin ◽  
Monoclonal Gammopathies ◽  
Plasma Cell Dyscrasias ◽  
Waldenström's Macroglobulinemia ◽  
Undetermined Significance

Abstract Several disorders are associated with a monoclonal immunoglobulin detected by serum or urine electrophoresis, the most common being a monoclonal gammopathy of undetermined significance, multiple myeloma, Waldenström’s macroglobulinemia, and amyloidosis. The clinical features of these conditions, as well as other similar entities, are described in this review. The objective is to demonstrate the importance of electrophoretic studies in the differential diagnosis of plasma cell dyscrasias and in guiding the decision for rational therapies.

scholarly journals A Rare Cause of Acquired Factor X Deficiency in an 87-Year-Old Female

2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Ayrton Bangolo ◽  
Trupti Waykole ◽  
Bilal Niazi ◽  
Chandini Sajja ◽  
Mahabuba Akhter ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Rare Case ◽  
Vitamin K Antagonists ◽  
Immunoglobulin A ◽  
Al Amyloidosis ◽  
Factor X ◽  
Factor X Deficiency ◽  
Plasma Cell Dyscrasias ◽  
Undetermined Significance

Factor X deficiency is a rare coagulopathy that can be inherited or acquired. Acquired factor X deficiency has been associated with plasma cell dyscrasias, amyloids, and use of vitamin K antagonists. Of plasma cell dyscrasias, most cases in the literature have been associated with multiple myeloma with or without concomitant AL amyloidosis. Here, we present a rare case of acquired isolated factor X deficiency in an elderly patient with immunoglobulin A (Ig A) monoclonal gammopathy of undetermined significance (MGUS). Herein, we highlight a rare cause of acquired factor X deficiency, and we hope to contribute to the growing literature of plasma cell dyscrasias associated with factor X deficiency.

scholarly journals A Prospective Study and Identification of Genomewide Association Markers of Familial Predisposition to Plasma Cell Dyscrasias

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 8-8
Author(s):  
Adam S Sperling ◽  
Rebecca Georgakopoulou ◽  
Mehmet Kemal Samur ◽  
Christine Ivy Liacos ◽  
Brittany E Sandoval ◽  
...  
Keyword(s):  
Genetic Analysis ◽  
B Cell ◽  
Board Of Directors ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Research Funding ◽  
Advisory Committees ◽  
Familial Predisposition ◽  
Plasma Cell Dyscrasias ◽  
Second Degree

Introduction: An increased inherited risk for the development of plasma cell dyscrasias (PCDs) has long been suspected, however to date, only a limited number of potential genomic risk loci have been described. To characterize the inherited risk and facilitate identification of additional risk loci it is important to combine detailed pedigrees with extensive genetic analysis. To identify familial PCDs we initiated a prospective study with active recruitment of a large cohort of patients with PCDs and active screening of their relatives combined with tissue banking and subsequent genetic analysis. Methods: All patients in the Department of Clinical Therapeutics diagnosed with PCDs between January 2017 and January 2019, were offered enrollment in the study. Following informed consent, 1st and 2nd degree relatives over the age of 30 were eligible for screening. A detailed family pedigree was created for each index case with special focus on family history of PCDs, B-cell lymphomas, or other hematologic or solid malignancies. As a control, subjects' spouses were also screened. Screening included serum protein electrophoresis with immunofixation. In families where an additional member was identified with a PCD or B-cell malignancy, peripheral blood was collected from consenting family members over the age of 18 for further genetic analysis. Samples from affected individuals were profiled using whole genome sequencing (WGS) and unaffected individuals were genotyped using Axiom Arrays. Data were analyzed using Axion Array Suite and plink and GATK toolkit with BWA. Results: Of 1,084 patients screened for participation in the study; 752 had multiple myeloma (MM), 77 had smoldering MM, 81 a monoclonal gammopathy of undetermined significance, 93 Waldenström's Macroglobulinemia and 81 had AL amyloidosis. 176 (16.2%) patients refused to participate in the study, while 44 (4.1%) patients were ineligible for further screening due to the absence of a living first- or second-degree relative. The median number of screened first or second-degree relatives per index patient was 3 (range 1 to 10). The median age of index cases was 65 years, offspring was 37 years, second-degree relatives was 65 years, and spouses was 65 years. The incidence of a PCD among second-degree relatives was 4.5%, while it was 0.6% among offspring. As a control group, the incidence of PCDs among spouses was 2.6%. Overall at least one additional member (beyond the index patient) with a monoclonal gammopathy was detected in 98 families (11.3%). In 57 families (6.6%) there was a positive history of at least one additional first- or second-degree relative with a PCD or B-cell malignancy. In addition, 41 new cases of monoclonal gammopathy (4.7%) were identified through the screening process associated with this study. To identify genetic loci that could be associated with a predisposition to development of PCDs, genetic analysis was performed on the most heavily affected 18 families, those with at least three affected members or with early onset disease (i.e. PCD diagnosed before age 50). We have evaluated 838,750 SNPs from 103 samples from 18 families. 30 samples were from affected members and 73 from unaffected members. We found eight SNPs (rs13233413, rs11648113, rs59444635, rs148480125, rs113556240, rs11547122, rs671880, rs4726610) that are significantly enriched in affected members with a p-value below the suggestive cut-off of &lt;1e-5. The top candidate was in the untranslated region (UTR) of TSPAN33, a marker of activated and malignant B-cells. We did not detect any significant enrichment in germline mutations in previously reported genes associated with familial PCD risk such as KDM1a, KRAS or DIS3. Functional annotation of the 8 SNPs identified here showed that rs148480125, located in the promoter region of the apoptosis regulator SIVA1, is predicted to impact the allele specific expression level. Further validation work is ongoing. Conclusions: Our active prospective screening approach to identify familial predisposition to PCDs revealed that 11.3% of patients had families with at least one additional affected member and some families had a substantially higher incidence of PCDs with earlier onset. Study of these high-risk families have identified genomewide association markers which in future may help us define familial predisposition to plasma cell dyscrasias. Disclosures Gavriatopoulou: Karyopharm: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria; Janssen: Consultancy, Honoraria; Takeda: Consultancy, Honoraria; Amgen: Consultancy, Honoraria. Terpos:Amgen: Honoraria, Research Funding; Genesis pharma SA: Honoraria, Other: travel expenses , Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria, Other: travel expenses , Research Funding; Celgene: Honoraria; Sanofi: Honoraria; BMS: Honoraria. Kastritis:Amgen: Consultancy, Honoraria, Research Funding; Janssen: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; Pfizer: Consultancy, Honoraria; Genesis Pharma: Consultancy, Honoraria. Munshi:Janssen: Consultancy; OncoPep: Consultancy, Current equity holder in private company, Membership on an entity's Board of Directors or advisory committees, Patents & Royalties; BMS: Consultancy; Legend: Consultancy; Amgen: Consultancy; AbbVie: Consultancy; Karyopharm: Consultancy; Takeda: Consultancy; C4: Current equity holder in private company; Adaptive: Consultancy. Dimopoulos:Amgen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Celgene: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Speakers Bureau; BMS: Consultancy, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees; Takeda: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau; Janssen: Consultancy, Honoraria, Membership on an entity's Board of Directors or advisory committees, Other: Personal fees, Research Funding, Speakers Bureau.

scholarly journals Prevalence of Monoclonal Gammopathy of Undetermined Significance in a Large Population with Annual Physical Examination in Beijing, China

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 5519-5519
Author(s):  
Jinuo Wang ◽  
Jian-Hua Han ◽  
Yue-lun Zhang ◽  
Xin-xin Cao ◽  
Dao-Bin Zhou ◽  
...  
Keyword(s):  
Physical Examination ◽  
Light Chain ◽  
Chinese Population ◽  
Monoclonal Gammopathy ◽  
Conflicts Of Interest ◽  
Large Population ◽  
M Protein ◽  
Monoclonal Protein ◽  
Significant Difference ◽  
Undetermined Significance

Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a clinically asymptomatic premalignant plasma cell disorder. Previous studies in Western countries have described the prevalence of MGUS in Caucasians. However, data is limited in Chinese population. We therefore performed this study to ascertain the prevalence and characteristics of MGUS among Chinese population. Methods A total of 154597 consecutive healthy participants from Beijing who underwent annual physical examination between December 2013 and April 2019 at Peking Union Medical College Hospital were enrolled. Serum M protein was evaluated by capillary electrophoresis. Patients with a positive or suspicious serum M protein were suggested to be referred to the hematological clinic for immunofixation electrophoresis (IFE) and free light chain (FLC) assays. MGUS was defined in accordance with previous definitions. We calculated age-specific and sex-specific prevalence and described laboratory characteristics of patients with MGUS among those participants. Results MGUS were diagnosed in 843 patients (0.55%, 95%CI 0.51% to 0.59%). The median age at presentation was 58 years, with a range of 25-96 years. The overall prevalence of MGUS was 1.14% among participants aged 50 years or older and 2.6% among those aged 70 years or older. In both sexes, the prevalence increased with age: 0.1% (<40 years), 0.36% (40-49 years), 0.78% (50-59 years), 1.28% (60-69 years), 2.19% (70-79 years), and 3.77% (≥80 years) separately (Figure 1). The prevalence among men were higher than that among women (0.67% vs. 0.40%, OR =1.719, 95% CI 1.490 to 1.983, P<0.001) (Figure 1). The median concentration of serum Monoclonal protein was 1.4 g/L (0.1 -27.8 g/L). M protein level was less than 0.5g/L in 220 patients (26.1%), less than 5 g/L in 81.1% and more than 15 g/L in only 1.9% of 843 persons. There was no significant difference in the concentration of the monoclonal protein among the age groups. Of the 519 patients who were tested for IFE, the isotype of the monoclonal immunoglobulin was IgG in 344 (66.3%), IgA 112 (21.6%), IgM in 48 (9.2%), IgD in 2 (0.4%), light-chain in 3 (0.6%) and biclonal in 10 (1.9%). The serum light-chain type was kappa in 260 (50.1%), lambda in 255 (49.1%) patients, while 4 patients (0.8%) with biclonal M protein have both kappa and lambda light-chain. Of the 180 people who were tested for FLC, 42 (23.3%) had an abnormal FLC ratio. IgG isotype, M protein <15 g/L and normal FLC ratio were found in 102 patients (56.7%) and the remaining 78 people (43.4%) had 1(30.6%) or 2(12.8%) abnormal factors. Conclusions MGUS was found in 1.14% of persons 50 years of age or older and 2.6% among those 70 years of age or older among healthy Chinese population. The prevalence of MGUS increases with age. Males have a higher frequency of MGUS than Females. These observations offer the overall situation of MGUS epidemiology in a large Chinese population. Disclosures No relevant conflicts of interest to declare.

Sign in / Sign up

Export Citation Format

Share Document