Presence Of Monoclonal Gammopathy Of Undetermined Significance Research Articles

Inflammatory features in sporadic late-onset nemaline myopathy are independent from monoclonal gammopathy.

ABSTRACTSporadic late‐onset nemaline myopathy (SLONM) is a rare adult‐onset non‐hereditary disease with subacute proximal muscle and often axial muscle weakness, characterized by the presence of nemaline bodies in skeletal muscle biopsies. Considering its association with concurrent monoclonal gammopathy of undetermined significance (MGUS), the disease is classified into two major subtypes (1) SLONM without MGUS (SLONM‐noMGUS) and (2) with MGUS (SLONM‐MGUS) association. SLONM associated with HIV infection (SLONM‐HIV) is also reported. SLONM‐MGUS has been shown to be associated with poorer prognosis and required aggressive treatment including high‐dose melphalan and autologous stem cell transplantation. The approach is currently debatable as recent reports suggested effectiveness of intravenous immunoglobulin as initial treatment with indifference of overall survival despite the presence of MGUS. Our study aimed to find an underlying basis by review of pathological features in 49 muscle biopsy proven‐SLONM from two large tertiary centers in Japan and Germany (n = 49: SLONM‐noMGUS = 34, SLONM‐MGUS = 13, SLONM‐HIV = 2). We compared pathological findings in SLONM‐noMGUS and SLONM‐MGUS and focused on the presence of any detectable inflammatory features by immunohistochemistry. The clinical and histological features in SLONM‐noMGUS and SLONM‐MGUS were not distinctively different except for more common regenerating fibers (>5% of myofibers) present in SLONM‐MGUS (p < 0.01). HLA‐ABC expression and fine granular p62 were observed in 66.7% and 78.3% of SLONM, respectively. The predominant inflammatory cells were CD68+ cells. The inflammatory cells showed positive correlations with the percentage of nemaline‐containing fibers (p < 0.001). In conclusion, inflammatory features are present although rather mild in SLONM. This finding contributes to the hypothesis of an acquired inflammatory disease pathogenesis and opens the possibility to offer immunotherapy in SLONM with inflammatory features regardless of the monoclonal gammopathy status.

Analyzing Relationship Between Monoclonal Gammopathy of Undetermined Significance (MGUS) with Different Types of Neuropathy: An Observational Study.

To analyze multiple variables, including immunoglobulin subtypes in patients with monoclonal gammopathy of undetermined significance (MGUS) and different types of neuropathy. This was a retrospective, single center study done in a tertiary care hospital in the United States. The data was collected for years 2001-2011. Inclusion criteria were the presence of MGUS and neuropathy. Exclusion criteria were the presence of other factors such as diabetes, vitamin B12 deficiency, alcoholism etc. which can cause neuropathy. Patients with IgM MGUS were compared with patients having Non-IgM MGUS. A total of 281 patients were analyzed in this study. The average age at the time of diagnosis of MGUS and neuropathy was 68years. The most common type of neuropathy was sensorimotor peripheral neuropathy (46%). The most common location of neuropathy was the lower extremities (68%). Among our patients, 52% had their neuropathy symptoms for 1-5years before presenting to the clinic. When IgM MGUS was compared with Non-IgM MGUS, a statistically significant difference was found in terms of race (White vs. Others, OR 4.43, 95% CI 2.13, 9.19, p<0.001) and survival status (OR 1.98, 95% CI 1.01, 3.90, p=0.046). Patients with MGUS are prone to develop different types of neuropathies. Caucasians are more likely to have IgM MGUS as compared to other races. IgM MGUS is generally related to worse outcomes as compared to Non-IgM MGUS. Medical therapies, including gabapentin and pregabalin are effective treatments and the response rate can be as high as 80-90% with these medications.

Five-Years' Follow-up Study for Frequency of Monoclonal Gammopathy of Undetermined Significance (MGUS) in a Korean Elderly Urban Cohort

AbstractAbstract 5007We previously reported the prevalence of MGUS in a Korean Elderly Urban Cohort recruited from 2005 to 2006 (First Wave, Park HK Am J Hematol. 2011;86:752–5). Their plasma samples were screened using immunofixation and free light chain (FLC) assays. Age and gender-adjusted prevalence rates of MGUS were estimated as 3. 3% (95% CI=2. 0–4. 6%), and the age-adjusted prevalence of MGUS was 4. 3% in men (95% CI=1. 9–6. 6%) and 2. 6% in women (95% CI=1. 0–4. 2%). And then we followed them and collected their serum between 2010 and 2011(Second Wave). Among 1, 000 participants of First Wave, 497 participated to the Second Wave and 419 agreed with the donation of serum for protein electrophoresis, immunofixation and FLC assays. Causes of nonattendance were death in 200 (40%), refusal in 197 (40%), move to other area in 69 (14%), and impossible contact in 37 (7%). The frequency of MGUS in Second Wave was 3. 10% (95% CI=1. 44–4. 76%) in all, 4. 27% (95% CI=1. 54–6. 99%) in men, and 1. 92% (95% CI=0. 06–3. 79%) in women. Among 35 MGUS patients in First Wave, 11 were followed. Eight of 11 had persistent MGUS and other 2 showed the disappearance of M protein in Second Wave. The last one showed mild anemia with persistent M protein of 1. 4g/dL suggestive of progression to MM, but was not confirmed because of early death just after Second Wave. Additional 4 MGUS newly developed in Second Wave among 408 persons without MGUS at First Wave. The mean amount of M protein in 13 patients with MGUS was 0. 55g/dL (range: 0. 2∼1. 4). Subtypes of M protein were predominantly A and G in 8 and 5 patients. Light chain was lambda, kappa and none in 8, 4, and 1 patient. Abnormal ratio of FLC was correlated with the presence of MGUS (p=0. 000). In conclusions, the frequency of MGUS is persistently lower in elderly Koreans (3. 1%) than other races. Disclosures:No relevant conflicts of interest to declare.

Prevalence and risk factors of monoclonal proteinemia in Thai population

Abstract Abstract 1416 Poster Board I-439 Background: Monoclonal gammopathy of undetermined significance (MGUS) is associated with progression to multiple myeloma and related hematologic malignancies at the rate of 1% per year in western population. Reliable information on prevalence, risk factors and natural history of MGUS in general population are necessary for designing an early detection strategy for myeloma in Thailand. Patients and methods: The study was performed in subjects, 50 years of age or older, in Bangkok, one nearby province and 2 remote provinces of Thailand. The demographic data and suspected risk factor history were collected by questionnaires. Complete blood count as well as blood chemistry were done to exclude underlying hematologic and/or systemic conditions. Serum monoclonal proteins were detected using high-resolution gel electrophoresis. Results: Serum samples were obtained from 3,261 participants. There were 1,105 males (33.9%) and 2,156 females (66.1%). The median age was 57. Abnormal protein electrophoresis findings were detected in 76 samples (prevalence 2.3%, 95% confidence interval [CI] 1.8% - 2.8%) showing small M-spikes at gamma-globulin region in 50 (1.5%) or at beta-globulin region in 25 (0.8%) or hypogammaglobulinemia in 1 case (0.03%). The prevalence of MGUS in subjects less than 60, 60-69 and 70 yrs or more was 2.0% (41/1975), 2.6% (22/851) and 3.0% (13/435), respectively. Using multivariate analysis, presence of MGUS was strongly associated with history of drug abuse (odd ratio 4.63, 95%CI 1.14-22.08) and current residences outside Bangkok (odd ratio 2.30, 95%CI 1.18-4.79). Radiation and chemical exposure, hair and nail-coloring products and pesticides were not statistically significant risk factors in our population. Conclusions: The overall prevalence of MGUS in Thai population was 2.3%, lower than those of western countries but comparable to what reported from Japan and Taiwan. Disclosures: No relevant conflicts of interest to declare.

Monoclonal Gammopathy of Undetermined Significance (MGUS) Does Not Affect Outcomes in Patients Undergoing Solid Transplants.

Abstract 2834Poster Board II-810 Background:Monoclonal gammopathy of undetermined significance (MGUS) results arises from a clonal proliferation of differentiated plasma cells and is a necessary precursor to development of multiple myeloma and some other B cell malignancies. Despite a high incidence in the general population (1-2% of adults in the 6th and 7th decades) and increased relative risk for later malignancy, there are few reports about the clinical course and prognosis of MGUS in long-term immunosuppressed patients. We aimed to evaluate the significance of MGUS in patients undergoing solid transplants in terms of clinical outcomes and rate of transformation to secondary B cell malignancy. Material and methods:We reviewed the medical records of 1493 patients on which kidney (living donor related, living donor-unrelated and deceased donor), liver and pancreatic transplants were performed at Mayo Clinic Arizona, between January 1, 1999 and July 31, 2009 to determine the incidence of MGUS and to further evaluate long-term follow up. At MCA patients are routinely screened using SPEP and for those where an M-spike is detected or suspected immunofixation is required for confirmation. MGUS was defined as previously reported. Patients who had anemia unrelated to their PCD were included. Statistical Methods:Patients were observed until death or, for those still alive, until July 2009. The major goal of the study was to assess the impact of MGUS on transplant outcomes and progression to active myeloma or related disorders. Patients who did not experience progression were censored at the time of last follow-up. Nominal variables were compared using Fisher's exact test. A two-tailed P value less than .05 was considered significant. ResultsIn this series, SPEP was performed in 1199 out of 1593 cases (75%) before transplantation. The most common abnormalities detected by SPEP included a normal pattern (70%), polyclonal pattern (16.8%), hypoalbuminemia (8%), hypogammaglobulinemia (2.4%) and the presence of M spike (2.8%). Immunofixation revealed the presence of a monoclonal immunoglobulin in 34 patients: IgG 30 cases (88%), IgM in 2 (6%) and biclonal disease in 2 (6%). The median age at diagnosis of MGUS was 60 years (range, 46 to 84 years), and included 63.7% of males. Clinical characteristics of the MGUS cases are seen in Table 1. Two MGUS patients were diagnosed only after the transplant was performed (338 and 1082 days respectively). There was no association between post-transplant lymphoproliferative (PTLPD) and MGUS and even when some MGUS patients died (7/34, 20%) death was not associated with progression of the monoclonal clone or development of a PTLPD or other malignancy. MGUS does not impact transplant outcomes. PTLPD disorders developed in 6 cases and none was associated with a MGUS. After a median of 88 months no MGUS patient developed transformation to active myeloma or a related disorder. Overall survival after transplantation was not significantly different among MGUS and Non- MGUS cases (6.48 vs 8.36 years p>0.05). DiscussionDespite the frequency of MGUS in the general population there are few studies which have assessed MGUS in solid organ transplant patients. An increased incidence of monoclonal gammopathy in patients with autoimmune disease and in older non-transplant populations suggests that impaired immunity might lead to development of MGUS and later monoclonal B-cell malignancies. Interestingly, we identified two cases where MGUS appeared after transplant. In this series, we report on the incidence and follow/up of MGUS in patients screened before transplantation. The primary outcome for transplant recipients is unaffected by the presence of MGUS and incidence is in accordance with the expected frequency (2.8%). Patients with MGUS do not appear to be at risk for progression due to chronic immunosuppression. Testing for MGUS before transplantation is not cost-efficient and therefore would not be recommended. To our knowledge this is the largest series of MGUS and transplant outcome yet reported.Table 1Clinical characteristics among MGUS casesCharacteristicMedian and RangeN=34Age60 (46-84)GenderMale 25Female 9IgG30IgM2Biclonal2Kappa24Lambda9Kappa and lambda1BMPC (17)Median 3 (0-7%)M spikeMedian 0.4 (0.2-2.3)Evolving type0/34Progression to active myeloma0/34Abb: BMPC: Bone marrow plasma cell number Disclosures:Stewart:Takeda-Millenium, Celgene, Novartis, Amgen: Consultancy; Takeda, Millenium: Research Funding; Genzyme, Celgene, Millenium, Proteolix: Honoraria.

Prevalence and Risk Factors of Monoclonal Proteinemia in Thai Population.

Abstract 1416Poster Board I-439 Background:Monoclonal gammopathy of undetermined significance (MGUS) is associated with progression to multiple myeloma and related hematologic malignancies at the rate of 1% per year in western population. Reliable information on prevalence, risk factors and natural history of MGUS in general population are necessary for designing an early detection strategy for myeloma in Thailand. Patients and methods:The study was performed in subjects, 50 years of age or older, in Bangkok, one nearby province and 2 remote provinces of Thailand. The demographic data and suspected risk factor history were collected by questionnaires. Complete blood count as well as blood chemistry were done to exclude underlying hematologic and/or systemic conditions. Serum monoclonal proteins were detected using high-resolution gel electrophoresis. Results:Serum samples were obtained from 3,261 participants. There were 1,105 males (33.9%) and 2,156 females (66.1%). The median age was 57. Abnormal protein electrophoresis findings were detected in 76 samples (prevalence 2.3%, 95% confidence interval [CI] 1.8% - 2.8%) showing small M-spikes at gamma-globulin region in 50 (1.5%) or at beta-globulin region in 25 (0.8%) or hypogammaglobulinemia in 1 case (0.03%). The prevalence of MGUS in subjects less than 60, 60-69 and 70 yrs or more was 2.0% (41/1975), 2.6% (22/851) and 3.0% (13/435), respectively. Using multivariate analysis, presence of MGUS was strongly associated with history of drug abuse (odd ratio 4.63, 95%CI 1.14-22.08) and current residences outside Bangkok (odd ratio 2.30, 95%CI 1.18-4.79). Radiation and chemical exposure, hair and nail-coloring products and pesticides were not statistically significant risk factors in our population. Conclusions:The overall prevalence of MGUS in Thai population was 2.3%, lower than those of western countries but comparable to what reported from Japan and Taiwan. Disclosures:No relevant conflicts of interest to declare.

The relationship between monoclonal gammopathy of undetermined significance and venous thromboembolic disease

Introduction Monoclonal gammopathy of undetermined significance (MGUS) has been proposed to be a risk factor for venous thromboembolic disease (VTE). However, no series published to date has been population-based or included a control group with similar comorbidities to people with MGUS. Patients/Methods We reviewed the records of all the male veterans in a single VA healthcare system with MGUS between January 1, 1996 and December 31, 2005. We compared the rate of VTE in 166 patients with MGUS with the rate of VTE in an age-matched control group of 465 patients who had tested negative for monoclonal gammopathy by serum protein electrophoresis (SPEP). Results The VTE rate in the MGUS group was 2.2 per 100 person-years, which was not significantly different from the rate in the control group, 1.4 per 100 person-years (HR 1.38, CI 0.63-3.01, p = 0.42). Most VTE events occurred within 4 months of the diagnosis of MGUS. In univariate analysis, albumin level (HR 0.21, CI 0.1-0.41, p < 0.001), abnormal leukocyte count (HR 2.53, CI 1.09-5.86, p = 0.03), and history of prior VTE (HR 4.41, CI 1.69-11.54, p = 0.003) were associated with increased risk of VTE. On multivariate analysis, albumin level and history of prior VTE remained significant, but presence of MGUS was still not significantly associated with VTE risk. Conclusion Our results suggest that the increased rate of VTE in people with MGUS may be primarily due to other underlying conditions that led to testing for a monoclonal gammopathy rather than to the monoclonal gammopathy itself.