Monoclonal gammopathy of undetermined significance (MGUS) in patients with solid tumors: effects of chemotherapy on the monoclonal protein

2004 ◽  
Vol 83 (10) ◽  
Author(s):  
Athanasios Anagnostopoulos ◽  
Eleni Galani ◽  
Dimitra Gika ◽  
Danai Sotou ◽  
Aikaterini Evangelopoulou ◽  
...  
Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4496-4496
Author(s):  
Holly Lee ◽  
Lesley Street ◽  
Jason Tay ◽  
Jennifer Grossman ◽  
John F Thaell ◽  
...  

Abstract Introduction Monoclonal gammopathy of undetermined significance (MGUS) is a prevalent hematological condition among elderly population with incidence rates of 3% and 5% over the age of 50 and 70 years, respectively (Kyle et al., 2018). It is considered a premalignant state of multiple myeloma with a risk of progression of 1% per year. It has also been shown that MGUS patients have a shorter survival compared to the age- and sex-matched cohort (Kyle et al., 2018). Recent reports have highlighted the clinical significance of monoclonal gammopathy and the organ injury that may result from the effects of paraproteinemia (Fermand et al., 2018). With new insights into the significance of monoclonal gammopathy, the purpose of our study was to characterize the MGUS patient population referred at our hematology clinics by observing the reason for monoclonal protein testing and assessing patient comorbidities at the time of MGUS diagnosis. Methods We collaborated with three different clinicians who see the majority of MGUS patients at the University of Calgary Medical Group (UCMG) clinics. Patients who were referred and diagnosed with MGUS at the hematology clinic at UCMG since 2014 were assessed. Retrospective chart reviews were performed and reasons for monoclonal testing were recorded as indicated in referral request notes or initial consult notes. Data on patient comorbidities was collected as indicated in the initial consult notes. MGUS risk stratification was calculated per previous reports (Katzmann et al., 2013; Kyle et al., 2018) Results A total of 606 MGUS patients were seen at our clinic from February 2014 to June 2018. There were 565 patient charts available for complete review. 56% of the patients were male. Median age was 72 and median follow up was 2 years. MGUS risk stratification showed that 33.2% had low, 47.9% intermediate-low, 17.8% intermediate-high, and 1.2% high-risk MGUS. There were 55.5% IgG-MGUS, 20.5% IgM-MGUS, 12.3% IgA-MGUS, and 8.4% light chain-MGUS patients. 3% had biclonal gammopathy. Patient comorbidities at time of diagnosis are reported in table 1. The most common conditions were hypertension (50.4%), dyslipidemia (33.1%), chronic kidney disease (22.4%), diabetes (21.6%), coronary artery disease (18.6%), and solid tumors (14.6%). The most common solid tumors were prostate cancer (22/ 83, 25%), colon cancer (12/83, 14.4%), and breast cancer (10/83, 12.0%). Of the 565 patient charts, 140 had either missing referral sheets or had no record of the reasons for paraproteinemia investigations in the notes. In the rest of the 425 patients, the most common reason for monoclonal protein testing by referring physician was for renal dysfunction, which included work up for acute kidney injury, chronic kidney injury, proteinuria and hematuria. The next most common reason was work up of neuropathy, followed by anemia, and constitutional symptoms (figure 1). The patients in the 'Others' group had various reasons for testing including work up for seizure, forgetfulness, stroke, headache, chronic pancreatitis, multiple sclerosis, myasthenia gravis, family history of myeloma, history of venous thromboembolism, splenomegaly, bronchiectasis, chest pain, and as part of routine physical and blood donor testing. Discussion and Conclusion MGUS is often incidentally detected as part of a work up for other medical conditions, and our results reveal that there is a variety of reasons for which monoclonal testing is performed. With recent developments in our understanding of the significance of monoclonal gammopathy and its association with certain renal and organ damage (Fermand et al., 2018; Leung et al., 2012), there may be a change in how the paraproteinemia investigations are utilized by clinicians in different disciplines. It will be important to recognize and establish appropriate indications for testing. Furthermore, MGUS patients present with a wide range of comorbidities at the time of diagnosis. Interdisciplinary care will play a key role in discerning how much of the organ dysfunction and patients' symptoms are secondary to their underlying medical conditions versus the effect of monoclonal gammopathy. Disclosures McCulloch: Celgene: Honoraria; Takeda: Other: Travel expenses. Neri:Celgene: Consultancy, Honoraria; Janssen: Consultancy, Honoraria.


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 ◽  
...  

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.


Hematology ◽  
2012 ◽  
Vol 2012 (1) ◽  
pp. 595-603 ◽  
Author(s):  
Giampaolo Merlini ◽  
Giovanni Palladini

Abstract Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic plasma cell disorder occurring in 4.2% of adults > 50 years of age, which can progress into symptomatic diseases either through proliferation of the plasma cell clone, giving rise to multiple myeloma and other lymphoplasmacellular neoplasms, or through organ damage caused by the monoclonal protein, as seen in light-chain amyloidosis and related conditions. Differential diagnosis of asymptomatic and symptomatic monoclonal gammopathies is the determinant for starting therapy. The criteria for determining end-organ damage should include markers of organ injury caused by the monoclonal protein. Patient assessment and optimal follow-up are now performed using risk stratification models that should also take into account the risk of developing AL amyloidosis. Patients with low-risk MGUS (approximately 40% of all MGUS patients) need limited assessment and very infrequent follow-up. The ongoing development of novel molecular biomarkers and advanced imaging techniques will improve the identification of high-risk patients who may benefit from early therapeutic intervention through innovative clinical trials.


2019 ◽  
Vol 28 (12) ◽  
pp. 2055-2061
Author(s):  
Su-Hsin Chang ◽  
Jason Gumbel ◽  
Suhong Luo ◽  
Theodore S. Thomas ◽  
Kristen M. Sanfilippo ◽  
...  

2020 ◽  
Vol 8 ◽  
pp. 232470962094050
Author(s):  
Asim Kichloo ◽  
Najma Nawaz ◽  
Jagmeet Singh ◽  
Michael Aljadah ◽  
Michael Stanley Albosta ◽  
...  

Monoclonal gammopathy of undetermined significance is a precursor to multiple myeloma characterized by monoclonal gammopathy without evidence of end organ damage. Some patients with clonal plasma cell disorder that do not meet the requirements for multiple myeloma have been seen to develop pathologic renal disease due to direct effects from deposition of monoclonal protein, referred to as monoclonal gammopathy of renal significance. In this article, we present a rare renal manifestation of monoclonal gammopathy of renal significance as focal segmental glomerulosclerosis.


Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 5123-5123
Author(s):  
Federico Sackmann ◽  
Claudia Corrado ◽  
Isolda Fernandez ◽  
Miguel A Pavlovsky ◽  
Pablo Mountford ◽  
...  

Abstract Background: monoclonal gammopathy of undetermined significance (MGUS) has a prevalence of 1 to 3%. Although it has an indolent evolution, some patients (pts) will develop a malignant transformation. Thus, prognostic factors that may identify pts who will progress are important. We update our experience published before. Methods: we performed a retrospective analysis of 387 pts with MGUS diagnosed between 1982 and 2008 in our institution to identify simple haematological variables associated with progression. Actuarial progression free survival (PFS) and overall survival (OS) were also calculated. MGUS was diagnosed when monoclonal component (MC) was present at a concentration of 3 gr per decilitre or less, no or only moderate amounts of monoclonal light chains in the urine, absence of lytic bone lesions, anemia, hypercalcemia and renal insufficiency related to monoclonal protein; and if performed a proportion of plasma cells of 10 percent or less. MC was detected by agarose gel and/or cellulose acetate electrophoresis in serum and/or urine. The identification of the MC was performed by immunoelectrophoresis or immunofixation and the quantification of immunoglobulins, by radial immunodifussion. Progression to myeloma was defined by: MC &gt; 3 gr/dl, plasma cell infiltration &gt; 10%, or associated lytic bone lesions. Progression to another B-cell neoplasm was considered when there was histologic evidence of the disease. The identification of prognostic factors was made using Cox models. PFS and OS were calculated using the Kaplan Meier method and the curves were compared with the log-rank test. Results: The median (md) age at diagnosis was 62 years (range 24–89 years) and 18% of the pts were younger than 50. Anemia not related to the monoclonal protein was present in 18% of the pts. Albumin, beta 2 microglobulin and erythrocyte sedimentation rate (ESR) were normal in 88%, 50% and 41% of the pts, respectively. MC was 0.6 gr/dl (range 0.1–2.9). In 70% of the cases it was IgG, 15% IgA, 13% IgM and 2% biclonal. The light chain was Kappa in 65% of the pts. Bence Jones was detected in only 9%. Uninvolved immunoglobulins (UI) were reduced in 21% of the pts. Bone marrow analysis were performed in 79 pts (20%) and md plasma cell infiltration was 3 (range 0 – 10). The 387 pts were followed for 2340 person-years (md 4.75 years, range 0 – 31) during which 31 pts (8%) evolved to a malignancy (23 multiple myeloma, 7 NHL, and 1 amyloidosis) and 17 (4.6%) died (3 related to progressive disease, 6 related to non hematological malignancy, 2 associated to cardiovascular disorders, 2 secondary to infection and 4 of unknown cause). PFS and OS at 10 years were 89% and 91%, respectively. The overall risk of progression was 1.3% per year. Among all the variables analysed (age, gender, hemoglobin, albumin, beta 2 microglobulin, ESR, type and concentration of MC, Bence Jones and reduction of UI), only MC concentration (HR 4.81, CI 2.2 – 10.32, p = 0.00007) and ESR (HR 3.67, CI 1.7 – 7.88, p = 0.001) had prognostic value for progression. Conclusions: MC concentration and ESR at diagnosis identified a subgroup of pts with higher risk of transformation in our experience.


1987 ◽  
Vol 2 (3) ◽  
pp. 169-172 ◽  
Author(s):  
Samuele Di Giovanni ◽  
Gaetano Valentini ◽  
Emma Ravazzolo ◽  
Paolo Carducci ◽  
Paolo Giallonardo ◽  
...  

Beta-2-microglobulin concentrations were determined in serum samples from 45 patients with benign and malignant monoclonal gammopathies. In the group of patients suffering from multiple myeloma or Waldenström macroglobulinemia the mean β2-microglobulin level was significantly higher than in the group with monoclonal gammopathy of undetermined significance. Values above 3 mg/L were highly indicative of a neoplastic process and were observed in all the Waldenström patients and in > 90% of myeloma patients. No significant correlation was noticed between β2-microglobulin and monoclonal protein levels in any of the groups examined.


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