Light Chain Predominant Intact Immunoglobulin Monoclonal Gammopathy Disorders: Shorter Survival in Light Chain Predominant Multiple Myelomas

2020 ◽  
Author(s):  
Gurmukh Singh ◽  
Hongyan Xu
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Change Point ◽  
Monoclonal Gammopathy ◽  
Biological Significance ◽  
Data Set ◽  
Serum Free ◽  
Associated Lesions ◽  
Multiple Myelomas ◽  
Undetermined Significance

Abstract Background A proportion of intact immunoglobulin (Ig)–producing multiple myelomas (MMs) was observed to secrete much higher amounts of free light chains (LCs) than usual. Objectives To determine the change point between usual and LC-predominant intact Ig-secreting MMs and other monoclonal gammopathic manifestations and the biological significance of the observation. Methods We conducted retrospective examination of laboratory findings in 386 MM, 27 smoldering MM, and 179 monoclonal gammopathy of undetermined significance (MGUS) cases that secreted intact Igs. We recorded the highest levels of involved serum free LC, highest ratio of involved to uninvolved LC, highest concentration of involved LC per g of monoclonal Ig, and highest value for ratio of involved to uninvolved LCs divided by the monoclonal Ig concentration. Each data set was sorted into kappa- and lambda LC-associated lesions. Length of time, in months, between diagnosis and last contact with the patients having myeloma was recorded. Results Change point analysis of data revealed a subgroup of cases with distinctly higher levels of free LCs. In myelomas, including plasma cell leukemias, 16.4% of myelomas with kappa LCs and 22.3% of myelomas with lambda LCs, the LC secretion was distinctly higher than in the remaining cases, by a combination of 4 parameters, listed herein. Corresponding figures for smoldering myeloma (SMM) and monoclonal gammopathy of undetermined significance (MGUS) were 12.5, 27.3, 3.8, and 6.8, respectively. Ten of the 13 (77%) cases of plasma cell leukemia) and all cases of IgD myeloma (n = 4) showed excess secretion of serum free LCs. Among IgG and IgA myelomas, including plasma cell leukemias, the LC-predominant lesions had shorter survival, by an average of 22.5 months. Conclusions In total, 18.4% of MMs, including plasma cell leukemias, secrete distinctly higher amounts of serum free LCs than other intact Ig-secreting myelomas and confer significantly lower survival. Quantification of monoclonal serum free LCs may be useful in this subgroup in monitoring progress and potentially in ascertaining minimal residual disease. The findings also stress the need for separate criteria for kappa and lambda LC associated monoclonal gammopathic manifestations. The significantly shorter survival of patients with LC-predominant myelomas warrants consideration in prospective trials of treatments.

scholarly journals Incidentally Detected Amyloid Light-Chain Amyloidosis Caused by Monoclonal Gammopathy of Undetermined Significance: Possible Time-Dependent Change in Colonic Findings

2018 ◽  
Vol 12 (3) ◽  
pp. 737-746
Author(s):  
Toshiro Fukui ◽  
Yuji Tanimura ◽  
Yasushi Matsumoto ◽  
Shunsuke Horitani ◽  
Takashi Tomiyama ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Amyloid Deposition ◽  
Fecal Occult Blood ◽  
Al Amyloidosis ◽  
Plasma Cell Disorder ◽  
Amyloid Light Chain ◽  
Cell Disorder ◽  
Undetermined Significance

Amyloid light-chain (AL) amyloidosis is associated with plasma cell disorder and monoclonal light chains. This type of amyloidosis is the prominent type involving the gastrointestinal tract. Monoclonal gammopathy of undetermined significance (MGUS) is the most common plasma cell disorder and a known precursor of more serious diseases. A 72-year-old male was treated for high blood pressure, diabetes, and gout at the clinic of a private physician. Due to a positive fecal occult blood test discovered during colon cancer screening, he underwent colonoscopy and was diagnosed with adenomatous polyps by biopsies. Two months later, he was referred to our hospital for endoscopic resection of the polyps. Although the polyps were successfully removed, a colonoscopy revealed two types of ulcerative lesions. Immunohistopathological evaluations obtained from these lesions and polyps confirmed amyloid deposition. Although esophagogastroduodenoscopy results were normal, a biopsy specimen from the patient’s stomach showed the same type of amyloid deposition. Immunoelectrophoresis showed M-proteins for anti-IgG-λ in the serum and λ type Bence-Jones protein in the urine. His blood, bone marrow, and urine test results led to a diagnosis of MGUS. A coronary angiography revealed multivessel stenosis, and the patient’s cardiac function improved after coronary artery stenting. Hereafter, a combination therapy with bortezomib, lenalidomide, and dexamethasone is planned. This is a case report of systemic AL amyloidosis caused by MGUS, which was incidentally detected by colonoscopy.

scholarly journals A monoclonal gammopathy precedes multiple myeloma in most patients

Blood ◽  
2009 ◽  
Vol 113 (22) ◽  
pp. 5418-5422 ◽  
Author(s):  
Brendan M. Weiss ◽  
Jude Abadie ◽  
Pramvir Verma ◽  
Robin S. Howard ◽  
W. Michael Kuehl
Keyword(s):  
Multiple Myeloma ◽  
Serum Protein ◽  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Protein Electrophoresis ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Chain Analysis ◽  
Immunofixation Electrophoresis

Preexisting plasma cell disorders, monoclonal gammopathy of undetermined significance, or smoldering myeloma are present in at least one-third of multiple myeloma patients. However, the proportion of patients with a preexisting plasma cell disorder has never been determined by laboratory testing on prediagnostic sera. We cross-referenced our autologous stem cell transplantation database with the Department of Defense Serum Repository. Serum protein electrophoresis, immunofixation electrophoresis, and serum free light-chain analysis were performed on all sera collected 2 or more years before diagnosis to detect a monoclonal gammopathy (M-Ig). In 30 of 90 patients, 110 prediagnostic samples were available from 2.2 to 15.3 years before diagnosis. An M-Ig was detected initially in 27 of 30 patients (90%, 95% confidence interval, 74%-97%); by serum protein electrophoresis and/or immunofixation electrophoresis in 21 patients (77.8%), and only by serum free light-chain analysis in 6 patients (22.2%). Four patients had only one positive sample within 4 years before diagnosis, with all preceding sera negative. All 4 patients with light-chain/nonsecretory myeloma evolved from a light-chain M-Ig. A preexisting M-Ig is present in most multiple myeloma patients before diagnosis. Some patients progress rapidly through a premalignant phase. Light-chain detected M-Ig is a new entity that requires further study.

scholarly journals Serum free light chain ratio is an independent risk factor for progression in monoclonal gammopathy of undetermined significance

Blood ◽  
2005 ◽  
Vol 106 (3) ◽  
pp. 812-817 ◽  
Author(s):  
S. Vincent Rajkumar ◽  
Robert A. Kyle ◽  
Terry M. Therneau ◽  
L. Joseph Melton ◽  
Arthur R. Bradwell ◽  
...  
Keyword(s):  
Risk Factors ◽  
Risk Factor ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
M Protein ◽  
Intermediate Risk ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Risk Of Progression ◽  
Undetermined Significance

AbstractWe hypothesized that the presence of monoclonal free kappa or lambda immunoglobulin light chains in monoclonal gammopathy of undetermined significance (MGUS), as detected by the serum free light chain (FLC) assay increases the risk of progression to malignancy. Of 1384 patients with MGUS from Southeastern Minnesota seen at the Mayo Clinic from 1960 to 1994, baseline serum samples obtained within 30 days of diagnosis were available in 1148. At a median follow-up of 15 years, malignant progression had occurred in 87 (7.6%) patients. An abnormal FLC ratio (kappa-lambda ratio < 0.26 or > 1.65) was detected in 379 (33%) patients. The risk of progression in patients with an abnormal FLC ratio was significantly higher compared with patients with a normal ratio (hazard ratio, 3.5; 95% confidence interval [CI], 2.3-5.5; P < .001) and was independent of the size and type of the serum monoclonal (M) protein. Patients with an abnormal serum FLC ratio, non–immunoglobulin G (non-IgG) MGUS, and a high serum M protein level (≥ 15 g/L) had a risk of progression at 20 years of 58% (high-risk MGUS) versus 37% with any 2 of these risk factors (high-intermediate risk), 21% with one risk factor (low-intermediate risk), and 5% when none of the risk factors were present (low risk).

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.

scholarly journals Ig VH gene mutational patterns indicate different tumor cell status in human myeloma and monoclonal gammopathy of undetermined significance

Blood ◽  
1996 ◽  
Vol 87 (2) ◽  
pp. 746-755 ◽  
Author(s):  
SS Sahota ◽  
R Leo ◽  
TJ Hamblin ◽  
FK Stevenson
Keyword(s):  
Multiple Myeloma ◽  
Tumor Cell ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Somatic Hypermutation ◽  
Wide Spectrum ◽  
Malignant Potential ◽  
Gene Sequences ◽  
Vh Gene ◽  
Undetermined Significance

Plasma cell tumors display a wide spectrum of clinical progression, ranging from aggressive multiple myeloma to a benign form known as monoclonal gammopathy of undetermined significance (MGUS), which requires no treatment. Because both diseases involve mature Ig- secreting plasma cells, the reason for this variation in malignant behavior is unclear. However, assessment of malignant potential is desirable for choice of treatment protocols. Ig variable (VH) gene sequences analysis has previously shown the tumor cell of multiple myeloma to be postfollicular, with mutated homogeneous clonal sequences indicating no continuing exposure to the somatic hypermutation mechanism, and this was confirmed in 7 of 7 patients. Comparison of the VH gene sequences in the monoclonal cells in MGUS yielded a different result, with 3 of 7 patients demonstrating mutated heterogeneous sequences consistent with the tumor cells remaining under the influence of the mutator. In 1 of 3 of these patients, an IgM-positive precursor cell was identified that expressed heterogeneous VH sequences similar to those of the isotype-switched plasma cell. These results indicate that the clonal cells in MGUS differ from those in myeloma and suggest that the difference may reflect malignant potential.

Kidney disease and plasma cell dyscrasias: ambiguous cases solved by serum free light chain dimerization analysis

2019 ◽  
Vol 23 (6) ◽  
pp. 763-772
Author(s):  
Olga Kukuy ◽  
Batia Kaplan ◽  
Sizilia Golderman ◽  
Alexander Volkov ◽  
Adrian Duek ◽  
...  
Keyword(s):  
Kidney Disease ◽  
Plasma Cell ◽  
Light Chain ◽  
Free Light Chain ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Plasma Cell Dyscrasias
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