Patterns of Monoclonal Immunoglobulins and Serum Free Light Chains Are Significantly Different in African-American Compared to Caucasian MGUS Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 2838-2838
Author(s):  
Brendan Weiss ◽  
Alex Minter ◽  
Matthew Laquer ◽  
Robin Howard ◽  
Jude Abadie ◽  
...  
Keyword(s):  
Light Chain ◽  
Mayo Clinic ◽  
Medical Center ◽  
Prospective Trial ◽  
Retrospective Chart Review ◽  
Lower Proportion ◽  
Walter Reed Army Medical ◽  
Lambda Light Chain ◽  
Serum Free ◽  
Risk Of Progression

Abstract Abstract 2838 Poster Board II-814 Background. Monoclonal gammopathy of undetermined significance (MGUS), the precursor of multiple myeloma (MM), is 2- to 3-fold more common in African-Americans (AA) than Caucasians (CA). Prior studies have reported clinical features of MGUS and MM to be different among AA compared to CA. Recent studies on CA MGUS cases have found serum free kappa and lambda light chain assays (sFLC) to be highly predictive of MM progression. We have conducted the first study designed to evaluate patterns of sFLC markers in AA. Methods. All AA MGUS patients seen at Walter Reed Army Medical Center (WR) and the Washington DC Veteran's Affairs Medical Center (VA) 2005-2009 were eligible. WR patients were enrolled through a retrospective chart review as sFLC has been performed routinely on MGUS patients. VA patients were enrolled in a prospective trial and sFLC was performed at WR. All patients were categorized for their risk of progression using the Mayo Clinic model (Rajkumar SV Blood 2005) and compared to the Caucasian Mayo Clinic population by the Fisher's exact test (2-tailed). Results. Eighty-six patients were enrolled, the median age was 73 yrs (42-92) and 74% were male. The MGUS isotype was 87% IgG, 10% IgA, 2% IgM and 1% biclonal. Kappa and lambda light chain disorders were present in 61% and 38%, respectively. The median monoclonal Ig concentration was 0.56 gm/dL (trace-2.33), 47% had a concentration '0.5 g/dL, 30% 0.51-1.0, 20% 1-2 g/dL, and 2% 2-3 g/dL. An abnormal sFLC ratio was present in 49% of patients. Based on the Mayo Clinic model, the risk of progression was: low 42% (95%CI 32-52), low-intermediate 49% (39-59), high-intermediate 8% (4-16) and high 1% (0-7). In comparing our data to the Mayo Clinic data, AA have significantly different distributions of MGUS isotype (p =0.001), lower monoclonal Ig concentration (p=0.0005), presence of an abnormal sFLC ratio (p=0.004) and distributions of Mayo Clinic risk groups (p=0.008) (see table). Conclusions. The clinical and laboratory features of AA patients with MGUS are distinctly different than in Caucasians, in particular a lower proportion of IgM MGUS, lower monoclonal Ig levels, a higher proportion of abnormal sFLC ratios, and fewer higher-risk patients. IgM MGUS is the precursor to Waldenstrom's macroglobulinemia (WM) and the lower proportion of IgM MGUS in AA is consistent with the very low rate of WM in AA. Non-IgM MGUS should be considered a separate entity and a direct comparison of AA and CA non-IgM MGUS patients using the Mayo Clinic data is planned. The significance of these differences on the risk of malignant progression will require prospective studies in racially diverse populations. Disclosures: Weiss: The Binding Site, Inc.: Research Funding.

Rare Concomitance of Primary Systemic Amyloidosis with Immunoglobulin M Monoclonal Gammopathy or Waldenstrom Macroglobulinemia.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1502-1502
Author(s):  
Kathleen A. Hecksel ◽  
Martha Q. Lacy ◽  
Angela Dispenzieri ◽  
Morie A. Gertz
Keyword(s):  
Median Survival ◽  
Light Chain ◽  
Mayo Clinic ◽  
Plasma Cells ◽  
Systemic Amyloidosis ◽  
Lambda Light Chain ◽  
Waldenström Macroglobulinemia ◽  
Waldenstrom Macroglobulinemia ◽  
Amyloid Cardiomyopathy ◽  
Echocardiographic Evidence

Abstract Introduction: Primary systemic amyloidosis occurs when a clonal plasma cell population secretes light chains (or light chain fragments) that deposit in tissues as amyloid and cause organ failure and ultimately patient death. Primary systemic amyloidosis generally results from non-proliferative small populations of plasma cells. While it is known that IgG, IgA and light chain producing plasma cells can secrete amyloid in association with myeloma, fewer medical professionals recognize that IgM-secreting lymphoplasmacytic cells can produce amyloid proteins. When monoclonal IgM secreting marrow lymphocytes are present, amyloidosis can result with or without overt Waldenstrom Macroglobulinemia. Patients and Methods: All patients seen at the Mayo Clinic between January 1968 and August 2000 with both a serum IgM monoclonal protein and biopsy-proven amyloidosis were analyzed. The Mayo Clinic Dysproteinemia Database recognized 128 patients (42 female, 86 male) with a median age of 65 years. Results: Seventy-two percent (n=92) of the patients have died with a median survival of 1.72 years following biopsy proven amyloidosis (figure 1). Median serum IgM monoclonal spike was 1.38 g/dL. In addition, serum IgM kappa to lambda light chain ratios (1:3) were found to be reversed in patients with IgM gammopathy when amyloid was present (compared to the reverse ratio (3:1) in patients with Waldenstrom macroglobulinemia in the absence of amyloidosis). Subcutaneous fat, rectum and bone marrow revealed amyloid in 72%, 69% and 70%, respectively, providing non-invasive techniques for amyloidosis diagnosis without the risks of bleeding associated with renal or hepatic percutaneous biopsy. Variables not shown to affect survival included the following: age, gender, serum M spike, urine protein, alkaline phosphatase, creatinine, light chain isotype, ejection fraction, and percent marrow plasma cells. The presence of amyloid cardiomyopathy (defined as a cardiac interventricular septal thickness greater than 12 mm.) was the only variable to adversely affect survival. Of the patients with echocardiographic evidence of cardiomyopathy, the median survival was 10.8 months. In contrast, the patients without echocardiographic evidence of cardiomyopathy at diagnosis had a median survival of 39 months (figure 2). Conclusion: Amyloidosis is underappreciated and should be considered in the differential diagnosis of all patients presenting with IgM gammopathy. Patients found to have amyloidosis in this setting should be tested for amyloid cardiomyopathy, as its presence predicts poor outcome. Lambda light chain in serum IgM samples should increase the index of suspicion for the presence of amyloid since IgM lambda is present in only 25% of IgM MGUS or Macroglobulinemia patients but is seen in 75% of IgM amyloidosis patients. Figure Figure

A Pre-Existing Plasma Cell Disorder Occurs in Most Patients with Multiple Myeloma.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1693-1693 ◽  
Author(s):  
Brendan M Weiss ◽  
Pramvir Verma ◽  
Jude Abadie ◽  
Robin Howard ◽  
Michael Kuehl
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Light Chain ◽  
Medical Center ◽  
Walter Reed Army Medical ◽  
Cell Transplant ◽  
Serum Samples ◽  
Published Evidence ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Abstract Background. A pre-existing plasma cell disorder (PPCD), such as monoclonal gammopathy of undetermined significance (MGUS), is thought to be present in at least one-third of patients presenting with symptomatic multiple myeloma (MM). However, no study has comprehensively evaluated the proportion of patients with MM that had a PPCD by laboratory testing on pre-diagnostic sera. Methods. The Walter Reed Army Medical Center autologous stem cell transplant database was cross-referenced with the Department of Defense Serum Repository (DoDSR) database, which catalogs serum samples collected every 2 years on over 4 million active-duty service members. All samples 32 years prior to the diagnosis of MM were retrieved. Serum protein electrophoresis (SPEP), immunofixation electrophoresis (IFE) and serum free light chain analysis (sFLC) (The Binding Site, San Diego, CA) were performed on all samples. A PPCD was defined as a positive SPEP, IFE or abnormal sFLC ratio. Results. Serum samples prior to the diagnosis of MM were available for 30/90 patients, and the median number of samples per patient was 3.5 (range, 1–14). The median age at diagnosis of MM was 48.1 yrs (29–67), with 96% male, 53% Caucasian, and 47% African-American. The Ig isotype of MM was IgG 76%, IgD 10%, light-chain 7%, and non-secretory 7%. A PPCD was detected in 27/30 patients (90%, 95% CI 74–97%). The initial PPCD was detected by sFLC alone in 6/27 (22.2%), IFE alone 2/27 (7.4%), SPEP+IFE 5/27 (18.5%), SPEP+IFE+sFLC 13/27 (48.1%) and IFE+sFLC 1/27 (3.7%). There were 4 patients whose only positive sera was 2.5–3.5 years prior to diagnosis, with all preceding sera negative. Conclusions. First, a pre-existing plasma cell disorder is present in most MM patients at least 2.5 years prior to diagnosis. Second, consistent with published evidence for a small fraction of patients with high risk MGUS, 4/30 patients were documented to progress rapidly through an MGUS phase to MM. Third, 4/4 patients with light chain only or non-secretory MM had a PPCD that was detected only by sFLC, thereby indicating that all these tumors are preceded by a light chain only or non-secretory PPCD.

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 Judging disease activity in rheumatoid arthritis by serum free kappa and lambda light chain levels

2013 ◽  
Vol 29 (10) ◽  
pp. 547-553 ◽  
Author(s):  
Yun Ye ◽  
Su-Liang Li ◽  
Ming Xie ◽  
Ping Jiang ◽  
Kai-Ge Liu ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Disease Activity ◽  
Light Chain ◽  
Lambda Light Chain ◽  
Serum Free

Idiopathic Bence Jones Proteinuria: Clinical Course and Prognosis.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 3493-3493 ◽  
Author(s):  
Robert Kyle ◽  
Terry Therneau ◽  
Angela Dispenzieri ◽  
Dirk Larson ◽  
Matthew Plevak ◽  
...  
Keyword(s):  
Relative Risk ◽  
Plasma Cell ◽  
Light Chain ◽  
Mayo Clinic ◽  
Hazard Ratio ◽  
M Protein ◽  
Increased Risk ◽  
Risk Of Progression ◽  
Bence Jones Proteinuria

Abstract Chronic Idiopathic Bence Jones Proteinuria (first reported in 1982) is an asymptomatic plasma cell proliferative disorder that is associated with a risk of progression to symptomatic multiple myeloma (MM) or primary amyloidosis (AL). We defined it as the presence of a monoclonal light chain in the urine, absence of an intact immunoglobulin M protein (IgH expression) in the serum, fewer than 10% bone marrow plasma cells (if done), and no evidence of MM, AL or other related plasma cell proliferative disorders. Following approval by the Mayo Clinic Institutional Review Board, we searched a computerized database and reviewed the records of all patients who were seen at Mayo Clinic within 30 days of the recognition of a monoclonal light chain (Bence Jones protein) in the urine between 1960 and 1996. Patients found to have end-organ damage at diagnosis as the result of the plasma cell proliferative disorder (including MM or AL), received chemotherapy, or had a nephrotic syndrome were excluded. Follow-up included review of each subject’s medical record at Mayo Clinic as well as review of death certificates for patients who died. Patients were sent letters of inquiry if they had not visited Mayo Clinic in the preceding year. The risk of progression to MM and AL was compared to those expected on the basis of Surveillance, Epidemiology and End Results (SEER) rates for MM in Iowa and the prevalence of AL in Olmsted County, Minnesota. Two-hundred twenty-three patients fulfilled the criteria for Idiopathic Bence Jones Proteinuria during the 37-year period (1960 – 1996). The median age at diagnosis was 69 yrs (range, 36–90 yrs) and only 1% were < 40 years of age. Sixty-seven percent were male. The urine M protein ranged from unmeasurable to 4.7 g/24h. The median was 0.09 g/24h and only 8% were > 1 g/24h. Kappa light chain accounted for 57% while lambda was present in 43%. Eighty-one percent of patients died during follow-up. Twenty-six percent had a monoclonal light chain in the serum on immunofixation. Concentrations of uninvolved (normal, polyclonal or background) immunoglobulins were reduced in 45%. During 1408 person years of follow-up, 11 patients developed symptomatic MM (relative risk 28.5; 95% CI, 14.3 – 51.1) and an additional 9 patients developed AL (relative risk 61.8; 95% CI, 28.3 – 117.4). The cumulative probability of progression to active MM or AL was 7% at 5 yrs, 13.5% at 10 yrs., and 18% at 15 yrs. The factors evaluated with respect to predicting progression to MM or AL included sex, hemoglobin value, serum albumin, amount of urine M protein/24h, type of urine light chain (kappa or lambda), reduction of uninvolved (background) immunoglobulins, and elevation of serum calcium or creatinine. The amount of the urine M protein/24h was the only significantly predictive parameter for progression. As a continuous variable, a higher urine M protein was associated with an increased risk of progression (hazard ratio = 2.1 for a 1g increase, p=0.003). The amount of the urine M protein was also significant as a dichotomous variable. Patients who had a urine M protein ≥ 1g/24h had an increased risk of progression (hazard ratio = 3.6, p=0.007). We conclude that patients with Idiopathic Bence Jones Proteinuria are at risk for the development of MM or AL and need to be followed indefinitely.

scholarly journals Kappa and lambda light chain disease: survival rates and clinical manifestations

Blood ◽  
1976 ◽  
Vol 48 (1) ◽  
pp. 41-51 ◽  
Author(s):  
C Shustik ◽  
DE Bergsagel ◽  
W Pruzanski
Keyword(s):  
Light Chain ◽  
Clinical Stage ◽  
Survival Rates ◽  
Clinical Manifestations ◽  
Lower Proportion ◽  
Response To Treatment ◽  
Cell Leukemia ◽  
Lambda Light Chain ◽  
Osteolytic Lesions ◽  
Light Chain Disease

Abstract Ninety-seven patients with light chain disease (LCD) were studied. The median survival from diagnosis was 30 mo for 52 patients with kappa-LCD and 10 mo for 45 patients with lambda-LCD (p less than 0.0007). A lower proportion of kappa-LCD patients (15.7%) than lambda-LCD patients (42.2%) died within the first 6 mo after diagnosis. The survival of the remaining patients with kappa-LCD was still much longer than of those with lambda-LCD (p = 0.022). The shorter survival of lambda-LCD patients could not be ascribed to an increased incidence of recognized manifestations indicating a poor prognosis (e.g., anemia, hypercalcemia, azotemia, low albumin, the extent of osteolytic lesions, or proteinuria), the incidence of amyloidosis, the clinical stage of the disease at diagnosis, or the response to treatment, and remains unexplained. A comparison of the clinical manifestations of LCD with those of other myelomas revealed some differences. LCD patients were slightly younger than IgA and IgG patients but older than IgD patients. A 1:1 ratio of males to females was similar to the ratios in IgA and IgG myeloma, but differed from the 3:1 ratio reported for IgD myeloma. Plasma-cell leukemia developed in 7/97 LCD patients, an incidence that was higher than has been reported in other myelomas. The initial BUN was more than or equal to 30 mg/100 ml in 54 of 95 LCD patients, an incidence that was higher than has been reported for IgA and IgG myeloma, but lower than the incidence in IgD myeloma. The incidence of amyloidosis in LCD (23 of 97 patients) was similar to that reported for IgA and IgG myeloma, but less than the incidence in IgD myeloma.

scholarly journals Kappa and lambda light chain disease: survival rates and clinical manifestations

Blood ◽  
1976 ◽  
Vol 48 (1) ◽  
pp. 41-51
Author(s):  
C Shustik ◽  
DE Bergsagel ◽  
W Pruzanski
Keyword(s):  
Light Chain ◽  
Clinical Stage ◽  
Survival Rates ◽  
Clinical Manifestations ◽  
Lower Proportion ◽  
Response To Treatment ◽  
Cell Leukemia ◽  
Lambda Light Chain ◽  
Osteolytic Lesions ◽  
Light Chain Disease

Ninety-seven patients with light chain disease (LCD) were studied. The median survival from diagnosis was 30 mo for 52 patients with kappa-LCD and 10 mo for 45 patients with lambda-LCD (p less than 0.0007). A lower proportion of kappa-LCD patients (15.7%) than lambda-LCD patients (42.2%) died within the first 6 mo after diagnosis. The survival of the remaining patients with kappa-LCD was still much longer than of those with lambda-LCD (p = 0.022). The shorter survival of lambda-LCD patients could not be ascribed to an increased incidence of recognized manifestations indicating a poor prognosis (e.g., anemia, hypercalcemia, azotemia, low albumin, the extent of osteolytic lesions, or proteinuria), the incidence of amyloidosis, the clinical stage of the disease at diagnosis, or the response to treatment, and remains unexplained. A comparison of the clinical manifestations of LCD with those of other myelomas revealed some differences. LCD patients were slightly younger than IgA and IgG patients but older than IgD patients. A 1:1 ratio of males to females was similar to the ratios in IgA and IgG myeloma, but differed from the 3:1 ratio reported for IgD myeloma. Plasma-cell leukemia developed in 7/97 LCD patients, an incidence that was higher than has been reported in other myelomas. The initial BUN was more than or equal to 30 mg/100 ml in 54 of 95 LCD patients, an incidence that was higher than has been reported for IgA and IgG myeloma, but lower than the incidence in IgD myeloma. The incidence of amyloidosis in LCD (23 of 97 patients) was similar to that reported for IgA and IgG myeloma, but less than the incidence in IgD myeloma.

scholarly journals Comparison of lambda and kappa light-chain cardiac amyloidosis in Polish patients diagnosed in cardiology department

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
J.A Szczygiel ◽  
P Michalek ◽  
J Drozd-Sokolowska ◽  
M Ziarkiewicz ◽  
Z.T Bilinska ◽  
...  
Keyword(s):  
Light Chain ◽  
Cardiac Amyloidosis ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Free Light Chains ◽  
Lambda Light Chain ◽  
Serum Free ◽  
Kaplan Meier ◽  
Cardiology Department ◽  
Serum Free Light Chains

Abstract Background Lambda (λ) and kappa (κ) types of light-chain amyloidosis (AL amyloidosis) are believed to have a similar prognosis. Data on the comparison of these two types of cardiac amyloidosis is scanty. Objectives The aim of the study was to investigate wether lambda light-chain cardiac amyloidosis indicates worse prognosis than the kappa variety. Methods The initial analysis covered all consecutive pts with cardiac AL amyloidosis diagnosed in the cardiology department from August 2011 to August 2019. Diagnosis was confirmed by increased serum free light-chains and positive tissue biopsy. Amyloid type was identified using immunohistochemical reactions. Blood pressure and heart rate (HR) were measured on admission. The difference between involved and uninvolved serum free light chains (dFLC), NT-proBNP, high-sensitivity troponin T (hs-TnT), creatinine, potassium, albumin and total protein were measured. During echocardiography, tissue Doppler imaging was used to assess early lateral (e' lat) and septal mitral annulus velocities and longitudinal myocardial velocities of ventricles. Standard parameters were measured. The presence of pleural effusion was assessed in chest X-ray. Results Sixty-four pts were diagnosed with AL amyloidosis. Four pts were excluded from the final analysis due to ambiguous amyloid typing. Median (interquartile range, IQR) age was 61 (52–67) yrs. Median (IQR) dFLC was 19.9 (5.5–50.6) mg/dL. Median NT-proBNP and hs-TnT concentrations were 4948 (2251–10206) pg/ml and 77 (39–139) ng/l, respectively. Forty-four pts had a λ type AL amyloidosis (73.3%). There were significant differences (p&lt;0.05) between the λ and the κ groups in regard to: HR (80 vs. 73.5 BPM), systolic blood pressure (102 vs. 117 mmHg), serum creatinine (88 vs. 116 umol/L) and potassium (4.4 vs. 4.9 mmol/L), e' lat (5 vs. 7.5 cm/sec), left ventricular end-diastolic diameter (LVEDD, 42 vs. 46 mm), right ventricular end-diastolic diameter (RVEDD, 35 vs. 40 mm) and right ventricular wall thickness (8 vs. 6 mm). Pleural and pericardial effusions were more frequent in the λ group (59% vs. 19% and 80% vs. 44%, respectively) according to Fisher's exact test (p&lt;0.05). Median (IQR) survivals for the λ and the κ groups were 3 (2–9) and 16 (5.5–22) months, respectively (p=0.03). The Kaplan-Meier curves analysis showed a trend towards worse survival of the λ group (Log rank test, p=0.08). Conclusions Cardiologists should be aware that lambda light-chain cardiac amyloidosis may indicate shorter survival than the kappa variety, although kappa AL amyloidosis may be associated with worse kidney function. Further research would be worth considering. Kaplan-Meier curves, Time (months) Funding Acknowledgement Type of funding source: Public grant(s) – National budget only. Main funding source(s): Institute of Cardiology

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