Monoclonal Gammopathies: Electronic Subspecialty Consultation

Abstract Introduction : Non-visit electronic consultation (e-consult) is an important component of care for veterans in the VA healthcare system who require sub-specialty consultation but not urgent face to face evaluation. Since the majority of patients with monoclonal gammopathy of undetermined significance (MGUS) are low-risk of disease transformation, we reasoned that e-consult would be a safe and effective way to manage MGUS in most cases. Here we sought to characterize our current e-consult practice patterns for the surveillance of MGUS and identify key questions for future investigation. Methods : We performed a retrospective analysis of our electronic consult database from 1/1/2010-12/31/2014 to identify cases of monoclonal gammopathy. Monoclonal gammopathy was confirmed on chart review by an attending hematologist. To be included in the analysis, a patient had to have either 1) a monoclonal protein by serum or urine protein electrophoresis (SPEP/UPEP) or immunofixation or 2) abnormal serum free light chain (FLC) ratio, using a normal reference range of 0.26-1.65, with an increase in the involved light chain. Pertinent clinical and demographic data was abstracted and was used to analyze outcomes among the cohort. Results : We screened 3,217 electronic hematology consults to identify a cohort of 152 MGUS patients triaged for e-consult over a five-year period. E-consult services were provided for veterans from 23 different counties with an average time to completion of 3.4 days. The average size of monoclonal (M) protein was 0.25 g/dL (0-1.5 g/dL). 84% of patients had an M-protein concentration less than 0.5 g/dL. Following completion of risk-stratification studies, 113/121 (93%) of patients with available risk scores were lower risk for disease progression (0-1 risk factors). There were 11 cases with negative SPEP for whom a risk score could not be calculated. An additional 20 cases had a positive SPEP without available free light chain data. A minority of patients (29%) had FLC data available at the time of consult. At 3-months post-consult, 71% had completed FLC testing. One-third of patients had an abnormal hemoglobin (hgb) and 41% had an abnormal creatinine (cr) using the normal reference ranges. However, 96% of MGUS e-consults had a hgb >10 g/dL and 90% had a cr <2 mg/dL. Among those tested (n=91), one patient had skeletal abnormalities concerning for myelomatous bone disease on initial screening. One-third of cases utilized multiple e-consult encounters over time, while 15% of MGUS e-consults ultimately required a face-to-face visit with hematology. With an average follow-up of 47 months (median 44 months), there were 6 documented progression events, representing a mean rate of progression of 1% per year (Figure). Conclusions : We find that electronic consultation is a helpful mechanism for evaluating MGUS longitudinally, decreasing travel burden, and improving timely access to care for veterans. The majority of MGUS cases triaged for e-consult at our center are low-risk by established criteria and have very low amounts of monoclonal protein. Most of these patients can be followed with routine paraprotein surveillance and deferred skeletal imaging. Timely completion of biomarker studies is critical for appropriate risk-stratification and triage. The use of additional system tools (such as task trackers) to assist with follow-up of outstanding tests may help augment services provided electronically. These observations may be generalizable to other VA centers and other health-care systems where e-consult is becoming more widely adopted. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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

Blood ◽

10.1182/blood-2019-124715 ◽

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.

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Detection of free light chain monoclonal proteins co-migrating with intact monoclonal proteins in patients with monoclonal gammopathy

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/acb.2012.012012 ◽

2012 ◽

Vol 49 (6) ◽

pp. 603-605 ◽

Cited By ~ 1

Author(s):

Kate Wetenhall ◽

Rehana Saleem ◽

Anthony Rowbottom

Keyword(s):

Urine Sample ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Significant Proportion ◽

Free Light Chain ◽

M Protein ◽

Routine Testing ◽

M Proteins ◽

Immunofixation Electrophoresis ◽

Monoclonal Proteins

Background In a small, but potentially significant proportion of patients with a monoclonal gammopathy, patients show the existence of an intact monoclonal (M-) protein co-migrating with a free light chain (FLC) M-protein. Using traditional methods for detection of monoclonal immunoglobulins, only the intact M-protein may be detectable, and hence the FLC M-proteins may be missed. Methods Immunofixation electrophoresis (IFE) using two different sets of antisera were compared (one detecting both free and bound FLC epitopes, and one detecting only the free FLC epitopes), alongside urine protein electrophoresis and the Freelite assay in order to ascertain the best methods of detecting both types of M-proteins in this subset of patients. Results A total of 2% of the patient population tested were shown to have a FLC M-protein migrating coincidentally with an intact M-protein. These were not detected by IFE using the widely utilised antisera to both free and bound FLC epitopes, and hence may have been missed during routine testing, but were detectable using the other methods. Conclusions This study highlights the important finding that in some patients with both an intact and a FLC M-protein, the FLC M-protein may be missed during routine testing. In incidences where no corresponding urine sample is sent to the laboratory alongside the serum sample, we would suggest testing for the presence of FLC M-proteins in this subset of patients using the Freelite assay, if no urine sample can be obtained, to ensure all FLC M-proteins are appropriately detected.

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Monoclonal Gammopathy of Undetermined Significance (MGUS): Indications for Pre-Diagnostic Testing, Subsequent Diagnoses, and Follow-up Practice

Blood ◽

10.1182/blood-2018-99-118213 ◽

2018 ◽

Vol 132 (Supplement 1) ◽

pp. 2224-2224

Author(s):

Aishwarya Ravindran ◽

Kandace A. Lackore ◽

Amy E. Glasgow ◽

Matthew T. Drake ◽

Ronald S. Go

Keyword(s):

Heart Failure ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Laboratory Tests ◽

Office Visit ◽

Signs And Symptoms ◽

Low Risk ◽

Monoclonal Protein ◽

Face To Face

Abstract Introduction: MGUS is generally an incidental finding in the diagnostic work-up for clinical signs and symptoms suggestive of lymphoplasmacytic malignancies (multiple myeloma, light chain amyloidosis, and Waldenström macroglobulinemia), which are relatively rare (<35,000 annual new cases in the US). While much is known about the natural history of MGUS, information regarding the pre- and post-diagnostic part of MGUS patient care is lacking. Our study objectives were to determine the following: 1) indications for monoclonal protein testing; 2) subsequent diagnoses found for those indications; 3) specialty of ordering clinicians; 4) follow-up patterns after MGUS diagnosis. Methods: We identified MGUS patients residing in southeastern Minnesota who were diagnosed from 2011-2014 and followed at the Mayo Clinic. Medical records were reviewed to confirm the diagnosis and obtain relevant clinical data. Laboratory tests and visits were identified using Current Procedural Terminology-4th edition (CPT-4) codes from billing data. We defined a follow-up visit as: 1) any face-to-face encounter linked to MGUS diagnosis 30 days after the date of MGUS diagnosis regardless of whether ancillary test was performed or not; and 2) MGUS-specific tests or laboratory tests linked to an MGUS diagnosis claim performed without a face-to-face encounter. Based on the Mayo Clinic MGUS risk stratification model, we classified our cohort into either low-risk or non-low risk. Criteria for low-risk used were: serum monoclonal protein <1.5 g/dL, IgG subtype, and normal serum free light chain ratio. Follow-up patterns were analyzed according to year of diagnosis, demographics, and the specialty of clinicians performing the follow-up. Results: 330 MGUS patients were included in the study. The median age at diagnosis was 73 years (range, 21-98) and most were males (59.7%). The common indications for monoclonal protein studies were neuropathy (19.6%), kidney disease (13.6%), anemia (12.7%), bone symptoms/signs (12.7%), cutaneous disorders (5.8%), congestive heart failure (4.8%), and hypercalcemia (2.7%). The most common subsequent diagnoses for these indications were neuropathy not otherwise specified (NOS;100%), chronic kidney disease NOS (35.5%), anemia of chronic kidney disease (19%), osteopenia/osteoporosis (45.2%), congestive heart failure NOS (57.1%), and dermatitis NOS (100%), respectively. The practice specialties that most commonly diagnosed MGUS were internal medicine (31.3%), neurology (13.7%), nephrology (10.3%), family medicine (6.1%), and hematology (5.8%). Low risk MGUS comprised 44.8% of the cohort. After a median follow-up of 53.5 months (range, 13.0-77.4; IQR, 40.8-77.4), the total number of follow-up visits was 937. Majority (85.5%) of the visits were a combination of office visit with laboratory testing, while the rest were either office visit (11.2%) or laboratory tests (3.3%) only. The distribution of patients by mean interval between visits was: every <6 months (7.9%); every 6-12 months (19.4%); every 13-24 months (15.2%), and every >24 months or no follow-up at all (57.6%). The follow-up patterns did not change significantly (Kruskal Wallis; P=0.6759) over time (Figure 1) and were similar when age groups were compared (Figure 2; P=0.1328). However, males were followed more frequently than females (P=0.0365). Among patients 80 years and older, 32.1% continued to be followed at least once every 2 years (Figure 2). Hematologists were more likely than non-hematologists to follow MGUS patients regardless of the risk category (Figures 3-4). Among low risk patients, 31.1%, 22.2%, 20.7%, and 19.1% had at least one follow-up during years 2, 3, 4, and 5, after MGUS diagnosis (Figure 3). Conclusions: Approximately 1/3 of MGUS diagnoses were made during the evaluation of signs and symptoms not related to lymphoplasmacytic malignancies. The subsequent diagnoses found were a wide variety of common diseases. Most MGUS diagnoses were made by general internists, neurologists, and nephrologists. Follow-up practices varied between hematologists and non-hematologists. Nearly 1/3 of the oldest old patients continued to have follow-up, despite limited life expectancy. Disclosures No relevant conflicts of interest to declare.

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Serum Free Kappa to Free Lambda Ratios as an Adjunct to Serum Protein Electrophoresis for the Detection of Monoclonal Proteins in the Serum.

Blood ◽

10.1182/blood.v104.11.4856.4856 ◽

2004 ◽

Vol 104 (11) ◽

pp. 4856-4856

Author(s):

Arthur R. Bradwell ◽

Jean Garbincius ◽

Earle W. Holmes

Keyword(s):

Serum Protein ◽

Light Chain ◽

Protein Electrophoresis ◽

Free Light Chain ◽

Serum Protein Electrophoresis ◽

Serum Free ◽

Monoclonal Protein ◽

Serum Free Light Chain ◽

Monoclonal Proteins

Abstract Serum free light chain measurements have been shown to be useful in the diagnosis and monitoring of patients with monoclonal gammopathies. The present study was undertaken to evaluate the effect of adding the measurement of serum free light chain kappa to lambda ratios to the serum protein electrophoresis evaluation that we typically use as an initial screen for the detection of monoclonal proteins. We retrospectively tested 347 consecutive samples from individuals who had no previous history of plasma cell dyscrasia and had not previously had a serum or urine electrophoresis or immunofixation electrophoresis test at our institution. The quantitative serum protein electrophoresis test that was ordered was performed using Hydragel Beta 1- Beta 2 gels and Hydrasis instrument (Sebia, Inc., Norcross, GA). The protein content of the electrophoresis zones were quantitated by scanning densitometry and the electrophoresis pattern of each sample was qualitatively examined for abnormal bands and suspicious findings by a single, experienced observer. Serum free light chain concentrations and the serum free light chain kappa to lambda ratios were determined using the Freelite Human Kappa and Lambda Kits (The Binding Site Ltd, Birmingham, UK) and the Immage analyzer (Beckman Coulter Inc., Brea, CA). The serum free light chain kappa to lambda ratios were outside the reference interval (0.25 to1.65) in 23 of the samples. Ten abnormal ratios were observed among a group of 57 samples that had either positive or suspicious qualitative evaluations for the presence of a restriction or that demonstrated hypo-gammaglobulinemia. Both abnormalities led to recommendations for follow-up testing, which confirmed the presence of a monoclonal protein in 21 of the samples. Six abnormal ratios were observed among a group of 159 specimens that had quantitative abnormalities in albumin or one or more of globulin fractions (hypo-gammaglobulinemia excepted) and normal qualitative evaluations. Seven abnormal ratios were observed among a group of 131 samples that had normal quantitative results and normal qualitative evaluations. Follow-up testing is not usually recommended for serum protein electrophoresis results like those in the latter two groups. We found that the addition of the serum free light chain kappa to lambda ratio to the serum protein electrophoresis test increased the number of abnormal screens that would have required further clinical and/or laboratory evaluation by 23%(i.e. from 57 to 70). Given the high specificity of the serum free light chain kappa to lambda ratio for monoclonal light chains, the additional 13 abnormal samples identified by this test are expected to have a high likelihood of harboring a monoclonal protein that would have otherwise eluded detection. Pending a definitive prospective study, we estimate that the addition of a serum free light chain kappa to lambda ratio to the serum protein electrophoresis screen would increase the rate of detection of serum monoclonal proteins by as much as 1.6-fold.

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Prevalence of Post-Transplant Lymphoproliferative Disorder with Monoclonal Gammopathy of Unknown Significance in Patients Undergoing Kidney Transplantation.

Blood ◽

10.1182/blood.v110.11.4778.4778 ◽

2007 ◽

Vol 110 (11) ◽

pp. 4778-4778

Author(s):

Harris V.K. Naina ◽

Robert Kyle ◽

Thomas M. Habermann ◽

Samar Harris ◽

Fernando G. Cosio ◽

...

Keyword(s):

Multiple Myeloma ◽

Kidney Transplantation ◽

T Cell ◽

Organ Transplantation ◽

Monoclonal Gammopathy ◽

Lymphoproliferative Disorder ◽

M Protein ◽

Monoclonal Protein ◽

Post Transplant

Abstract Background: Post-transplant lymphoproliferative disorder (PTLD) represents one of the most serious consequences of immunosuppression in patients with solid organ transplantation. The incidence of PTLD is related to the organ transplanted and is dependent on the duration of follow-up. In various publications, the incidence of PTLD in renal transplantation ranges between 0.8% to 1.2%. In a previous study, the development of monoclonal (M) protein following liver transplantation is associated with the development of PTLD. In this study, we investigate this relationship in the kidney transplant population. Methods: A total of 3518 patients underwent kidney transplantation between 1963 to March 2006. These patients were cross referenced with the Monoclonal Gammopathy of Undetermined Significance (MGUS) database. Results: We identified 97 patients who had a monoclonal gammopathy either before or after transplantation. Patients with amyloidosis, multiple myeloma, heavy and light chain deposition disease and multi-organ transplantation were excluded from the analysis. A total of 69 patients met the inclusion criteria. Ten of the 69 (14.5%) patients developed PTLD. Median follow-up was 14.8 years. Twenty three patients had pretransplant MGUS, 20 patients developed MGUS following the transplant, and the other 26 did not have a monoclonal protein study prior to the transplant. Of the 23 patients who had a positive MGUS prior to the transplant, 4 patients (17.3%) developed PTLD, 1 patient developed EBV positive diffuse large cell lymphoma (DLCL), 1 developed EBV negative DLCL, 1 developed Hodgkin’s lymphoma and 1 developed increased plasma cells in bone marrow (20%) with stable M protein with no evidence of progression to multiple myeloma. None of these patients had a quantifiable M-protein prior to transplantation. The mean duration from diagnosis of MGUS to PTLD was 8.2 years (range 3 to 14 years). Of the 20 patients with a negative pre-transplant study for para proteniemia, 2 (10%) developed PTLD (T cell lymphoproliferative disorder). Two patients developed MGUS after the transplant at 1 and 12 years post transplant. It took an average of 15 years to develop PTLD after the diagnosis of MGUS. Four of the 26 patients who did not have a pretransplant study for MGUS developed PTLD. These included an EBV positive gamma delta type T cell lymphoproliferative disorder, an EBV positive plasmablastic lymphoma, one multiple myeloma and a plasmacytoma. The latter two patients had M-protein > 3g/dL. It took an average of 14 years after their transplant for these patients to develop PTLD. Conclusion: Our study showed that the development of a monoclonal protein in patients undergoing kidney transplantation is a strong risk factor for PTLD. Monoclonal protein study should be performed pretransplant and monitored post transplant as a surveillance of PTLD. Those who are positive or convert should be monitored closely for development of lymphoproliferative disorder.

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Immunoglobulin Heavy/Light Chain Ratios as An Alternative to Immunofixation In the Identification of Monoclonal Gammopathies

Blood ◽

10.1182/blood.v116.21.5018.5018 ◽

2010 ◽

Vol 116 (21) ◽

pp. 5018-5018

Author(s):

Anandram Seetharam ◽

Tracy Lovatt ◽

Alan Macwhannell ◽

Abe Jacob ◽

Sunil Honda ◽

...

Keyword(s):

Light Chain ◽

Hematological Malignancies ◽

Protein Electrophoresis ◽

Free Light Chain ◽

Low Risk ◽

Close Monitoring ◽

Haematological Malignancies ◽

Monoclonal Protein ◽

M Proteins ◽

Monoclonal Proteins

Abstract Abstract 5018 Introduction Historically, serum protein electrophoresis (SPE), urine protein electrophoresis (UPE) and immunofixation (IFE) have been used to identify and quantify monoclonal proteins (M-proteins). Whilst this approach is adequate for the identification of intact immunoglobulin multiple myeloma (MM), it is not sensitive enough to detect free light chain MM (LCMM). Therefore, an algorithm which utilises SPE, serum free light chain (FLC) immunoassays and IFE for the identification of M-proteins has been suggested. Assays have now been developed which utilise polyclonal antisera raised against the kappa and lambda light chain types of IgG, IgA and IgM immunoglobulins (HLC). Here we report the use of these assays as an alternative to IFE and propose a screening algorithm which utilises SPE, FLC and HLC Materials and Methods Serum FLC measurement was added to 1063 requests for SPE, from primary care or from a hospital source. Samples from patients with previously diagnosed MM, Waldenstrom's Macroglobulinemia and lymphoma were, where possible, removed. Sera showing monoclonal proteins or hypogammaglobulinemia (by SPE) or an abnormal FLC ratio were tested further by IFE and IgG, IgA, IgM HLC assays. SPE and IFE were performed on a SEBIA Hydrasys system, and gels were interpreted by experienced clinical chemists. FLC and HLC measurements were performed on a Siemens BN™II nephelometer. HLC results were compared with IFE results and clinical diagnoses. The study was approved by the Wolverhampton, New Cross, NHS Trust Review Board Results 80/1063 patients were identified as having abnormal SPE or abnormal FLC results. 42/80 patients had positive IFE results. 24/42 of these patients were positive by HLC (Table 1), 11/42 had light chain only myeloma/MGUS, the remaining 7/42 were MGUS patients. The 7 MGUS patients (6 IgG and 1 IgM) with normal HLC ratios and positive IFE all had less than 2g/L monoclonal protein measured by SPE densitometry and a normal FLC ratio. Of the 38/80 with normal IFE's all had been investigated further because of abnormal FLC results. 9/38 had abnormal HLC ratios of which 3/9 had confirmed hematological malignancies (1× chronic lymphocytic leukemia (CLL), 1× small lymphocytic lymphoma (SLL) and 1× asymptomatic MM (ASMM)). The use of FLC immunoassays alongside SPE as part of the primary screening protocol identified 10 additional hematological malignancies (1× ASMM, 6×CLL, 2× non-Hodgkin lymphoma, 1× SLL). Discussion HLC ratio analysis matched IFE for the identification of all symptomatic haematological malignancies. Abnormal FLC ratios identified 10 additional haematological malignancies of which 3 also had abnormal HLC ratios, which would have been missed using SPE/ IFE. In 7/19 MGUS (6×IgG, 1×IgM) patients there were normal HLC ratios. In all cases the monoclonal protein load was below 2g/L and the FLC ratio was normal; identifying the IgG patients as having a low risk and the IgM patient as having a low/intermediate risk of progression. It may be beneficial not to identify these patients, who do not require therapeutic intervention or justify close monitoring. Another advantage of using HLC analysis instead of IFE is that the HLC ratio has been found to be a prognostic indicator in myeloma and MGUS. It would also form a useful “baseline” comparison if HLC assays were used in monitoring or for the detection of residual disease. Conclusions HLC analysis identified all symptomatic patients who were IFE positive and in an additional 3 hematological malignancies. Low risk MGUS patients may not be identified using these tests but this might be beneficial to patients and physicians alike Disclosures: Harding: Binding Site Group Ltd: Employment.

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Bone Marrow Biopsy May Be Required During the Initial Evaluation of Individuals with Asymptomatic Monoclonal Gammopathy

Blood ◽

10.1182/blood.v118.21.5067.5067 ◽

2011 ◽

Vol 118 (21) ◽

pp. 5067-5067

Author(s):

Meletios Athanasios Dimopoulos ◽

Evangelos Terpos ◽

Maria Gkotzamanidou ◽

Evangelos Eleutherakis-Papaiakovou ◽

Magdalini Migkou ◽

...

Keyword(s):

Bone Marrow ◽

Bone Marrow Biopsy ◽

Plasma Cell ◽

Light Chain ◽

Monoclonal Gammopathy ◽

Plasma Cells ◽

Conflicts Of Interest ◽

Incidental Finding ◽

M Protein ◽

Monoclonal Protein

Abstract Abstract 5067 The incidental finding of a monoclonal gammopathy during workup for various conditions or in the context of a routine check-up is increasingly common. Several “patients” are then referred for diagnostic evaluation of their monoclonal gammopathy and additional workup is needed. It has been proposed that a bone marrow (BM) aspirate and biopsy is indicated when the monoclonal protein (M-protein) is ≥1.5 g/dL, when abnormalities are noted in the complete blood cell count, serum creatinine level, serum calcium level, or radiographic bone survey, in individuals with non-IgG monoclonal gammopathy and in those with an abnormal serum free light chain (FLC) ratio. The aim of this study was to identify factors that could aid in the evaluation of individuals presenting with asymptomatic monoclonal gammopathy and in whom invasive diagnostic testing with a bone marrow biopsy is considered. Thus, we analyzed our database and identified patients who were referred to the Department of Clinical Therapeutics of the University of Athens, Greece, for evaluation of asymptomatic monoclonal gammopathy and in whom a BM trephine biopsy, a serum and urine protein electrophoresis (SPEP) with immunofixation and quantitative immunoglobulins were performed. SPEPs were scanned and M-protein was measured using imaging analysis software. Patients with a monoclonal M-protein ≥ 3 g/dl (30 g/L), i.e. those diagnosed with asymptomatic/smoldering myeloma (SMM) or Waldenstrom's macorglobulinemia based on the standard criteria, were not included in the analysis. Clonality of BM plasma cells or lymphoplasmacytes was assessed by immunohistochemistry. Patients who eventually were diagnosed with plasma cell related conditions (i.e. amyloidosis, peripheral neuropathy, dermatoses, etc.) were also excluded from the analysis. Our analysis included 161 patients: 53% were females, median age was 64 year (range 33–89 years), 53% had a monoclonal IgG protein, 15.5% had a monoclonal IgA protein, 24% a monoclonal IgM protein and 2.5% had only a monoclonal light chain, while 4% had a biclonal protein. In 64% of patients the monoclonal light chain was kappa and in 37% was lambda. The median serum M-protein was 0.948 g/dl (range 0.1–2.99 g/dl); 52% of patients had an M-protein of <1 g/dl and 79% of <2 g/dl. Immunoparesis of at least one of the uninvolved immunoglobulins was present in 38% of cases and of both of the uninvolved immunoglobulins in 6%. Median BM infiltration by monoclonal plasma cells or lymphoplasmacytes was 15%. In 66.5% of individuals there was a BM infiltration of ≥10% by monoclonal plasma cells or lymphoplasmacytes, while in 10% of the studied cases the BM infiltration was ≥50%. A significant correlation of the size of M-protein and of the infiltration of the BM was found (R=0.592, p<0.001). However, 27% of patients with M-protein <0.5 g/dl had ≥10% clonal plasma cells or lymphoplasmacytes in their BM biopsies. The respective rates were 46% for those with M-protein <1 g/dl, 54% for those with M-protein 1.5 g/dl and 58% for those with M-protein <2 g/dl. Ninety per cent of those who had immunoparesis of at least one of the uninvolved immunoglobulins had ≥10% clonal plasma cells or lymphoplasmacytes. A BM infiltration of ≥10% was more frequent in individuals with a monoclonal IgG or IgA protein (72% and 80%, respectively) vs. 45% of those with a monoclonal IgM protein (p=0.015). Light chain isotype, age and gender were not predictive of the degree of BM plasma cell infiltration. In multivariate analysis, immunoparesis of at least one of the uninvolved immunoglobulins (OR: 6.45, 95% CI: 2.32–18, p<0.001), an IgG or IgA monoclonal protein (OR: 2.67, 95% CI: 1.1–6.4, p=0.028) and an M-protein of ≥1 g/dl (OR: 5.4, 95% CI: 2.23–13) were independently associated with the presence of ≥10% of clonal infiltration in BM biopsy. By combining the above risk factors we found that in those who had all three, 97% had ≥10% clonal cells in the BM biopsy, while in those with 0–1 of the above factors the probability to find ≥10% clonal cells was 43%. These findings indicate that even patients with low risk for BM infiltration by clonal plasma cells, may be diagnosed as SMM when a BM biopsy is performed. In conclusion, our data on a large number of individuals with asymptomatic monoclonal gammopathy who underwent a BM biopsy may indicate that the latter exam may provide useful information and could be included in the standard initial workup of these individuals. Disclosures: No relevant conflicts of interest to declare.

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Progression and Outcome in Patients with Biclonal Gammopathies

Blood ◽

10.1182/blood.v124.21.5699.5699 ◽

2014 ◽

Vol 124 (21) ◽

pp. 5699-5699

Author(s):

Trey Carlton Mullikin ◽

S. Vincent Rajkumar ◽

Angela Dispenzieri ◽

Morie A Gertz ◽

Martha Q Lacy ◽

...

Keyword(s):

Heavy Chain ◽

Light Chain ◽

Research Funding ◽

Initial Diagnosis ◽

M Protein ◽

Unique Type ◽

Monoclonal Protein ◽

Rate Of Progression ◽

Monoclonal Proteins

Abstract Background: Patients with monoclonal gammopathies typically have a single clone making a unique type of monoclonal protein, one heavy chain and one light chain. In a small proportion of patients, more than one (typically two) types of monoclonal protein can be seen and differ with respect to the heavy chain or light chain or both. There is limited information on the clinical course of patients with more than one monoclonal protein identified in their serum or urine. Objectives: We report outcomes of patients with more than one monoclonal protein at our institution over the past thirty years. Patients and Methods: We queried the existing clinical database to identify all patients with at least two different monoclonal protein types identified on serum or urine studies during the course of their disease. Retrospective chart review was performed on 551 patients, who had more than one type of monoclonal protein on electrophoresis and/or immunofixation. Results: Among the entire study cohort (N=551), 461 pts (84%) had a biclonal pattern, 7 (1%) had a triclonal pattern and the remaining 83 (15%) had a monoclonal pattern at the time of initial positive study. The median age at the time of initial diagnosis was 69.7 years (range; 32-93); 359 (65%) were male. Among these, 390 were diagnosed as MGUS/BGUS, 18 with SMM, 36 with MM, 20 with WM, and rest with another lymphoproliferative disorders. The median duration between the initial detection of monoclonal protein and the emergence of the biclonal protein was 40 months for the 83 patients, who were monoclonal initially. The distributions of the dominant monoclonal proteins were GK (30%), GL (21%), MK (22%), ML (9%), AK (9%), and AL (8%). The distributions of the second monoclonal proteins were GK (27%), GL (24%), MK (16%), ML (15%), AK (10%), and AL (7%). Overall, 20 patients with a MGUS/BGUS progressed to smoldering or symptomatic myeloma, while 12 patients with an initial diagnosis of SMM progressed to MM. The median estimated follow up for the MGUS/BGUS group and those with SMM were 6.5 years (95% CI; 5, 7) and 9.8 (95% CI; 4, 13), respectively. This translates to 20 progressions over 3822 person years of follow up for the MGUS/BGUS patient group and 12 progressions over 131 person years of follow up for the SMM group. The rate of progression was ~1% per year for patients with MGUS/BGUS and the median estimated time to progression was 2.6 years for the SMM group. (Figure). In majority of patients, the dominant M spike increased with the disease progression. Conclusion: Patients with biclonal gammopathies appear to have a similar rate of progression compared to what has been historically described for MGUS/ SMM population. For the patients who progressed and received treatment, both M proteins typically responded to therapy, and during relapse, the original dominant M protein typically reemerged as the dominant M protein. Figure 1 Figure 1. Disclosures Kumar: Janssen: Consultancy, Research Funding; Array BioPharma: Consultancy, Research Funding; Sanofi-Aventis: Consultancy, Research Funding; Onyx Pharmaceuticals: Consultancy, Research Funding; Millennium: The Takeda Oncology Co.: Consultancy, Research Funding; Celgene: Consultancy, Research Funding; Skyline Diagnostics: Membership on an entity's Board of Directors or advisory committees.

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Serum free light chain assay reduces the need for serum and urine immunofixation electrophoresis in the evaluation of monoclonal gammopathy

Annals of Clinical Biochemistry International Journal of Laboratory Medicine ◽

10.1258/acb.2009.009038 ◽

2009 ◽

Vol 46 (5) ◽

pp. 407-412 ◽

Cited By ~ 11

Author(s):

Richard B Fulton ◽

Suran L Fernando

Keyword(s):

Light Chain ◽

Monoclonal Gammopathy ◽

Free Light Chain ◽

Light Chains ◽

Serum Free ◽

Monoclonal Protein ◽

Serum Free Light Chain ◽

Immunofixation Electrophoresis ◽

Monoclonal Proteins ◽

Testing Algorithm

Background The potential for serum free light chain (sFLC) assay measurements to replace urine electrophoresis (uEPG) and to also diminish the need for serum immunofixation (sIFE) in the screening for monoclonal gammopathy was assessed. A testing algorithm for monoclonal protein was developed based on our data and cost analysis. Methods Data from 890 consecutive sFLC requests were retrospectively analysed. These included 549 samples for serum electrophoresis (sEPG), 447 for sIFE, and 318 for uEPG and urine immunofixation (uIFE). A total of 219 samples had sFLC, sEPG, sIFE and uEPG + uIFE performed. The ability of different test combinations to detect the presence of monoclonal proteins was compared. Results The sFLC κ/ λ ratio (FLC ratio) indicated monoclonal light chains in 12% more samples than uEPG + uIFE. The combination of sEPG and FLC ratio detected monoclonal proteins in 49% more samples than the combination of sEPG and sIFE. Furthermore, the sEPG + FLC ratio combination detected monoclonal protein in 6% more samples than were detected by the combined performance of sEPG, sIFE, uEPG and uIFE. However, non-linearity of the assay, the expense of repeat determinations due to the narrow measuring ranges, and frequent antigen excess checks were found to be limitations of the sFLC assay in this study. Conclusion The FLC ratio is a more sensitive method than uIFE in the detection of monoclonal light chains and may substantially reduce the need for onerous 24 h urine collections. Our proposed algorithm for the evaluation of monoclonal gammopathy incorporates the sFLC assay, resulting in a reduction in the performance of labour intensive sIFE and uEPG + uIFE while still increasing the detection of monoclonal proteins.

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