Correlation Among Different Plasma Cell Disorders Markers and Immunoglobulin Heavy Light Chains (HLC)

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3148-3148
Author(s):  
Ajay K. Nooka ◽  
Jonathan L. Kaufman ◽  
Nishi N Shah ◽  
Bilal Hassan ◽  
Lawrence H. Boise ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Strong Correlation ◽  
Research Funding ◽  
Light Chains ◽  
Free Light Chains ◽  
Plasma Cell Disorders ◽  
Plasma Cell Disorder ◽  
Serum Free Light Chains ◽  
M Spike ◽  
Cell Disorder

Abstract Background Heavy light chain (HLC) assays allow for accurate quantification of involved and uninvolved immunoglobulins (Ig) of the affected isotype. HLC ratio is of particular interest in measuring low level disease where there is limited utility for serum protein electrophoresis (SPEP) to measure the low M-spike and challenging to quantify. Serum immunofixation (SIFx), being a non-quantitative test cannot accurately define the amount of disease. Limited data exists to understand the utility of HLC testing, hence we tried to study the correlation of this test to some of the established plasma cell disorder markers: serum free light chains (SFLC), SPEP (M-spike) and involved total Ig levels. Methods A total of 1098 samples from 480 patients with IgG [315 IgG Kappa (k) and 165 IgG Lambda (l)] plasma cell disorders (multiple myeloma, monoclonal gammopathy of undetermined significance, smoldering multiple myeloma and plasmacytoma) and 329 samples from 160 IgA (98 IgAk patients and 60 IgAl) plasma cell disorder patients were included in analysis. Correlation was determined between HLC levels, HLC ratio and SFLC levels for all patients. Correlation was determined for each isotype separately using non parametric Spearman Correlation co-efficient (SCC). Results In IgA patients, there is strong correlation between HLC levels (IgAk and IgAl) and M-spike (0.85; p<0.0001 and 0.82; p<0.0001, respectively) as well as involved Ig (0.99; p<0.0001; 0.99; p<0.0001, respectively). Similar strong correlation was seen between HLC ratios and M-spike and involved Ig. In IgG patients, there is strong correlation, but smaller than IgA, between HLC levels (IgGk and IgGl) and M-spike (0.72; p<0.0001 and 0.75; p<0.0001, respectively) as well as involved Ig (0.91; p<0.0001; 0.78; p<0.0001, respectively). Similar correlation was seen between HLC ratios and M-spike and involved Ig. We also observed a strong correlation of FLCk with IgAk (0.65; p<0.0001) as well as of FLCl with IgA l too (0.69; p<0.0001). Similarly, FLCk with IgGk (0.56; p<0.0001) and FLCl with IgG l (0.69; p<0.0001) exhibited strong correlation. Conclusion The presence of strong correlation between M-spike quantification, serum free light chains, as well as total involved immunoglobulins in the largest sample size reported to date, suggests the feasibility of detection of isotype bands with HLC antibodies and its potential role for clinical utility in disease staging and monitoring. Prognostic usefulness of this testing in identifying residual disease and its correlation with survival in myeloma patients will be presented at the meeting. Disclosures: Kaufman: Onyx: Consultancy; Celgene: Consultancy, Research Funding; Novartis: Consultancy, Research Funding; Janssen: Consultancy; Millenium: Consultancy; Merck: Research Funding. Boise:Onyx Pharmaceuticals: Consultancy. Lonial:Millennium: Consultancy; Celgene: Consultancy; Novartis: Consultancy; BMS: Consultancy; Sanofi: Consultancy; Onyx: Consultancy.

Quantification by Ultrafiltration and Immunofixation Electrophoresis Testing for Monoclonal Serum Free Light Chains

2020 ◽  
Vol 51 (6) ◽  
pp. 592-600 ◽  
Author(s):  
Gurmukh Singh ◽  
Roni Bollag
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Limit Of Detection ◽  
Light Chains ◽  
Total Serum ◽  
Reliable Estimate ◽  
Free Light Chains ◽  
Serum Free ◽  
Immunofixation Electrophoresis ◽  
Serum Free Light Chains

Abstract Objective Measurement of monoclonal immunoglobulins is a reliable estimate of the plasma cell tumor mass. About 15% of plasma cell myelomas secrete light chains only. The concentration of serum free light chains is insufficient evidence of the monoclonal light chain burden. A sensitive quantitative estimate of serum free monoclonal light chains could be useful for monitoring patients with light chain myeloma. We describe such an assay that does not require mass-spectrometry equipment or expertise. Methods Serum specimens from patients with known light chain myelomas and controls were subjected to ultrafiltration through a membrane with pore size of 50 kDa. The filtrate was concentrated and tested by immunofixation electrophoresis. The relative area under the monoclonal peak, compared to that of the total involved light chain composition, was estimated by densitometric scanning of immunofixation gels. The proportion of the area occupied by the monoclonal peak in representative densitometric scans was used to arrive at the total serum concentration of the monoclonal serum free light chains. Results Using an ultracentrifugation and concentration process, monoclonal serum free light chains were detectable, along with polyclonal light chains, in all 10 patients with active light chain myelomas. Monoclonal light chains were identified in serum specimens that did not reveal monoclonal light chains by conventional immunofixation electrophoresis. The limit of detection by this method was 1.0 mg/L of monoclonal serum free light chains. Conclusion The method described here is simple enough to be implemented in academic medical center clinical laboratories and does not require special reagents, equipment, or expertise. Even though urine examination is the preferred method for the diagnosis of light chain plasma cell myelomas, measurement of the concentration of serum free light chains provides a convenient, albeit inadequate, way to monitor the course of disease. The method described here allows effective electrophoretic differentiation of monoclonal serum free light chain from polyclonal serum free light chains and provides a quantitation of the monoclonal serum free light chains in monitoring light chain monoclonal gammopathies.

T Cell Large Granular Lymphocytic Leukemia and Co-Existing Plasma Cell Disorders

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5368-5368
Author(s):  
M Hasib Sidiqi ◽  
Mohammed A Aljama ◽  
David S. Viswanatha ◽  
David Dingli
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Mayo Clinic ◽  
Monoclonal Gammopathy ◽  
Specific Therapy ◽  
Plasma Cell Disorders ◽  
Plasma Cell Disorder ◽  
Cell Disorder ◽  
Lgl Leukemia

Abstract T cell large granular lymphocytic (T-LGL) leukemia has been reported to occur in patients with plasma cell disorders (PCD). We conducted a retrospective review of patients diagnosed with T-LGL leukemia and a PCD at the Mayo Clinic. 22 patients were identified with T-LGL leukemia and a plasma cell disorder. The T-LGL leukemia preceded the PCD in 18% (n=4), was synchronous in 50% (n=11) and diagnosed post plasma cell disorder in 32% (n=7) of patients. The PCD diagnosis varied and included monoclonal gammopathy of undetermined significance (MGUS, n=13), multiple myeloma (MM, n=5), smoldering multiple myeloma (SMM. N=2), lymphoplasmacytic lymphoma (LPL, n=1) and monoclonal gammopathy of renal significance (MGRS, n=1). 5 patients developed T-LGL leukemia after treatment for a PCD (4 with MM and 1 with LPL). 4 patients with MGUS progressed to a more aggressive disease, 3 to MM and 1 to LPL. Neutropenia (76%) and anemia (70%) were the most common clinical presentation. None of the patients had rheumatoid arthritis. Treatment for the TLGL was variable with a number of different agents used listed in Table 1. 45% (n=10) of patients had an indolent course and did not receive specific therapy for TLGL. 6 patients responded to a single line of therapy, all of whom received either cyclophosphamide or methotrexate based regimens. The remainder had a relapsing course with multiple lines of therapy including 2 patients that received splenectomy. Nine patients were identified as having symptomatic multiple myeloma and TLGL, Table 2. Four patients had progressed from a preexisting plasma cell disorder, 3 with MGUS and 1 with SMM. The diagnosis of TLGL preceded myeloma in 1 patient was concurrent in 4 and post myeloma diagnosis in 4 patients. Time to diagnosis of TLGL post myeloma ranged from 10 to 63 months. At time of LGL diagnosis neutropenia was present in 7/9 patients and anemia in 6/8 (data unavailable for 1 patient). Cytogenetics data was available in 7 patients. Hyperdiploidy was the most common abnormality (3/7) followed by deletion 13q (2/7), t(14;16) in 1 patient and 1q amplification in 1 patient. The majority of patients were treated with novel agents with 7 receiving bortezomib based therapy. 3 patients underwent autologous stem cell transplantation. Therapy directed at the TLGL was given to 4/9 patients. This consisted of a combination of cyclophosphamide and prednisone in 3/4 patients all of whom responded to therapy with resolution of cytopenias. One patient had TLGL with multiple relapses and required multiple lines of therapy including eventual splenectomy. 3 patients with TLGL diagnosed after the diagnosis of myeloma did not receive specific therapy directed at the TLGL. The clinical course of the TLGL in these 3 patients was indolent and did not appear to be affected by therapy for multiple myeloma. At last follow up 5 patients have died. After a median follow up of 76 months post TLGL diagnosis the median overall survival (OS) post TLGL diagnosis was not reached for the entire cohort. In the cohort of patients with multiple myeloma, median OS from time of myeloma diagnosis was 71 months. Median OS from time of TLGL diagnosis was not reached. T-LGL leukemia can present in patients with a variety of plasma cell disorders and occur at any stage of the disease process. It is an important differential to consider in patients with unexplained cytopenias that are incongruent with the activity of the plasma cell disorder. Disclosures Dingli: Millennium Takeda: Research Funding; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Alexion Pharmaceuticals, Inc.: Other: Participates in the International PNH Registry (for Mayo Clinic, Rochester) for Alexion Pharmaceuticals, Inc.; Millennium Takeda: Research Funding.

Expression of CD126 (IL-R alpha) on Plasma Cells in Monoclonal Gammopathies.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 5066-5066
Author(s):  
Syed T. Mahmood ◽  
Shaji Kumar ◽  
Teresa K. Kimlinger ◽  
Jessica L. Haug ◽  
Michael Timm ◽  
...  
Keyword(s):  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Cell Subset ◽  
Primary Amyloidosis ◽  
Normal Plasma ◽  
Plasma Cell Disorders ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Abstract Background: IL-6 is important for proliferation and inhibition of apoptosis in malignant plasma cells. Understanding the role of IL-6 receptor alpha chain (CD126) in the pathogenesis of plasma cell disorders may help in developing future treatment therapies for these diseases. A previous study has shown that CD126 (alpha subunit of IL-6 receptor) is expressed distinctly in myeloma, monoclonal gammopathy of unknown significance (MGUS), and plasmacytomas when compared to normal. We performed this study in order to confirm and describe the expression of CD126 in different plasma cell disorders. Design and Methods: Using flow cytometry we assessed CD126 expression on clonal plasma cells from patients with Primary Amyloidosis (n=7), monoclonal gammopathy of undetermined significance (MGUS) (n=13), smoldering Myeloma (SMM) (n=19) and active Myeloma (n=22), as well as normal plasma cells (n=9). Plasma cells were identified by their characteristic CD38/45 expression. The expression of CD126 was separately analyzed on the CD45 positive and negative plasma cells. CD 126 expression was considered significant when more than 20% of the cells had expression. Results: CD126 expression was seen distinctly in plasma cell disorder plasma cells and not in normal plasma cells when all plasma cells were studied together. The highest expression percentages were found in Amyloid (28%) followed closely by MGUS 29(%), then SMM (23%), and Myeloma (12%) cells. The CD45 neg subset was similarly positive in the plasma cell disorder group. In this group, MGUS showed the highest expression percentage followed distantly by Amyloid, Myeloma, and SMM. The CD45 pos subset was uniformly positive in expression of CD126. If was found that this subset expressed higher levels of CD126 in all the studied plasma cell disorders and normal plasma cells when compared to the CD45 neg subset. Conclusion: The findings of this study confirm the increased expression of CD126 in plasma cell disorders when compared to normal plasma cells. The higher expression of CD126 in the CD45 pos plasma cell subset has not been previously described. In addition, the CD45 pos subset expressed higher levels of CD126 in all study groups when compared to the CD45 pos subset. This data contributes to the understanding of IL-6 receptor physiology and confirms the important role of the CD45 pos subset in the proliferation of neoplastic plasma cells. The findings are in accordance with the increased proliferative rates seen in the CD45 fraction of malignant plasma cells.

Natural History of Amyloidosis Isolated to Fat and Bone Marrow Aspirate

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5303-5303
Author(s):  
Rajshekhar Chakraborty ◽  
Morie A. Gertz ◽  
Angela Dispenzieri ◽  
Wilson I. Gonsalves ◽  
Ronald S. Go ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Natural History ◽  
Plasma Cell ◽  
Light Chain ◽  
Research Funding ◽  
Bone Marrow Aspirate ◽  
Systemic Amyloidosis ◽  
Plasma Cell Disorder ◽  
Cell Disorder

Abstract Background: Light chain Amyloidosis (AL) is characterized by deposition of light chain derived amyloid fibrils in major organs and/or soft tissue. An observational study on natural history and outcome of localized immunoglobulin light-chain amyloidosis without vital organ (liver, heart, kidney, peripheral and autonomic nervous system) involvement has shown extremely low rate of progression (1%) to systemic amyloidosis at a median follow-up of 74.4 months (Mahmood S et al. The Lancet Haematology; 2015; 6:e241-e250). There is, however, limited evidence in published literature on natural history of AL amyloidosis confined to fat and/or bone marrow biopsy, without involvement of vital organs or other soft tissues. Methods: We retrospectively identified patients with AL amyloidosis limited to fat and/or bone marrow aspirate in a single-institution database. Patients were evaluated for progression to systemic amyloidosis. Statistical analysis was done using JMP 10.0.0 (SAS Institute Inc.). Results: We identified 117 patients, with a median age of 70 years, who had light chain amyloidosis detected in abdominal fat aspirate and/or bone marrow biopsy, without systemic involvement. Amyloid was seen in fat only in 39%, marrow only in 54% and in both sites in 7%. The median follow up was 45.6 months (95% CI-38.1-57.7) from detection of amyloid. Of these, 64% were alive at the time of analysis. Among 117 patients, 65 were treated for a diagnosis of another plasma cell disorder made prior to or concurrent with detection of amyloid. The remaining 52 patients only had isolated fat or marrow amyloid. Among 65 patients with another diagnosis of plasma cell disorder requiring treatment, 3 progressed to systemic amyloidosis, one each with cardiac, renal and lymph node (LN) involvement detected at 32, 42 and 65 months respectively from the detection of amyloid. The first 2 patients had underlying multiple myeloma, and the third patient with LN involvement had underlying Waldenström macroglobulinemia. Among 52 patients without another diagnosis of a plasma cell disorder requiring treatment, at a median follow up of 32 months, no progression to systemic amyloidosis was observed. Median overall survival (OS) in 117 patients from detection of amyloid, using Kaplan-Meier survival estimates, was 60.2 months (95% CI-48.9-146.1). Conclusion: Our study highlights the fact that isolated amyloidosis detected in fat and/or bone marrow aspirate, in the absence of another plasma cell dyscrasias that require therapy, is unlikely to progress to systemic amyloidosis. Watchful waiting might be considered in such patients after a thorough evaluation to rule out systemic involvement. Disclosures Gertz: Smith Kline: Honoraria; Novartis: Honoraria; Onyx: Honoraria; millenium: Consultancy, Honoraria; Celgene: Honoraria. Kumar:Celgene: Consultancy, Research Funding; Abbvie: Research Funding; Millenium: Consultancy, Research Funding; Novartis: Research Funding; Onyx: Consultancy, Research Funding; Janssen: Consultancy, Research Funding; BMS: Consultancy, Research Funding.

Free light chains in plasma cell disorders: measurement and therapeutic implications

2009 ◽  
Vol 30 (1) ◽  
pp. 21-23
Author(s):  
Arthur R. Bradwell ◽  
Colin A. Hutchison ◽  
Paul Cockwell
Keyword(s):  
Plasma Cell ◽  
Light Chains ◽  
Free Light Chains ◽  
Therapeutic Implications ◽  
Plasma Cell Disorders

scholarly journals Recommendations for Use of Free Light Chain Assay in Monoclonal Gammopathies

2010 ◽  
Vol 29 (1) ◽  
pp. 1-8 ◽  
Author(s):  
Vesna Radović
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
High Sensitivity ◽  
Protein Electrophoresis ◽  
Free Light Chain ◽  
Light Chains ◽  
Free Light Chains ◽  
Bone Marrow Biopsies ◽  
Monoclonal Gammopathies ◽  
Plasma Cell Disorders

Recommendations for Use of Free Light Chain Assay in Monoclonal GammopathiesThe serum immunoglobulin free light chain assay measures levels of free κ and λ immunoglobulin light chains. There are three major indications for the free light chain assay in the evaluation and management of multiple myeloma and related plasma cell disorders. In the context of screening, the serum free light chain assay in combination with serum protein electrophoresis and immunofixation yields high sensitivity, and negates the need for 24-hour urine studies for diagnoses other than light chain amyloidosis. Second, the baseline free light chains measurement is of major prognostic value in virtually every plasma cell disorder. Third, the free light chain assay allows for quantitative monitoring of patients with oligosecretory plasma cell disorders, including AL, oligosecretory myeloma, and nearly twothirds of patients who had previously been deemed to have non-secretory myeloma. In AL patients, serial free light chains measurements outperform protein electrophoresis and immunofixation. In oligosecretory myeloma patients, although not formally validated, serial free light chains measurements reduce the need for frequent bone marrow biopsies. In contrast, there are no data to support using free light chain assay in place of 24-hour urine electrophoresis for monitoring or for serial measurements in plasma cell disorders with measurable disease by serum or urine electrophoresis.

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