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Vincent S Rajkumar - One of the best experts on this subject based on the ideXlab platform.
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monoclonal Gammopathy associated peripheral neuropathy diagnosis and management
Mayo Clinic Proceedings, 2017Co-Authors: Hafsa M. Chaudhry, Michelle L. Mauermann, Vincent S RajkumarAbstract:Abstract Monoclonal gammopathies comprise a spectrum of clonal plasma cell disorders that include monoclonal Gammopathy of undetermined significance, multiple myeloma, and Waldenstrom macroglobulinemia. In this review, we outline the epidemiology, etiology, classification, diagnosis, and treatment of monoclonal Gammopathy–associated peripheral neuropathy. Monoclonal Gammopathy of undetermined significance is relatively common in the general population, with a prevalence of 3% to 4% among individuals older than age 50 years. Therefore, the presence of M protein in a patient with neuropathy does not automatically indicate a causal relationship. Monoclonal Gammopathy–associated peripheral neuropathy is often a difficult diagnosis with limited treatment options. Studies addressing the optimal approach to diagnosis and management of this entity are limited. In addition to a review of the literature, we present a diagnostic approach to patients with monoclonal Gammopathy–associated peripheral neuropathy and discuss available data and options for treatment.
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clinical features and treatment outcomes of patients with necrobiotic xanthogranuloma associated with monoclonal gammopathies
Clinical Lymphoma Myeloma & Leukemia, 2015Co-Authors: Larissa Higgins, Vincent S Rajkumar, John A Lust, Angela Dispenzieri, Martha Q Lacy, David Dingli, Shaji Kumar, Francis K Buadi, Prashant Kapoor, Nelson LeungAbstract:Abstract Introduction Necrobiotic xanthogranuloma (NXG) is a rare chronic granulomatous disorder of the skin associated with a monoclonal Gammopathy. Patients and Methods The present report describes the findings from a single tertiary medical center retrospective study, including the clinical features of 35 patients with NXG and monoclonal Gammopathy from 2000 to 2015 and their subsequent disease course and treatment response. The median age at diagnosis was 56 years (range, 26-88 years). Results Most patients had a plasma cell dyscrasia consisting of monoclonal Gammopathy of undetermined significance in 28 patients and smoldering multiple myeloma in 5 patients; the remaining 2 patients had chronic lymphocytic leukemia. An IgG isotype of monoclonal Gammopathy was present in almost all the patients (97%). The most common site of cutaneous involvement of NXG was periorbital (66%). The treatments were heterogeneous and included excision, intralesional injection, radiotherapy, and systemic chemotherapy. The median follow-up period was 46 months (range, 4 to 234 months). The median overall survival had not been reached at the analysis, and 80% of the patients were still alive. Eight patients (23%) had disease progression to multiple myeloma at a median of 67 months (range, 21 to 107 months), demonstrating that although the clinical course is generally indolent, malignant transformation is not uncommon. At the last follow-up visit, 80% had signs of either clinical improvement or stable skin disease. Conclusion Cutaneous objective responses can be achieved with treatment of lymphoplasmacytic malignancies.
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monoclonal Gammopathy associated proliferative glomerulonephritis
Mayo Clinic proceedings, 2013Co-Authors: Sanjeev Sethi, Vincent S RajkumarAbstract:Abstract Monoclonal Gammopathy is characterized by circulating monoclonal immunoglobulin owing to clonal proliferation of immunoglobulin-producing B lymphocytes or plasma cells. Clonal proliferation of B lymphocytes is seen in B-cell lymphoma/leukemia, and clonal plasma cell proliferation is seen in multiple myeloma and monoclonal Gammopathy of undetermined significance. The monoclonal immunoglobulin in the setting of a B-cell or plasma cell disorder can cause a proliferative glomerulonephritis via 2 mechanisms: (1) glomerular deposition of the monoclonal immunoglobulin with activation of the classical pathway of complement (direct mechanism), resulting in an immunoglobulin-positive C3-positive glomerulonephritis, and (2) glomerular deposition of complement factors of the alternative and terminal pathway via inhibition of alternative pathway–regulating proteins by the monoclonal immunoglobulin (indirect mechanism), resulting in immunoglobulin-negative C3-positive glomerulonephritis (C3 glomerulopathy). Evaluation should include serum and urine electrophoresis and immunofixation as well as serum-free light-chain assay. If a monoclonal immunoglobulin is detected on these tests, bone marrow biopsy or imaging is needed to exclude more advanced plasma cell dyscrasia. Evaluation of alternative pathway of complement should be done in patients with Ig-negative C3-positive glomerulonephritis. If monoclonal Gammopathy is due to an underlying malignant disease such as myeloma, lymphoma, or chronic lymphocytic leukemia, then specific treatment should be aimed at treating the malignant disease, with the goal of eradicating the clonal cells producing the immunoglobulin. In contrast, if monoclonal Gammopathy is due to a monoclonal Gammopathy of undetermined significance, treatment options include bortezomib, cyclophosphamide, and dexamethasone for a non-IgM monoclonal immunoglobulin and rituximab alone or in combination with cyclophosphamide and dexamethasone for an IgM monoclonal immunoglobulin.
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elimination of the need for urine studies in the screening algorithm for monoclonal gammopathies by using serum immunofixation and free light chain assays
Mayo Clinic Proceedings, 2006Co-Authors: Jerry A Katzmann, Melissa R Snyder, Matthew F Plevak, Roshini S Abraham, John A Lust, Dirk R Larson, Joseph L Melton, Angela Dispenzieri, Vincent S RajkumarAbstract:OBJECTIVE To determine the relative diagnostic contribution of urine assays as part of the screening algorithm for monoclonal gammopathies. PATIENTS AND METHODS We identified 428 patients with a monoclonal Gammopathy and monoclonal urinary protein at initial diagnosis of plasma cell dyscrasia who had also undergone serum immunofixation and serum free light chain quantitation within 30 days of diagnosis. The laboratory results for serum protein electrophoresis, serum immunofixation, serum free light chain, urine protein electrophoresis, and urine immunofixation were reviewed. RESULTS The patients had diagnoses of multiple myeloma, primary amyloid, monoclonal Gammopathy of undetermined significance, smoldering multiple myeloma, solitary plasmacytomas, and other less frequently detected monoclonal gammopathies. All 428 had a monoclonal urine protein, 85.7% had an abnormal serum free light chain κ/λ ratio, 80.8% had an abnormal serum protein electrophoresis, and 93.5% had an abnormal serum immunofixation result. All 3 serum assays were normal in only 2 patients, 1 of whom had monoclonal Gammopathy of undetermined significance (idiopathic Bence Jones proteinuria) and 1 whose urine sample contained an intact monoclonal immunoglobulin but whose serum and subsequent urine samples showed no evidence of a monoclonal Gammopathy. CONCLUSION Discontinuation of urine studies and reliance on a diagnostic algorithm using only serum studies (protein electrophoresis, immunofixation, and free light chain quantitation) missed 2 (0.5%) of the 428 monoclonal gammopathies with urinary monoclonal proteins, and these 2 cases required no medical intervention.
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acquired fanconi syndrome is an indolent disorder in the absence of overt multiple myeloma
Blood, 2004Co-Authors: Cynthia X, Vincent S Rajkumar, Robert A Kyle, Angela Dispenzieri, Martha Q Lacy, John F Rompala, Philip R Greipp, Rafael Fonseca, Morie A GertzAbstract:Adult-acquired Fanconi syndrome (FS) is a rare complication of monoclonal Gammopathy. We retrospectively reviewed 32 patients diagnosed with adult-acquired FS between April 1968 and June 2002 at Mayo Clinic (Rochester, MN). At diagnosis, most patients had monoclonal Gammopathy of undetermined significance (MGUS) or smoldering multiple myeloma (SMM), with a median creatinine level of 176.8 μM (2.0 mg/dL; range, 79.56-327.08 μM [0.9-3.7 mg/dL]) and evidence of osteomalacia. During the average 65 months (range, 2-238 months) of follow-up, 5 patients developed end-stage renal disease (ESRD) and only 1 of 14 patients with MGUS transformed to multiple myeloma (MM). Also, 14 deaths occurred, with only 1 from ESRD but 4 from alkylator-related leukemia or myelodysplastic syndrome. Chemotherapy offered little benefit on renal functions of MGUS or SMM patients. In conclusion, FS associated with monoclonal Gammopathy does not appear to confer an additional risk of subsequent evolution to MM. ESRD occurs late in the disease process.
Gyorgy Csako - One of the best experts on this subject based on the ideXlab platform.
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Protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high-risk phenotype in familial Waldenström macroglobulinemia.
International journal of cancer, 2008Co-Authors: Mary L. Mcmaster, Gyorgy CsakoAbstract:Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal Gammopathy (MG) conditions such as Waldenstrom macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal Gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal Gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal Gammopathy, were then followed for a median of 17 years (range, 13-25). The monoclonal Gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal Gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations.
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protein electrophoresis immunoelectrophoresis and immunofixation electrophoresis as predictors for high risk phenotype in familial waldenstrom macroglobulinemia
International Journal of Cancer, 2007Co-Authors: Mary L. Mcmaster, Gyorgy CsakoAbstract:Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal Gammopathy (MG) conditions such as Waldenstrom macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal Gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal Gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal Gammopathy, were then followed for a median of 17 years (range, 13–25). The monoclonal Gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal Gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations. © 2007 Wiley-Liss, Inc.
Sanjeev Sethi - One of the best experts on this subject based on the ideXlab platform.
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thrombotic microangiopathy associated with monoclonal Gammopathy
Kidney International, 2017Co-Authors: Aishwarya Ravindran, Fernando C Fervenza, Sanjeev SethiAbstract:Thrombotic microangiopathy (TMA) is a rare disease comprising of a diverse set of disorders linked by a common histologic finding of endothelial injury. Monoclonal immunoglobulins may act as a potential trigger in the pathogenesis of TMA. To determine the prevalence of monoclonal Gammopathy and clinicopathological features of TMA associated with monoclonal immunoglobulin, we performed a retrospective study in adults (18 and older) with a clinical diagnosis of TMA. Of 146 patients with TMA, we detected monoclonal immunoglobulin in 20 patients (13.7%). Among patients 50 and older, the prevalence of monoclonal Gammopathy was 21%, which is approximately five-fold higher than the 4.2% expected rate in this population. Fifteen patients had monoclonal Gammopathy of undetermined significance, one had multiple myeloma, one with smoldering myeloma, two had POEMS syndrome, and one had T-cell lymphocytic leukemia. Renal biopsy was performed in 15 cases, of which six showed thrombi, 11 showed mesangiolysis, and all showed double contours along glomerular capillary walls. Acute tubular injury was present in 12 cases. Treatment options were varied and included therapeutic plasma exchange in 11 patients. Ten patients progressed to end-stage renal disease, of which two received kidney transplant. Thus, our study shows an unexpectedly high prevalence of monoclonal Gammopathy in patients with TMA, suggesting a potential pathogenetic mechanism. This study underscores the importance of evaluating for a monoclonal Gammopathy in patients with TMA as well as the potential for targeting the underlying hematologic disorder as an approach to treating TMA.
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membranoproliferative glomerulonephritis the role for laser microdissection and mass spectrometry
American Journal of Kidney Diseases, 2014Co-Authors: Deepika Jain, Jason D Theis, Jamie A Green, Sheldon I Bastacky, Sanjeev SethiAbstract:Monoclonal Gammopathy is increasingly recognized as a common cause of membranoproliferative glomerulonephritis (MPGN); however, establishing this diagnosis can be challenging. We report the case of a 58-year-old asymptomatic woman who presented with proteinuria with protein excretion of 5,000mg/d, microscopic hematuria, and normal kidney function. Kidney biopsy was consistent with MPGN pattern of injury. Immunofluorescence studies were positive for nonspecific segmental immunoglobulin M (IgM) and C3 staining. Electron microscopy showed subendothelial, subepithelial, and mesangial electron-dense deposits. The workup excluded an infectious or autoimmune disease, but IgG κ monoclonal protein was detected in serum at a concentration of 0.4mg/dL. Because there was a mismatch between the serum monoclonal protein (IgG κ) and immunofluorescence staining pattern (nonspecific IgM, no light chain restriction), laser microdissection and mass spectrometry were performed on the kidney biopsy tissue. This identified the deposits as monoclonal IgG κ, thereby leading to the diagnosis of monoclonal Gammopathy–associated MPGN. Our case emphasizes the importance of searching for an underlying cause of MPGN, reviews the technique of laser microdissection–mass spectrometry, and highlights its application as a pathology tool for the evaluation of monoclonal Gammopathy–related glomerulonephritis.
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monoclonal Gammopathy associated proliferative glomerulonephritis
Mayo Clinic proceedings, 2013Co-Authors: Sanjeev Sethi, Vincent S RajkumarAbstract:Abstract Monoclonal Gammopathy is characterized by circulating monoclonal immunoglobulin owing to clonal proliferation of immunoglobulin-producing B lymphocytes or plasma cells. Clonal proliferation of B lymphocytes is seen in B-cell lymphoma/leukemia, and clonal plasma cell proliferation is seen in multiple myeloma and monoclonal Gammopathy of undetermined significance. The monoclonal immunoglobulin in the setting of a B-cell or plasma cell disorder can cause a proliferative glomerulonephritis via 2 mechanisms: (1) glomerular deposition of the monoclonal immunoglobulin with activation of the classical pathway of complement (direct mechanism), resulting in an immunoglobulin-positive C3-positive glomerulonephritis, and (2) glomerular deposition of complement factors of the alternative and terminal pathway via inhibition of alternative pathway–regulating proteins by the monoclonal immunoglobulin (indirect mechanism), resulting in immunoglobulin-negative C3-positive glomerulonephritis (C3 glomerulopathy). Evaluation should include serum and urine electrophoresis and immunofixation as well as serum-free light-chain assay. If a monoclonal immunoglobulin is detected on these tests, bone marrow biopsy or imaging is needed to exclude more advanced plasma cell dyscrasia. Evaluation of alternative pathway of complement should be done in patients with Ig-negative C3-positive glomerulonephritis. If monoclonal Gammopathy is due to an underlying malignant disease such as myeloma, lymphoma, or chronic lymphocytic leukemia, then specific treatment should be aimed at treating the malignant disease, with the goal of eradicating the clonal cells producing the immunoglobulin. In contrast, if monoclonal Gammopathy is due to a monoclonal Gammopathy of undetermined significance, treatment options include bortezomib, cyclophosphamide, and dexamethasone for a non-IgM monoclonal immunoglobulin and rituximab alone or in combination with cyclophosphamide and dexamethasone for an IgM monoclonal immunoglobulin.
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c3 glomerulonephritis associated with monoclonal Gammopathy a case series
American Journal of Kidney Diseases, 2013Co-Authors: Ladan Zand, Nelson Leung, Richard J H Smith, Fernando C Fervenza, Samih H Nasr, Andrea G Kattah, Yuzhou Zhang, Julie A Vrana, Lynn D Cornell, Sanjeev SethiAbstract:Background C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal Gammopathy. Study Design Case series. Setting & Participants 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. Outcomes Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal Gammopathy. Results Mean age of patients with C3 GN associated with monoclonal Gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal Gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal Gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. Limitations Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. Conclusions The study highlights the association of C3 GN and monoclonal Gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN.
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membranoproliferative glomerulonephritis secondary to monoclonal Gammopathy
Clinical Journal of The American Society of Nephrology, 2010Co-Authors: Sanjeev Sethi, Ladan Zand, Nelson Leung, Richard J H Smith, Dragan Jevremonic, Sandra S Herrmann, Fernando C FervenzaAbstract:Background and objectives: Membranoproliferative glomerulonephritis (MPGN) is an immune complex–mediated glomerulonephritis characterized by subendothelial and mesangial deposition of immune complexes. Autoimmune diseases and chronic infections, such as hepatitis C, are commonly recognized causes of MPGN; however, monoclonal Gammopathy is a less widely recognized cause of MPGN. Design, setting, participants, & measurements: We reviewed all renal biopsies of MPGN in Mayo Clinic patients during a 6-year period to determine the association of monoclonal Gammopathy with MPGN. Results were correlated with electrophoresis studies and bone marrow biopsies to clarify the relationship between MPGN and gammopathies. Results: Of 126 patients with MPGN, 20 did not have workup for hepatitis B or C. Of the remaining 106 patients, 25 (23.5%) were positive for hepatitis B or C. Of the 81 hepatitis-negative patients, 13 were not evaluated for gammopathies. Of the remaining 68 patients, 28 (41.1%) had serum and/or urine electrophoresis studies positive for monoclonal Gammopathy. Serum immunofixation electrophoresis was the most sensitive method for diagnosing monoclonal Gammopathy. Renal biopsy showed a membranoproliferative pattern of injury; immunofluorescence microscopy was often instrumental in diagnosing the underlying Gammopathy. On the basis of the bone marrow biopsy, monoclonal Gammopathy of undetermined significance was the most common entity associated with MPGN. Other, less common causes included multiple myeloma, low-grade B cell lymphoma, and chronic lymphocytic leukemia. Conclusions: Monoclonal Gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal Gammopathy.
Mary L. Mcmaster - One of the best experts on this subject based on the ideXlab platform.
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immunoglobulin type m monoclonal Gammopathy of undetermined significance igm mgus
2017Co-Authors: Mary L. Mcmaster, Helga M Ogmundsdottir, Sigurdur Y Kristinsson, Robert A KyleAbstract:The term monoclonal Gammopathy pertains to the expansion of a single clone of B lymphocytes that produce an excess of a homogeneous immunoglobulin. Monoclonal Gammopathy of undetermined significance (MGUS) is diagnosed in a patient who presents with a monoclonal Gammopathy in the absence of histologic evidence, signs, or symptoms of a malignant lymphoproliferative or plasmacytic disorder. MGUS is among the most common premalignant conditions in Western populations, having a prevalence of about 4 % in white adults older than age 50. The immunoglobulin type M (IgM) subtype of MGUS (IgM-MGUS) exhibits unique features that distinguish it from non-IgM MGUS, including a distinctive racial prevalence pattern and spectrum of malignant outcomes. Putative risk factors predisposing to development of IgM-MGUS have been identified, but most await confirmation. The MYD88 L265P mutation that is characteristic of Waldenstrom macroglobulinemia (WM) is found in about half of IgM-MGUS patients. The most common malignant outcome is WM, but patients can develop other lymphoproliferative B-cell diseases. Patients progress to WM at a rate of 1.5 % per year, and they continue to be at risk of progression more than 20 years following diagnosis. Size of the monoclonal component at diagnosis has been the most consistent predictor of prognosis. IgM MGUS is also associated with other nonmalignant comorbidities, and patients diagnosed with it have inferior survival compared to the general population. Thus, there is growing consensus that IgM monoclonal Gammopathy may indeed have clinical significance. Further, while routine screening for IgM-MGUS is not widely advocated, it is recommended that, when discovered, IgM-MGUS patients should be followed for life.
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Protein electrophoresis, immunoelectrophoresis and immunofixation electrophoresis as predictors for high-risk phenotype in familial Waldenström macroglobulinemia.
International journal of cancer, 2008Co-Authors: Mary L. Mcmaster, Gyorgy CsakoAbstract:Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal Gammopathy (MG) conditions such as Waldenstrom macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal Gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal Gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal Gammopathy, were then followed for a median of 17 years (range, 13-25). The monoclonal Gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal Gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations.
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protein electrophoresis immunoelectrophoresis and immunofixation electrophoresis as predictors for high risk phenotype in familial waldenstrom macroglobulinemia
International Journal of Cancer, 2007Co-Authors: Mary L. Mcmaster, Gyorgy CsakoAbstract:Protein electrophoresis is used for the detection, evaluation and follow-up of monoclonal Gammopathy (MG) conditions such as Waldenstrom macroglobulinemia (WM). Immunofixation electrophoresis (IFE) is currently the most common method for isotyping of monoclonal Gammopathy because of its superior sensitivity relative to immunoelectrophoresis (IEP). We designed a study to evaluate the clinicobiological relevance of small monoclonal bands detected by serum protein electrophoresis, IEP, and IFE. Serum protein electrophoresis, IEP, and IFE were used to evaluate possible monoclonal Gammopathy in 46 members (29 relatives and 17 nonbloodline spouses) from 3 families with multiple cases of WM. IFE identified small monoclonal bands initially missed by IEP in 5 individuals (2 blood relatives, 3 spouses) among 46 study participants. All bands were IgM type. Twenty-three individuals, including the 2 blood relatives and 2 of 3 spouses with monoclonal Gammopathy, were then followed for a median of 17 years (range, 13–25). The monoclonal Gammopathy progressed in the 2 relatives but disappeared in the spouses, and new IgM MG developed in 2 additional relatives with a prior history of IgM polyclonal Gammopathy. Small monoclonal bands detected by IFE in a familial context may be biologically meaningful, both as phenotypic biomarkers and possibly as predictors of high risk for WM. Polyclonal IgM may also be a marker of genetic susceptibility in WM families. Larger studies are needed to confirm these observations. © 2007 Wiley-Liss, Inc.
Nelson Leung - One of the best experts on this subject based on the ideXlab platform.
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monoclonal Gammopathy the good the bad and the ugly
Blood Reviews, 2016Co-Authors: Siobhan Glavey, Nelson LeungAbstract:Monoclonal Gammopathy of undetermined significance (MGUS) is a condition characterized by the presence of a monoclonal Gammopathy (MG) in which the clonal mass has not reached a predefined state in which the condition is considered malignant. It is a precursor to conditions such as multiple myeloma or lymphoma at a rate of ~1%/year. Thus, from a hematologic standpoint, MGUS is a fairly benign condition. However, it is now recognized that organ damage resulting from just the MG without the need MM or lymphoma can occur. One of the most recognized is nephropathy secondary to monoclonal Gammopathy of renal significance (MGRS). Other well-recognized conditions include neuropathies, oculopathies and dermopathies. Some conditions such as autoimmune diseases and coagulopathies are less common and recognized. Finally, systemic involvement of multiple organs is well described in several entities. In all of these conditions, the role of the MG is no longer insignificant. Thus, the term MGUS should be avoided when describing these entities.
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clinical features and treatment outcomes of patients with necrobiotic xanthogranuloma associated with monoclonal gammopathies
Clinical Lymphoma Myeloma & Leukemia, 2015Co-Authors: Larissa Higgins, Vincent S Rajkumar, John A Lust, Angela Dispenzieri, Martha Q Lacy, David Dingli, Shaji Kumar, Francis K Buadi, Prashant Kapoor, Nelson LeungAbstract:Abstract Introduction Necrobiotic xanthogranuloma (NXG) is a rare chronic granulomatous disorder of the skin associated with a monoclonal Gammopathy. Patients and Methods The present report describes the findings from a single tertiary medical center retrospective study, including the clinical features of 35 patients with NXG and monoclonal Gammopathy from 2000 to 2015 and their subsequent disease course and treatment response. The median age at diagnosis was 56 years (range, 26-88 years). Results Most patients had a plasma cell dyscrasia consisting of monoclonal Gammopathy of undetermined significance in 28 patients and smoldering multiple myeloma in 5 patients; the remaining 2 patients had chronic lymphocytic leukemia. An IgG isotype of monoclonal Gammopathy was present in almost all the patients (97%). The most common site of cutaneous involvement of NXG was periorbital (66%). The treatments were heterogeneous and included excision, intralesional injection, radiotherapy, and systemic chemotherapy. The median follow-up period was 46 months (range, 4 to 234 months). The median overall survival had not been reached at the analysis, and 80% of the patients were still alive. Eight patients (23%) had disease progression to multiple myeloma at a median of 67 months (range, 21 to 107 months), demonstrating that although the clinical course is generally indolent, malignant transformation is not uncommon. At the last follow-up visit, 80% had signs of either clinical improvement or stable skin disease. Conclusion Cutaneous objective responses can be achieved with treatment of lymphoplasmacytic malignancies.
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c3 glomerulonephritis associated with monoclonal Gammopathy a case series
American Journal of Kidney Diseases, 2013Co-Authors: Ladan Zand, Nelson Leung, Richard J H Smith, Fernando C Fervenza, Samih H Nasr, Andrea G Kattah, Yuzhou Zhang, Julie A Vrana, Lynn D Cornell, Sanjeev SethiAbstract:Background C3 glomerulonephritis (GN) is a proliferative GN resulting from glomerular deposition of complement factors due to dysregulation of the alternative pathway of complement. Dysregulation of the alternative pathway of complement may occur as a result of mutations or functional inhibition of complement-regulating proteins. Functional inhibition of the complement-regulating proteins may result from a monoclonal Gammopathy. Study Design Case series. Setting & Participants 32 Mayo Clinic patients with C3 GN, 10 (31%) of whom had evidence of a monoclonal immunoglobulin in serum. Outcomes Clinical features, hematologic and bone marrow biopsy findings, kidney biopsy findings, kidney measures, complement pathway abnormalities, treatment, and follow-up of patients with C3 GN that was associated with a monoclonal Gammopathy. Results Mean age of patients with C3 GN associated with monoclonal Gammopathy was 54.5 years. Bone marrow biopsy done in 9 patients revealed monoclonal Gammopathy of undetermined significance in 5 patients, small lymphocytic lymphoma/chronic lymphocytic leukemia in one patient, and no abnormal clones in the other 3 patients. Kidney biopsy showed membranoproliferative GN with bright capillary wall C3 staining in all 10 patients. Evaluation of the alternative pathway of complement showed abnormalities in 7 of 9 patients tested. No mutation in complement-regulating proteins was detected in any patient. As an index case, one patient with C3 GN and chronic lymphocytic leukemia was treated with rituximab, cyclophosphamide, vincristine, and prednisone, and one patient with C3 GN and monoclonal Gammopathy of undetermined significance was treated with dexamethasone and bortezomib. Both patients showed significant decreases in hematuria and proteinuria and stabilization of kidney function. Limitations Studies to show evidence of direct activation of the alternative pathway by monoclonal immunoglobulin were not done. Conclusions The study highlights the association of C3 GN and monoclonal Gammopathy, in particular in the older population, and the importance of targeting the underlying hematologic malignancy as an approach to treating C3 GN.
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Monoclonal Gammopathy of renal significance: when MGUS is no longer undetermined or insignificant.
Blood, 2012Co-Authors: Nelson Leung, Robert A Kyle, Franck Bridoux, Colin A Hutchison, Samih H Nasr, Paul Cockwell, Jean-paul Fermand, Angela Dispenzieri, Kevin W Song, Non RenseignéAbstract:Multiple myeloma is the most frequent monoclonal Gammopathy to involve the kidney; however, a growing number of kidney diseases associated with other monoclonal gammopathies are being recognized. Although many histopathologic patterns exist, they are all distinguished by the monoclonal immunoglobulin (or component) deposits. The hematologic disorder in these patients is more consistent with monoclonal Gammopathy of undetermined significance (MGUS) than with multiple myeloma. Unfortunately, due to the limitations of the current diagnostic schema, they are frequently diagnosed as MGUS. Because treatment is not recommended for MGUS, appropriate therapy is commonly withheld. In addition to end-stage renal disease, the persistence of the monoclonal Gammopathy is associated with high rates of recurrence after kidney transplantation. Preservation and restoration of kidney function are possible with successful treatment targeting the responsible clone. Achievement of hematologic complete response has been shown to prevent recurrence after kidney transplantation. There is a need for a term that properly conveys the pathologic nature of these diseases. We think the term monoclonal Gammopathy of renal significance is most helpful to indicate a causal relationship between the monoclonal Gammopathy and the renal damage and because the significance of the monoclonal Gammopathy is no longer undetermined.
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membranoproliferative glomerulonephritis secondary to monoclonal Gammopathy
Clinical Journal of The American Society of Nephrology, 2010Co-Authors: Sanjeev Sethi, Ladan Zand, Nelson Leung, Richard J H Smith, Dragan Jevremonic, Sandra S Herrmann, Fernando C FervenzaAbstract:Background and objectives: Membranoproliferative glomerulonephritis (MPGN) is an immune complex–mediated glomerulonephritis characterized by subendothelial and mesangial deposition of immune complexes. Autoimmune diseases and chronic infections, such as hepatitis C, are commonly recognized causes of MPGN; however, monoclonal Gammopathy is a less widely recognized cause of MPGN. Design, setting, participants, & measurements: We reviewed all renal biopsies of MPGN in Mayo Clinic patients during a 6-year period to determine the association of monoclonal Gammopathy with MPGN. Results were correlated with electrophoresis studies and bone marrow biopsies to clarify the relationship between MPGN and gammopathies. Results: Of 126 patients with MPGN, 20 did not have workup for hepatitis B or C. Of the remaining 106 patients, 25 (23.5%) were positive for hepatitis B or C. Of the 81 hepatitis-negative patients, 13 were not evaluated for gammopathies. Of the remaining 68 patients, 28 (41.1%) had serum and/or urine electrophoresis studies positive for monoclonal Gammopathy. Serum immunofixation electrophoresis was the most sensitive method for diagnosing monoclonal Gammopathy. Renal biopsy showed a membranoproliferative pattern of injury; immunofluorescence microscopy was often instrumental in diagnosing the underlying Gammopathy. On the basis of the bone marrow biopsy, monoclonal Gammopathy of undetermined significance was the most common entity associated with MPGN. Other, less common causes included multiple myeloma, low-grade B cell lymphoma, and chronic lymphocytic leukemia. Conclusions: Monoclonal Gammopathy is an important and common cause of MPGN; therefore, all patients with a diagnosis of MPGN should be evaluated for an underlying monoclonal Gammopathy.
