scholarly journals Epidemiological and Clinical Characteristics of Monoclonal Gammopathy of Renal Significance (MGRS) in South America

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 5856-5856
Author(s):  
Camila Peña ◽  
Gonzalo P Mendez ◽  
Natalia Paola Schutz ◽  
Eloisa Riva ◽  
Ricardo Valjalo ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Biopsy ◽  
Plasma Cell ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Clinical Characteristics ◽  
Protein Electrophoresis ◽  
Renal Response ◽  
Series Study

Abstract Background Monoclonal gammopathy of renal significance (MGRS) is a recently defined entity. It is a group of renal diseases due to paraprotein deposition from a small B lymphocyte or plasma cell clon, not meeting the criteria for an overt gammopathy-associated neoplasm. Despite this feature, the secondary kidney damage may be severe and irreversible; therefore, its early recognition and treatment are crucial. There are few studies on MGRS in the international literature, and no reported data from Latin America (LA). Aims To describe epidemiological and clinical characteristics of patients diagnosed with MGRS in LA. To evaluate patients outcomes. Material and methods This is an international multicentric retrospective case series study. All members of GELAMM (Grupo de estudio latinoamericano de Mieloma Múltiple) were invited to participate. Patients with diagnosis of MGRS according to the IMWG definition were included. All cases had pathological diagnosis provided by a renal biopsy. Epidemiological and clinical data were collected from clinical records in a standardized report form. Renal response was arbitrarily defined as the partial or total recovery of renal failure or renal symtoms at the end of treatment. Statistical analysis was performed by descriptive statistics using STATA 12. Results We received data from 18 patients, from centers in Chile, Argentina and Uruguay. Median follow up was 22,5 months. The patients characteristics are shown in table 1. The median age was 58 years (36 to 78 years). Male to female ratio was 1:1,25. Twelve had history of hypertension and one patient of renal transplantation. Anemia was present in 78% of cases (mean 10,7g/dL +/-2,3), hypoalbuminemia in 72% (mean 2,8g/dL +/-0,7), renal failure in 83% (mean creatinine of 4,6mg/dL +/- 4,8) with 47% of these (7 patients) requiring renal replacement therapy (RRT). Proteinuria was measured in 16 patients. Its average was 4,4gr (range 0,12 - 11,5gr/24hrs). LDH and calcemia were normal in all cases. Half of the patients presented as a nephrotic syndrome. Regarding histological subtypes, the most frequently diagnosed was the proliferative glomerulonephritis with monoclonal immunoglobulin deposits (PGNMID). The paraprotein most frequently found was Kappa, and in the renal biopsy was IgG Kappa deposition (table 1). Serum protein electrophoresis (sPEP) was performed in all cases. Only 8 out 18 patients underwent urine protein electrophoresis (uPEP) and 14 had urine and serum immunofixation (IFX) done. Serum free light chain (sFLC) were performed in 94% of the patients. The paraprotein identification according to each of this exams is shown in figure 1. Seventeen patients received treatment; 13 received an anti-plasma cell drug, 7 a thalidomide based regimen and 6 a bortezomib based regimen. The patient with IgM MGRS was treated with a rituximab based regimen. Regarding renal responses, there were no data in 5 patients. Nine out 13 of the patients achieved renal response: 3 achieved partial recovery and 9 complete recovery. Three patients become RRT independent. There was no mortality in our cohort. No patient relapsed, but 3 progressed: 1 to multiple myeloma (MM), 1 to systemic amyloidosis and another to systemic light chain deposition disease (LCDD). Discussion Only 18 cases from 3 South American countries were collected. The lack of hematologists in some countries, difficulties in achieving a renal biopsy, non-availability of immunofluorescence in the histological studies and few experienced pathologists could be some of the problems in our region. Our cohort is of rather young patients, which is probably related to the fact that these patients are mostly undergoing renal biopsy. We believe, however, that the incidence of MGRS (similar to what happens with MGUS), increases with age, which could mean a problem of underdiagnoses. As expected, nephropathies frequently associated with MM were found: AL amyloidosis and LCDD. However, the most common renal pathology was PGNMID, a rare entity. This data must be corroborated with a larger study. The high sensitivity of sFLC to identify the paraprotein was corroborated and highlighted the importance of this test in the follow up. Half of patients achieved a renal response, which reinforces the fact that they must be promptly treated. Conclusion According to our knowledge, this is the larger cases series study in LA, and we hope it will be a contribution to the knowledge of this pathology. Disclosures No relevant conflicts of interest to declare.

Renal involvement in plasma cell dyscrasias, immunoglobulin-based amyloidoses, and fibrillary glomerulopathies, lymphomas, and leukaemias

2020 ◽  
pp. 5016-5027
Author(s):  
Pierre Ronco ◽  
Frank Bridoux ◽  
Arnaud Jaccard
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Nephrotic Syndrome ◽  
Renal Biopsy ◽  
Plasma Cell ◽  
Heavy Chain ◽  
Light Chain ◽  
Failure Diagnosis ◽  
Immunotactoid Glomerulopathy ◽  
Plasma Cell Dyscrasias

Plasma cell dyscrasias are characterized by uncontrolled proliferation of a single clone of B cells which is responsible for the secretion of a monoclonal immunoglobulin (Ig) or Ig subunit that can deposit in tissues. They can cause a wide range of renal diseases. Light-chain amyloidosis—renal presentation is usually with proteinuria, often progressing to nephrotic syndrome. A progressive decline in renal function may occur, leading finally to endstage renal failure. Diagnosis is made by the detection of monoclonal gammopathy and free light-chain excess in the serum (90% of cases), in combination with biopsy evidence of amyloid-forming light-chain deposits. Myeloma—renal failure is found at presentation in 20% of patients, occurs in 50% at some time, and is most commonly caused by cast nephropathy, with renal biopsy typically showing ‘fractured’ casts. Chemotherapy should be introduced promptly. Light-chain, light- and heavy-chain, and heavy-chain deposition disease—collectively known as monoclonal Ig deposition diseases, present with proteinuria and renal failure. Diagnosis is by renal biopsy. Treatment strategy is based on chemotherapy (bortezomib-based regimens) followed by autologous stem cell transplantation in selected cases. Fibrillary glomerulonephritis and immunotactoid glomerulopathy—usual presentation is with nephrotic syndrome, microscopic haematuria, and hypertension. Immunotactoid glomerulopathy usually responds to chemotherapy. Cryoglobulinaemia—type II (‘essential mixed’) may present with proteinuria, haematuria, hypertension, and gradually declining renal function, or with an acute nephritic picture. Renal biopsy typically reveals membranoproliferative glomerulonephritis with massive subendothelial deposits. Treatment involves antiviral agents and/or immunosuppression. Tumour lysis syndrome—a life-threatening metabolic emergency that occurs in patients with haemopathies with high cell turnover, mostly at the onset of chemotherapy. Treatment is based on saline diuresis (if possible), rasburicase, and haemodialysis (if required).

scholarly journals A monoclonal gammopathy precedes multiple myeloma in most patients

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

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

scholarly journals Monoclonal Gammopathy of Clinical Significance - a Single Center Experience

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 4495-4495
Author(s):  
Holly Lee ◽  
Lesley Street ◽  
Jason Tay ◽  
Jennifer Grossman ◽  
John F Thaell ◽  
...  
Keyword(s):  
Clinical Significance ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Renal Diseases ◽  
Cell Transplant ◽  
Intermediate Risk ◽  
Light Chain Deposition Disease ◽  
Renal Response ◽  
Schnitzler Syndrome

Abstract Introduction Monoclonal gammopathy of clinical significance (MGCS) is a newly described entity that defines clinical conditions and organ damage resulting from the effects of monoclonal proteins (Fermand et al., 2018). In MGCS, the underlying clone burden resembles an MGUS state, and does not meet criteria for multiple myeloma or lymphoma. A wide spectrum of conditions has been described in MGCS (Fermand et al., 2018). In this retrospective study, our purpose was to identify the incidences of patients with MGCS at our hematology clinics. Methods We collaborated with three clinicians who see the majority of MGUS patients at the University of Calgary Medical Group clinics (UCMG). Patients who were referred and diagnosed with MGUS at the hematology clinic at UCMG since 2014 were assessed. The diagnosis of MGUS and MGCS were made based on consensus criteria (Rajkumar et al., 2014) and the recent publication (Fermand et al., 2018). Retrospective chart reviews were performed and cases with MGCS were analyzed. MGUS risk stratification score was calculated per previous reports (Katzmann et al., 2013; Kyle et al., 2018). Hematological response was assessed using the International Myeloma Working Group criteria (Rajkumar et al., 2014), and renal response was measured using KDIGO guidelines (Radhakrishnan & Cattran, 2012). Results A total of 606 MGUS patients were seen at our clinic from February 2014 to June 2018. Patients who had MGUS and co-existing conditions which met MGCS criteria (Fermand et al., 2018) were evaluated. There were 25 MGCS patients identified. Median age at diagnosis was 60, and 28% were female. Clinical characteristics are outlined in Table 1. Three patients had light chain MGUS. Among the non-light chain MGUS patients, there were 11 high-intermediate risk (55%), 1 intermediate risk (5%), 5 low-intermediate risk (25%), and 3 low risk MGUS (15%). At the time of analysis all patients were alive, and 3 patients have progressed. Median follow up was 2 years (0-16 years). Renal involvement was the most common with 14 patients having biopsy proven renal pathologies that met criteria for monoclonal gammopathy of renal significance (MGRS) (Leung et al., 2012). Four patients had neuropathies, including Anti-MAG, chronic inflammatory demyelinating polyneuropathy (CIDP), distal acquired demyelinating symmetric neuropathy (DADS-M), and autonomic neuropathy. Three patients had skin manifestations (Schnitzler syndrome, necrobiotic xanthogranuloma, scleromyxedema), 1 patient had corneal involvement (crystalline keratopathy), 1 patient had gastrointestinal manifestation (mixed light chain deposition disease), 1 patient had acquired C1 esterase inhibitor deficiency with angioedema, and 1 patient was diagnosed with Sweet syndrome in 1993 which had led to her original monoclonal gammopathy workup. Five out of the 14 patients with MGRS received plasma cell directed chemotherapy, and 1 patient with crystalloid podocytopathy underwent auto-stem cell transplant. Of these 5 patients, 4 had renal response. Treatment for other MGCS cases are indicated in Table 1. Discussion and Conclusion Our series demonstrates that cases of MGCS represent a small minority within our larger MGUS cohort. The most common organ involvements seen in our MGCS patients were renal, nerve and skin. One of the major diagnostic challenges is confirming that the organ dysfunction and MGUS co-exist by true association, and not by coincidence. In our patient cohort, tissue biopsies were obtained when possible (all renal, skin, and GI cases), and others were diagnosed through review with local experts and relying on published literature. The distinction of MGCS from MGUS is important, as it may change treatment decisions. In renal diseases associated with monoclonal gammopathy, referred to as MGRS, renal prognosis is poor and clone directed treatment is associated with improved renal outcomes (Fermand et al., 2013). As prospective or randomized trials are unavailable for MGRS or MGCS, the treatments given at our center were determined on a case-by-case basis relying on expert opinions, local experiences, and a recent guideline (Fermand et al., 2013). Interdisciplinary care is required for both the diagnosis and management of MGCS. Further studies with long term follow-up are needed. Disclosures McCulloch: Takeda: Other: Travel expenses; Celgene: Honoraria. Neri:Janssen: Consultancy, Honoraria; Celgene: Consultancy, Honoraria.

scholarly journals Development of Renal Failure without Proteinuria in a Patient with Monoclonal Gammopathy of Undetermined Significance: An Unusual Presentation of AL Kappa Amyloidosis

2012 ◽  
Vol 2012 ◽  
pp. 1-5 ◽  
Author(s):  
Yijuan Sun ◽  
Amarpreet Sandhu ◽  
Darlene Gabaldon ◽  
Jonathan Danaraj ◽  
Karen S. Servilla ◽  
...  
Keyword(s):  
Renal Failure ◽  
Renal Biopsy ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Outlet Obstruction ◽  
Renal Ultrasound ◽  
Al Amyloidosis ◽  
Kappa Light Chain ◽  
Severe Renal Failure ◽  
Undetermined Significance

AL amyloidosis complicating monoclonal gammopathy of undetermined significance (MGUS) has usually a predominant glomerular deposition of lambda light chain. Heavy proteinuria is one of its cardinal manifestations. A 78-year-old man with a 9-year history of IgG kappa light-chain-MGUS and normal urine protein excretion developed severe renal failure. Serum levels of kappa light chain and serum IgG had been stable while proteinuria was absent throughout the nine-year period. For the first eight years, he had stable stage III chronic kidney disease attributed to bladder outlet obstruction secondary to prostatic malignancy. In the last year, he developed progressive serum creatinine elevation, without any increase in the serum or urine levels of paraproteins or any sign of malignancy. Renal ultrasound and furosemide renogram showed no evidence of urinary obstruction. Renal biopsy revealed AL amyloidosis, with reactivity exclusive for kappa light chains, affecting predominantly the vessels and the interstitium. Glomerular involvement was minimal. Melphalan and prednisone were initiated. However, renal function continues deteriorating. Deposition of AL kappa amyloidosis developing during the course of MGUS predominantly in the wall of the renal vessels and the renal interstitium, while the involvement of the glomeruli is minimal, leads to progressive renal failure and absence of proteinuria. Renal biopsy is required to detect both the presence and the sites of deposition of renal AL kappa light chain amyloidosis.

scholarly journals Single Arm, Prospective, Open-Label Phase II Trial to Evaluate the Efficacy of Isatuximab in Patients with Monoclonal Gammopathy of Renal Significance

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3161-3161 ◽  
Author(s):  
Vikram Premkumar ◽  
Suzanne Lentzsch ◽  
Divaya Bhutani
Keyword(s):  
Multiple Myeloma ◽  
B Cell ◽  
Plasma Cell ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Cell Clone ◽  
Advisory Committees ◽  
Renal Response ◽  
Hematologic Response ◽  
Stable Renal Function

Background: Monoclonal gammopathy of renal significance (MGRS) is a monoclonal B cell disorder, not meeting the definition of lymphoma or myeloma, that produces monoclonal proteins which deposit in the kidneys. Permanent renal damage can occur either as a consequence of direct deposition of toxic proteins or by an induced inflammatory response. Due to the low burden of the plasma cell clone, patients do not otherwise qualify for potentially toxic anti-plasma cell treatments and treatment is generally based on consensus opinion. To date there are no clinical trials exploring treatment options. Isatuximab is a chimeric mouse/human IgG1k monoclonal antibody which targets CD38 on both malignant and normal plasma cells and exhibits it antitumor effects primarily by antibody-dependent cellular toxicity. Isatuximab has recently been shown to be an active drug in the treatment of multiple myeloma, with improvements seen in hematologic and renal markers, and has been shown to have manageable toxicity. Given the efficacy of isatuximab in multiple myeloma, we propose a trial evaluating isatuximab monotherapy to treat the small plasma cell clone in MGRS with the hopes of maximizing response and minimizing toxicity. Study Design and Methods: The primary objective of this study is to evaluate efficacy of isatuximab monotherapy in patients with MGRS in order to establish a standard of care treatment for patients with this disease. Adult patients with proteinuria of at least 1 gram in 24 hours and a histopathological diagnosis of MGRS on renal biopsy in the last 24 months will be eligible for the trial. Patients will be excluded if their estimated GFR is below 30 mL/min, they have multiple myeloma, high risk smoldering myeloma, other B cell neoplasm meeting criteria for treatment, concurrent diabetic nephropathy, or require dialysis. Patients will be screened for B cell disorders with bone marrow biopsy and aspirate, serum protein electrophoresis (SPEP) with immunofixation (IFE), 24-hour urine protein electrophoresis (UPEP), free light chain (FLC) testing and screening PET/CT at time of enrollment. Enrolled patients will be administered isatuximab 20 mg/kg IV weekly for 4 weeks and then will receive the same dose every 2 weeks thereafter for a total of 6 months. Patients may be continued on treatment following completion of the 6 months at the discretion of the provider. To reduce the risk of infusion related reactions, patients will receive premedications with corticosteroids, diphenhydramine, H2 blockade and acetaminophen at least 60 minutes prior to infusion. Patients will have repeat SPEP + IFE, 24-hour UPEP + IFE and FLC testing every 4 weeks. There will be an optional repeat kidney biopsy 9-12 months following treatment initiation to assess pathologic response in the kidneys. Statistical Methods: The study will be comprised of 20 patients being treated with isatuximab over a span of 24-30 months. Ten patients will be initiated on the therapy for a period of 6 months. Interim analysis will be done after these patients have completed all the treatment cycles. If 4 out of 10 patients show response in form of improved/stable renal function, the study will proceed to include next 10 patients. If >50% of the first group of 10 patients show doubling of creatinine while on therapy, that would be considered as an indication to discontinue the therapy and the study due to drug toxicity. Endpoints: The primary endpoint will be efficacy as measured by renal response and hematologic response. Renal response will be measured by assessing the amount of proteinuria in a 24 hour urine sample. A sustained reduction in proteinuria by 30% from the patient's baseline amount of proteinuria with stable renal function (serum eGFR within 20% of baseline) will be considered a positive renal response. Hematologic response will be quantified per the 2016 International Myeloma Working Group (IMWG) uniform response criteria for multiple myeloma. An important secondary endpoint will be safety and will be analyzed from all patients who receive any study drug. Adverse events will be characterized and graded according to the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Other endpoints include time to dialysis and rate of minimal residual disease (MRD) negativity. Disclosures Lentzsch: Caelum Biosciences: Equity Ownership, Membership on an entity's Board of Directors or advisory committees; Bayer: Consultancy; Janssen: Consultancy; Takeda: Consultancy; BMS: Consultancy; Proclara: Consultancy; Abbvie: Consultancy; Clinical Care Options: Speakers Bureau; Sanofi: Consultancy, Research Funding; Multiple Myeloma Research Foundation: Honoraria; International Myeloma Foundation: Honoraria; Karyopharm: Research Funding; Columbia University: Patents & Royalties: 11-1F4mAb as anti-amyloid strategy. Bhutani:Sanofi: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: Our trial will be evaluating the efficacy of targeting CD38 on plasma cells with isatuximab in patients with monoclonal gammopathy of renal significance (MGRS). We will evaluate the effects of this drug on 24 hour proteinuria and hematologic response.

Cancer Development and Mortality Differences in Patients with Glomerulonephritis after Renal Biopsy: A Single Center Retrospective Cohort Study

2020 ◽  
Author(s):  
Hyunjin Ryu ◽  
Kipyo Kim ◽  
Jiwon Ryu ◽  
Hyung-Eun Son ◽  
Ji-Young Ryu ◽  
...  
Keyword(s):  
Cohort Study ◽  
Renal Biopsy ◽  
Retrospective Cohort Study ◽  
Retrospective Cohort ◽  
Clinical Characteristics ◽  
De Novo ◽  
Hazard Ratio ◽  
Cancer Development ◽  
De Novo Cancer

Abstract Background: The association between glomerulonephritis (GN) and cancer has been well known for decades. However, studies evaluating long-term de novo cancer development in patients with GN are limited. This study aimed to evaluate the incidence of cancer development among patients with renal biopsy-proven GN during post-biopsy follow-up and the differences in outcomes according to cancer occurrence. Methods: We conducted a retrospective cohort study of adult patients who underwent renal biopsy at Seoul National Bundang Hospital between 2003 and 2017. After excluding 671 patients who are inappropriate for the analysis, 929 patients were included in the analysis. Data on baseline clinical characteristics, renal biopsy results, and types and doses of immunosuppressant agents used during follow-up were collected from electronic medical records. The incidence of cancer was censored on the date when the first cancer was diagnosed. We evaluated rates of mortality and end-stage renal disease (ESRD) development during follow-up. Results: During a mean follow-up period of 52.4 (range: 1.0–166.7) months, 49 subjects (5.3%) developed de novo cancer. A comparison of clinical characteristics between subjects who did and did not develop cancer revealed that cancer patients were older and had higher comorbidities and immunosuppressant use. Overall, patients with GN had an elevated standardized incidence ratio (SIR) of 7.17 (95% confidence interval (CI): 5.3–9.51) relative to the general population. In particular, the SIR was significantly higher in GNs such as membranous nephropathy (MN), IgA nephropathy, lupus nephritis, and focal segmental glomerulosclerosis. Multivariable Cox proportional hazard model adjusted for confounding variables revealed that patients with a pathologic diagnosis of MN had an increased risk of cancer development, with a hazard ratio of 2.6 [95% CI: 1.32–5.30]. Patients with MN who developed cancer had a significantly higher risk of mortality (hazard ratio: 5.95; 95% CI: 1.36–26.09, P=0.018) than those without cancer, but there was a non-significant difference in ESRD development. Conclusions: Patients with GN without concurrent cancer, particularly those with MN, have significantly higher risks of cancer development and subsequent mortality and should remain aware of the potential development of malignancy during follow-up.

scholarly journals Crescentic Glomerulonephritis with Anti-GBM and p-ANCA Antibodies

2012 ◽  
Vol 2012 ◽  
pp. 1-4 ◽  
Author(s):  
Tariq Javed ◽  
Parag Vohra
Keyword(s):  
Renal Failure ◽  
Renal Biopsy ◽  
Recurrence Rate ◽  
Crescentic Glomerulonephritis ◽  
Diagnosis And Treatment ◽  
Atypical Presentation ◽  
Long Term Follow Up ◽  
Pulmonary Renal Syndrome

We are presenting a case of renal failure with anti-GBM and p-ANCA antibodies positive. Patients with dual antibodies are considered to be a vasculitis-variant of anti-GBM antibody nephritis. These patients may have atypical presentation and it may delay diagnosis and treatment. Recurrence rate is higher in these patients. We reviewed the literature of cases and studies on cresenteric glomerulonephritis with anti-GBM and p-ANCA positive patients. We recommend that patients suspected with pulmonary-renal syndrome should be checked for anti-GBM and p-ANCA antibodies, should undergo renal biopsy and should should have close long term follow up to watch for recurrence.

scholarly journals Screening and Diagnosis of Monoclonal Gammopathies: An International Survey of Laboratory Practice

2017 ◽  
Vol 142 (4) ◽  
pp. 507-515 ◽  
Author(s):  
Jonathan R. Genzen ◽  
David L. Murray ◽  
Gyorgy Abel ◽  
Qing H. Meng ◽  
Richard J. Baltaro ◽  
...  
Keyword(s):  
Capillary Electrophoresis ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Protein Electrophoresis ◽  
Agarose Gel ◽  
Laboratory Practice ◽  
Serum Free ◽  
Serum Free Light Chain ◽  
Capillary Zone ◽  
Screening And Diagnosis

Context.— Serum tests used for the screening and diagnosis of monoclonal gammopathies include serum protein electrophoresis (SPE; agarose gel or capillary zone), immunofixation (IFE) and immunosubtraction capillary electrophoresis, serum free light chains, quantitative immunoglobulins, and heavy/light–chain combinations. Urine protein electrophoresis and urine IFE may also be used to identify Bence-Jones proteinuria. Objective.— To assess current laboratory practice for monoclonal gammopathy testing. Design.— In April 2016, a voluntary questionnaire was distributed to 923 laboratories participating in a protein electrophoresis proficiency testing survey. Results.— Seven hundred seventy-four laboratories from 38 countries and regions completed the questionnaire (83.9% response rate; 774 of 923). The majority of participants (68.6%; 520 of 758) used agarose gel electrophoresis as their SPE method, whereas 31.4% (238 of 758) used capillary zone electrophoresis. The most common test approaches used in screening were SPE with reflex to IFE/immunosubtraction capillary electrophoresis (39.3%; 299 of 760); SPE only (19.1%; 145 of 760); SPE and IFE or immunosubtraction capillary electrophoresis (13.9%; 106 of 760); and SPE with IFE, serum free light chain, and quantitative immunoglobulins (11.8%; 90 of 760). Only 39.8% (305 of 767) of laboratories offered panel testing for ordering convenience. Although SPE was used by most laboratories in diagnosing new cases of myeloma, when laboratories reported the primary test used to follow patients with monoclonal gammopathy, only 55.7% (403 of 724) chose SPE, with the next most common selections being IFE (18.9%; 137 of 724), serum free light chain (11.7%; 85 of 724), and immunosubtraction capillary electrophoresis (2.1%; 15 of 724). Conclusions.— Ordering and testing practices for the screening and diagnosis of monoclonal gammopathy vary widely across laboratories. Improving utilization management and report content, as well as recognition and development of laboratory-directed testing guidelines, may serve to enhance the clinical value of testing.

scholarly journals Role of different hematologic variables in defining the risk of malignant transformation in monoclonal gammopathy

Blood ◽  
1996 ◽  
Vol 87 (3) ◽  
pp. 912-918 ◽  
Author(s):  
L Baldini ◽  
A Guffanti ◽  
BM Cesana ◽  
M Colombi ◽  
O Chiorboli ◽  
...  
Keyword(s):  
Malignant Transformation ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Cox Model ◽  
Univariate Analysis ◽  
Cost Benefit ◽  
Cumulative Probability ◽  
Relative Risks ◽  
Monoclonal Component

The presenting clinico-hematologic features of 386 patients with nonmyelomatous monoclonal gammopathy (MG) were correlated with the frequency of malignant transformation to evaluate the most important variables conditioning its evolution into multiple myeloma (MM) or Waldenstrom macroglobulinemia (WM). Most of the patients (335) had monoclonal gammopathy of undetermined significance (MGUS: 39 IgA, 242 IgG, 54 IgM): the remaining 51 patients (12 IgA, 39 IgG) fulfilled all of the MGUS diagnostic criteria (according to Durie) except that bone marrow plasma cell (BMPC) content was 10% to 30%, and so they were defined as having monoclonal gammopathy of borderline significance (MGBS). There were no significant differences between the MGUS and MGBS groups in terms of age, sex, or median follow-up. After a median follow- up of 70 and 53 months, respectively, 23 of 335 MGUS and 19 of 51 MGBS patients had undergone a malignant evolution. Univariate analysis of the IgA and IgG patients showed that the cumulative probability of the disease evolving into MM correlated with diagnostic definition (MGBS v MGUS), BMPC content (> or = 10% v < 5% and < or = 5% v > 5%) and reduced serum polyclonal Ig. In the IgG cases, there was also a significant correlation with detectable Bence Jones proteinuria, serum monoclonal component (MC) levels and age at diagnosis (> 70 v < = or 55 years). In the IgG cases as a whole, the same variables remained in the Cox model where the BMPC percentage was considered after natural logarithmic transformation and the monoclonal component as g/dL value. The relative risks of developing MM are the following: 2.4 for each 1 g/dL increase of IgG, serum MC, 3.5 for detectable light chain proteinuria, 4.4 for the increase of 1 unit in log. BMPC percentage, 6.1 for age > 70, 3.6 and 13.1 for a reduction in one or two polyclonal Ig. In conclusion, our study allows the identification of a particular subset of MGUS patients (MC < = or 1.5 g/dL, BMPC < 5%, no reduction in polyclonal Ig and no detectable light chain proteinuria) at very low- risk of evolution, who can be considered as having benign monoclonal gammopathies. We also describe a previously undefined group of MG patients (with monoclonal gammopathy of borderline significance) who are at high-risk of malignant evolution. These findings could have a considerable impact on the cost/benefit ratio of monitoring programs in these patients.

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