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Blood Cancer Journal Dec 2023Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early...
Immunophenotypic assessment of clonal plasma cells and B-cells in bone marrow and blood in the diagnostic classification of early stage monoclonal gammopathies: an iSTOPMM study.
Monoclonal gammopathy of undetermined significance (MGUS) is the earliest discernible stage of multiple myeloma (MM) and Waldenström's macroglobulinemia (WM). Early diagnosis of MG may be compromised by the low-level infiltration, undetectable to low-sensitive methodologies. Here, we investigated the prevalence and immunophenotypic profile of clonal (c) plasma cells (PC) and/or cB-lymphocytes in bone marrow (BM) and blood of subjects with a serum M-component from the iSTOPMM program, using high-sensitive next-generation flow cytometry (NGF), and its utility in the diagnostic classification of early-stage MG. We studied 164 paired BM and blood samples from 82 subjects, focusing the analysis on: 55 MGUS, 12 smoldering MM (SMM) and 8 smoldering WM (SWM). cPC were detected in 84% of the BM samples and cB-lymphocytes in 45%, coexisting in 39% of cases. In 29% of patients, the phenotypic features of cPC and/or cB-lymphocytes allowed a more accurate disease classification, including: 19/55 (35%) MGUS, 1/12 (8%) SMM and 2/8 (25%) SWM. Blood samples were informative in 49% of the BM-positive cases. We demonstrated the utility of NGF for a more accurate diagnostic classification of early-stage MG.
Topics: Humans; Plasma Cells; Bone Marrow; Paraproteinemias; B-Lymphocytes; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Waldenstrom Macroglobulinemia; Smoldering Multiple Myeloma
PubMed: 38072838
DOI: 10.1038/s41408-023-00944-1 -
Journal of Medical Case Reports Apr 2023Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light... (Review)
Review
BACKGROUND
Systemic amyloidosis is group of disorders characterized by the accumulation of insoluble proteins in tissues. The most common form of systemic amyloidosis is light chain amyloidosis, which results from the accumulation of misfolded immunoglobulins. The disease is progressive, with treatment targeted at the underlying plasma cell dyscrasia. Since essentially any organ system can be affected, the presentation is variable and delays in diagnosis are common. Given this diagnostic difficulty, we discuss four different manifestations of light chain amyloidosis.
CASE PRESENTATIONS
In this case series, we discuss four cases of light chain amyloidosis. These include cardiac, hepatic, and gastrointestinal as well as autonomic and peripheral nerve involvement with amyloidosis. The patients in our series are of Caucasian background and include a 69-year-old female, a 29-year-old female, a 68-year-old male, and a 70-year-old male, respectively. The case discussions highlight variability in presentation and diagnostic challenges.
CONCLUSIONS
Amyloidosis is a rare but serious disease that is often complicated by long delays in diagnosis. Morbidity and mortality can sometimes be limited if diagnosed earlier. We hope our real life cases will contribute to understanding and to early suspicion that can lead to early diagnosis and management.
Topics: Male; Female; Humans; Aged; Adult; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Paraproteinemias; Heart
PubMed: 37081462
DOI: 10.1186/s13256-023-03886-1 -
Frontiers in Immunology 2020
Topics: Animals; Antibodies; Cellular Microenvironment; Humans; Hypersensitivity; Paraproteinemias; Parasitic Diseases; Phenotype; Plasma Cells; Time Factors
PubMed: 33193457
DOI: 10.3389/fimmu.2020.606737 -
Continuum (Minneapolis, Minn.) Oct 2020Neurologists commonly evaluate patients with a monoclonal gammopathy and peripheral neuropathy. As both monoclonal gammopathy and peripheral neuropathy are common in the... (Review)
Review
PURPOSE OF REVIEW
Neurologists commonly evaluate patients with a monoclonal gammopathy and peripheral neuropathy. As both monoclonal gammopathy and peripheral neuropathy are common in the general population, their coexistence may, in some instances, be purely coincidental. However, monoclonal gammopathies or underlying lymphoplasmacytic disorders can affect the peripheral nervous system by various mechanisms. This article discusses how to approach patients with monoclonal gammopathy and peripheral neuropathy, highlighting clinical and laboratory clues that may aid in establishing a diagnosis in a timely manner.
RECENT FINDINGS
From a hematologic standpoint, a monoclonal gammopathy may be of undetermined significance or can be associated with an underlying myeloma, lymphoplasmacytic lymphoma, or amyloidosis. Each of these conditions can cause peripheral neuropathy, with varying clinical and electrodiagnostic profiles. Treatment usually consists of treating the underlying hematologic disorder. IgM-associated peripheral neuropathy may not require treatment from a hematologic standpoint, and only anecdotal evidence exists for the use of immunotherapy in such patients. Therefore, treatment should be determined on a case-by-case basis.
SUMMARY
Evaluating for an association between a monoclonal gammopathy and a peripheral neuropathy in a patient depends on the monoclonal gammopathy subtype and the clinical and electrodiagnostic characteristics of the peripheral neuropathy.
Topics: Adult; Aged; Humans; Paraproteinemias; Peripheral Nervous System Diseases
PubMed: 33003006
DOI: 10.1212/CON.0000000000000919 -
Acta Haematologica 2019
Topics: B-Lymphocytes; Hematopoietic Stem Cell Transplantation; Homeostasis; Humans; Paraproteinemias; Prognosis; Stem Cell Transplantation
PubMed: 30439698
DOI: 10.1159/000494426 -
Seminars in Nephrology Jan 2024Recent advances in the treatment of plasma cell disorders (PCDs) have provided a wealth of therapy alternatives and improved overall survival tremendously. Various types... (Review)
Review
Recent advances in the treatment of plasma cell disorders (PCDs) have provided a wealth of therapy alternatives and improved overall survival tremendously. Various types of PCDs are associated with kidney injury and end-stage kidney disease in a considerable number of patients. Kidney transplantation (KTx) is the best option for renal replacement therapy in select patients in terms of both quality of life parameters and overall survival. Even with modern therapies, all PCDs carry the risk of hematologic progression, whereas histologic recurrence and graft loss are other prevailing concerns in these patients. The risk of mortality is also higher in some of these disorders compared with KTx recipients who suffer from other causes of kidney disease. Unlike solid cancers, there is no well-defined "waiting time" after hematologic remission before proceeding to KTx. Thus, clinicians are usually reluctant to recommend KTx to patients who develop end-stage kidney disease due to PCDs. This review aims to provide the current evidence on KTx outcomes in patients with monoclonal gammopathy of renal significance and multiple myeloma. Although immunoglobulin light chain amyloidosis is a monoclonal gammopathy of renal significance subtype, KTx outcomes in this group are mentioned in another chapter of this issue.
Topics: Humans; Kidney Transplantation; Multiple Myeloma; Kidney Failure, Chronic; Paraproteinemias
PubMed: 38485643
DOI: 10.1016/j.semnephrol.2024.151497 -
La Revue de Medecine Interne May 2019Serum free light chains (sFLC) assay is an important marker in plasma cell dyscrasia. It is thus recommended for the diagnosis of monoclonal gammopathy, together with... (Review)
Review
Serum free light chains (sFLC) assay is an important marker in plasma cell dyscrasia. It is thus recommended for the diagnosis of monoclonal gammopathy, together with serum protein electrophoresis and immunofixation. sFLC assay has also a prognostic value and is a criterion for treatment response and relapse of some monoclonal gammopathies. Three assays are currently available in France, the gold standard being the Freelite assay, the two others requiring further validation. These three assays are not interchangeable during patient's follow-up. The Freelite assay is integrated in the myeloma diagnostic criteria from the International Myeloma Working Group 2014, and has a higher sensitivity than Bence Jones protein test for diagnosis, treatment response and follow-up of light chain myeloma. The Freelite assay is the main marker of therapeutic response in light chain amyloidosis and allows to stratify the risk for progression in monoclonal gammopathy of undetermined significance. Some studies have also shown its value in diagnosis of multiple sclerosis and in screening for monoclonal gammopathy in the cases of acute renal failure. The Freelite assay is then currently essential in myeloma or amyloidosis, and could be soon extended to the management of autoimmune diseases.
Topics: Humans; Immunoassay; Immunoglobulin Light Chains; Multiple Myeloma; Paraproteinemias; Prognosis; Serologic Tests
PubMed: 30862366
DOI: 10.1016/j.revmed.2019.01.005 -
PET Clinics Apr 2015This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography... (Review)
Review
This article presents a review of multiple myeloma, precursor states, and related plasma cell disorders. The clinical roles of fluorodeoxyglucose PET/computed tomography (CT) and the potential to improve the management of patients with multiple myeloma are discussed. The clinical and research data supporting the utility of PET/CT use in evaluating myeloma and other plasma cell dyscrasias continues to grow.
Topics: Aged; Disease Progression; Female; Fluorodeoxyglucose F18; Humans; Male; Middle Aged; Multimodal Imaging; Multiple Myeloma; Neoplasm Metastasis; Neoplasm Staging; Paraproteinemias; Positron-Emission Tomography; Radiopharmaceuticals; Tomography, X-Ray Computed
PubMed: 25829088
DOI: 10.1016/j.cpet.2014.12.008 -
Haematologica Dec 2023Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been...
Disease associations with monoclonal gammopathy of undetermined significance can only be evaluated using screened cohorts: results from the population-based iStopMM study.
Monoclonal gammopathy of undetermined significance (MGUS) is an asymptomatic precursor condition that precedes multiple myeloma and related disorders but has also been associated with other medical conditions. Since systematic screening is not recommended, MGUS is typically diagnosed due to underlying diseases and most cases are not diagnosed. Most previous studies on MGUS disease associations have been based on clinical cohorts, possibly resulting in selection bias. Here we estimate this selection bias by comparing clinically diagnosed and screened individuals with MGUS with regards to demographics, laboratory features, and comorbidities. A total of 75,422 participants in the Iceland Screens, Treats, or Prevents Multiple Myeloma (iStopMM) study were screened for MGUS by serum protein electrophoresis, immunofixation and free light chain assay (clinicaltrials gov. Identifier: NCT03327597). We identified 3,352 individuals with MGUS, whereof 240 had previously been clinically diagnosed (clinical MGUS), and crosslinked our data with large, nationwide registries for information on comorbidities. Those with clinical MGUS were more likely to have at least one comorbidity (odds ratio=2.24; 95% confidence interval: 1.30-4.19), and on average had more comorbidities than the screened MGUS group (3.23 vs. 2.36, mean difference 0.68; 95% confidence interval: 0.46-0.90). They were also more likely to have rheumatological disease, neurological disease, chronic kidney disease, liver disease, heart failure, or endocrine disorders. These findings indicate that individuals with clinical MGUS have more comorbidities than the general MGUS population and that previous studies have been affected by significant selection bias. Our findings highlight the importance of screening data when studying biological and epidemiological implications of MGUS.
Topics: Humans; Multiple Myeloma; Monoclonal Gammopathy of Undetermined Significance; Iceland; Paraproteinemias; Comorbidity; Disease Progression
PubMed: 37439374
DOI: 10.3324/haematol.2023.283191 -
Frontiers in Immunology 2022Various epidemiological studies, including case reports and -series in addition to larger, population-based studies, have reported an increased prevalence of monoclonal... (Review)
Review
Various epidemiological studies, including case reports and -series in addition to larger, population-based studies, have reported an increased prevalence of monoclonal gammopathy of undetermined significance (MGUS) and multiple myeloma in individuals with a prior history of immune-related conditions. This is believed to support the role of chronic antigen stimulation in the pathogenesis of these conditions. In this short review, we summarize some of the largest population-based studies researching autoimmune diseases, infections, and the subsequent risk of MGUS, and discuss our understanding on its etiology and pathogenesis. Furthermore, we highlight important methodological limitations of previous studies in the field, but almost all studies on MGUS have been based on clinical, possibly biased, cohorts. Finally, we discuss future directions in researching the associations of MGUS and other disorders, including immune-related conditions, where screening studies play an important role.
Topics: Autoimmune Diseases; Autoimmunity; Humans; Immune System Diseases; Monoclonal Gammopathy of Undetermined Significance; Multiple Myeloma; Paraproteinemias
PubMed: 35572590
DOI: 10.3389/fimmu.2022.876271