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Acta Haematologica 2020Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different... (Review)
Review
Cardiac amyloidosis, the majority of cases of which are due to immunoglobulin light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR), affects different aspects of the heart and cardiovascular system. Amyloid-induced cardiomyopathy, clinically manifesting with heart failure and electrophysiological abnormalities, has distinct characteristics compared to non-amyloid cardiomyopathies. Accordingly, specific management strategies are required. This paper will review the cardiovascular manifestations of patients with cardiac amyloidosis and their suggested treatment strategies, emphasizing the importance of multidisciplinary care.
Topics: Amyloidosis; Cardiomyopathies; Combined Modality Therapy; Disease Management; Disease Susceptibility; Heart Function Tests; Humans; Immunoglobulin Light-chain Amyloidosis; Phenotype
PubMed: 32408301
DOI: 10.1159/000506919 -
Acta Haematologica 2020Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding... (Review)
Review
Amyloidosis comprises a diverse group of diseases characterized by misfolding of precursor proteins which eventually form amyloid aggregates and preceding intermediaries, which are deposited in target tissues causing progressive organ damage. In all forms of amyloidosis, vital organs may fail; depending on the specific amyloidosis type, this may occur rapidly or progress slowly. Beyond therapies to reduce the precursor protein (chemotherapy for light chain [AL] amyloidosis, anti-inflammatory therapy in serum A amyloid-osis [AA], and antisense RNA therapy in transthyretin amyloidosis [ATTR]), organ transplantation may also be a means to reduce amyloidogenic protein, e.g., in types of amyloid-osis in which the variant precursor is produced by the liver. Heart transplantation is a life-saving approach to the treatment of patients with advanced cardiac amyloidosis; however, amyloidosis may still be considered a contraindication to the procedure despite data supporting improved outcomes, similar to patients with other indications. Kidney transplantation is associated with particularly favorable outcomes in patients with amyloidosis, especially if the precursor protein has been eliminated. Overall, outcomes of solid organ transplantation are improving, but more data are needed to refine the selection criteria and the timing for organ transplantation, which should be performed in highly experienced centers involving multidisciplinary teams with close patient follow-up to detect amyloid recurrence.
Topics: Amyloidosis; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Transplantation; Treatment Outcome
PubMed: 32535598
DOI: 10.1159/000508262 -
International Journal of Molecular... Oct 2022Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses,... (Review)
Review
Amyloidoses is a group of diseases characterized by the accumulation of abnormal proteins (called amyloids) in different organs and tissues. For systemic amyloidoses, the disease is related to increased levels and/or abnormal synthesis of certain proteins in the organism due to pathological processes, e.g., monoclonal gammopathy and chronic inflammation in rheumatic arthritis. Treatment of amyloidoses is focused on reducing amyloidogenic protein production and inhibition of its aggregation. Therapeutic approaches critically depend on the type of amyloidosis, which underlines the importance of early differential diagnostics. In fact, the most accurate diagnostics of amyloidosis and its type requires analysis of a biopsy specimen from the disease-affected organ. However, absence of specific symptoms of amyloidosis and the invasive nature of biomaterial sampling causes the late diagnostics of these diseases, which leads to a delayed treatment, and significantly reduces its efficacy and patient survival. The establishment of noninvasive diagnostic methods and discovery of specific amyloidosis markers are essential for disease detection and identification of its type at earlier stages, which enables timely and targeted treatment. This review focuses on current approaches to the diagnostics of amyloidoses, primarily with renal involvement, and research perspectives in order to design new specific tests for early diagnosis.
Topics: Humans; Amyloidosis; Amyloid; Immunoglobulin Light-chain Amyloidosis; Amyloidogenic Proteins; Biocompatible Materials
PubMed: 36293523
DOI: 10.3390/ijms232012662 -
Acta Haematologica 2020The treatment options for systemic light chain amyloidosis (AL) are currently widening in an unprecedented way, brought about by an expanding arsenal of anti-myeloma... (Review)
Review
The treatment options for systemic light chain amyloidosis (AL) are currently widening in an unprecedented way, brought about by an expanding arsenal of anti-myeloma therapy as well as by novel approaches to target toxic light chains and, most recently, deposited amyloid directly. In this context, accurate estimates of prognosis in AL, which allow for reliable patient advice and for example comparison of different therapies, are particularly important to clinicians. Some biomarkers and especially the genetic background of the underlying clonal disease as evaluated by interphase fluorescence in situ hybridization even have predictive value, enabling an appropriate treatment selection. Derived from the most frequently involved organs in AL, heart and kidney, this review focuses on overall survival and renal survival. A comprehensive overview and summary of reported prognostic factors and biomarkers in AL is given and the most important and validated factors are highlighted. Finally, established staging systems in AL as well as validated and perspective response criteria are presented.
Topics: Biomarkers; Disease Management; Disease Susceptibility; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Specificity; Prognosis; Severity of Illness Index
PubMed: 32570242
DOI: 10.1159/000508287 -
Leukemia & Lymphoma Feb 2019Autologous stem cell transplantation (ASCT) has been used as treatment for immunoglobulin light-chain (AL) amyloidosis for over two decades with improving outcomes;... (Review)
Review
Autologous stem cell transplantation (ASCT) has been used as treatment for immunoglobulin light-chain (AL) amyloidosis for over two decades with improving outcomes; however, the majority of patients are not candidates for this therapy at diagnosis. Novel agents such as immunomodulatory drugs, proteasome inhibitors, and immunotherapy with monoclonal antibodies targeting CD38 have been adopted from the multiple myeloma spheres with encouraging results. Herein, we discuss the role of daratumumab, a monoclonal antibody to CD38, in the treatment of AL amyloidosis. We focus on its mechanism of action, tolerability, and the current published data on its use in AL amyloidosis. Early data from phase I and phase II studies show that daratumumab is tolerated well in this population and induces rapid and deep responses. Phase III trials are currently accruing and we envision daratumumab becoming a key component in the treatment of AL amyloidosis in the future.
Topics: ADP-ribosyl Cyclase 1; Antibodies, Monoclonal; Antineoplastic Agents, Immunological; Antineoplastic Combined Chemotherapy Protocols; Disease Management; Hematopoietic Stem Cell Transplantation; Humans; Immunoglobulin Light-chain Amyloidosis; Membrane Glycoproteins; Molecular Targeted Therapy; Transplantation, Autologous; Treatment Outcome
PubMed: 30033840
DOI: 10.1080/10428194.2018.1485914 -
Blood Cancer Journal May 2021Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral... (Review)
Review
Immunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Overlooking the diagnosis of light chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Herein we provide a review of established and investigational treatments for patients with AL amyloidosis and provide algorithms for workup and management of these patients.
Topics: Amyloid; Animals; Antibodies, Monoclonal; Antineoplastic Agents; Biopsy; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Transplantation
PubMed: 33993188
DOI: 10.1038/s41408-021-00483-7 -
Annals of Medicine Dec 2023Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis... (Review)
Review
BACKGROUND
Amyloid light chain (AL) amyloidosis is the most common systemic amyloidosis. The objective of this scoping review was to map the available literature on the diagnosis of AL amyloidosis in China.
MATERIALS AND METHODS
The published academic papers related to the diagnosis of AL amyloidosis were screened from 1 January 2000 to 15 September 2021. Chinese patients who have suspected AL amyloidosis were included. The included studies were categorized into accuracy studies and descriptive studies based on if the studies supplied the diagnostic accuracy data or not. The information on the diagnostic methods reported by included studies was synthesized.
RESULTS
Forty-three articles were included for the final scoping review, with 31 belonging to descriptive studies and 12 having information on diagnostic accuracy. Although cardiac involvement was second top in Chinese patients with AL amyloidosis, a cardiac biopsy was rare. Next, we found light chain classification and monoclonal (M-) protein identification were essential methods for the diagnosis of AL amyloidosis in China. In addition, some combined tests (e.g. immunohistochemistry and serum free light chain, immunohistochemistry and immunofixation electrophoresis, and serum free light chain and immunofixation electrophoresis) can increase the sensitivity of the diagnosis. Finally, several adjuvant methods (e.g. Imaging, N-terminal-pro hormone BNP, and brain natriuretic peptide test) were important for AL amyloidosis diagnosis.
CONCLUSION
This scoping review details the characteristics and results of the recently published studies on diagnosing AL Amyloidosis in China. Biopsy is the most important method for AL Amyloidosis diagnosis in China. In addition, combined tests and some adjuvant methods played essential roles in the diagnosis. Further research is required to determine an acceptable and feasible diagnostic algorithm after symptom onset. INPLASY2022100096KEY MESSAGESThis scoping review details the characteristics and results of the recently published studies on diagnosing Amyloid light chain (AL) Amyloidosis in China.Biopsy is the most important method for AL Amyloidosis diagnosis in China.Combined tests and some adjuvant methods played essential roles in the diagnosis.
Topics: Humans; Adjuvants, Immunologic; Amyloidosis; East Asian People; Immunoglobulin Light-chain Amyloidosis
PubMed: 37387123
DOI: 10.1080/07853890.2023.2227425 -
JNMA; Journal of the Nepal Medical... Oct 2023Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in...
UNLABELLED
Primary systemic amyloidosis is a systemic disease characterised by the deposition of misfolded proteins extracellularly in different organs without any known cause in the background, eventually leading to multiorgan dysfunction and death. The incidence of primary amyloidosis is estimated at 5.1-12.8 cases per million, with a poor prognosis. We report a case of a 69-year male with lower back pain, shortness of breath, and anasarca diagnosed as primary systemic amyloidosis by serum-free light chain assay and kidney needle biopsy. He was started on intravenous bortezomib and dexamethasone. Though he adhered to his medications, with time he developed renal insufficiency marked by azotemia following which hemodialysis was performed. Primary systemic amyloidosis is a rare clinical condition with a very poor prognosis. Further studies are needed to understand the proper pathophysiology and treatment of the disease.
KEYWORDS
cardiomyopathies; case reports; primary amyloidosis.
Topics: Humans; Male; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Bortezomib; Renal Insufficiency; Prognosis
PubMed: 38289775
DOI: 10.31729/jnma.8297 -
Blood Dec 2021
Topics: Amyloidosis; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis
PubMed: 34940822
DOI: 10.1182/blood.2021013817 -
Haematologica Dec 2023Systemic light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains (LC) as insoluble fibrils...
Systemic light chain amyloidosis (AL) is a clonal plasma cell disorder characterized by the deposition of misfolded immunoglobulin light chains (LC) as insoluble fibrils in organs. The lack of suitable models has hindered the investigation of the disease mechanisms. Our aim was to establish AL LC-producing plasma cell lines and use them to investigate the biology of the amyloidogenic clone. We used lentiviral vectors to generate cell lines expressing LC from patients suffering from AL amyloidosis. The AL LC-producing cell lines showed a significant decrease in proliferation, cell cycle arrest, and an increase in apoptosis and autophagy as compared with the multiple myeloma LC-producing cells. According to the results of RNA sequencing the AL LC-producing lines showed higher mitochondrial oxidative stress, and decreased activity of the Myc and cholesterol pathways. The neoplastic behavior of plasma cells is altered by the constitutive expression of amyloidogenic LC causing intracellular toxicity. This observation may explain the disparity in the malignant behavior of the amyloid clone compared to the myeloma clone. These findings should enable future in vitro studies and help delineate the unique cellular pathways of AL, thus expediting the development of specific treatments for patients with this disorder.
Topics: Humans; Plasma Cells; Cell Survival; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Amyloid; Immunoglobulin Light Chains; Multiple Myeloma
PubMed: 37381778
DOI: 10.3324/haematol.2022.282484