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International Journal of Cardiology Nov 2018Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis, affecting around 10 people per million per year. This serious disorder is characterized by... (Review)
Review
Light-chain (AL) amyloidosis is the most common type of systemic amyloidosis, affecting around 10 people per million per year. This serious disorder is characterized by the presence of a clone of bone marrow plasma cells that produces monoclonal light chains (LCs) of the κ or predominantly λ type. These amyloidogenic LCs undergo extracellular misfolding and aggregation into proteotoxic soluble oligomers and amyloid fibrils that deposit within tissues. The lethal consequences of AL amyloidosis are due to the toxic products (the LCs) and not to the malignant behaviour of the plasma cell clone. Almost 80% of patients with AL amyloidosis have some degree of cardiac involvement, manifesting as heart failure (HF), and carrying a particularly poor prognosis. The past decade has seen major advances in the treatment of AL amyloidosis, and a rapidly fatal disease has become a treatable and possibly curable condition. The number of therapeutic options is rapidly expanding, offering hope to address currently unmet needs (most notably, the treatment of frail patients). The treatment of AL amyloidosis consists in a combination of agents targeting multiple steps of the amyloid cascade, associated with effective HF management, and there is ground for hope for dramatically improving the outcome in the near future. In the present review we will summarize our current knowledge on therapy for cardiac AL amyloidosis, targeting clinical cardiologists involved in the care of this serious disorder.
Topics: Animals; Cell- and Tissue-Based Therapy; Humans; Immunoglobulin Light-chain Amyloidosis; Plasma Cells
PubMed: 30223349
DOI: 10.1016/j.ijcard.2018.05.018 -
Current Medicinal Chemistry 2019Deposition of amyloidogenic proteins leading to the formation of amyloid fibrils in the myocardium causes cardiac amyloidosis. Although any form of systemic amyloidosis... (Review)
Review
Deposition of amyloidogenic proteins leading to the formation of amyloid fibrils in the myocardium causes cardiac amyloidosis. Although any form of systemic amyloidosis can affect the heart, light-chain (AL) or transthyretin amyloidosis (ATTR) account for the majority of diagnosed cardiac amyloid deposition. The extent of cardiac disease independently predicts mortality. Thus, the reversal of arrest of adverse cardiac remodeling is the target of current therapies. Here, we provide a condensed overview on the pathophysiology of AL and ATTR cardiac amyloidoses and describe treatments that are currently used or investigated in clinical or preclinical trials. We also briefly discuss acquired amyloid deposition in cardiovascular disease other than AL or ATTR.
Topics: Amyloid Neuropathies, Familial; Animals; Heart Diseases; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Immunotherapy; Liver Transplantation; Prealbumin; Protein Multimerization; Stem Cell Transplantation
PubMed: 29303069
DOI: 10.2174/0929867325666180104153338 -
Expert Review of Hematology Feb 2018The most common form of systemic amyloidosis in Western countries is light chain amyloidosis. It is characterized by the deposition of a misfolded light chain in target... (Review)
Review
The most common form of systemic amyloidosis in Western countries is light chain amyloidosis. It is characterized by the deposition of a misfolded light chain in target organs. This amyloid precursor is produced by a usually small but dangerous B-cell clone. Areas covered: This review examines the diagnostic workup of this disease and current knowledge of biomarker-based staging systems. In addition, a risk-adapted treatment approach is presented, as well as an overview of the new treatment strategies. Expert commentary: The cornerstone of treatment is rapid and effective chemotherapy targeting the underlying plasma cell clone. In the near future, this will probably be associated with novel approaches targeting other steps of the amyloid cascade that result in amyloid deposits. Currently available effective treatments can alter its natural history if an early diagnosis is made. The availability of novel, more powerful drugs, and identification of the cellular mechanisms of organ damage and of the characteristics of the amyloidogenic plasma-cell clone all give grounds to hope that a dramatic improvement in the treatment of this disease will be seen in the near future.
Topics: B-Lymphocytes; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 29307226
DOI: 10.1080/17474086.2018.1424534 -
Leukemia & Lymphoma Feb 2021Retroperitoneal involvement is rare in patients with light chain (AL) amyloidosis and has only been published as case reports. Only 5 cases of retroperitoneal deposition... (Review)
Review
Retroperitoneal involvement is rare in patients with light chain (AL) amyloidosis and has only been published as case reports. Only 5 cases of retroperitoneal deposition have previously been reported in the setting of systemic AL amyloidosis. Data regarding the characteristics and clinical course of these patients are scarce. Herein we report on eleven patients with systemic AL amyloidosis diagnosed with retroperitoneal deposition at all three Mayo Clinic sites and Davidoff cancer center in Israel. All patients had retroperitoneal amyloid deposition at presentation. All patients received systemic treatment. Eight patients presented with hydronephrosis and 7 had nephrostomy tubes or stents inserted. Regression of the deposition was documented in one patient and one patient was able to have his nephrostomy tube removed. The median OS from diagnosis was 150 months, suggesting that retroperitoneal deposition might confer improved prognosis compared to the general amyloid population.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Israel; Prognosis
PubMed: 33118418
DOI: 10.1080/10428194.2020.1832670 -
JCO Oncology Practice May 2023Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for... (Review)
Review
Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for clinicians across practice settings. There is, however, a reason for optimism with the advent of new combination therapy approaches and novel targets offering the promise of improvement in end organ function, survival, and quality of life. This review offers a clinically applicable overview of an approach to diagnosis, risk stratification, and clinical management of AL amyloidosis in an era of rapid therapeutic innovation.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Quality of Life
PubMed: 36854070
DOI: 10.1200/OP.22.00396 -
Current Problems in Cancer Jun 2022Immunoglobulin light chain (AL) amyloidosis is a complex disease marked by a poor clinical portrait and prognosis generally leading to organ dysfunction and shortened... (Review)
Review
BACKGROUND
Immunoglobulin light chain (AL) amyloidosis is a complex disease marked by a poor clinical portrait and prognosis generally leading to organ dysfunction and shortened survival. We aimed to review the available evidence on whether AL amyloidosis can lead to malnutrition, thus having a negative impact on quality of life (QoL) and survival.
MATERIALS
We searched Pubmed for studies that assessed malnutrition in amyloidosis patients, with no restrictions to the year of publication or language. Retrospective or prospective, observational, and interventional studies that reported data regarding AL amyloidosis and nutritional status were included.
RESULTS
From 62 articles retrieved, 23 were included. Malnutrition was prevalent in up to 65% of patients with AL Amyloidosis. Prevalence of weight loss of 10% or more ranged from 6 to 22% of patients, while a body mass index of < 22 kg/m2 was found in 22 to 42%. Weight loss, lower BMI and other indicators of poor nutritional status were negatively associated with quality of life and survival. Only one RCT focused on nutritional counseling was found and reported positive results on patients QoL and survival.
CONCLUSION
Despite inconsistencies across assessment criteria, the available data reveal that weight loss and malnutrition are common features in patients with AL amyloidosis. This review reinforces the premise that an impaired nutritional status can be negatively associated with QoL and survival in patients with AL amyloidosis, and therefore should be further investigated.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Malnutrition; Nutritional Status; Prospective Studies; Quality of Life; Retrospective Studies; Weight Loss
PubMed: 35101705
DOI: 10.1016/j.currproblcancer.2021.100833 -
European Heart Journal Dec 2019
Topics: Echocardiography; Female; Heart Failure; Heart Valve Diseases; Hospitalization; Humans; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin lambda-Chains; Macroglossia; Middle Aged
PubMed: 31364714
DOI: 10.1093/eurheartj/ehz534 -
Acta Haematologica 2020Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare, life-threatening disease characterized by the deposition of misfolded proteins in vital organs such as... (Review)
Review
Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare, life-threatening disease characterized by the deposition of misfolded proteins in vital organs such as the heart, the lungs, the kidneys, the peripheral nervous system, and the gastrointestinal tract. This causes a direct toxic effect, eventually leading to organ failure. The underlying B-cell lymphoproliferative disorder is almost always a clonal plasma cell disorder, most often a small plasma cell clone of <10%. Current therapy is directed toward elimination of the plasma cell clone with the goal of preventing further organ damage and reversal of the existing organ damage. Autologous stem cell transplantation has been shown to be a very effective treatment in patients with AL amyloidosis, although it cannot be widely applied as patients are often frail at presentation, making them ineligible for transplantation. Treatment with cyclophosphamide, bortezomib, and dexamethasone has emerged as the standard of care for the treatment of AL amyloidosis. Novel anti-plasma cell therapies, such as second generation proteasome inhibitors, immunomodulators, monoclonal antibodies targeting a surface protein on the plasma cell (daratumumab, elotuzumab), and the small molecular inhibitor venetoclax, have continued to emerge and are being evaluated in combination with the standard of care. However, there is still a need for therapies that directly target the amyloid fibrils and reverse organ damage. In this review, we will discuss current and emerging nonchemotherapy treatments of AL amyloidosis, including antifibril directed therapies under current investigation.
Topics: Combined Modality Therapy; Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Treatment Outcome
PubMed: 32526750
DOI: 10.1159/000507724 -
International Journal of Molecular... Jun 2022In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free... (Review)
Review
In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free light chains (FLCs), which form amyloid fibrils that deposit in the interstitial tissue, resulting in organ injury and dysfunction. AL amyloidosis progresses much faster than other types of amyloidosis, with a slight delay in diagnosis leading to a marked exacerbation of cardiomyopathy. In some cases, the resulting heart failure is so severe that chemotherapy cannot be administered, and death sometimes occurs within a few months. To date, many clinical studies have focused on therapeutics, especially chemotherapy, to treat this disease. Because it is necessary to promptly lower FLC, the causative protein of amyloid, to achieve a hematological response, various anticancer agents targeting neoplastic plasma cells are used for the treatment of this disease. In addition, many basic studies using human specimens to elucidate the pathophysiology of AL have been conducted. Gene mutations associated with AL, the characteristics of amyloidogenic LC, and the structural specificity of amyloid fibrils have been clarified. Regarding the mechanism of cellular and tissue damage, the mass effect due to amyloid deposition, as well as the toxicity of pre-fibrillar LC, is gradually being elucidated. This review outlines the pathogenesis and treatment strategies for AL amyloidosis with respect to its molecular mechanisms.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis
PubMed: 35683015
DOI: 10.3390/ijms23116336 -
Clinical Lymphoma, Myeloma & Leukemia Aug 2022
Standard 30-minute Monitoring Time and Less Intensive Pre-medications is Safe in Patients Treated With Subcutaneous Daratumumab for Multiple Myeloma and Light Chain Amyloidosis.
Topics: Amyloidosis; Antibodies, Monoclonal; Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma
PubMed: 35367193
DOI: 10.1016/j.clml.2022.03.003