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American Journal of Hematology Jun 2022Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in...
DISEASE OVERVIEW
Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)."
DIAGNOSIS
Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.
PROGNOSIS
N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5 months.
THERAPY
All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.
FUTURE CHALLENGES
Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.
Topics: Amyloidosis; Bortezomib; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Prognosis
PubMed: 35429180
DOI: 10.1002/ajh.26569 -
Mayo Clinic Proceedings Jun 2021Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the... (Review)
Review
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder leading to progressive and life-threatening organ failure. The heart and the kidneys are the most commonly involved organs, but almost any organ can be involved. Because of the nonspecific presentation, diagnosis delay is common, and many patients are diagnosed with advanced organ failure. In the era of effective therapies and improved outcomes for patients with AL amyloidosis, the importance of early recognition is further enhanced as the ability to reverse organ dysfunction is limited in those with a profound organ failure. As AL amyloidosis is an uncommon disorder and given patients' frailty and high early death rate, management of this complex condition is challenging. The treatment of AL amyloidosis is based on various anti-plasma cell therapies. These therapies are borrowed and customized from the treatment of multiple myeloma, a more common disorder. However, a growing number of phase 2/3 studies dedicated to the AL amyloidosis population are being performed, making treatment decisions more evidence-based. Supportive care is an integral part of management of AL amyloidosis because of the inherent organ dysfunction, limiting the delivery of effective therapy. This extensive review brings an updated summary on the management of AL amyloidosis, sectioned into the 3 pillars for survival improvement: early disease recognition, anti-plasma cell therapy, and supportive care.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Risk Assessment
PubMed: 34088417
DOI: 10.1016/j.mayocp.2021.03.012 -
Hematology/oncology Clinics of North... Dec 2020
Topics: History, 19th Century; History, 20th Century; History, 21st Century; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 33099437
DOI: 10.1016/j.hoc.2020.08.008 -
Innere Medizin (Heidelberg, Germany) Sep 2023Light chain amyloidosis (AL) is a rare protein deposition disease. It is caused by a clonal plasma cell or B‑cell disease in the bone marrow. With the exception of... (Review)
Review
Light chain amyloidosis (AL) is a rare protein deposition disease. It is caused by a clonal plasma cell or B‑cell disease in the bone marrow. With the exception of the central nervous system, all organs can be affected by amyloid deposits. Cardiac involvement is the most frequent organ manifestation that leads to significantly increased mortality when it is diagnosed at an advanced stage. The causal treatment of AL amyloidosis is reduction of amyloidogenic light chains by chemotherapy. Early diagnosis of the disease is essential to reduce early mortality, to effectively treat patients and to prevent further deterioration of organ function. New treatment approaches for AL amyloidosis are aimed at inhibiting amyloid formation or degradation of amyloid in organs.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Amyloid
PubMed: 37540260
DOI: 10.1007/s00108-023-01568-0 -
Journal of Cutaneous Medicine and... 2022
Topics: Amyloidosis, Familial; Humans; Immunoglobulin Light-chain Amyloidosis; Skin Diseases, Genetic
PubMed: 34878924
DOI: 10.1177/12034754211064314 -
American Journal of Hematology Feb 2024Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in...
DISEASE OVERVIEW
Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or MGUS."
DIAGNOSIS
Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.
PROGNOSIS
N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T(or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four stages; 5-year survivals are 82%, 62%, 34%, and 20%, respectively.
THERAPY
All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a ≥VGPR. In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.
FUTURE CHALLENGES
Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to deplete deposited fibrils are underway.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Prognosis; Immunoglobulin Light Chains; Hematopoietic Stem Cell Transplantation
PubMed: 38095141
DOI: 10.1002/ajh.27177 -
Methodist DeBakey Cardiovascular Journal 2022Amyloidosis encompasses a collection of disorders of pathological protein folding. The extracellular location where these "amyloid fibril" proteins are deposited... (Review)
Review
Amyloidosis encompasses a collection of disorders of pathological protein folding. The extracellular location where these "amyloid fibril" proteins are deposited determines the clinical presentation of the disease. The abnormal architecture of these fibrils makes them insoluble and not easily removed, leading to disruption of normal tissue structure and interference with normal physiology. Amyloidosis of the heart and kidney can be inherited, secondary to unrelated diseases, or due to a plasma cell disorder. This review will focus on immunoglobulin light chain amyloidosis, which is life-threatening and must be diagnosed as early as possible by employing precise and accurate typing to ensure timely and frequently curative therapy.
Topics: Amyloid; Amyloidosis; Heart; Humans; Immunoglobulin Light-chain Amyloidosis; Kidney
PubMed: 36132587
DOI: 10.14797/mdcvj.1150 -
Hematology/oncology Clinics of North... Dec 2020Opportunities and challenges in the field of systemic amyloidosis can be grouped into 4 categories. First, a deeper understanding of the pathogenesis of the disease is... (Review)
Review
Opportunities and challenges in the field of systemic amyloidosis can be grouped into 4 categories. First, a deeper understanding of the pathogenesis of the disease is required. Second, a greater awareness of the disease, which will lead to an earlier diagnosis, is imperative. Third, end points for interventional trials are required to convey us to our fourth aspirations, which are novel therapies for patients with light chain amyloidosis.
Topics: Clinical Trials as Topic; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 33099434
DOI: 10.1016/j.hoc.2020.08.009 -
Current Heart Failure Reports Dec 2019Amyloidosis represents an increasingly recognized but still frequently missed cause of heart failure. In the light of many effective therapies for light chain (AL)... (Review)
Review
PURPOSE
Amyloidosis represents an increasingly recognized but still frequently missed cause of heart failure. In the light of many effective therapies for light chain (AL) amyloidosis and promising new treatment options for transthyretin (ATTR) amyloidosis, awareness among caregivers needs to be raised to screen for amyloidosis as an important and potentially treatable differential diagnosis. This review outlines the diversity of cardiac amyloidosis, its relation to heart failure, the diagnostic algorithm, and therapeutic considerations that should be applied depending on the underlying type of amyloidosis.
RECENT FINDINGS
Non-biopsy diagnosis is feasible in ATTR amyloidosis in the absence of a monoclonal component resulting in higher detection rates of cardiac ATTR amyloidosis. Biomarker-guided staging systems have been updated to facilitate risk stratification according to currently available biomarkers independent of regional differences, but have not yet prospectively been tested. Novel therapies for hereditary and wild-type ATTR amyloidosis are increasingly available. The complex treatment options for AL amyloidosis are improving continuously, resulting in better survival and quality of life. Mortality in advanced cardiac amyloidosis remains high, underlining the importance of early diagnosis and treatment initiation. Cardiac amyloidosis is characterized by etiologic and clinical heterogeneity resulting in a frequently delayed diagnosis and an inappropriately high mortality risk. New treatment options for this hitherto partially untreatable condition have become and will become available, but raise challenges regarding their implementation. Referral to specialized centers providing access to extensive and targeted diagnostic investigations and treatment initiation may help to face these challenges.
Topics: Algorithms; Amyloidosis; Cardiac Imaging Techniques; Cardiomyopathies; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 31782077
DOI: 10.1007/s11897-019-00446-x -
Hematology/oncology Clinics of North... Dec 2020Peripheral nervous system involvement in primary systemic amyloidosis is another important organ involvement in the spectrum of this disease entity. Early recognition... (Review)
Review
Peripheral nervous system involvement in primary systemic amyloidosis is another important organ involvement in the spectrum of this disease entity. Early recognition may lead to an earlier diagnosis and treatment with improvement in prognosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Peripheral Nervous System; Peripheral Nervous System Diseases
PubMed: 33099426
DOI: 10.1016/j.hoc.2020.07.004