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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 -
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 -
European Journal of Haematology Nov 2023This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated...
OBJECTIVES
This study evaluated data from six Swedish national registries to fill current evidence gaps on the epidemiology, clinical burden, and overall survival (OS) associated with light-chain (AL) amyloidosis.
METHODS
Patients newly diagnosed with AL amyloidosis were identified using six linked Swedish nationwide population-based registers. For each case, individuals from the general population were selected and matched with a maximum ratio of 1:5 based on age, sex, calendar year, and county.
RESULTS
846 patients newly diagnosed with AL amyloidosis and 4227 demographically matched individuals were identified. From 2011 to 2019, annual AL amyloidosis incidence increased from 10.5 to 15.1 cases per million. At baseline, patients with AL amyloidosis had a significantly higher disease burden including higher rates of cardiac and renal failure relative to the comparison group. Among patients with AL amyloidosis, 21.5% had incident heart failure and 17.1% had incident renal failure after initial diagnosis. Median OS for patients with AL amyloidosis was 56 months versus not reached in the matched general population comparison group.
CONCLUSION
The incidence of newly diagnosed AL amyloidosis in Sweden increased over time with AL amyloidosis being associated with a higher risk of cardiac/renal failure and all-cause mortality compared with the general population.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Sweden; Amyloidosis; Heart Failure; Renal Insufficiency; Retrospective Studies
PubMed: 37533343
DOI: 10.1111/ejh.14063 -
Hematology. American Society of... Dec 2023Diagnosing amyloidosis can be challenging due to its clinical heterogeneity, need for multiple specialists to make a diagnosis, and lack of a single diagnostic test for...
Diagnosing amyloidosis can be challenging due to its clinical heterogeneity, need for multiple specialists to make a diagnosis, and lack of a single diagnostic test for the disease. Patients are often diagnosed late, in advanced stage, and after exhibiting multiple symptoms and signs for a long period. It is important to develop a clinical suspicion of amyloidosis, particularly in those with multisystemic symptoms and high-risk patient populations such as those with precursor hematologic conditions. A systematic approach to the workup of suspected amyloidosis is key, including a comprehensive clinical assessment, laboratory tests to assess organ involvement, advanced imaging studies, screening for plasma cell disorder, and tissue biopsy when necessary. After making a diagnosis of amyloidosis, accurate typing of amyloid deposits, differentiating between localized and systemic amyloidosis, and appropriately staging the disease is important. Early diagnosis is crucial for improving patient outcomes and quality of life in light chain amyloidosis.
Topics: Humans; Quality of Life; Amyloid; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Paraproteinemias
PubMed: 38066929
DOI: 10.1182/hematology.2023000440 -
European Journal of Internal Medicine Dec 2018Systemic immunoglobulin light chain (AL) amyloidosis is an aging-associated protein misfolding and deposition disease. This condition is caused by a small and otherwise... (Review)
Review
Systemic immunoglobulin light chain (AL) amyloidosis is an aging-associated protein misfolding and deposition disease. This condition is caused by a small and otherwise indolent plasma cell (or B cell) clone secreting an unstable circulating light chain, which misfolds and deposits as amyloid fibrils possibly leading to progressive dysfunction of affected organs. AL amyloidosis can occur in the typical setting of other, rarer forms of systemic amyloidosis and can mimic other more prevalent conditions of the elderly. Therefore, its diagnosis requires a high degree of clinical suspicion and reliable diagnostic tools for accurate amyloid typing, available at specialized referral centers. In AL amyloidosis, frailty is dictated by the type and severity of organ involvement, with heart involvement being the main determinant of morbidity and mortality. Still, given a similar disease stage, elderly patients with AL amyloidosis are often an even frailer group, due to significant comorbidities, associated disability and polypharmacotherapy, socioeconomic restrictions, and limited access to clinical trials. Recent improvements in the use of biomarkers for early diagnosis, risk stratification and response monitoring, the flourishing of novel, effective anti-plasma cell therapies developed against multiple myeloma and adapted to treat AL amyloidosis, and possibly the introduction of anti-amyloid therapies are rapidly changing the clinical management of this disease and are reflected by improved outcomes. Of note, hematologic and organ responses in elderly patients with AL amyloidosis do translate in better outcome, advocating the importance of treating these patients and striving for a rapid response to therapy also in this challenging clinical setting.
Topics: Aged; Biomarkers; Diagnosis, Differential; Disease Management; Frail Elderly; Geriatric Assessment; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 29801808
DOI: 10.1016/j.ejim.2018.05.004 -
Hematology/oncology Clinics of North... Dec 2020Immunoglobulin light chain amyloidosis is the most common systemic amyloidosis. The pathogenetic mechanism is deposition of fibrils of misfolded immunoglobulin free... (Review)
Review
Immunoglobulin light chain amyloidosis is the most common systemic amyloidosis. The pathogenetic mechanism is deposition of fibrils of misfolded immunoglobulin free light chains, more often lambda, typically produced by clonal plasma cells. Distinct Ig light chain variable region genotypes underlie most light chain amyloidosis and dictate tissue tropism. Light chain amyloidosis fibrils cause distortion of the histologic architecture and direct cytotoxicity, leading to rapidly progressive organ dysfunction and eventually patient demise. A high index of clinical suspicion with rapid tissue diagnosis and commencement of combinatorial, highly effective cytoreductive therapy is crucial to avoid irreversible organ damage and early mortality.
Topics: Amyloid; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis; Plasma Cells
PubMed: 33099420
DOI: 10.1016/j.hoc.2020.08.001 -
Journal of General Internal Medicine Aug 2021
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma; Tongue; Tongue Diseases
PubMed: 34027604
DOI: 10.1007/s11606-021-06890-7 -
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 -
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 -
JAMA Cardiology Jan 2020
Topics: Cardiomyopathies; Gastrointestinal Diseases; Heart Failure; Humans; Ileus; Immunoglobulin Light-chain Amyloidosis; Male; Medicine in Literature; Middle Aged; Multiple Myeloma; Pain; Peripheral Nervous System Diseases; Physician-Patient Relations; Terminally Ill
PubMed: 31774453
DOI: 10.1001/jamacardio.2019.4545