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Journal of the National Comprehensive... Jan 2023Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index... (Review)
Review
Immunoglobulin light chain (AL) amyloidosis is a clonal plasma cell disorder with multiple clinical presentations. The diagnosis of AL amyloidosis requires a high index of suspicion, making a delay in diagnosis common, which contributes to the high early mortality seen in this disease. Establishing the diagnosis of AL amyloidosis requires the demonstration of tissue deposition of amyloid fibrils. A bone marrow biopsy and fat pad aspirate performed concurrently have a high sensitivity for the diagnosis of AL amyloidosis and negate the need for organ biopsies in most patients. An accurate diagnosis requires amyloid typing via additional testing, including tissue mass spectrometry. Prognostication for AL amyloidosis is largely driven by the organs impacted. Cardiac involvement represents the single most important prognostic marker, and the existing staging systems are driven by cardiac biomarkers. Apart from organ involvement, plasma cell percentage on the bone marrow biopsy, specific fluorescence in situ hybridization findings, age at diagnosis, and performance status are important prognostic markers. This review elaborates on the diagnostic testing and prognostication for patients with newly diagnosed AL amyloidosis.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; In Situ Hybridization, Fluorescence; Plasma Cells; Risk Assessment
PubMed: 36630897
DOI: 10.6004/jnccn.2022.7077 -
JACC. Cardiovascular Imaging Nov 2019Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart... (Review)
Review
Cardiac involvement drives prognosis and treatment choices in cardiac amyloidosis. Echocardiography is the first-line examination for patients presenting with heart failure, and it is the imaging modality that most often raises the suspicion of cardiac amyloidosis. Echocardiography can provide an assessment of the likelihood of cardiac amyloid infiltration versus other hypertrophic phenocopies and can assess the severity of cardiac involvement. Visualizing myocardial amyloid infiltration is challenging and, until recently, was restricted to the domain of the pathologist. Two tests are transforming this: cardiac magnetic resonance (CMR) imaging and bone scintigraphy. After the administration of contrast, CMR is highly sensitive and specific for the 2 main types of ventricular myocardial amyloidosis, light chain amyloidosis (AL) and transthyretin amyloidosis (ATTR). CMR structural and functional assessment combined with tissue characterization can redefine cardiac involvement by tracking different disease processes, ranging from amyloid infiltration, to the myocardial response associated with amyloid deposition, through the visualization and quantification of myocardial edema and myocyte response. Bone scintigraphy (paired with exclusion of serum free light chains) is emerging as the technique of choice for distinguishing ATTR from light chain cardiac amyloidosis and other cardiomyopathies; it has transformed the diagnostic pathway for ATTR, allowing noninvasive diagnosis of ATTR without the need for a tissue biopsy in the majority of patients. CMR with tissue characterization and bone scintigraphy are rewriting disease understanding, classification, and definition, and leading to a change in patient care.
Topics: Amyloid Neuropathies, Familial; Cardiomyopathies; Diagnosis, Differential; Extracellular Space; Fibrosis; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Myocardium; Predictive Value of Tests; Radionuclide Imaging; Reproducibility of Results; Ventricular Remodeling
PubMed: 31422120
DOI: 10.1016/j.jcmg.2019.06.023 -
International Journal of Molecular... Oct 2021Systemic AL amyloidosis is a rare complex hematological disorder caused by clonal plasma cells which produce amyloidogenic immunoglobulins. Outcome and prognosis is the... (Review)
Review
Systemic AL amyloidosis is a rare complex hematological disorder caused by clonal plasma cells which produce amyloidogenic immunoglobulins. Outcome and prognosis is the combinatory result of the extent and pattern of organ involvement secondary to amyloid fibril deposition and the biology and burden of the underlying plasma cell clone. Prognosis, as assessed by overall survival, and early outcomes is determined by degree of cardiac dysfunction and current staging systems are based on biomarkers that reflect the degree of cardiac damage. The risk of progression to end-stage renal disease requiring dialysis is assessed by renal staging systems. Longer-term survival and response to treatment is affected by markers of the underlying plasma cell clone; the genetic background of the clonal disease as evaluated by interphase fluorescence in situ hybridization in particular has predictive value and may guide treatment selection. Free light chain assessment forms the basis of hematological response criteria and minimal residual disease as assessed by sensitive methods is gradually being incorporated into clinical practice. However, sensitive biomarkers that could aid in the early diagnosis and that could reflect all aspects of organ damage and disease biology are needed and efforts to identify them are continuous.
Topics: Amyloid; Biomarkers; Disease Progression; Early Diagnosis; Humans; Immunoglobulin Light-chain Amyloidosis; Peptide Fragments; Prognosis; Survival Analysis
PubMed: 34681575
DOI: 10.3390/ijms222010916 -
Acta Haematologica 2020Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different... (Review)
Review
Immunoglobulin light-chain (AL) amyloidosis is a systemic disease characterized by the production and deposition of light chain-derived amyloid fibrils in different organs. Prompt treatment directed to the underlying plasma cell clone is crucial in order to achieve a rapid, deep and durable hematologic response. The decrease in the production of the amyloidogenic light chains is a required condition to obtain the organ response, which is commonly delayed. Meanwhile, supportive treatment is aimed to maintain quality of life of these patients and preserve their involved organs' function. From simple measures, such as salt restriction or compressive stockings, to very complex interventions, such as heart transplantation in very selected patients with isolated severe cardiac involvement, this supportive care is essential and has to be necessarily included in the multidisciplinary management of this disease.
Topics: Disease Management; Humans; Immunoglobulin Light-chain Amyloidosis; Organ Specificity; Palliative Care
PubMed: 32235118
DOI: 10.1159/000506760 -
Journal of UOEH 2021A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24...
A 75-year-old-man experienced liver dysfunction and was diagnosed with decompensated liver cirrhosis. His serum hepatocyte growth factor (HGF) was very high (16.24 ng/ml). Because the etiology was unclear, we considered the possibility of amyloidosis. Biopsy of the mucosa of the stomach, duodenum and rectum demonstrated amyloid deposition. From the findings of Congo red staining and immunohistochemical analyses, we made a diagnosis of systemic amyloid light-chain amyloidosis. Unfortunately, the patient died one month after the diagnosis. We considered that serum HGF was useful for the diagnosis and prediction of prognosis of primary systemic amyloidosis.
Topics: Aged; Amyloidosis; Biopsy; Hepatocyte Growth Factor; Humans; Immunoglobulin Light-chain Amyloidosis; Stomach
PubMed: 34092767
DOI: 10.7888/juoeh.43.227 -
Internal and Emergency Medicine Oct 2023Cardiac amyloidosis (CA) is an uncommon, progressive, and fatal disease; the two main forms that can affect the heart are transthyretin CA and light chain CA (AL-CA).... (Review)
Review
Cardiac amyloidosis (CA) is an uncommon, progressive, and fatal disease; the two main forms that can affect the heart are transthyretin CA and light chain CA (AL-CA). AL-CA is a medical urgency for which a diagnostic delay can be catastrophic for patients' outcome. In this manuscript, we focus on the pearls and pitfalls that are relevant to achieve a correct diagnosis and to avoid diagnostic and therapeutical delays. Through the aid of three unfortunate clinical cases, some fundamental diagnostic aspects are addressed, including the following: first, a negative bone scintigraphy does not exclude CA, with patients with AL-CA frequently showing no or mild cardiac uptake, and its execution should not delay hematological tests; second, fat pad biopsy does not have a 100% sensitivity for AL amyloidosis and, if negative, further investigations should be performed, particularly if the pre-test probability is high. Third, Congo Red staining is not sufficient to reach a definitive diagnosis and amyloid fibrils typing with mass spectrometry, immunohistochemistry, or immunoelectron microscopy is crucial. To achieve a timely and correct diagnosis, all the necessary investigations must be performed, always considering the yield and diagnostic accuracy of each examination.
Topics: Humans; Delayed Diagnosis; Amyloidosis; Immunoglobulin Light-chain Amyloidosis; Biopsy; Congo Red; Cardiomyopathies
PubMed: 37338717
DOI: 10.1007/s11739-023-03335-3 -
Indian Journal of Dermatology,... 2016
Topics: Adult; Amyloidosis; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Skin Neoplasms
PubMed: 25994889
DOI: 10.4103/0378-6323.157454 -
ESC Heart Failure Feb 2022The assessment of both thromboembolic and haemorrhagic risks and their management in systemic amyloidosis have been poorly emphasized so far. This narrative review... (Review)
Review
The assessment of both thromboembolic and haemorrhagic risks and their management in systemic amyloidosis have been poorly emphasized so far. This narrative review summarizes main evidence from literature with clinical perspective. The rate of thromboembolic events is as high as 5-10% amyloidosis patients, at least in patients with cardiac involvement, with deleterious impact on prognosis. The most known pro-thrombotic factors are heart failure, atrial fibrillation, and atrial myopathy. Atrial fibrillation could occur in 20% to 75% of systemic amyloidosis patients. Cardiac thrombi are frequently observed in patients, particularly in immunoglobulin light chains (AL) amyloidosis, up to 30%, and it is advised to look for them systematically before cardioversion. In AL amyloidosis, nephrotic syndrome and the use of immunomodulatory drugs also favour thrombosis. On the other hand, the bleeding risk increases because of frequent amyloid digestive involvement as well as factor X deficiency, renal failure, and increased risk of dysautonomia-related fall.
Topics: Amyloid; Amyloidosis; Heart Failure; Humans; Immunoglobulin Light-chain Amyloidosis; Thromboembolism
PubMed: 34784656
DOI: 10.1002/ehf2.13701 -
Orphanet Journal of Rare Diseases Jul 2022Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of...
BACKGROUND
Amyloid light-chain (AL) amyloidosis is an ultra-rare disease associated with significant morbidity and mortality. Few studies have examined the global epidemiology of this condition.
METHODS
This study estimated the diagnosed incidence and 1-year, 5-year, 10-year, and 20-year period prevalence of AL amyloidosis in 2018 for countries in and near Europe, and in the United States (US), Canada, Brazil, Japan, South Korea, Taiwan, and Russia. A systematic literature review (SLR) was conducted to identify country-specific, age- and gender-specific diagnosed incidence of AL amyloidosis and observed survival data-point inputs for an incidence-to-prevalence model. Extrapolations were used to estimate incidence and prevalence for countries without registry or published epidemiological data.
RESULTS
Of 171 publications identified in the SLR, 10 records met the criteria for data extraction, and two records were included in the final incidence-to-prevalence model. In 2018, an estimated 74,000 AL amyloidosis cases worldwide were diagnosed during the preceding 20 years. The estimated incidence and 20-year prevalence rates were 10 and 51 cases per million population, respectively.
CONCLUSIONS
Orphan medicinal product designation criteria of the European Medicines Agency or Electronic Code of Federal Regulations indicate that a disease must not affect > 5 in 10,000 people across the European Union or affect < 200,000 people in the US. This study provides up-to-date epidemiological patterns of AL amyloidosis, which is vital for understanding the burden of the disease, increasing awareness, and to further research and treatment options.
Topics: Europe; Humans; Immunoglobulin Light-chain Amyloidosis; Incidence; Prevalence; Registries; United States
PubMed: 35854312
DOI: 10.1186/s13023-022-02414-6 -
Acta Haematologica 2020The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional... (Review)
Review
The vast majority of patients with light-chain (AL) amyloidosis are not eligible for stem cell transplant and are treated with conventional chemotherapy. Conventional regimens are based on various combinations of dexamethasone, alkylating agents, proteasome inhibitors, and immunomodulatory drugs. The choice of these regimens requires a careful risk stratification, based on the extent of amyloid organ involvement, comorbidities, and the characteristics of the amyloidogenic plasma cell clone. Most patients are treated upfront with bortezomib and dexamethasone combined with cyclophosphamide or melphalan. Cyclophosphamide does not compromise stem cell mobilization and harvest and is more manageable in renal failure. Melphalan can overcome the effect of t(11;14), which is associated with lower response rates and shorter survival in subjects treated with bortezomib and dexamethasone, or in combination with cyclophosphamide. Lenalidomide and pomalidomide are the mainstay of rescue treatment. They are effective in patients exposed to bortezomib, dexamethasone, and alkylators, but deep hematologic responses are rare. Ixazomib, alone or in combination with lenalidomide, increases the rate of complete responses in relapsed/refractory patients. Conventional chemotherapy regimens will represent the backbone for future combinations, particularly with anti-plasma-cell immunotherapy, that will further improve response rates and outcomes.
Topics: Biomarkers; Combined Modality Therapy; Disease Management; Disease Susceptibility; Humans; Immunoglobulin Light-chain Amyloidosis; Recurrence; Risk Factors; Treatment Outcome
PubMed: 32353854
DOI: 10.1159/000507072