-
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 -
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 -
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 -
BMC Surgery Sep 2016Primary amyloidosis of the breast is an unusual benign disease that mostly occurs in postmenopausal elderly women. Amyloidosis is the deposition of amorphous protein... (Review)
Review
BACKGROUND
Primary amyloidosis of the breast is an unusual benign disease that mostly occurs in postmenopausal elderly women. Amyloidosis is the deposition of amorphous protein within tissues. Breast biopsy is necessary to make a definite diagnosis in order to avoid unnecessary surgical methods. Localized primary amyloidosis of the breast has a good prognosis. However, secondary amyloidosis is a systemic disease and has a poor prognosis.
CASE PRESENTATION
We report the case of a 77-year-old female with primary amyloidosis of the breast. She noticed a lump in her left breast. Mammographic and ultrasonographic examinations indicated breast cancer. However, core needle biopsy showed amyloidosis, not cancer of the breast. For further examinations, the patient visited the outpatient clinics of the hematology, dermatology, and gastroenterology departments. She underwent bone marrow aspiration, computed tomography, cardiac ultrasonography, random skin biopsy, gastrofiberscopy, and colonofiberscopy. Plasma cell myeloma and systemic amyloidosis were ruled out, and localized breast amyloidosis was highly suspected. Lumpectomy was performed to make a definite diagnosis, and histological evaluations revealed that this patient had localized amyloidosis of the breast, and the deposited amyloid protein was of the amyloid light chain kappa type.
CONCLUSIONS
Breast biopsy is necessary in order to avoid unnecessary surgical technique. A diagnosis should be achieved only through a histological evaluation. The main treatment of localized primary amyloidosis of the breast is surgical removal.
Topics: Aged; Amyloidosis; Biopsy; Breast; Breast Neoplasms; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Mammography; Mastectomy, Segmental
PubMed: 27624800
DOI: 10.1186/s12893-016-0178-6