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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 -
Vnitrni Lekarstvi 2021Amyloidosis is a rare disorder caused by amyloid deposits in various organs and tissues resulting in vital organ dysfunction, eventually death. There are two forms of...
Amyloidosis is a rare disorder caused by amyloid deposits in various organs and tissues resulting in vital organ dysfunction, eventually death. There are two forms of amyloidosis - systemic, characterized by multiple organs affected, and localized (focal). Localized forms of amyloidosis usually affect urinary bladder, skin and lungs. Pulmonary amyloidosis may be localized or systemic such as diffuse alveolo-septal pulmonary amyloidosis which usually accompanies systemic AL amyloidosis. Other two forms of pulmonary amyloidosis are tracheobronchial and nodular. All three forms are usually detected by accident when patients undergo chest examination for different reasons as most cases of pulmonary amyloidosis are asymptomatic. The prognosis of localized amyloidosis is good with 5-year overall survival being 90,6 %. In our case report we present three patients diagnosed with localized pulmonary amyloidosis at our center. In all cases the diagnoses were made following the resection of affected lung segments with no further treatment needed.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Lung Diseases; Prognosis
PubMed: 35459379
DOI: No ID Found -
Circulation Research Sep 2019Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL...
Cardiac involvement and hypotension dominate the prognosis of light-chain amyloidosis (AL). Evidence suggests that there is also peripheral vascular involvement in AL but its prognostic significance is unknown. To evaluate vascular dysfunction in patients with AL as a potential future area of intervention, we assessed the prognostic utility of flow-mediated dilatation (FMD), a marker of vascular reactivity, which is augmented under conditions of hypotension and autonomic dysfunction. We prospectively evaluated 115 newly diagnosed untreated AL patients in whom FMD was measured. FMD in AL patients was significantly higher than age-, sex- and risk factors-matched controls (4.0% versus 2.32%; =0.006) and comparable with control groups at lower cardiovascular risk (>0.1). Amyloidosis patients presented increased plasma and exhaled markers of the NO pathway while their FMD significantly correlated with augmented sustained vasodilatation after sympathetic stimulation. Increased FMD (≥4.5%) was associated with early mortality (hazard ratio, 4.36; 95% CI, 1.41-13.5; =0.010) and worse survival (hazard ratio, 2.11; 95% CI, 1.17-3.82; =0.013), even after adjustment for Mayo stage, nerve involvement and low systolic blood pressure. This finding was confirmed in a temporal validation AL cohort (n=55; hazard ratio, 4.2; 95% CI, 1.45-12.3; =0.008). FMD provided significant reclassification value over the best prognostic model (continuous Net Reclassification Index, 0.61; =0.001). Finally, better hematologic response was associated with lower posttreatment FMD. FMD is relatively increased in AL and independently associated with inferior survival with substantial reclassification value. Reactive vasodilation merits further investigation as a novel risk biomarker in AL.Visual Overview: An online visual overview is available for this article.
Topics: Aged; Blood Pressure; Female; Humans; Immunoglobulin Light-chain Amyloidosis; Laser-Doppler Flowmetry; Male; Middle Aged; Regional Blood Flow; Survival Rate; Vasodilation
PubMed: 31401949
DOI: 10.1161/CIRCRESAHA.119.314862 -
The Journal of Urology May 1955
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Urinary Bladder Diseases
PubMed: 14368726
DOI: 10.1016/S0022-5347(17)67479-2 -
Cardiovascular & Hematological... 2020The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement,... (Review)
Review
The estimated prevalence of AL CA in the US is approximately 8-12 cases per million. Almost 30-50% diagnosed cases of AL amyloid in the US have multisystem involvement, including cardiac involvement. Even with the availability of advanced diagnostic testing and novel therapies, prognosis remains poor. It is overlooked as a cause of heart failure with preserved ejection fraction leading to a delay in diagnosis when management options are limited and associated with poor survival outcomes. Therefore, the education of physicians is needed to ensure that it would be highly considered as a differential diagnosis. The purpose of this manuscript is to review the advances in the diagnosis and management of cardiac amyloidosis with the aim of educating colleagues who provide care in the primary care setting. We have summarized the pathogenesis of amyloidosis, its association with plasma cell dyscrasias, novel diagnostic and surveillance approaches including echocardiography, cardiovascular magnetic resonance imaging, histopathologic techniques, systemic biomarkers, and advanced treatment approaches including supportive symptomatic management and standard of care chemotherapy targeting the amyloid deposits. Given the overall poor prognosis of amyloidosis, we have also discussed the role of palliative and hospice care.
Topics: Animals; Biomarkers; Disease Management; Echocardiography; Heart Diseases; Humans; Immunoglobulin Light-chain Amyloidosis; Magnetic Resonance Imaging; Myocardium; Paraproteinemias
PubMed: 33256586
DOI: 10.2174/1871529X20666201130110036 -
The New England Journal of Medicine Jun 2024
Review
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin Light Chains; Amyloidosis; Male
PubMed: 38924733
DOI: 10.1056/NEJMra2304088 -
The British Journal of Dermatology Sep 1953
Topics: Amyloidosis; Immunoglobulin Light-chain Amyloidosis
PubMed: 13081917
DOI: No ID Found -
Archives of Pathology Jan 1948
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma
PubMed: 18921355
DOI: No ID Found -
The American Journal of the Medical... Sep 1954
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma
PubMed: 13197384
DOI: No ID Found -
Journal of the Indian Medical... Oct 1953
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma
PubMed: 13109196
DOI: No ID Found