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Leukemia & Lymphoma Feb 2021Retroperitoneal involvement is rare in patients with light chain (AL) amyloidosis and has only been published as case reports. Only 5 cases of retroperitoneal deposition... (Review)
Review
Retroperitoneal involvement is rare in patients with light chain (AL) amyloidosis and has only been published as case reports. Only 5 cases of retroperitoneal deposition have previously been reported in the setting of systemic AL amyloidosis. Data regarding the characteristics and clinical course of these patients are scarce. Herein we report on eleven patients with systemic AL amyloidosis diagnosed with retroperitoneal deposition at all three Mayo Clinic sites and Davidoff cancer center in Israel. All patients had retroperitoneal amyloid deposition at presentation. All patients received systemic treatment. Eight patients presented with hydronephrosis and 7 had nephrostomy tubes or stents inserted. Regression of the deposition was documented in one patient and one patient was able to have his nephrostomy tube removed. The median OS from diagnosis was 150 months, suggesting that retroperitoneal deposition might confer improved prognosis compared to the general amyloid population.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Israel; Prognosis
PubMed: 33118418
DOI: 10.1080/10428194.2020.1832670 -
Nephrology (Carlton, Vic.) Nov 2022Early symptoms of primary (AL) amyloidosis are non-specific. Any delay in diagnosis and treatment results in poor outcome despite increasing treatment options. We aimed...
AIM
Early symptoms of primary (AL) amyloidosis are non-specific. Any delay in diagnosis and treatment results in poor outcome despite increasing treatment options. We aimed to determine baseline risk factors that identify patients with poor kidney outcomes and overall survivals.
METHODS
We recruited all patients aged 18 years or above with biopsy-proven renal amyloidosis between years 2000 and 2019 in three Hong Kong regional hospitals. Patients' clinical and pathological parameters, treatment response, kidney outcomes and overall survivals were recorded and analysed.
RESULTS
Thirty-six cases of renal amyloidosis were recruited. Four cases were diagnosed to have multiple myeloma. Edema was the most common presenting symptom. The mean estimated glomerular filtration rate (eGFR) was 98.8 ml/min/1.73 m at presentation. Autologous stem cell transplant conferred the best renal outcomes as well as patients' survival. Twenty-two patients had 50% decrease in eGFR, 12 patients developed end-stage kidney disease (ESKD) and 22 patients died. Hypertension, diabetes mellitus, proteinuria and low eGFR were identified as independent baseline risk factors for ESKD. Proteinuria, hyperlipidemia, and cardiac involvement were independent baseline risk factors for death.
CONCLUSION
Amyloidosis, a rare disease with poor prognosis without treatment. Hypertension, diabetes mellitus, heavy proteinuria and low eGFR at diagnosis were associated with poor kidney outcome.
Topics: Amyloidosis; Diabetes Mellitus; Glomerular Filtration Rate; Hong Kong; Humans; Hypertension; Immunoglobulin Light-chain Amyloidosis; Kidney; Kidney Failure, Chronic; Proteinuria
PubMed: 36054582
DOI: 10.1111/nep.14089 -
JCO Oncology Practice May 2023Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for... (Review)
Review
Despite significant progress and improving outcomes in the management of plasma cell disorders, AL amyloidosis remains diagnostically and therapeutically challenging for clinicians across practice settings. There is, however, a reason for optimism with the advent of new combination therapy approaches and novel targets offering the promise of improvement in end organ function, survival, and quality of life. This review offers a clinically applicable overview of an approach to diagnosis, risk stratification, and clinical management of AL amyloidosis in an era of rapid therapeutic innovation.
Topics: Humans; Immunoglobulin Light-chain Amyloidosis; Amyloidosis; Quality of Life
PubMed: 36854070
DOI: 10.1200/OP.22.00396 -
Current Problems in Cancer Jun 2022Immunoglobulin light chain (AL) amyloidosis is a complex disease marked by a poor clinical portrait and prognosis generally leading to organ dysfunction and shortened... (Review)
Review
BACKGROUND
Immunoglobulin light chain (AL) amyloidosis is a complex disease marked by a poor clinical portrait and prognosis generally leading to organ dysfunction and shortened survival. We aimed to review the available evidence on whether AL amyloidosis can lead to malnutrition, thus having a negative impact on quality of life (QoL) and survival.
MATERIALS
We searched Pubmed for studies that assessed malnutrition in amyloidosis patients, with no restrictions to the year of publication or language. Retrospective or prospective, observational, and interventional studies that reported data regarding AL amyloidosis and nutritional status were included.
RESULTS
From 62 articles retrieved, 23 were included. Malnutrition was prevalent in up to 65% of patients with AL Amyloidosis. Prevalence of weight loss of 10% or more ranged from 6 to 22% of patients, while a body mass index of < 22 kg/m2 was found in 22 to 42%. Weight loss, lower BMI and other indicators of poor nutritional status were negatively associated with quality of life and survival. Only one RCT focused on nutritional counseling was found and reported positive results on patients QoL and survival.
CONCLUSION
Despite inconsistencies across assessment criteria, the available data reveal that weight loss and malnutrition are common features in patients with AL amyloidosis. This review reinforces the premise that an impaired nutritional status can be negatively associated with QoL and survival in patients with AL amyloidosis, and therefore should be further investigated.
Topics: Amyloidosis; Humans; Immunoglobulin Light-chain Amyloidosis; Malnutrition; Nutritional Status; Prospective Studies; Quality of Life; Retrospective Studies; Weight Loss
PubMed: 35101705
DOI: 10.1016/j.currproblcancer.2021.100833 -
European Heart Journal Dec 2019
Topics: Echocardiography; Female; Heart Failure; Heart Valve Diseases; Hospitalization; Humans; Immunoglobulin Light-chain Amyloidosis; Immunoglobulin lambda-Chains; Macroglossia; Middle Aged
PubMed: 31364714
DOI: 10.1093/eurheartj/ehz534 -
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 -
International Journal of Molecular... Jun 2022In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free... (Review)
Review
In amyloid light-chain (AL) amyloidosis, small B-cell clones (mostly plasma cell clones) present in the bone marrow proliferate and secrete unstable monoclonal free light chains (FLCs), which form amyloid fibrils that deposit in the interstitial tissue, resulting in organ injury and dysfunction. AL amyloidosis progresses much faster than other types of amyloidosis, with a slight delay in diagnosis leading to a marked exacerbation of cardiomyopathy. In some cases, the resulting heart failure is so severe that chemotherapy cannot be administered, and death sometimes occurs within a few months. To date, many clinical studies have focused on therapeutics, especially chemotherapy, to treat this disease. Because it is necessary to promptly lower FLC, the causative protein of amyloid, to achieve a hematological response, various anticancer agents targeting neoplastic plasma cells are used for the treatment of this disease. In addition, many basic studies using human specimens to elucidate the pathophysiology of AL have been conducted. Gene mutations associated with AL, the characteristics of amyloidogenic LC, and the structural specificity of amyloid fibrils have been clarified. Regarding the mechanism of cellular and tissue damage, the mass effect due to amyloid deposition, as well as the toxicity of pre-fibrillar LC, is gradually being elucidated. This review outlines the pathogenesis and treatment strategies for AL amyloidosis with respect to its molecular mechanisms.
Topics: Amyloid; Amyloidogenic Proteins; Amyloidosis; Humans; Immunoglobulin Light Chains; Immunoglobulin Light-chain Amyloidosis
PubMed: 35683015
DOI: 10.3390/ijms23116336 -
Clinical Lymphoma, Myeloma & Leukemia Aug 2022
Standard 30-minute Monitoring Time and Less Intensive Pre-medications is Safe in Patients Treated With Subcutaneous Daratumumab for Multiple Myeloma and Light Chain Amyloidosis.
Topics: Amyloidosis; Antibodies, Monoclonal; Humans; Immunoglobulin Light-chain Amyloidosis; Multiple Myeloma
PubMed: 35367193
DOI: 10.1016/j.clml.2022.03.003 -
Hematology/oncology Clinics of North... Dec 2020In systemic light-chain amyloidosis, monoclonal antibodies target antigens that are either membrane-bound or circulating or deposited in the organs. CD38 holds high... (Review)
Review
In systemic light-chain amyloidosis, monoclonal antibodies target antigens that are either membrane-bound or circulating or deposited in the organs. CD38 holds high promise as a target against clonal plasma cells. Multiple anti-CD38 antibodies are either approved for use or being investigated in clinical trials. Daratumumab has been investigated and has clinical efficacy in upfront or refractory settings. High rates of hematologic response are seen with daratumumab, which translates to high organ response rates. Rituximab is usually integrated into the treatment regimen for IgM amyloidosis. Anti-amyloid therapies have shown preclinical proof of principle, but lack confirmation of improvement.
Topics: Antibodies, Monoclonal; Humans; Immunoglobulin Light-chain Amyloidosis; Rituximab
PubMed: 33099430
DOI: 10.1016/j.hoc.2020.08.005 -
The American Journal of Medicine Apr 2022Light chain (AL) amyloidosis is challenging to diagnose, and it should be considered a cardiac emergency. There have been a great deal of advances in the treatment of AL...
Light chain (AL) amyloidosis is challenging to diagnose, and it should be considered a cardiac emergency. There have been a great deal of advances in the treatment of AL amyloidosis from initial descriptions of melphalan therapy until the recent approval of the first AL amyloidosis specific drug (daratumumab). Comprehension of the pathophysiology and biology of AL amyloidosis is crucial to understanding the major therapeutic targets in which light chain stability remains as a major key target of therapy. Organ dysfunction is a result not only from disruption of organ architecture but also direct cellular toxicity. Novel antiplasma cell agents for AL like isatuximab (anti CD-38 monoclonal antibody), belantamab (anti-BCMA monoclonal antibody), and elotuzumab (anti-SLAMF7 monoclonal antibody) are currently under investigation. Both diagnostic and therapeutic advances make the future of AL management bright while acknowledging the complexity of this patient population and focusing on a multidisciplinary approach.
Topics: Amyloidosis; Antibodies, Monoclonal; Antineoplastic Agents; Humans; Immunoglobulin Light-chain Amyloidosis
PubMed: 35081388
DOI: 10.1016/j.amjmed.2022.01.007