scholarly journals Immunoglobulin light chain amyloidosis

2021 ◽  
Author(s):  
Hermine Agis ◽  
Maria T. Krauth
Keyword(s):  
Light Chain ◽  
Systemic Disease ◽  
Correct Diagnosis ◽  
Organ Damage ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Multiprofessional Team ◽  
Assessment And Treatment ◽  
Life Threatening ◽  
Immunoglobulin Light Chain Amyloidosis

SummaryImmunoglobulin light chain (AL) amyloidosis is a rare and underdiagnosed life-threatening systemic disease, primarily caused by insoluble depositions of misfolded monoclonal light chains. The monoclonal light chain paraprotein originates from a small clonal B‑cell or a clonal plasma cell population. If left undetected the paraprotein can induce a number of complications based on organ damage. The most dangerous and life-threatening organ dysfunction emerges from cardiac involvement. Thus, patients overall survival depends on early detection. Establishing the correct diagnosis and clear characterization of the amyloid-forming protein, staging, risk assessment and treatment are crucial and depend on a highly experienced interdisciplinary, multiprofessional team.

Nonchemotherapy Treatment of Immunoglobulin Light Chain Amyloidosis

2020 ◽  
Vol 143 (4) ◽  
pp. 373-380
Author(s):  
Layla Van Doren ◽  
Suzanne Lentzsch
Keyword(s):  
Plasma Cell ◽  
Light Chain ◽  
Cell Clone ◽  
Standard Of Care ◽  
Organ Damage ◽  
Current Therapy ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

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.

scholarly journals A Unique Case of Combined Nodular and Tracheobronchial Amyloidosis

2021 ◽  
Vol 2021 (2) ◽  
Author(s):  
Feihong Ding ◽  
Yun Li ◽  
Shailesh Balasubramanian ◽  
Subha Ghosh ◽  
Jason N Valent ◽  
...  
Keyword(s):  
Light Chain ◽  
Systemic Disease ◽  
Amyloid Deposition ◽  
Misfolded Proteins ◽  
Immunoglobulin Light Chain ◽  
Anatomic Site ◽  
Unique Case ◽  
Pulmonary Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis ◽  
Tracheobronchial Amyloidosis

ABSTRACT Amyloidosis is a heterogeneous group of diseases characterized by the extracellular deposition of misfolded proteins that can affect either systemically or locally confined to one system. Pulmonary amyloidosis is rare and can be classified into three forms according to the anatomic site of involvement: nodular pulmonary amyloidosis, tracheobronchial amyloidosis and diffuse alveolar-septal amyloidosis. The former two usually represent localized amyloid disease and the latter represents systemic disease. Typically lung parenchymal and tracheobronchial amyloidosis do not present together in localized forms of pulmonary amyloidosis. Here we report a unique case of localized pulmonary immunoglobulin light-chain amyloidosis, manifested as both parenchymal nodules and tracheobronchial amyloid deposition.

scholarly journals Beyond the plasma cell: emerging therapies for immunoglobulin light chain amyloidosis

Blood ◽  
2016 ◽  
Vol 127 (19) ◽  
pp. 2275-2280 ◽  
Author(s):  
Brendan M. Weiss ◽  
Sandy W. Wong ◽  
Raymond L. Comenzo
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Organ Damage ◽  
Immunoglobulin Light Chain ◽  
Organ Function ◽  
Fatal Disease ◽  
Mortality And Morbidity ◽  
Amyloid Deposits ◽  
Emerging Therapies ◽  
Immunoglobulin Light Chain Amyloidosis

Abstract Systemic immunoglobulin light chain (LC) amyloidosis (AL) is a potentially fatal disease caused by immunoglobulin LC produced by clonal plasma cells. These LC form both toxic oligomers and amyloid deposits disrupting vital organ function. Despite reduction of LC by chemotherapy, the restoration of organ function is highly variable and often incomplete. Organ damage remains the major source of mortality and morbidity in AL. This review focuses on the challenges posed by emerging therapies that may limit the toxicity of LC and improve organ function by accelerating the resorption of amyloid deposits.

scholarly journals Hereditary systemic immunoglobulin light-chain amyloidosis

Blood ◽  
2015 ◽  
Vol 125 (21) ◽  
pp. 3281-3286 ◽  
Author(s):  
Merrill D. Benson ◽  
Juris J. Liepnieks ◽  
Barbara Kluve-Beckerman
Keyword(s):  
Light Chain ◽  
Plasma Cell Dyscrasia ◽  
Al Amyloidosis ◽  
Constant Region ◽  
Immunoglobulin Light Chain ◽  
Region Gene ◽  
Dna Analyses ◽  
Key Points ◽  
Constant Region Gene ◽  
Immunoglobulin Light Chain Amyloidosis

Key Points Protein and DNA analyses reveal that mutation in the immunoglobulin κ light-chain constant region gene may cause hereditary amyloidosis. Sequencing of immunoglobulin light-chain constant region genes is indicated for patients with AL amyloidosis and no evidence of a plasma cell dyscrasia.

scholarly journals Immunoglobulin Light-Chain Amyloidosis: From Basics to New Developments in Diagnosis, Prognosis and Therapy

2016 ◽  
Vol 135 (3) ◽  
pp. 172-190 ◽  
Author(s):  
Eli Muchtar ◽  
Francis K. Buadi ◽  
Angela Dispenzieri ◽  
Morie A. Gertz
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Treatment Options ◽  
Organ Damage ◽  
Major Effect ◽  
Response To Treatment ◽  
Al Amyloidosis ◽  
Prognostic Effect ◽  
Amyloid Light Chain ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin amyloid light-chain (AL) amyloidosis is the most common form of systemic amyloidosis, where the culprit amyloidogenic protein is immunoglobulin light chains produced by marrow clonal plasma cells. AL amyloidosis is an infrequent disease, and since presentation is variable and often nonspecific, diagnosis is often delayed. This results in cumulative organ damage and has a negative prognostic effect. AL amyloidosis can also be challenging on the diagnostic level, especially when demonstration of Congo red-positive tissue is not readily obtained. Since as many as 31 known amyloidogenic proteins have been identified to date, determination of the amyloid type is required. While several typing methods are available, mass spectrometry has become the gold standard for amyloid typing. Upon confirming the diagnosis of amyloidosis, a pursuit for organ involvement is essential, with a focus on heart involvement, even in the absence of suggestive symptoms for involvement, as this has both prognostic and treatment implications. Details regarding initial treatment options, including stem cell transplantation, are provided in this review. AL amyloidosis management requires a multidisciplinary approach with careful patient monitoring, as organ impairment has a major effect on morbidity and treatment tolerability until a response to treatment is achieved and recovery emerges.

scholarly journals CD38 and Anti-CD38 Monoclonal Antibodies in AL Amyloidosis: Targeting Plasma Cells and beyond

2020 ◽  
Vol 21 (11) ◽  
pp. 4129 ◽  
Author(s):  
Dario Roccatello ◽  
Roberta Fenoglio ◽  
Savino Sciascia ◽  
Carla Naretto ◽  
Daniela Rossi ◽  
...  
Keyword(s):  
Monoclonal Antibodies ◽  
Plasma Cells ◽  
Nk Cell ◽  
Therapeutic Potential ◽  
Systemic Disease ◽  
Neoplastic Transformation ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin light chain amyloidosis (AL amyloidosis) is a rare systemic disease characterized by monoclonal light chains (LCs) depositing in tissue as insoluble fibrils, causing irreversible tissue damage. The mechanisms involved in aggregation and deposition of LCs are not fully understood, but CD138/38 plasma cells (PCs) are undoubtedly involved in monoclonal LC production.CD38 is a pleiotropic molecule detectable on the surface of PCs and maintained during the neoplastic transformation in multiple myeloma (MM). CD38 is expressed on T, B and NK cell populations as well, though at a lower cell surface density. CD38 is an ideal target in the management of PC dyscrasia, including AL amyloidosis, and indeed anti-CD38 monoclonal antibodies (MoAbs) have promising therapeutic potential. Anti-CD38 MoAbs act both as PC-depleting agents and as modulators of the balance of the immune cells. These aspects, together with their interaction with Fc receptors (FcRs) and neonatal FcRs, are specifically addressed in this paper. Moreover, the initiallyavailable experiences with the anti-CD38 MoAb DARA in AL amyloidosis are reviewed.

Rapid Complete Response to Single-Agent Bcl-2 Inhibitor Venetoclax in a Heart-Transplanted Patient with Triple Refractory Immunoglobulin Light-Chain Amyloidosis

2020 ◽  
Vol 143 (5) ◽  
pp. 500-503 ◽  
Author(s):  
Charlotte Gran ◽  
Johanna Borg Bruchfeld ◽  
Fredrik Ellin ◽  
Hareth Nahi
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Treatment Options ◽  
Single Agent ◽  
Complete Response ◽  
Organ Damage ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Cytogenetic Aberration ◽  
Immunoglobulin Light Chain Amyloidosis

Immunoglobulin light-chain amyloidosis (AL) is a disease with limited treatment options due to the frailty of patients caused by organ damage. Since the clonal plasma cells often contain the cytogenetic aberration t(11;14), the Bcl-2 inhibitor venetoclax is suggested to have a role in the treatment of AL. Here, we report of a heart-transplanted patient, refractory to multiple therapies, reaching a rapid complete response with single-agent venetoclax.

scholarly journals Systemic Light Chain Amyloidosis (Congo Red Inconclusive) with Underlyng Clonal Expansion Not Meeting the Criteria of Light Chain Monoclonal Gammopathy of Renal Significance or Light Chain Myeloma:A Case Report

2020 ◽  
Vol 07 (04) ◽  
pp. 15-19
Author(s):  
Sanjay Kumar ◽  
Keyword(s):  
Light Chain ◽  
Congo Red ◽  
Monoclonal Gammopathy ◽  
Plasma Cells ◽  
Clonal Expansion ◽  
Chronic Diarrhoea ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis

Fifty-eight-year-old male admitted for evaluation of nephrotic syndrome and chronic diarrhoea was detected to have Immunoglobulin light chain amyloidosis (AL Amyloidosis) which was congo red inconclusive from renal biopsy. Bone marrow biopsy showed monoclonal plasma cells of 40% and light chain assay showed predominance of immunoglobulin lambda light chain. The diagnosis was neither fitting into the current diagnostic criteria for light chain Monoclonal Gammopathy of Renal Significance (MGRS) nor light chain myeloma. Literature is scarce regarding patients with AL amyloidosis having underlying clonal expansion not meeting the criteria of light chain myeloma or light chain MGRS.

scholarly journals Dysphagia unveiling systemic immunoglobulin light-chain amyloidosis with multiple myeloma

2018 ◽  
pp. bcr-2018-226331 ◽  
Author(s):  
Juan Gonzalez ◽  
Ahsan Wahab ◽  
Kavitha Kesari
Keyword(s):  
Multiple Myeloma ◽  
Plasma Cell ◽  
Light Chain ◽  
Amyloid Deposition ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Percutaneous Gastrostomy ◽  
Uncommon Presentation ◽  
Immunoglobulin Light Chain Amyloidosis ◽  
Percutaneous Gastrostomy Tube

Dysphagia is an uncommon presentation of systemic immunoglobulin light-chain (AL) amyloidosis with multiple myeloma (MM). Gastrointestinal (GI) involvement usually manifests with altered motility, malabsorption or bleeding. Furthermore, patients identified with GI amyloidosis, without previous diagnosis of a plasma cell disorder, are extremely rare. We report an elderly woman who presented with acute on chronic cardiac dysfunction, sick sinus syndrome and acute renal failure. While admitted, she developed intermittent dysphagia to both solids and liquids. Oesophagogastroduodenoscopy showed ulcerations of oesophagus and duodenum. Biopsies revealed focal amyloid deposition, stained with Congo red. Renal biopsy revealed amyloid deposition in renal arterioles. She underwent a bone marrow biopsy confirming MM, represented by more than 15% plasma cell population. She was started on treatment for heart failure, induction chemotherapy for MM and percutaneous gastrostomy tube for feeding. However, she continued to deteriorate, eventually opting for hospice, and ultimately died 2 days after discharge from hospital.

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