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.

How I treat monoclonal gammopathy of renal significance (MGRS)

Blood ◽  
2013 ◽  
Vol 122 (22) ◽  
pp. 3583-3590 ◽  
Author(s):  
Jean-Paul Fermand ◽  
Frank Bridoux ◽  
Robert A. Kyle ◽  
Efstathios Kastritis ◽  
Brendan M. Weiss ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Light Chain ◽  
Monoclonal Gammopathy ◽  
Kidney Diseases ◽  
Treatment Recommendations ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Immunoglobulin Light Chain Amyloidosis ◽  
Definition Of ◽  
Monoclonal Proteins

Abstract Recently, the term monoclonal gammopathy of renal significance (MGRS) was introduced to distinguish monoclonal gammopathies that result in the development of kidney disease from those that are benign. By definition, patients with MGRS have B-cell clones that do not meet the definition of multiple myeloma or lymphoma. Nevertheless, these clones produce monoclonal proteins that are capable of injuring the kidney resulting in permanent damage. Except for immunoglobulin light chain amyloidosis with heart involvement in which death can be rapid, treatment of MGRS is often indicated more to preserve kidney function and prevent recurrence after kidney transplantation rather than the prolongation of life. Clinical trials are rare for MGRS-related kidney diseases, except in immunoglobulin light chain amyloidosis. Treatment recommendations are therefore based on the clinical data obtained from treatment of the clonal disorder in its malignant state. The establishment of these treatment recommendations is important until data can be obtained by clinical trials of MGRS-related kidney diseases.

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.

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 Light Chain Stabilization: A Therapeutic Approach to Ameliorate AL Amyloidosis

Hemato ◽  
2021 ◽  
Vol 2 (4) ◽  
pp. 645-659
Author(s):  
Gareth J. Morgan ◽  
Joel N. Buxbaum ◽  
Jeffery W. Kelly
Keyword(s):  
Light Chain ◽  
Plasma Cells ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Organ Function ◽  
Conserved Residues ◽  
Light Chain Amyloidosis ◽  
Emerging Therapies ◽  
Chain Conformations

Non-native immunoglobulin light chain conformations, including aggregates, appear to cause light chain amyloidosis pathology. Despite significant progress in pharmacological eradication of the neoplastic plasma cells that secrete these light chains, in many patients impaired organ function remains. The impairment is apparently due to a subset of resistant plasma cells that continue to secrete misfolding-prone light chains. These light chains are susceptible to the proteolytic cleavage that may enable light chain aggregation. We propose that small molecules that preferentially bind to the natively folded state of full-length light chains could act as pharmacological kinetic stabilizers, protecting light chains against unfolding, proteolysis and aggregation. Although the sequence of the pathological light chain is unique to each patient, fortunately light chains have highly conserved residues that form binding sites for small molecule kinetic stabilizers. We envision that such stabilizers could complement existing and emerging therapies to benefit light chain amyloidosis patients.

scholarly journals Immunoglobulin light chain amyloidosis diagnosis and treatment algorithm 2021

2021 ◽  
Vol 11 (5) ◽  
Author(s):  
M. Hasib Sidiqi ◽  
Morie A. Gertz
Keyword(s):  
At Risk ◽  
Light Chain ◽  
Treatment Algorithm ◽  
Al Amyloidosis ◽  
Preserved Ejection Fraction ◽  
Immunoglobulin Light Chain ◽  
Light Chain Amyloidosis ◽  
Unexplained Weight Loss ◽  
Immunoglobulin Light Chain Amyloidosis ◽  
Nephrotic Range Proteinuria

AbstractImmunoglobulin light chain amyloidosis (AL) commonly presents with nephrotic range proteinuria, heart failure with preserved ejection fraction, nondiabetic peripheral neuropathy, unexplained hepatomegaly or diarrhea, and should be considered in patients presenting with these symptoms. More importantly, patients being monitored for smoldering multiple myeloma and a monoclonal gammopathy of undetermined significance (MGUS) are at risk for developing AL amyloidosis. MGUS and myeloma patients that have atypical features, including unexplained weight loss; lower extremity edema, early satiety, and dyspnea on exertion should be considered at risk for light chain amyloidosis. Overlooking the diagnosis of light chain amyloidosis leading to therapy delay is common, and it represents an error of diagnostic consideration. Herein we provide a review of established and investigational treatments for patients with AL amyloidosis and provide algorithms for workup and management of these patients.

scholarly journals Increased Serum Free Light Chains Precede the Presentation of Immunoglobulin Light Chain Amyloidosis

2014 ◽  
Vol 32 (25) ◽  
pp. 2699-2704 ◽  
Author(s):  
Brendan M. Weiss ◽  
Joseph Hebreo ◽  
Daniel V. Cordaro ◽  
Mark J. Roschewski ◽  
Thomas P. Baker ◽  
...  
Keyword(s):  
Light Chain ◽  
Early Death ◽  
Immunoglobulin M ◽  
Light Chains ◽  
Al Amyloidosis ◽  
Immunoglobulin Light Chain ◽  
Serum Free ◽  
Light Chain Amyloidosis ◽  
Serum Free Light Chain ◽  
Immunoglobulin Light Chain Amyloidosis

PurposePatients with immunoglobulin light chain amyloidosis (AL amyloidosis) generally present with advanced organ dysfunction and have a high risk of early death. We sought to characterize monoclonal immunoglobulin (M-Ig) light chains before clinical presentation of AL amyloidosis.Patients and MethodsWe obtained prediagnostic sera from 20 cases with AL amyloidosis and 20 healthy controls matched for age, sex, race, and age of serum sample from the Department of Defense Serum Repository. Serum protein electrophoresis with immunofixation and serum free light chain (FLC) analysis were performed on all samples.ResultsAn M-Ig was detected in 100% of cases and 0% of controls (P < .001). The M-Ig was present in 100%, 80%, and 42% of cases at less than 4 years, 4 to 11 years, and more than 11 years before diagnosis, respectively. The median FLC differential (FLC-diff) was higher in cases compared with controls at all time periods, less than 4 years (174.8 v 0.3 mg/L; P < .001), 4 to 11 years (65.1 v 2.2 mg/L; P < .001), and more than 11 years (4.5 v 0.4 mg/L; P = .03) before diagnosis. The FLC-diff was greater than 23 mg/L in 85% of cases and 0% of controls (P < .001). The FLC-diff level increased more than 10% per year in 84% of cases compared with 16% of controls (P < .001).ConclusionIncrease of FLCs, including within the accepted normal range, precedes the development of AL amyloidosis for many years.

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