Understanding Amyloidosis: Unraveling the Complexities and Therapeutic Approaches for Oncology Nurses.

BACKGROUND:  Primary systemic light-chain (AL) amyloidosis is a rare clonal plasma cell disorder characterized by the production of abnormal immunoglobulin fragments, which form insoluble fibrils that aggregate as amyloid deposits in organs and tissues, leading to organ dysfunction and death. OBJECTIVES:  The aim of this literature review is to increase awareness of AL amyloidosis and educate nurses on the care of this patient population. METHODS:  This overview is based on a literature search of AL amyloidosis, including its pathogenesis, prognosis, and presentation. Guidance for nursing assessment, intervention, and patient education throughout the disease trajectory is presented. FINDINGS:  AL amyloidosis is a rare disease resulting in organ impairment and death if untreated. Nursing management includes knowledge of key assessment, monitoring, intervention, and education strategies with goals to preserve organ function and improve survival and quality of life in patients with AL amyloidosis.

Unraveling a rare cause of spinal stenosis: Coexistent AL and ATTR amyloidosis involving the ligamentum flavum.

BACKGROUND: Amyloidosis is a protein misfolding disorder that leads to the deposition of beta-pleated sheets of a fibrillar derivative of various protein precursors. Identification of the type of precursor protein is integral in treatment decision-making. The presence of two different types of amyloid in the same patient is unusually rare, and there are no previous reports of two different types of amyloid deposition in the ligamentum flavum (LF) in the same patient. CASE DESCRIPTION: Here, we describe two patients with spinal stenosis who underwent laminectomies and were found to have AL and ATTR amyloid deposits in the LF. CONCLUSION: As the spine is becoming recognized as a site for ATTRwt amyloid deposition, patients undergoing spinal decompression surgery may potentially benefit from evaluation for amyloidosis in the LF.

Association between spinal stenosis and wild-type ATTR amyloidosis.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay, TTR gene sequencing and technetium 99 m-pyrophosphate-scintigraphy. In 2018-2019, 324 patients underwent surgery for SS and 43 patients (13%) had ATTR in the LF with wild-type TTR gene sequences. Two cases of ATTRwt cardiac amyloidosis were diagnosed and received treatment. In this large series, ATTRwt was identified in 13% of the patients undergoing laminectomy for SS. Patients with amyloid in the ligamentum flavum were older and had a higher prevalence of CTS, suggesting a systemic form of ATTR amyloidosis involving connective tissue. Further prospective study of patients with SS at risk for systemic amyloidosis is warranted.

Supportive Care for Patients with Systemic Light Chain Amyloidosis.

Light chain amyloidosis is a disease in which clonal plasma cells produce toxic immunoglobulin light chains that form amyloid fibrils with deposition in organs, most commonly the heart and kidneys, but also the nervous system, gastrointestinal tract, and soft tissues. Treatment directed at the clonal cells eliminates light chain production and further deposition and may enable organ improvement and decrease the risk of organ failure. Supportive care manages the symptoms of organ involvement and the side effects of treatment. Supportive care also addresses the psychological and social issues that may arise in patients with light chain amyloidosis.

Dual Monoclonal Antibody Therapy in Patients With Systemic AL Amyloidosis and Cardiac Involvement.

BACKGROUND: Systemic AL amyloidosis (AL) is a rare disease in which clonal immunoglobulin light chains produced by monoclonal plasma cells circulate and misfold, resulting in direct toxicity and fibrillar deposition of amyloid in numerous tissues. Early mortality from cardiac damage remains high. As depth of organ response carries a prognostic significance, combining anti-plasma cell and anti-amyloid therapies might hold the key to achieving long lasting responses. We report a series of patients who received 2 monoclonal antibodies, anti-CD38 and anti-amyloid, simultaneously. MATERIALS AND METHODS: We describe the characteristics and outcomes of 19 patients who received daratumumab (anti-CD38) on progression with front-line therapy for AL, 9 of whom were on concurrent dual monoclonal antibody treatment with daratumumab and NEOD001 (anti-amyloid), and also provide data on the schedule, safety, and tolerability of intravenous infusions of these monoclonal antibodies. RESULTS: The 9 patients who received treatment with dual monoclonal antibodies achieved a high rate (100%) of hematologic response in a median of 33 days. There was no significant toxicity to dual monoclonal antibody therapy. Seven of the 8 met criteria for cardiac response, achieved in less than 3 months of combined therapy. Ten patients who received daratumumab alone also had high rates of hematologic and organ responses. CONCLUSIONS: Monoclonal antibodies with distinctly different targets can be safely combined in patients with AL and cardiac involvement. Patients experienced high rates of hematologic and cardiac response with combined anti-CD38 and anti-amyloid monoclonal antibody therapies. Further study of this combined approach is warranted.

Where Neurosurgery Meets Heart Failure: A Case Report of a Patient with Amyloid Transthyretin Wild Type in the Ligamentum Flavum and Cardiac Tissue with Bilateral Carpal Tunnel Syndrome.

BACKGROUND: Transthyretin wild-type (ATTRwt) amyloidosis is a systemic process resulting in deposition of misfolded transthyretin protein in several different tissues throughout the body. It is known to be a cause of progressive, life-threatening cardiomyopathy and lumbar spinal stenosis and carpal tunnel syndrome. CASE DESCRIPTION: Here we present the case of a 71-year-old man who has clinical manifestations of all 3 entities over several years, providing a picture of the natural history of ATTRwt amyloidosis. This patient eventually underwent a heart transplant because of progressive cardiac amyloidosis (CA) resulting in end-stage heart failure. However, symptoms in carpal tunnel and lumbar spine manifested years before the symptoms of heart failure. ATTRwt amyloidosis may present as a clinical triad of lumbar stenosis, carpal tunnel syndrome, and heart failure. Recently developed medications have shown efficacy in slowing the progress of systemic and cardiac amyloidosis. CONCLUSIONS: Knowing that extracardiac symptoms may occur first, we propose that sending ligamentum flavum and flexor tenosynovium for pathologic evaluation may be a unique opportunity to screen and treat a population of patients at risk for developing CA and heart failure.

A Case of T-Cell Large Granular Lymphocytic Leukemia and Renal Immunoglobulin Heavy Chain Amyloidosis.

BACKGROUND T-cell large granular lymphocytic leukemia (T-LGL) is a rare hematological malignancy that currently has no standard therapy. Immunoglobulin heavy chain amyloidosis (AH) involving the kidney is a rare condition and the pathology, diagnosis, clinical characteristics, and prognosis are becoming understood. This report is of a rare case of T-LGL associated with renal AH and discusses the approach to management. CASE REPORT A 57-year-old woman presented with symptoms of fatigue and she had proteinuria. A diagnosis of T-LGL associated with renal AH was made, which is an association that has not been previously reported in the literature. Given the dysregulation of her immune function due to her underlying T-LGL and her comorbidities, treatment options were limited. She was clinically stable and was initially observed. After one year, her symptoms of fatigue became worse, and her proteinuria increased. Treatment was initiated with the triple drug combination of bortezomib, cyclophosphamide, and dexamethasone (CyBorD) with consideration for future hematopoietic stem cell transplantation (HSCT). Her clinical condition improved, with a reduction in proteinuria. CONCLUSIONS A rare case of T-LGL and renal AH is presented. Currently, there is no standard therapy for T-LGL and AH amyloidosis, and the approach, in this case, was to manage the patient initially with CyBorD triple chemotherapy.

Immunoglobulin Light-Chain Amyloidosis: Clinical Presentations and Diagnostic Approach.

Systemic immunoglobulin light-chain (AL) amyloidosis is a rare disorder arising from a plasma cell clone that produces misfolded immunoglobulin light chains, which are deposited in various tissues and organs as amyloid fibrils. Signs and symptoms are typically vague and overlap with those arising from other common diseases; consequently, diagnosis of AL amyloidosis is challenging for clinicians. Substantial delays between onset of symptoms and diagnosis are common, and result in poorer outcomes, particularly in patients with cardiac AL amyloidosis and others who develop advanced organ dysfunction. With the need to identify AL amyloidosis as early as possible, it is important for health-care practitioners, including advanced practice clinicians and nurses, to be aware of the hallmark presenting signs and symptoms, as well as the latest practice for evaluation and diagnosis. Increased awareness of signs and symptoms associated with AL amyloidosis, particularly relating to the most frequently involved organs, the heart and kidneys, represents an opportunity for achieving earlier diagnosis. Here we review these issues in AL amyloidosis, summarize the key presenting symptoms that clinicians need to be alert to, and discuss the latest diagnostic tests, with the aim of expediting patient identification and diagnosis with the goal of improving patient outcomes.

Primary Amyloidosis With Renal Involvement: Outcomes in 77 Consecutive Patients at a Single Center.

BACKGROUND: Outcomes in primary amyloid renal patients are of interest as the era of monoclonal antibody therapies begins. PATIENTS AND METHODS: We studied 77 consecutive primary amyloid renal patients (58% men) for renal progression (end stage renal disease [ESRD]), renal response (RR), and overall survival (OS). RESULTS: At diagnosis median age was 63 (range, 35-81) years, estimated glomerular filtration rate 70 mL/min (range, 5-114), difference between involved and uninvolved free light chains 127 mg/L (range, 1-9957), ESRD 4%, renal stage 2 and 3 78%, and cardiac stage 2 and 3 56%. Ninety-six percent received bortezomib and 44% stem cell transplantation as well as bortezomib, 68% achieved complete or very good partial hematologic response (CR/VGPR), 34% had ESRD, and 39% RR. Median times to ESRD and RR were 18 (range, 3-81) and 12 (range, 2-30) months, respectively. Median OS was not reached in this cohort and was not reached from onset of ESRD. More than two-thirds of patients with ESRD also achieved CR/VGPR. In those without ESRD at diagnosis, baseline creatinine and absent RR predicted progression to ESRD in multivariate Cox regression analysis, whereas CR/VGPR predicted RR. In multivariate Cox regression analysis, cardiac stage and achievement of CR/VGPR predicted OS, enabling construction of a prognostic model. CONCLUSION: Anti-plasma cell therapies provide a definite albeit limited benefit and new approaches to amyloid-related organ dysfunction are needed.