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Introduction: light chain (AL) amyloidosis complexity requires specialized laboratories and use of highly sensitive methods for disease monitoring. During COVID-19 outbreak, access to our diagnostic facility was limited and a telemedicine (TM) program was established to maintain patients' management. Methods: patients were asked to perform specific blood and urine tests at a local laboratory. Biopsy samples were shipped to Pavia for amyloid typing. Results: in 2020, 369 TM were performed. For 102 (27%) patients, this was the first contact with our center, 73 (71%) of them received a final diagnosis and the specific therapeutic treatment, whereas in 29 (28%) the diagnostic suspicion was not confirmed. A TM was done in 276 (72%) patients previously evaluated, 214 (80%) of them had systemic AL with 99 (46%) receiving chemotherapy [89 (41%) proceeded with therapy, 10 (4%) suspended due to sustained hematologic response]. Seven (3%) started a new treatment due to loss of hematologic response. In all other cases, hematologic response was confirmed, and treatment free interval was prolonged. In 2021, 109 patients previously evaluated in our Center performed TM, of them 54 (50%) had a systemic AL. In 11 (19%) patients ongoing chemotherapy was proceeded and in one case a new therapy was suggested due to disease progression. Discussion: through this TM based-approach we reached a final diagnosis in 71% of cases and we assessed hematologic and organ response in local laboratories making clinical decisions. Despite being a response to pandemic, this hub and spoke TM model proved effective in a complex disease. [ABSTRACT FROM AUTHOR]

Amyloidosis reactive to chronic inflammation (AA amyloidosis) is a rare type of systemic amyloidosis, with prevalent renal involvement and a generally good overall survival (OS). However, progression to end-stage renal failure is frequent. Compared to other types of systemic amyloidosis, the role of prognostic biomarkers has been poorly explored in AA amyloidosis. Moreover, validated staging systems for the identification of patients with a more advanced disease are lacking. The acute phase reactant serum amyloid A (SAA) is the amyloid precursor protein and its concentration is associated with outcome. SAA concentration <10 mg/L after treatment translates in longer OS and lower incidence of end-stage renal failure. Boston researchers proposed a staging system for OS using estimated glomerular filtration rate (eGFR; cut-off, <35 mL/min/1.73 m2) and erythrocyte sedimentation rate (ESR; cut-off, >80 mm/h). Although it lacks validation, this staging system identified three groups with significant different OS. Pavia and Heidelberg researchers identified and validated a staging system for OS based on eGFR (cut-off, <45 mL/min/1.73 m2), serum albumin (cutoff, <30 g/L) and natriuretic peptides [type-B natriuretic peptide (BNP)] cut-off, >130 ng/L and/or N-terminal BNP (NT-proBNP) cut-off, >1000 ng/L). This staging system identified patients with low risk (5-year survival rate: 84%), intermediate risk (5-year survival rate: 55%) and high risk (5-year survival rate: 12%). Moreover, they proposed and validated a renal staging system using proteinuria (cut-off, >3 g/24h) and eGFR (cut-off, <35 mL/min/1.73m2). These data confirm the central role of the clinical laboratory in clinical management of systemic AA amyloidosis. [ABSTRACT FROM AUTHOR]

Rapid discrimination between transthyretin-related (ATTR) and immunoglobulin light chain (AL) amyloidosis is crucial to start specific, disease-modifying therapies to interfere with the production or deposition of liver-derived transthyretin or eradicate the underlying B cell/plasma cell clone, respectively. Differential diagnosis between these two clinical entities is particularly challenging in patients with isolated cardiac involvement, with potentially overlapping clinical presentations.Leveraging on the differential cardiac uptake of specific bone radiotracers, usually negative in AL amyloidosis, and positive in ATTR amyloidosis, a validated diagnostic algorithm can guide the diagnostic procedure. Here, we present the case of a patient with suspected cardiac amyloidosis exemplifying the importance of thorough M protein studies, along with the investigation of biomarkers of potential extra-cardiac amyloid involvement, to guide towards the correct diagnostic pathway. [ABSTRACT FROM AUTHOR]

Acquired systemic immunoglobulin light chain (AL) amyloidosis invariably occurs in the context of a monoclonal gammopathy. The underlying clone is the source of aggregation-prone circulating light chains which misfold and deposit in target tissues, leading to potentially fatal (multi)organ dysfunction. Demonstrating the underlying clone is mandatory to confirm the diagnosis, justify anti-clonal therapy, and monitor hematologic response to treatment and potential relapse. The combination of serum/urine protein electrophoresis with immunofixation and serum free light chain measurements detects an M protein in the vast majority of cases at diagnosis. Yet, rare cases with particularly low clonal burden, conventional M protein and bone marrow studies are negative, requiring the use of advanced diagnostic evaluations with increased sensitivity. Here, we present the case of a patient with suspected AL amyloidosis and negative conventional M protein and bone marrow studies, where high-resolution electrophoresis/immunofixation, next-generation flow cytometry and next-generation sequencing promptly detected the disease-causing clone. [ABSTRACT FROM AUTHOR]