AL Amyloidosis

Abstract

Definition of the diseaseAL amyloidosis results from extra-cellular deposition of fibril-forming monoclonal immunoglobulin (Ig) light chains (LC) (most commonly of lambda isotype) usually secreted by a small plasma cell clone. Most patients have evidence of isolated monoclonal gammopathy or smoldering myeloma, and the occurrence of AL amyloidosis in patients with symptomatic multiple myeloma or other B-cell lymphoproliferative disorders is unusual. The key event in the development of AL amyloidosis is the change in the secondary or tertiary structure of an abnormal monoclonal LC, which results in instable conformation. This conformational change is responsible for abnormal folding of the LC, rich in β leaves, which assemble into monomers that stack together to form amyloid fibrils.EpidemiologyAL amyloidosis is the most common type of systemic amyloidois in developed countries with an estimated incidence of 9 cases/million inhabitant/year. The average age of diagnosed patients is 65 years and less than 10% of patients are under 50.Clinical descriptionThe clinical presentation is protean, because of the wide number of tissues or organs that may be affected. The most common presenting symptoms are asthenia and dyspnoea, which are poorly specific and may account for delayed diagnosis. Renal manifestations are the most frequent, affecting two thirds of patients at presentation. They are characterized by heavy proteinuria, with nephrotic syndrome and impaired renal function in half of the patients. Heart involvement, which is present at diagnosis in more than 50% of patients, leading to restrictive cardiopathy, is the most serious complication and engages prognosis.Diagnostic methodsThe diagnosis relies on pathological examination of an involved site showing Congo red-positive amyloid deposits, with typical apple-green birefringence under polarized light, that stain positive with an anti-LC antibody by immunohistochemistry and/or immunofluorescence. Due to the systemic nature of the disease, non-invasive biopsies such as abdominal fat aspiration should be considered before taking biopsies from involved organs, in order to reduce the risk of bleeding complications.Differential diagnosisSystemic AL amyloidosis should be distinguished from other diseases related to deposition of monoclonal LC, and from other forms of systemic amyloidosis. When pathological studies have failed to identify the nature of amyloid deposits, genetic studies should be performed to diagnose hereditary amyloidosis.ManagementTreatment of AL amyloidosis is based on chemotherapy, aimed at controlling the underlying plasma clone that produces amyloidogenic LC. The hematological response should be carefully checked by serial measurements of serum free LC. The association of an alkylating agent with high-dose dexamethasone has proven to be effective in two thirds of patients and is considered as the current reference treatment. New agents used in the treatment of multiple myeloma are under investigation and appear to increase hematological response rate...

Oral melphalan and dexamethasone grants extended survival with minimal toxicity in AL amyloidosis: long-term results of a risk-adapted approach

“…[5][6][7] Oral MDex has been adopted as standard treatment for AL amyloidosis in several referral centers. [8][9][10][11][12][13][14][15][16] At our center, MDex was offered to all patients with AL amyloidosis who did not satisfy eligibility criteria for ASCT between 2004 and 2009. 10 To increase the tolerability of this regimen, the dose of dexamethasone was reduced in subjects with advanced disease.…”

Successful Treatment of Amyloid Light-chain Amyloidosis in a Charcot-Marie-Tooth Disease Patient with Lenalidomide, Cyclophosphamide, and Dexamethasone

“…High-dose melphalan with PBSCT is an effective therapy for AL amyloidosis, however, patients with organ damage, especially heart impairment, are ineligible for this treatment (17). In addition, only approximately 50% of patients demonstrate a hematological response.…”

Immunohistochemical Typing of Gastrointestinal Amyloid Deposits Using an Expanded Panel of Antibodies Directed Against Al-Kappa Amyloidosis

“…После гистологического подтверждения ами-лоидоза необходимо его типирование для вы-бора правильного метода лечения, который мо-жет состоять из химиотерапии или транспланта-ции органа [7][8][9]. Наиболее точным является им-муногистохимическое типирование с использо-ванием моноклональных антител к белкам-пред-шественникам амилоида [10][11][12].…”