Transthyretin amyloidosis is a progressive and eventually fatal disease primarily characterized by sensory, motor, and autonomic neuropathy and/or cardiomyopathy. Given its phenotypic unpredictability and variability, transthyretin amyloidosis can be difficult to recognize and manage. Misdiagnosis is common, and patients may wait several years before accurate diagnosis, risking additional significant irreversible deterioration. This article aims to help physicians better understand transthyretin amyloidosis—and, specifically, familial amyloidotic polyneuropathy—so they can recognize and manage the disease more easily and discuss it with their patients. We provide guidance on making a definitive diagnosis, explain methods for disease staging and evaluation of disease progression, and discuss symptom mitigation and treatment strategies, including liver transplant and several pharmacotherapies that have shown promise in clinical trials.

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Treatment of selected patients with AL amyloidosis by using high-dose melphalan and stem-cell transplantation resulted in hematologic remission, improved 5-year survival, and reversal of amyloid-related disease in a substantial proportion.

Previous studies have suggested that, in patients with AL amyloidosis treated with high-dose melphalan and autologous stemcell transplantation (HDM/SCT), the greatest benefit is seen in those patients achieving a hematologic complete response (CR). We analyzed a series of 421 consecutive patients treated with HDM/SCT at a single referral center and compared outcomes for patients with and without CR. Treatmentrelated mortality was 11.4% overall (5.6% in the last 5 years). By intention-to-treat analysis, the CR rate was 34% and the median event-free survival (EFS) and overall survival (OS) were 2.6 and 6.3 years, respectively. Eighty-one patients died within the first year after HDM/SCT and were not evaluable for hematologic and organ response. Of 340 evaluable patients, 43% achieved CR and 78% of them experienced an organ response. For CR patients, median EFS and OS were 8.3 and 13.2 years, respectively. Among the 195 patients who did not obtain CR, 52% achieved an organ response, and their median EFS and OS were 2 and 5.9 years, respectively. Thus, treatment of selected AL patients with HDM/SCT resulted in a high organ response rate and long OS, even for those patients who did not achieve CR. (Blood. 2011;118(16):4346-4352) IntroductionImmunoglobulin light chain (AL) amyloidosis is the most common form of systemic amyloidosis, with an incidence of 5-12 persons per million per year. 1 In AL amyloidosis, clonal bone marrow plasma cells produce monoclonal light chains that misfold and deposit in tissues and organs as amyloid fibrils, resulting in progressive system and organ failure, and ultimately in death. Untreated patients with this disease have a dismal outcome, with a median survival of 10-14 months from diagnosis. 2 Moreover, fewer than 5% of patients survived for Ͼ 10 years before the introduction of high-dose melphalan and stem cell transplantation (HDM/ SCT). 3 Oral melphalan and prednisone (MP) modestly increases the median survival to 16-18 months and rarely induces hematologic complete responses (CRs) or reversal of organ dysfunction. 2,4,5 The introduction of HDM/SCT in the 1990s appears to have markedly improved these results. 6 Single and multicenter studies show CR rates of 16%-67%, organ responses in 25%-45% of patients, and a median overall survival (OS) of ϳ 5 years. [7][8][9][10][11][12][13][14][15][16] A case-control study demonstrated the benefit of this procedure for patients younger than 70 years compared with nontransplant regimens, most of them alkylator-based oral chemotherapy. 17 A major issue in HDM/SCT for AL amyloidosis is the potential for high treatment-related mortality (TRM) because of underlying organ dysfunction in this disease. Some early multicenter series reported TRM as high as 40%, but recent reports from experienced single centers have reported a TRM rate in the range of 10%-15% as a result of improved selection of patients and better peritransplantation management. [17][18][19] In previous reports, we and others have shown that patients who achieve CR after HDM/SCT have ...