Division of Hematology, Mayo Clinic, Rochester, Minnesota, USA.
Am J Hematol. 2022 Jun 1;97(6):818-829. doi: 10.1002/ajh.26569. Epub 2022 Apr 25.
Immunoglobulin light chain amyloidosis is a clonal, nonproliferative plasma cell disorder in which fragments of immunoglobulin light or heavy chain are deposited in tissues. Clinical features depend on organs involved but can include heart failure with preserved ejection fraction, nephrotic syndrome, hepatic dysfunction, peripheral/autonomic neuropathy, and "atypical smoldering multiple myeloma or monoclonal gammopathy of undetermined significance (MGUS)."
Tissue biopsy stained with Congo red demonstrating amyloid deposits with apple-green birefringence is required for the diagnosis of AL amyloidosis. Invasive organ biopsy is not required in 85% of patients. Verification that amyloid is composed of immunoglobulin light chains is mandatory. The gold standard is laser capture mass spectroscopy.
N-terminal pro-brain natriuretic peptide (NT-proBNP or BNP), serum troponin T (or I), and difference between involved and uninvolved immunoglobulin free light chain values are used to classify patients into four groups of similar size; median survivals are 73, 35, 15, and 5 months.
All patients with a systemic amyloid syndrome require therapy to prevent deposition of amyloid in other organs and prevent progressive organ failure. Current first-line therapy with the best outcome is daratumumab, bortezomib, cyclophosphamide, and dexamethasone. The goal of therapy is a complete response (CR). In patients failing to achieve this depth of response options for consolidation include pomalidomide, stem cell transplantation, venetoclax, and bendamustine.
Delayed diagnosis remains a major obstacle to initiating effective therapy prior to the development of end-stage organ failure. Trials of antibodies to catabolize deposited fibrils are underway.
免疫球蛋白轻链淀粉样变性是一种克隆性、非增殖性浆细胞疾病，其中免疫球蛋白轻链或重链片段沉积在组织中。临床特征取决于受累器官，但可包括射血分数保留的心力衰竭、肾病综合征、肝肾功能障碍、周围/自主神经病和“非典型惰性多发性骨髓瘤或意义未明的单克隆丙种球蛋白病（MGUS）”。
刚果红染色的组织活检显示淀粉样沉积物具有苹果绿双折射，这是诊断 AL 淀粉样变性所必需的。85%的患者不需要进行有创性器官活检。必须验证淀粉样物质由免疫球蛋白轻链组成。金标准是激光捕获质谱。
N 末端脑钠肽前体（NT-proBNP 或 BNP）、血清肌钙蛋白 T（或 I）以及受累和未受累免疫球蛋白游离轻链值之间的差异用于将患者分为四组，每组大小相似；中位生存期分别为 73、35、15 和 5 个月。
所有有系统性淀粉样综合征的患者都需要治疗，以防止淀粉样物质在其他器官中沉积并防止进行性器官衰竭。目前，疗效最佳的一线治疗方法是达雷妥尤单抗、硼替佐米、环磷酰胺和地塞米松。治疗的目标是完全缓解（CR）。对于未能达到这一反应深度的患者，巩固治疗的选择包括泊马度胺、干细胞移植、维奈托克和苯达莫司汀。
延迟诊断仍然是在终末期器官衰竭发生之前开始有效治疗的主要障碍。正在进行针对代谢沉积纤维的抗体的试验。
