Diagnostic challenges in light chain (AL) amyloidosis for high-risk patients

Introduction Immunoglobulin light-chain (AL) amyloidosis is associated with high early mortality, particularly when the diagnosis occurs after advanced cardiac or multiorgan dysfunction has developed. Existing reviews have addressed diagnosis and management, but the evolving concept of high-risk disease in the modern therapeutic era has received less attention.Areas covered This review explores how the definition of high-risk AL amyloidosis has evolved, with attention to organ involvement, cardiac biomarkers, clonal characteristics, tissue diagnosis, amyloid typing, multimodality imaging, artificial intelligence (AI)-supported diagnostic tools, multidimensional prognostic models, and novel B-cell maturation antigen (BCMA)-targeted immunotherapies. A focused Mayo Clinic literature search, supplemented by targeted PubMed searches by the authors, prioritized recent studies together with relevant consensus documents and landmark publications.Expert opinion Improving outcomes in AL amyloidosis will depend not only on the development of more potent therapies but also on the ability to deliver them before irreversible organ damage dictates the course of the illness. If advances in artificial intelligence, multimodal diagnostic tools, and highly active immunotherapies can be incorporated into everyday practice, the field may gradually move away from reacting to established high-risk disease and toward preventing patients from reaching that stage.