American Society of Hematology (ASH) 2026 Guidelines on Diagnosis of Light Chain Amyloidosis

Light chain (AL) amyloidosis is a rare disease caused by the misfolding of immunoglobulin light chains produced by a plasma cell dyscrasia. Patients can present with involvement of many organs, including the heart, kidneys, liver, nerves and other sites, resulting in a high symptom burden. Timely and accurate diagnosis is important to prevent organ failure and improve patient survival. These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients and clinicians in the timely and effective diagnosis of AL amyloidosis. ASH formed a multidisciplinary guideline panel that included 22 individuals representing various medical specialties (academic/community hematology, nephrology, neurology, cardiology, internal medicine and pathology) as well as one patient representative. The group was balanced to minimize potential bias from conflicts of interest. Kansas University Medical Center supported the guideline development process, including updating or performing systematic evidence reviews (up to 6th of March 2023). The panel prioritized clinical questions and outcomes according to their importance for clinicians and patients. The panel used the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach, including GRADE Evidence-to-Decision frameworks, to assess evidence and make recommendations, which were subject to public comment. The panel agreed on 12 recommendations. The use of serum immunofixation, urine immunofixation and serum free light chains enhances the clinical suspicion of AL amyloidosis. The diagnosis of AL amyloidosis can be made effectively through surrogate biopsies which require both a bone marrow biopsy and fat pad sampling However, target organ biopsies maybe favoured in certain clinical situations.