ASH Releases New Clinical Practice Guidelines for Diagnosing AL Amyloidosis

The American Society of Hematology (ASH) has published new clinical practice guidelines aimed at improving the early, timely, and accurate diagnosis of light chain (AL) amyloidosis.1

The guidelines were published January 28, 2026, in Blood Advances and outline best practices to support clinicians in recognizing and diagnosing AL amyloidosis, a disease frequently missed or diagnosed late due to its heterogeneous presentation.1

“These guidelines will be a valuable resource not only for hematologists, but for clinicians across other specialties who care for patients with AL amyloidosis,” said Robert Negrin, MD, ASH President, in a statement. “Because this is a rare and often underrecognized disorder, these recommendations are particularly important for coordinating care and increasing awareness.”

AL amyloidosis is typically a multisystem disease, with amyloid deposits affecting multiple organs. The heart and kidneys are most commonly involved, potentially resulting in cardiomyopathy, renal failure, and pleural or pericardial effusions. Multiorgan dysfunction is strongly associated with poorer outcomes and reduced survival, while 51% to 80% of patients present with cardiac involvement, a major cause of morbidity and mortality in these patients.2,3

The pathogenesis of AL amyloidosis is caused by the misfolding and tissue deposition of monoclonal immunoglobulin light chains produced by abnormal plasma cells. These amyloid deposits, along with circulating free light chains, disrupt normal tissue structure and function, leading to progressive organ damage and increased risk of death, particularly when diagnosis is delayed.2,3,4

In the past, patients have reported diagnostic delays of >1 year from symptom onset, especially since the presenting symptoms are non-specific, and first-line clinicians may not have disease awareness.4

For example, one primary risk factor for AL amyloidosis is increased age, with a median age at diagnosis of approximately 64 years. Since the disease often presents later in life, nonspecific symptoms such as fatigue, weight loss, or reduced appetite are frequently misattributed to aging or more common chronic conditions, contributing to prolonged diagnostic delays.2

Despite existing diagnostic tools, the absence of a standardized, evidence-based diagnostic pathway has contributed to prolonged delays and missed diagnoses in AL amyloidosis.4

To address this diagnostic gap, the multidisciplinary guideline panel included hematologists, cardiologists, a neurologist, a nephrologist, an internist, a pathologist, and one patient representative. For each recommendation, the Evidence-Based Practice and Impact Center at the University of Kansas Health System conducted systematic evidence reviews and developed GRADE Evidence-to-Decision frameworks to guide recommendations.1

The guidelines recommend the use of blood and urine testing, including serum immunofixation, urine immunofixation, and serum free light chain assays, when clinical suspicion for AL amyloidosis exists. To confirm diagnosis, the panel supports the use of surrogate biopsies through combined bone marrow biopsy and fat pad sampling in most cases, while recognizing that target organ biopsies may be appropriate in select clinical scenarios.1

“For these patients, time is of the essence,” said Vishal Kukreti, MD, chair of the ASH Guidelines on Diagnosis of Light Chain Amyloidosis and a malignant hematologist at Princess Margaret Cancer Centre, in a statement. “These guidelines will help clinicians across disciplines think of this disease in the right scenarios and provide them with the necessary tools to obtain a clear, accurate diagnosis as quickly as possible.”1

Currently, the panel is developing follow-up guidelines focused on the treatment of AL amyloidosis.1

1. ASH publishes clinical practice guidelines on diagnosis of light chain amyloidosis. EurekAlert! Published January 28, 2026. Accessed January 28, 2026. https://www.eurekalert.org/news-releases/1114078

2. ‌McCausland KL, White MK, Guthrie SD, et al. Light Chain (AL) Amyloidosis: The Journey to Diagnosis. The Patient - Patient-Centered Outcomes Research. 2017;11(2):207-216. doi:https://doi.org/10.1007/s40271-017-0273-5

3. Chatzileontiadou S, Zegkos T, Frouzaki C, et al. Real world data on light chain cardiac amyloidosis: Still a delayed diagnosis. Frontiers in Oncology. 2022;12. doi:https://doi.org/10.3389/fonc.2022.944503

4. ‌Hester LL, Gifkins DM, Bellew KM, et al. Diagnostic delay and characterization of the clinical prodrome in AL amyloidosis among 1523 US adults diagnosed between 2001 and 2019. European journal of haematology. 2021;107(4):428-435. doi:https://doi.org/10.1111/ejh.13679