Key Insights on New ASH Guidelines for AL Amyloidosis, With Joselle Cook, MD

Recently, the American Society of Hematology (ASH) published new clinical practice guidelines aimed at improving the early, timely, and accurate diagnosis of light chain (AL) amyloidosis, a disease frequently missed or diagnosed late due to its heterogeneous presentation

The recommendations emphasize blood and urine testing, including serum immunofixation, urine immunofixation, and serum free light chain assays, whenever clinical suspicion for AL amyloidosis arises. To confirm diagnosis, the panel supports surrogate tissue sampling through combined bone marrow biopsy and fat pad aspirate in most cases, while noting that target organ biopsies may be warranted in select scenarios.

HCPLive spoke with panel member Joselle Cook, MD, MBBS, a hematologist and oncologist, specializing in Myeloma, Amyloid and Plasma cell disorders at the Mayo Clinic in Rochester Minnesota for insight into the rationale behind the guidelines.

HCPLive: What gap in current clinical practice did ASH most urgently aim to address with these new diagnostic guidelines for AL amyloidosis?

Cook:

This gap for AL amyloidosis really is the delay and inconsistency in the diagnosis of light chain amyloidosis, and that is what really results in the significant morbidity and mortality, especially if diagnosed late across multiple specialties. There really hasn't been any shared evidence pathway for when to order prior protein testing, which biopsies to do first, and how to distinguish from, etc, cardiac amyloid. So these guidelines are really unique because they give a common roadmap for patient workup to lead to the most efficient diagnosis, whether they start with a cardiologist, nephrologist, neurologist, or with a hematologist.

HCPLive: Which of the 12 recommendations represents the most meaningful shift from current diagnostic practice?

Cook:

The important shift to me is the emphasis of combined serum and urine immunofixation, plus serum free light chains obtained all together and up front and clearly defined red flag scenarios such as cardiac amyloidosis or unexplained proteinuria. Too often we have seen missed or delayed diagnoses of AL amyloid if only the serum protein electrophoresis was obtained without the free light chains or immunofixation because the amyloid clone is so small. This triad of tests really is essential to support earlier suspicion and diagnosis of the monoclonal protein and, therefore, appropriate referral to hematology. So for me, those are the most meaningful shifts with these guidelines. This pathway is more efficient because it replaces fragmented, sequential workup with a standardized strategy.

The guidelines outline a stepwise approach that starts with combined blood and urine testing and moves to surrogate biopsies using bone marrow and fat pad sampling. How does this diagnostic pathway work mechanistically to both raise clinical suspicion earlier and confirm AL amyloidosis more efficiently than prior approaches?

Cook:

In the past, patients often underwent multiple isolated evaluations, so a cardiologist would order imaging, and the patient would visit a neurologist who would focus on the neuropathy and so forth, and the monoclonal protein testing was sometimes delayed or incomplete, which led to repeated visits, organ biopsies, and months of diagnostic drift. So this new approach really does three things differently. Number one, it standardizes early testing when red flags appear. Clinicians order this triad of serum immunofixation, urine immunofixation, and free light chains together, and that would really immediately identify or exclude a clonal process. Then, number two, the guidelines move quickly to recommend surrogate tissue confirmation, which diagnoses the majority of light chain amyloid cases; the bone marrow and fat aspirate together has a sensitivity of about 89%, which is really excellent. And then third, it aligns specialties all around the same pathway. So this would reduce redundant imaging and prevent delays caused by uncertainty about next steps.

HCPLive: For patients with suspected cardiac involvement, how do the guidelines help clinicians decide between surrogate biopsies and endomyocardial biopsy in real-world settings?

Cook:

Patients with suspected cardiac amyloidosis or light chain cardiac amyloidosis, who have positive monoclonal testing, abnormal cardiac biomarkers, and an echocardiogram consistent with amyloid. The key issue here is not whether to biopsy, it's which biopsy to start with. And so the guidelines support two reasonable pathways. One is to begin with the surrogate sites, meaning the fat pad sampling and the bone marrow biopsy, which is less invasive, as I said, really great sensitivity of about 89%, and often confirm systemic AL with proper subtyping, which may altogether eliminate the need for heart biopsy. But the other option is to proceed directly to an endomyocardial biopsy, and this actually may be preferred in certain instances where rapid diagnostic certainty is needed, or where there's a strong local expertise in doing endomyocardial biopsies, or if there's concern for ATTR amyloid, including other hereditary forms. And so the central message here really is simple: imaging can raise suspicion, but you really need tissue to establish the diagnosis and the subtype of amyloid, and the biopsy strategy should be individualized to the patient and to the clinical scenario

HCPLive: Because patients often present outside hematology, which specialties need to be most aware of these guidelines, and why?

Cook:

The clinical guidelines were intentionally multidisciplinary, since all specialties are likely to encounter patients at various stages along their symptom journey. So general internists, cardiologists, nephrologists, neurologists, gastroenterologists, they all need to have a clear, evidence-based framework to recognize amyloidosis and how to initiate an appropriate workup. And I would also add that the companion scoping review on symptoms and red flags across the different amyloid subtypes is equally important, and I would encourage everyone to read that as well. It gives clinicians the practical clinical clues that should trigger testing, and together, the two papers aim to shorten diagnostic delay by aligning suspicion and diagnostic strategy across specialties.

HCPLive: If clinicians take away just one action item from these new ASH guidelines, what should it be?

Cook:

For adults with otherwise unexplained red flag features for systemic amyloidosis, please order serum immunofixation, urine immunofixation, and serum free light chains together, and if they're abnormal, involve a center with amyloidosis expertise for bone marrow and fat pad biopsy. If that habit spreads across cardiology, nephrology, neurology, and internal medicine, we will shorten the time to diagnosis, avoid inappropriate testing, and give more patients a chance at organ-saving treatment."

Editor’s Note: Cook reports no relevant disclosures.

References

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. Hillenbrand A. ASH Releases New Clinical Practice Guidelines for Diagnosing AL Amyloidosis. HCPLive. Published January 28, 2026. Accessed February 25, 2026. https://www.hcplive.com/view/ash-releases-new-clinical-practice-guidelines-for-diagnosing-al-amyloidosis