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PubMed This is a summary of 15 peer-reviewed journal articles Updated
Hematology

Understanding Your Stage and Risk Score

At a Glance

AL amyloidosis staging does not measure tumor size; it measures organ function, specifically heart stress. The Mayo staging systems use blood tests for NT-proBNP, Troponin, and free light chains to calculate risk. Modern treatments like Daratumumab have significantly improved outlooks for all stages.

Staging in most cancers (like lung or breast cancer) is about the size and spread of a tumor. However, in AL amyloidosis, staging is fundamentally different. It is a measure of organ function—specifically, how much the toxic light chains have stressed your heart [1][2].

Because the heart is the primary driver of survival in this disease, your “Mayo Stage” helps your care team understand the urgency of your treatment and how aggressively they need to protect your organs [3][4].

The Three Key Biomarkers

Specialists use three specific blood tests to determine your stage. These markers act like “sensors” that detect damage or stress in the body:

  1. NT-proBNP (or BNP): A protein released by the heart when it is under pressure or being stretched [4].
  2. Troponin (T or I): A protein that leaks into the blood when heart muscle cells are damaged [5][6].
  3. dFLC (Difference between involved and uninvolved Free Light Chains): A measure of the “toxic load” or the amount of “broken” proteins circulating in your blood [1][7].

The Mayo 2004 vs. 2012 Systems

Over time, the way doctors calculate risk has evolved to become more precise.

  • Mayo 2004 (The Original): This system uses only the two heart markers (NT-proBNP and Troponin) [8].
    • Stage I: Both markers are low.
    • Stage II: One marker is high.
    • Stage III: Both markers are high [8][3].
  • Mayo 2012 (The Revised): This updated system adds the dFLC (the toxic load) to the equation, using a threshold of 180 mg/L [7]. Patients are assigned one point for each marker that is above the cutoff, resulting in four stages:
    • Stage I: 0 points
    • Stage II: 1 point
    • Stage III: 2 points
    • Stage IV: 3 points [7][9].

The “Daratumumab Effect”

It is important to know that these staging systems were built using data from patients treated years ago. In the modern era of Daratumumab-based therapy (like the Dara-CyBorD regimen), the outlook for patients—even those in Stage III or IV—has improved significantly [10][11].

Recent research suggests that a high dFLC (the toxic light chain load) may no longer be the negative predictor it once was, because modern drugs are so incredibly fast and effective at clearing those light chains from the blood [7]. While the cardiac markers (Troponin and NT-proBNP) remain very important, a “Stage IV” diagnosis today does not mean the same thing it did ten years ago [7][12].

Limitations to Keep in Mind

Staging models are helpful “maps,” but they aren’t perfect for every patient:

  • Kidney Function: If your kidneys are not working well (low eGFR), your NT-proBNP levels may be high because your body isn’t clearing the protein properly, not necessarily because your heart is failing [13][14].
  • Response Matters Most: Your baseline stage is just a starting point. The most important indicator of success is how quickly and deeply your light chain levels drop once you start treatment [10][15].

Common questions in this guide

How is AL amyloidosis staging different from other cancer stages?
Unlike other cancers where staging measures the size and spread of a tumor, AL amyloidosis staging measures organ function. It specifically looks at how much the toxic light chain proteins have stressed your heart using precise blood biomarkers.
What is the Mayo 2012 staging system for AL amyloidosis?
The Mayo 2012 system assigns a stage from I to IV based on three blood tests: NT-proBNP, Troponin, and the difference in free light chains (dFLC). You receive one point for each marker that is above a specific threshold, which helps doctors understand your risk level.
What are the most important biomarkers tracked in AL amyloidosis?
Specialists track three main blood markers to determine your stage. They look at NT-proBNP and Troponin, which measure heart stress and damage, as well as dFLC, which measures the amount of toxic light chain proteins circulating in your blood.
Does poor kidney function affect my AL amyloidosis stage?
Yes, if your kidneys are not working well, they may struggle to clear proteins from your blood properly. This can cause your NT-proBNP levels to appear artificially high, even if your heart is not experiencing additional stress or failure.
Does a high AL amyloidosis stage mean I have a poor prognosis?
Not necessarily. Modern treatments like Daratumumab-based regimens are highly effective at clearing toxic proteins quickly. Because of these advances, a Stage III or IV diagnosis today has a significantly better outlook than it did when the staging systems were first created.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.What is my current stage according to the Mayo 2012 system?
  2. 2.What are my exact numbers for NT-proBNP, Troponin, and dFLC?
  3. 3.Does my kidney function (eGFR) affect how we should interpret my high NT-proBNP levels?
  4. 4.Given that I am starting on a Daratumumab-based regimen, how much weight should we put on my baseline staging for my long-term outlook?
  5. 5.Will we be re-evaluating these biomarkers after my first or second cycle of treatment to see if my stage is 'improving'?

Questions For You

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References

References (15)
  1. 1

    Natriuretic Peptides and Cardiac Troponins: Markers of Disease Progression and Risk in Light Chain Cardiac Amyloidosis.

    Wees I, Hendren NS, Kaur G, et al.

    Current heart failure reports 2023; (20(5)):350-357 doi:10.1007/s11897-023-00616-y.

    PMID: 37428428
  2. 2

    Validation of the Boston University staging system in AL amyloidosis.

    Tomlinson R, Matigian N, Mollee P

    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2019; (26(3)):125-127 doi:10.1080/13506129.2019.1608941.

    PMID: 31145007
  3. 3

    Development and validation of a survival staging system incorporating BNP in patients with light chain amyloidosis.

    Lilleness B, Ruberg FL, Mussinelli R, et al.

    Blood 2019; (133(3)):215-223 doi:10.1182/blood-2018-06-858951.

    PMID: 30333122
  4. 4

    Amyloid Light Chain Proteins in Cardiovascular Disease: Pathogenesis and Emerging Therapies for Cardiac Amyloidosis.

    Hu H, Wang Y, Xu M

    Pharmaceutical research 2025; doi:10.1007/s11095-025-03965-6.

    PMID: 41291170
  5. 5

    Cardiac biomarkers are prognostic in systemic light chain amyloidosis with no cardiac involvement by standard criteria.

    Sharpley FA, Fontana M, Martinez-Naharro A, et al.

    Haematologica 2020; (105(5)):1405-1413 doi:10.3324/haematol.2019.217695.

    PMID: 31399529
  6. 6

    Successes in translation.

    Westermark P, Merlini G

    Amyloid : the international journal of experimental and clinical investigation : the official journal of the International Society of Amyloidosis 2024; (31(3)):159-167 doi:10.1080/13506129.2024.2387163.

    PMID: 39101820
  7. 7

    Predictive value of free light chain burden in patients with AL amyloidosis treated with bortezomib-based regimens.

    Saunders B, Theodorakakou F, Fotiou D, et al.

    Blood advances 2025; (9(15)):3771-3779 doi:10.1182/bloodadvances.2024015528.

    PMID: 40305663
  8. 8

    [Light Chain Amyloidosis: an Update for Treatment].

    Shen KN, Li J

    Zhongguo shi yan xue ye xue za zhi 2015; (23(3)):910-4 doi:10.7534/j.issn.1009-2137.2015.03.059.

    PMID: 26117060
  9. 9

    Incremental Value of Global Longitudinal Strain for Predicting Survival in Patients With Advanced AL Amyloidosis.

    Lee Chuy K, Drill E, Yang JC, et al.

    JACC. CardioOncology 2020; (2(2)):223-231 doi:10.1016/j.jaccao.2020.05.012.

    PMID: 33117993
  10. 10

    Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis.

    Kastritis E, Palladini G, Minnema MC, et al.

    The New England journal of medicine 2021; (385(1)):46-58 doi:10.1056/NEJMoa2028631.

    PMID: 34192431
  11. 11

    Daratumumab in the Treatment of Light-Chain (AL) Amyloidosis.

    Palladini G, Milani P, Malavasi F, Merlini G

    Cells 2021; (10(3)) doi:10.3390/cells10030545.

    PMID: 33806310
  12. 12

    A Changing Landscape of Mortality for Systemic Light Chain Amyloidosis.

    Barrett CD, Dobos K, Liedtke M, et al.

    JACC. Heart failure 2019; (7(11)):958-966 doi:10.1016/j.jchf.2019.07.007.

    PMID: 31606365
  13. 13

    Biomarkers and Prediction of Prognosis in Transthyretin-Related Cardiac Amyloidosis: Direct Comparison of Two Staging Systems.

    Cappelli F, Martone R, Gabriele M, et al.

    The Canadian journal of cardiology 2020; (36(3)):424-431 doi:10.1016/j.cjca.2019.12.020.

    PMID: 32145869
  14. 14

    A simple staging system using biomarkers for wild-type transthyretin amyloid cardiomyopathy in Japan.

    Nakashima N, Takashio S, Morioka M, et al.

    ESC heart failure 2022; (9(3)):1731-1739 doi:10.1002/ehf2.13847.

    PMID: 35191205
  15. 15

    Organ responses with daratumumab therapy in previously treated AL amyloidosis.

    Chung A, Kaufman GP, Sidana S, et al.

    Blood advances 2020; (4(3)):458-466 doi:10.1182/bloodadvances.2019000776.

    PMID: 32027745

This page explains AL amyloidosis staging and Mayo scores for educational purposes only. Always consult your hematologist or cardiologist to interpret your specific biomarker results and prognosis.

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