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What is the impact of the 5th WHO classification and ICC of AML on diagnosis and treatment of high-risk AML?
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The AML Hub was pleased to speak with Gail Roboz, Weill Cornell Medicine, New York, US. We asked, What is the impact of the 5th World Health Organization (WHO) classification and International Consensus Classification (ICC) of AML on diagnosis and treatment of high-risk acute myeloid leukemia (HR AML)?
The impact of the 5th WHO classification and ICC of AML on diagnosis and treatment of HR AML
Listen to this interview as a podcast:
The impact of the 5th WHO classification and ICC of AML on diagnosis and treatment of HR AML
In this interview, Roboz walks through the changes in the classification criteria for AML over the last 50 years, highlighting the implications of these changes and the lack of consensus on the diagnosis and management strategies for patients. Roboz goes on to discuss both classification and prognostic risk stratification tools to aid in the development of management strategies, including in HR AML, and concludes by highlighting the importance of considering patient preferences and health when making clinical decisions.
Key points and learnings:
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In the 5th WHO classification, the diagnosis of AML typically requires ≥20% blasts in the bone marrow or peripheral blood. However, there are specific genetic abnormalities which can indicate AML regardless of the blast percentage.1
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As a result, challenges exist in determining treatment intensity in patients with lower blast counts.
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The 5th WHO and the ICC now distinguish AML from related myeloid neoplasms, such as myelodysplastic syndromes (MDS)/AML, and this has led to confusion among patients due to lack of definitive boundaries for disease diagnosis.
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The latest WHO classification places a stronger emphasis on genetic abnormalities, recognizing them as primary drivers in AML classification.
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AML with mutated TP53 is recognized as a distinct category in the ICC but not in the WHO classification.
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The former category of AML with myelodysplasia-related changes (AML-MRC) is replaced with AML myelodysplasia-related (AML-MR) in the WHO classification and separated into two categories in the ICC; AML with MR gene mutations and AML with MR cytogenetic abnormalities.
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Both classifications now include mutation-based diagnostic criteria, potentially broadening the number of patients included in this category compared with the previous classification.1
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There are, however, some differences, for instance mutations in RUNX1 fall under AML with MR gene mutations in the ICC, but are not diagnostically defining in the WHO classification.
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The ICC eliminates the previous standalone category of therapy-related AML and instead includes therapy-related as a diagnostic qualifier that can be applied to other AML subgroups.2
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The differences between the two classification systems have resulted in pathologists reporting both the ICC and WHO classifications for individual patients.
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The median age for patients with AML is 67 years,3 and many of these older patients are now treated with a non-intensive regimen of a hypomethylating agent plus venetoclax.
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Not all risk stratification tools can correctly stratify these patients, meaning that outcomes are not necessarily determined by AML biology, but depend substantially on what treatments are available.
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It is vital to consider the patient as an individual when determining classification and treatment.
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Overall health status and patient preferences are key in determining treatment in addition to pathology data.
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10 votes - 80 days left
This educational resource is independently supported by Jazz Pharmaceuticals. All content is developed by SES in collaboration with an expert steering committee; funders are allowed no influence on the content of this resource.
- Lee C, Kim H, Kwon J, et al. Implications of the 5th edition of the World Health Organization Classification and International Consensus Classification of myeloid neoplasm in myelodysplastic syndrome with excess blasts and acute myeloid leukemia. Ann Lab Med. 2023;43(5):503-507. DOI: 10.3343/alm.2023.43.5.503
- Attardi E, Savi A, Borsellino B, et al. Unraveling the impact of 2022 classifications on secondary acute myeloid leukemia: Assessing the true qualification power of diagnostic qualifiers. Blood. 2023;142(Supplement 1):819. DOI: 10.1182/blood-2023-185709
- Almeida A, Ramos F. Acute myeloid leukemia in the older adults. Leuk Res Rep. 2016;6:1-7. DOI: 10.1016/j.lrr.2016.06.001
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