Diagnostic Precision or Pitfalls: How to Apply the New Acute Myeloid Leukemia Classification Systems?
Karen-Sue Carlson1, Ashley Cunningham2, Maximilian Stahl3
1Division of Hematology/Oncology, Department of Medicine, Medical College of Wisconsin, Milwaukee, Wisconsin, USA, kabarker@mcw.edu.
Insights
Two new classification systems for acute myeloid leukemia (AML), the World Health Organization (WHO) 5th edition and the International Consortium Classification (ICC), share similarities but have key differences impacting treatment and clinical trials.
Area of Science:
- Hematology
- Oncology
- Genetics
Background:
- The World Health Organization (WHO) classification has historically guided acute myeloid leukemia (AML) diagnosis and treatment.
- In 2022, two new parallel AML classification systems were published: the WHO 5th edition and the International Consortium Classification (ICC).
Purpose of the Study:
- To review and compare the organization, similarities, and differences between the WHO 5th edition and ICC AML classification systems.
- To highlight potential clinical challenges arising from discrepancies between the two systems.
Main Methods:
- Comparative analysis of the WHO 5th edition and ICC AML classification frameworks.
- Identification of key differences in classification criteria, including blast thresholds and modifier assignments.
Main Results:
- The WHO 5th edition and ICC systems demonstrate concordance for most AML cases.
- Significant differences exist in classification framework, AML-defining blast threshold, myelodysplasia-related AML definition, and therapy-related/germline-associated modifier assignment.
Conclusions:
- While largely concordant, the differences between the WHO 5th edition and ICC classifications may impact patient stratification, clinical trial eligibility, and treatment decisions.
- Understanding these distinctions is crucial for consistent application in clinical practice.
Background:
The classification of acute myeloid leukemia (AML) has long been overseen by the World Health Organization (WHO) and published into a series of "Blue Books." These ledgers serve as the reference manual for AML classification and, in turn, classification-based treatment decisions. In 2022, two separate groups, each of which included hematologic oncologists, hematopathologists, and geneticists - developed and published two parallel classification systems for AML. One is from the WHO (WHO 5th edition), and a second is from an International Advisory Consortium (International Consortium Classification [ICC]).
Summary:
Both modern classification systems originated from the revised 4th edition of the WHO Blue Books and thus share many similarities. There are never-the-less several important differences with the potential to substantially alter disease classification, access to clinical trials, and treatment decision-making. In this manuscript, we review the organization of the WHO and ICC classification systems for AML with emphasis on their similarities and differences, followed by areas in which their application to clinical scenarios may present difficulties.
Key Messages:
(1) The ICC and WHO 5th edition are concordant for the majority of AMLs. (2) Key differences between AML classification by the ICC and WHO 5th edition include (a) the overall framework of classification, (b) AML-defining blast threshold, definition of myelodysplasia-related AML, and (c) strategy for assigning therapy-related or germline-associated AML modifiers.
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