Lab Med Online.  2021 Apr;11(2):115-123. 10.47429/lmo.2021.11.2.115.

Revised World Health Organization Criteria-Defined Acute Myeloid Leukemia in a Large Cohort: Highlighting the Frequency and Characterization of Recategorized Cases

• Kim S
• Lee MY
• Cho YU
• Hwang SH
• Jang S
• Seo EJ
• Park CJ

• KMID: 2525793
• DOI: http://doi.org/10.47429/lmo.2021.11.2.115

Abstract

Background
Application of the 2016 revised WHO criteria for categorization of acute myeloid leukemia (AML) highlights certain discrepancies from that of the 2008 WHO criteria. We thus analyzed the frequency, categorization patterns, and features of discrepant cases, and characterized the AML subtypes that had undergone major changes under the revised criteria.
Methods
We divided the patients into the following seven categories based on the previous and the revised WHO criteria: AML with recurrent genetic abnormalities (RGA), AML with myelodysplasia-related changes (MRC), therapy-related AML, AML not otherwise specified (NOS), AML associated with Down syndrome, AML with subcategory not determined, and myelodysplastic syndrome (MDS).
Results
In total, 1,185 AML cases were reviewed. The concordance rate in categorization between the two criteria was 93.4%. Among 78 discrepant cases, the three most common discrepancy patterns were for the RGA to NOS, MRC to MDS, and MRC to RGA, representing cases with a single mutation in CEBPA, erythroleukemia, and recurrent genetic abnormalities showing myelodysplasia, respectively. We identified three cases of erythroleukemia harboring an NPM1 mutation, who might clinically benefit from chemotherapy rather than MDS-oriented treatment; we also found AML with del(9q) in 3% of patients, which might contribute to leukemogenesis either via haploinsufficiency of deleted genes or gene-togene interaction.
Conclusions
This study revealed that approximately 7% of patients with AML were reclassified into a different category due to the introduction of new entities, changed definitions, and refined subcategorization. Therefore, further refinement should be considered during the next revision.

Keyword

Acute myeloid leukemia; WHO classification; Revised; Recategorization; Myelodysplastic syndrome

Figure

• 

  Fig. 1 Comparison of categorization based on the previous and revised WHO criteria. Categories based on the previous 2008 WHO criteria are shown on the left, and categories based on the revised 2016 WHO criteria are shown on the right. The gradient colors represent the diagnostic categories and the widths of the bands are proportional to the counts of cases in each category based on the previous and revised criteria. Abbreviations: RGA, AML with recurrent genetic abnormalities; MRC, AML with myelodysplasia-related changes; NOS, AML not otherwise specified; TR, therapy-related AML; ND, AML with subcategory not determined; DS, AML associated with Down syndrome.

• 

  Fig. 2 Pattern and frequency of categorization in AML patients with (A) NPM1 mutation, (B) CEBPAbi mutation, (C) del(9q), and (D) erythroleukemia. The black-brimmed pieces indicate a discrepancy and non-brimmed pieces indicate an agreement. There may be overlapping cases in each patient group. Abbreviations: RGA, AML with recurrent genetic abnormalities; MRC, AML with myelodysplasia-related changes; NOS, AML not otherwise specified; TR, therapy-related AML; ND, AML with subcategory not determined; CEBPAbi, biallelic CEBPA.

• 

  Fig. 3 Influence of MDS history on the outcomes of patients with AML harboring gene mutations identified in the MRC to RGA recategorization. Kaplan-Meier plots for overall survival according to the defining criteria for the MRC category using the 2008 WHO criteria, including multilineage dysplasia or del(9q) (N=9) and a prior history of MDS or MDS/MPN (N=6). Abbreviations: MRC, AML with myelodysplasia-related changes; RGA, AML with recurrent genetic abnormalities; MDS/MPN, myelodysplastic/myeloproliferative neoplasm.

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