Researchers Assess Effects of Updated Myeloid Neoplasm Classifications

The fifth edition of the World Health Organization classification (2022 WHO) and the International Consensus Classification (2022 ICC) of myeloid neoplasms may lead to the identification of different subtypes from once heterogenous diagnostic categories based on genetic characteristics.

That’s according to new research published in Annals of Laboratory Medicine. The study also found “changes in the blast thresholds for defining [acute myeloid leukemia] in some genetic abnormality categories were not associated with the major reclassified cases in the clinical setting.”

Researchers reviewed changes in the diagnosis distribution in patients with myelodysplastic syndrome with excess blasts (MDS-EB) or acute myeloid leukemia (AML) using both new classifications.

Several major changes regarding AML and MDS were included in the updated classifications. These included the following:

• Changes in the blast thresholds defining AML, including the expansion of the genetic abnormality categories that may be diagnosed as AML with a blast cut-off requirement of 10%
• Introduction of an AML classification subtype termed “rare recurring translocation”
• Extension of mutation-based definitions

To better understand how these changes affected patient classification, investigators reclassified 47 individuals whose previous diagnosis was AML or MDS-EB. All patients had available mutation analysis data that included targeted next-generation and RNA-sequencing data, the authors wrote. Patients were initially classified according to the 2016 WHO.

However, individuals with AML with 2016 WHO–designated recurring balanced translocations were excluded from the study.

“As the blast percentage defining MDS-EB and AML has been lowered and various genetic alterations have been introduced in both classifications, we reviewed the changes in the diagnosis distribution of patients with MDS-EB and AML using both the 2022 WHO and 2022 ICC. In addition, we focused on a newly introduced classification category, including TP53 mutation,” the authors said.

A total of 15 (31.9%) and 27 (57.4%) patients were reclassified based on the 2022 WHO and 2022 ICC classifications, respectively. One patient was reclassified “as having a translocation categorized as a rare recurring translocation in both classifications.”

Reclassifications were typically based on the addition of mutation-based diagnostic criteria or a new entity associated with TP53 mutation, the researchers said. Furthermore, for both classifications, a diagnosis of MDS required confirmation of multihit TP53 alterations.

Analyses revealed:

• Among 14 patients with TP53 mutations, 11 harbored multihit TP53 alterations, including 4 with TP53 mutations and loss of heterozygosity
• Adverse prognosis was associated with multihit TP53 alterations (P = .009) in patients with MDS-EB, emphasizing the importance of detecting the mutations at diagnosis

Among the 37 patients who had AML, AML with recurrent genetic abnormalities made up 45.9% of the cohort based on 2016 WHO guidelines. However, 32.4% (12/37) of patients with AML were classified as AML with defining genetic abnormalities based on the 2022 WHO and as AML with recurrent genetic abnormalities based on the 2022 ICC.

The new classifications enabled investigators to improve diagnostic capability of defining a highly adverse prognostic group, especially among those with MDS and multihit TP53 alterations, the researchers explained. Because detecting multihit TP53 alterations in the new diagnostic approaches is increasingly important, they noted the adaption of different molecular test methods may be necessary in clinical settings.

“In addition, although with borderline significance, we observed an adverse prognostic impact of TP53 mutations in patients with AML, suggesting that AML with mutated TP53 may be a distinct group with poor prognosis, consistent with the 2022 ICC,” they concluded.

Reference

Lee C, Kim HN, Kwon JA, at 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. Published online April 21, 2023. doi:10.3343/alm.2023.43.5.503