331MO - Comparing data distribution and prognosis of acute myeloid leukemia according to 5th WHO classification and international consensus

Background

Recently, the diagnostic criteria for acute myeloid leukemia (AML) has been revised with the publication of the 5^th WHO classification (WHO 2022) and the International Consensus classification (ICC). We investigated the difference in distribution and outcomes of the two guidelines. Also, we aimed to compare the outcome of AML and the gene profile of AML-MR (myelodysplasia-related) and AML defined by differentiation (AML-Diff).

Methods

Chromosome banding and molecular analysis using NGS panel covering 67 genes were performed. Recurrent gene fusions were analyzed by multiplex reverse transcriptase PCR. We classified 861 initial AML patients according to WHO 2022 and ICC. Prognostic value of two classifications was analyzed by overall survival curves.

Results

In WHO 2022, 4.4% were AML with KMT2A rearrangement. ICC divided them into t(9;11) and other rearrangements. Prognosis of ICC subgroups showed no significant difference (p=0.9403). AML-MR patients with MDS or MDS/MPN history had shorter survival (p=0.0161). Among ICC subgroups, 'AML with mutated TP53' had the poorest prognosis (median OS: 3.0 months [95% CI: 2.0-6.0]). In AML-MR according to the WHO 2022, patients had worse survival than AML-Diff, supporting the removal of morphology as a diagnostic criterion (p<0.0001). AML-MR had cytogenetic abnormalities in 127/243 patients (complex karyotype being common) and mutations in 222/243 (ASXL1 and RUNX1 frequently mutated). AML-Diff had cytogenetic abnormalities in 53/142 (trisomy 8, del(20q), -Y common) and mutations in 124/142 (DNMT3A and DDX41 frequently mutated).

Conclusions

Both WHO 2022 and ICC classify AML based on genetic abnormalities, with similarities and differences. Notably, discrepancies are observed in KMT2A rearrangement and MR groups. Further research is needed to validate the prognostic value of both classifications.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

Seoul St. Mary’s Hospital, The Catholic University of Korea.

Disclosure

All authors have declared no conflicts of interest.