Myelodysplasia-Related Gene Mutation Burden Is Associated With Complete Remission After Induction Therapy in Acute Myeloid Leukemia, Not Otherwise Specified: Reclassification According to the Updated Classifications

초록

Introduction Updated classifications incorporating myelodysplasia-related (MR) gene mutations reclassify many cases previously diagnosed as acute myeloid leukemia, not otherwise specified (AML, NOS). We evaluated the clinical significance of MR gene mutation burden, defined by mutation number and variant allele frequency (VAF), in AML, NOS.Methods We retrospectively reviewed adults diagnosed with AML, NOS who underwent next-generation sequencing between 2018 and 2023. After excluding cases with KMT2A rearrangements or biallelic TP53 inactivation, 95 patients were included. Associations between MR gene mutation burden and complete remission (CR) failure were assessed using logistic regression; exploratory survival analyses were performed.Results MR gene mutations were identified in 57.9%-63.2% of patients. For CR analysis, 89 patients were evaluable after excluding five treated with FLT3 inhibitors and one lost to follow-up. The CR rate was lower in patients with MR gene mutations than in those without MR gene mutations (39.7% vs. 64.5%, p = 0.025). Patients with >= 2 MR gene mutations had the lowest CR rate (29.7%). An exploratory ROC-derived VAF cutoff of 28.6% predicted CR failure with modest discriminatory performance (AUC, 0.658). In multivariate analysis, the highest VAF among MR gene mutations was independently associated with CR failure (odds ratio, 1.022; p = 0.028). Exploratory survival analyses showed inferior outcomes in patients with high-VAF MR gene mutations.Conclusion A greater number of MR gene mutations and higher VAF were associated with inferior early treatment response in AML, NOS. MR gene mutation burden may provide additional prognostic information among patients reclassified as AML with MR gene mutations.

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