Acute Myeloid Leukemia With <i>NPM1</i> Mutation Presenting With Rapidly Progressing Hypereosinophilia

Hypereosinophilia presents a significant clinical challenge. We describe a case of severe, rapidly progressing hypereosinophilia, with the white blood cell count increasing from 40,000/μL to over 130,000/μL within days, and 70% eosinophils on differential count. The patient initially presented with diffuse symptoms but developed eosinophilic myocarditis during hospitalization. Targeted next-generation sequencing identified a mutation in <i>NPM1</i> and according to the WHO 5^th edition criteria, the patient was diagnosed with acute myeloid leukemia (AML) with <i>NPM1</i> mutation. Whole genome and transcriptome sequencing revealed a concurrent fusion <i>ETV6</i>::<i>ACSL6</i>. This fusion has been previously described in myeloid diseases with eosinophilia. Despite initial deep response to AML treatment, reaching MRD-negativity for <i>NPM1</i>, the patient relapsed shortly after stem cell transplantation and died.