Evaluation of hypereosinophilia in a case of FLT3 -mutant acute myeloid leukemia treated with gilteritinib

Acute myeloid leukemias (AMLs) frequently harbor activating mutations in ( ). The use of FLT3 inhibitors (FLT3i) is the standard of care for treatment of newly diagnosed and relapsed patients with AML. Differentiation responses including clinical differentiation syndrome have been previously reported with FLT3i when used as single agents in relapsed disease. We present a case of hypereosinophilia in a patient on FLT3i therapy with persistent polymerase chain reaction (PCR) positivity in peripheral blood. We sorted mature leukocytes by lineage to determine if the eosinophils were leukemia-derived. PCR and next-generation sequencing analysis demonstrated monocytic differentiation of the leukemic clone with reactive hypereosinophilia that was derived from a preleukemic , wild-type clone. Our case is the first to definitively demonstrate the emergence of clonal monocytes with FLT3i and the first to demonstrate a differentiation response following decitabine, venetoclax, and gilteritinib triplet therapy.