Leslie N. Martinez-Gutierrez1, Blake C. Burgher2, Manuel J. Glynias2, Daniel Alvarado1, Elizabeth A. Griffiths1, Sean T. Glenn2 and Pamela J. Sung1,3 1Department of Medicine, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA; 2Department of Pathology, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA; 3Department of Pharmacology and Therapeutics, Roswell Park Comprehensive Cancer Center, Buffalo, New York 14203, USA Corresponding author: Pamela.Sungroswellpark.org

Acute myeloid leukemias (AMLs) frequently harbor activating mutations in Fms-like tyrosine kinase 3 (FLT3). 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 FLT3 polymerase chain reaction (PCR) positivity in peripheral blood. We sorted mature leukocytes by lineage to determine if the eosinophils were leukemia-derived. FLT3 PCR and next-generation sequencing analysis demonstrated monocytic differentiation of the FLT3–ITD leukemic clone with reactive hypereosinophilia that was derived from a preleukemic SF3B1, FLT3 wild-type clone. Our case is the first to definitively demonstrate the emergence of clonal FLT3–ITD monocytes with FLT3i and the first to demonstrate a differentiation response following decitabine, venetoclax, and gilteritinib triplet therapy.

Received February 1, 2023. Accepted June 5, 2023.