ETV6::FLT3 Fusion as an Unfavorable Prognostic Factor in an AYA Patient with B-ALL

FLT3 inhibition through targeted therapy of the ETV6-FLT3 fusion driver mutation led to MRD negativity in a refractory B-ALL AYA patient. B-cell acute lymphoblastic leukemia (B-ALL) is a genetically heterogeneous disease in which molecular characterization guides prognosis and treatment. We report the first known case of B-ALL in an adolescent and young adult patient harboring an ETV6::FLT3 fusion. A 20-year-old woman presented with hyperleukocytosis, central nervous system involvement, and extramedullary disease. Cytogenetic analysis revealed t(12;13)(p13;q12), prompting further molecular investigation that identified an in-frame ETV6::FLT3 fusion. The disease was refractory to induction and progressed during blinatumomab, achieving remission only after sorafenib-based therapy followed by allogeneic stem cell transplantation, and remains MRD-negative eleven months post-transplant.