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Objective: Extramedullary relapse (EMR) is rare in acute promyelocytic leukemia (APL) and, there is a lack of information on its management. Current practices for EMR in APL are always to adopt strategies from other subtypes of Acute lymphoblastic leukemia (ALL) and Acute myeloid leukemia (AML). Gilteritinib, a highly selective FLT3 inhibitor, has demonstrated a remarkable effect on EMR in FLT3-mutant AML. Therefore, it is worthwhile exploring if FLT3 mutation can be a therapeutic target and assessing the efficacy of Gilteritinib on FLT3-mutant EMR in APL.Methods: We described three cases of FLT3-mutant EMR in APL, comprising two isolated EMR cases and one systemic relapse. The patients underwent treatment with Gilteritinib-based regimens based on FLT3 mutation.Results: All three patients achieved complete regression of EMR, and no signs of tumor lysis syndrome during Gilteritinib-based therapy, only patient 1 showed mild granulocytopenia. They all maintained molecular complete remission (mCR) during the follow-up period.Conclusions: The Gilteritinib-based regimen shows a high and sustained therapeutic effect with minimal adverse effects, and provides a valuable experience for further evaluation in EMR APL patients.