Therapeutics of acute myeloid leukemia with central nervous system involvement

<i>FLT3</i>-mutated acute myeloid leukemia (AML) with central nervous system (CNS) involvement poses therapeutic challenges. We describe two cases and performed a systematic review evaluating the efficacy of therapeutic strategies in CNS involvement for both <i>FLT3</i>-mutated and wild-type (WT) AML. A MEDLINE, EMBASE, and Cochrane literature search identified relevant studies. Although CNS involvement in AML is associated with poor prognosis, routine CNS prophylaxis is not standard. Due to the uncertainty regarding the effect of intermediate doses of cytarabine on CNS involvement, we support a diagnostic lumbar puncture (LP) after achieving complete remission in patients with risk factors for CNS infiltration. Consolidation management should be modified depending on the result of the LP. The impact of total body irradiation (TBI) as a conditioning regimen in allogeneic stem cell transplantation on CNS AML outcomes remains ambiguous. Routine craniospinal irradiation is not recommended due to its associated higher morbidity rates, while cranial radiotherapy is preferred, particularly when combined with TBI. Fortunately, currently we can employ a FLT3 inhibitor with CNS penetrance in <i>FLT3</i>-mutated (either gilteritinib or sorafenib) or <i>FLT3</i>-WT (sorafenib) AML patients.