A 14-year-old male with SDS presented with fever, pancytopenia, and peripheral blasts. Bone marrow biopsy confirmed a diagnosis of AML with 17% blasts, normal cytogenetics, and FISH. Targeted DNA panel sequencing revealed a somatic pathogenic mutation in IDH1 and a partial tandem duplication of KMT2A. Bone marrow examination showed a CR by morphology and negative MRD by flow cytometry after one cycle of venetoclax and decitabine. His first cycle was complicated by several episodes of febrile neutropenia and one episode of Rothia mucilaginosa bacteremia. He received a second cycle of venetoclax and decitabine and maintained his negative MRD status prior to receiving a matched unrelated donor HSCT. The patient has remained disease-free after 52 months of follow-up.