A 15-year-old with iAMP21-B-ALL presented with early medullary relapse during cycle 6 of maintenance therapy with bone marrow evaluation demonstrating 94% blasts by flow cytometry. She commenced re-induction with venetoclax in combination with vincristine, PEG-asparaginase, and dexamethasone. She experienced multiple infectious complications during treatment with this regimen, including recurrent and prolonged Enterococcus faecalis bacteremia, invasive Aspergillus pneumonia, and rim-enhancing brain lesions suspicious for bacterial brain abscesses, for which she was treated with a prolonged course of antibiotics. Bone marrow examination after one cycle showed a CR by morphology and MRD of 0.26% by flow cytometry. The patient achieved MRD negativity after receiving inotuzumab and subsequently underwent matched sibling HSCT.