Despite the progress achieved regarding survival rates in childhood B-acute lymphoblastic leukemia, relapsed and/or refractory disease still poses a therapeutic challenge. Inotuzumab ozogamicin is a CD22-directed monoclonal antibody conjugated to calicheamicin, which has been approved for adults with CD22+ refractory/relapsed B lineage acute lymphoblastic leukemia and has already demonstrated promising results in the pediatric setting. The Food and Drug Administration approved inotuzumab ozogamicin (Besponsa, Pfizer) for pediatric patients 1 year and older with relapsed or refractory CD22-positive B-cell precursor acute lymphoblastic leukemia. Herein, we present the case of a 23-month-old girl with high-risk B-acute lymphoblastic leukemia, who experienced very early isolated medullary relapse and invasive pulmonary aspergillosis. She was finally successfully transplanted upon achieving remission and minimal residual disease negativity with two cycles of inotuzumab ozogamicin after failure of three lines salvage treatment with conventional chemotherapy, blinatumomab and bortezomid.