CD19-negative relapse with an apparent cytogenetic shift after blinatumomab-induced measurable residual disease clearance in Philadelphia chromosome-negative B-cell acute lymphoblastic leukemia

Blinatumomab, a CD3/CD19 bispecific T-cell engager, improves outcomes in adult B-cell acute lymphoblastic leukemia (B-ALL), but CD19-negative relapse is an important mode of treatment failure. We report a 69-year-old woman with Philadelphia chromosome-negative B-ALL who achieved hematological complete remission after hyper-CVAD induction therapy but remained measurable residual disease (MRD)-positive. Blinatumomab was administered after one cycle of high-dose methotrexate/cytarabine, resulting in MRD negativity after one cycle. However, blinatumomab was discontinued after one cycle at the patient’s request, and hematological relapse occurred three months after MRD conversion. Relapsed blasts showed selective loss of CD19 expression, whereas cytoplasmic CD22 expression was retained. G-banding showed an apparent cytogenetic shift from a diagnostic hyperdiploid abnormal karyotype to a normal karyotype at first relapse. Inotuzumab ozogamicin induced a second hematological remission with MRD negativity, although disease control was not durable. This case highlights the importance of repeat immunophenotypic and cytogenetic assessment at relapse after blinatumomab treatment.