Lineage Switch of Adult B-Cell Acute Lymphoblastic Leukaemia to Acute Myeloid Leukaemia Following B-Cell-Directed Therapy.

Background: Blinatumomab and inotuzumab ozogamicin (InO) are B-cell targeted agents used in the frontline and relapsed/refractory treatment of B-cell acute lymphoblastic leukaemia (B-ALL). Blinatumomab, a bispecific T-cell engager that targets CD19 and CD3, and InO, an antibody-drug conjugate targeting CD22, have both shown efficacy. However, recent reports have noted lineage conversion as a complication when these agents are used individually or sequentially. We present a rare case of this phenomenon in a 79-year-old male patient. Case description: A 79-year-old male with refractory B-ALL underwent a lineage switch to acute myeloid leukaemia following treatment with blinatumomab and InO. The patient initially achieved remission after initial therapy but relapsed and was subsequently treated with blinatumomab. Due to adverse effects, the treatment was discontinued. He was then treated with InO but again relapsed. A subsequent bone marrow biopsy revealed morphologic evidence of residual B-ALL, but with the presence of acute monocytic leukaemia. Fluorescence in situ hybridisation (FISH) analysis demonstrated an additional copy of KMT2A in a large percentage of cells which was a feature present since the initial diagnosis. Unfortunately, the patient's condition deteriorated, and he died. Conclusion: This case underscores potential complication of lineage switch following treatment with B-cell directed therapies. Although such therapies have improved outcomes in B-cell malignancies, clinicians should remain aware of rare risks such as lineage transformation. Timely recognition is essential to guide appropriate clinical management. LEARNING POINTS: Lineage switch is a rare complication observed after B-cell targeted therapies; however, evidence remains limited.Specific genetic alterations, such as KMT2A abnormalities, may predispose leukemic clones to lineage plasticity.Close monitoring for immunophenotypic evolution is essential for timely recognition and clinical management of lineage switch.