Blinatumomab-induced lineage switch of B-ALL with t(4:11)(q21;q23) KMT2A/AFF1 into an aggressive AML: pre- and post-switch phenotypic, cytogenetic and molecular analysis

Lineage switch is a rare phenomenon in which acute leukemia transforms from lymphoid to myeloid lineage, or vice versa. It is typically seen following therapy or at the time of relapse. Among the chromosomal aberrations associated with lineage switch, the t(4;11)(q21;q23) rearrangement with KMT2A/AFF1 fusion protein (formerly, MLL/AFF1 or MLL/AF4) is the most common. In general, lineage switch disease is often refractory to therapy and portends a poor prognosis. Blinatumomab is a monoclonal antibody with bispecificity for both CD19 on B cells and CD3 on cytotoxic T cells. Following simultaneous binding to both epitopes, normal and neoplastic B cells are lysed by the host cytotoxic T cells. Recent reports have documented lineage switch of acute leukemias following CD19targeted therapy; however, the underlying mechanism and management of these events are unclear. Herein, we present a case of refractory B lymphoblastic leukemia (B-ALL) with t(4:11) (q21;q23) KMT2A/AFF1 transforming to acute myeloid leukemia (AML) shortly following blinatumomab therapy. We studied both molecular and cytogenetic abnormalities at the initial diagnosis of B-ALL and at the time of lineage switch, thereby providing insights into the underlying biology.