-rearranged B-cell ALL with extramedullary lineage switch to AML following CD19-targeted therapy.

Lineage switch (LS) refers to the immunophenotypic transformation of one leukemia lineage to another (ie, lymphoid to myeloid) with retention of baseline genetics. This phenomenon was originally observed in infants with B-lymphoblastic leukemia (B-ALL) with rearrangements following chemotherapy, but is now increasingly being observed as a form of immune escape following targeted therapies among children and adults with B-ALL with and without rearrangements. In this report, we present two cases of adolescents with B-ALL harboring rearrangements (Philadelphia-like phenotype) who developed LS to acute myeloid leukemia following CD19 targeted therapy. To our knowledge, these are the first cases of LS to be reported in patients with rearranged acute lymphoblastic leukemia. In addition to raising awareness that this genetic mutation may associate with lineage plasticity, our cases illustrate the importance of multi-modal disease surveillance in the diagnosis of LS.