Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy.

Publication Type:

Journal Article


Blood, Volume 127, Issue 20, p.2406-2410 (2016)


Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treat patients with relapsed and refractory CD19(+) B cell malignancies. We treated 7 patients with B-cell acute lymphoblastic leukemia (B-ALL) harboring rearrangement of the mixed lineage leukemia (MLL) gene with CD19 CAR-T cells. All patients achieved complete remission in the bone marrow by flow cytometry after CD19 CAR-T cell therapy; however, within one month of CAR-T cell infusion two of the patients developed acute myeloid leukemia that was clonally related to their B-ALL, a novel mechanism of CD19-negative immune escape. These reports have implications for the management of patients with relapsed and refractory MLL-B-ALL who receive CD19 CAR-T cell therapy.