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

Blood 2016 05 23;127(20):2406-10. Epub 2016 Feb 23.

Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle, WA.

Administration of lymphodepletion chemotherapy followed by CD19-specific chimeric antigen receptor (CAR)-modified T cells is a remarkably effective approach to treating 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 (CR) in the bone marrow by flow cytometry after CD19 CAR-T-cell therapy; however, within 1 month of CAR-T-cell infusion, 2 of the patients developed acute myeloid leukemia (AML) 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.

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http://dx.doi.org/10.1182/blood-2015-08-665547DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4874221PMC
May 2016
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Dorantes-Acosta et al.

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