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Blood. 2016 May 19;127(20):2406-10. doi: 10.1182/blood-2015-08-665547. Epub 2016 Feb 23.

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

Author information

1
Seattle Children's Research Institute, Department of Pediatrics, and.
2
Department of Laboratory Medicine, University of Washington, Seattle, WA;
3
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
4
Seattle Children's Research Institute.
5
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle, WA.

Abstract

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.

TRIAL REGISTRATION:

ClinicalTrials.gov NCT02028455.

PMID:
26907630
PMCID:
PMC4874221
DOI:
10.1182/blood-2015-08-665547
[Indexed for MEDLINE]
Free PMC Article

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