title: Acquisition of a CD19-negative myeloid phenotype allows immune escape of MLL-rearranged B-ALL from CD19 CAR-T-cell therapy.
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.
authors.affiliation: Seattle Children's Research Institute, Department of Pediatrics, and.
authors.forename: Rebecca
authors.initials: R
authors.lastname: Gardner
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA;
authors.forename: David
authors.initials: D
authors.lastname: Wu
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA;
authors.forename: Sindhu
authors.initials: S
authors.lastname: Cherian
authors.affiliation: Department of Laboratory Medicine, University of Washington, Seattle, WA;
authors.forename: Min
authors.initials: M
authors.lastname: Fang
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and.
authors.forename: Laïla-Aïcha
authors.initials: LA
authors.lastname: Hanafi
authors.affiliation: Seattle Children's Research Institute.
authors.forename: Olivia
authors.initials: O
authors.lastname: Finney
authors.affiliation: Seattle Children's Research Institute.
authors.forename: Hannah
authors.initials: H
authors.lastname: Smithers
authors.affiliation: Seattle Children's Research Institute, Department of Pediatrics, and.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Jensen
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Stanley R
authors.initials: SR
authors.lastname: Riddell
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle, WA.
authors.forename: David G
authors.initials: DG
authors.lastname: Maloney
authors.affiliation: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA; and Department of Medicine, University of Washington, Seattle, WA.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Turtle
mesh_terms: D018941:Antigens, CD19 / Q000235:genetics* / Q000276:immunology; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000627:therapeutic use; D001853:Bone Marrow / Q000473:pathology; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics; D002999:Clone Cells; D003131:Combined Modality Therapy; D005260:Female; D011495:Histone-Lysine N-Methyltransferase / Q000235:genetics*; D006801:Humans; D016130:Immunophenotyping; D016219:Immunotherapy, Adoptive; D007223:Infant; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology; D008212:Lymphocyte Depletion; D008875:Middle Aged; D051788:Myeloid-Lymphoid Leukemia Protein / Q000235:genetics*; D014411:Neoplastic Stem Cells; D015514:Oncogene Proteins, Fusion / Q000235:genetics*; D015452:Precursor B-Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D011948:Receptors, Antigen, T-Cell / Q000276:immunology*; D012008:Recurrence; D012074:Remission Induction; D016879:Salvage Therapy; D016176:T-Lymphocyte Subsets / Q000276:immunology*; D014178:Translocation, Genetic; D019139:Tumor Escape
chemical_list: D018941:Antigens, CD19; C000604811:CD19 molecule, human; C000605956:CD19-specific chimeric antigen receptor; C497422:KMT2A protein, human; D015514:Oncogene Proteins, Fusion; D011948:Receptors, Antigen, T-Cell; D051788:Myeloid-Lymphoid Leukemia Protein; D011495:Histone-Lysine N-Methyltransferase