title: Treatment of CD33-directed chimeric antigen receptor-modified T cells in one patient with relapsed and refractory acute myeloid leukemia.
abstract: We conducted a clinical trial to assess the feasibility and efficacy of CD33-directed chimeric antigen receptor-modified T cells (CART-33) for the treatment of refractory acute myeloid leukemia (AML). A 41-year-old male patient with AML was enrolled and received a total of 1.12 × 10(9) autologous CART-33 cells, of which ~38% were transduced with CAR. The CART-33 infusion alone induced rigorous chills and fevers; drastic fluctuations of his preexisting pancytopenia; elevated serum cytokine levels, including interleukin (IL)-6, IL-8, tumor necrosis factor-α, and interferon-γ; slight transient hyperbilirubinemia within 2 weeks; a subsequent intermittent moderate fever; and reversed fluctuation of the pancytopenia. A marked decrease of blasts in the bone marrow was observed on examination 2 weeks after therapy, and there was a gradual increase until florid disease progression occurred at 9 weeks after the cell infusion. These observations warrant further research on CART-33 treatment in refractory AML and may spur efforts to extend the CART-33-induced tumor burden to the preparation of other intensive strategies, such as hematopoietic stem cell transplantation. This study is registered at www.ClinicalTrials.gov as NCT01864902.
authors.affiliation: Department of Hematology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors.forename: Quan-shun
authors.initials: QS
authors.lastname: Wang
authors.affiliation: Department of Immunology/Department of Bio-therapeutic, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors.forename: Yao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Immunology/Department of Bio-therapeutic, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors.forename: Hai-yan
authors.initials: HY
authors.lastname: Lv
authors.affiliation: Department of Immunology/Department of Bio-therapeutic, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors.forename: Qing-wang
authors.initials: QW
authors.lastname: Han
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Fan
authors.affiliation: Department of Geriatric Hematology, Chinese PLA General Hospital, Beijing, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Guo
authors.affiliation: Department of Hematology, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors.forename: Li-li
authors.initials: LL
authors.lastname: Wang
authors.affiliation: Department of Immunology/Department of Bio-therapeutic, Institute of Basic Medicine, School of Life Sciences, Chinese PLA General Hospital, Beijing, China.
authors.forename: Wei-dong
authors.initials: WD
authors.lastname: Han
mesh_terms: D019264:Adoptive Transfer; D000328:Adult; D016207:Cytokines / Q000096:biosynthesis; D015870:Gene Expression; D005822:Genetic Vectors; D018922:HL-60 Cells; D006801:Humans; D020014:K562 Cells; D015470:Leukemia, Myeloid, Acute / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D008297:Male; D050506:Mutant Chimeric Proteins / Q000235:genetics / Q000276:immunology*; D012008:Recurrence; D063268:Sialic Acid Binding Ig-like Lectin 3 / Q000235:genetics / Q000276:immunology*; D057127:Single-Chain Antibodies / Q000235:genetics; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology / Q000637:transplantation*; D014182:Transplantation, Autologous
chemical_list: C571163:CD33 protein, human; D016207:Cytokines; D050506:Mutant Chimeric Proteins; D063268:Sialic Acid Binding Ig-like Lectin 3; D057127:Single-Chain Antibodies