title: Graft versus leukemia response without graft-versus-host disease elicited by adoptively transferred multivirus-specific T-cells.
abstract: A 12-year-old boy with refractory acute lymphoblastic leukemia received a haploidentical transplant from his mother. As prophylaxis for Epstein-Barr virus (EBV), cytomegalovirus (CMV) and adenovirus, he received ex vivo expanded virus-specific donor T cells 3.5 months after transplant. Four weeks later leukemic blasts bearing the E2A deletion, identified by fluorescent in situ hybridization (FISH), appeared transiently in the blood followed by a FISH-negative hematological remission, which was sustained until a testicular relapse 3.5 months later. Clearance of the circulating leukemic cells coincided with a marked increase in circulating virus-specific T cells. The virus-specific cytotoxic T-cell (CTL) line showed strong polyfunctional reactivity with the patient's leukemic cells but not phytohemagglutinin (PHA) blasts, suggesting that virus-specific CTL lines may have clinically significant antileukemia activity.
authors.affiliation: 1] Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA [2] Translational Research Program, Perelman School of Medicine, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
authors.forename: Jan J
authors.initials: JJ
authors.lastname: Melenhorst
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Paul
authors.initials: P
authors.lastname: Castillo
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Sheikh Zayed Institute for Pediatric Surgical Innovation, and Center for Cancer and Immunology Research, Children's National Health System, Washington, District of Columbia, USA.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.affiliation: Program for Cell Enhancement and Technologies for Immunotherapy, Sheikh Zayed Institute for Pediatric Surgical Innovation, and Center for Cancer and Immunology Research, Children's National Health System, Washington, District of Columbia, USA.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Keller
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Judith
authors.initials: J
authors.lastname: Margolin
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.affiliation: Hematology Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland, USA.
authors.forename: A John
authors.initials: AJ
authors.lastname: Barrett
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA.
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.affiliation: 1] Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital and Houston Methodist Hospital, Houston, Texas, USA [2] Program for Cell Enhancement and Technologies for Immunotherapy, Sheikh Zayed Institute for Pediatric Surgical Innovation, and Center for Cancer and Immunology Research, Children's National Health System, Washington, District of Columbia, USA.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
mesh_terms: D000256:Adenoviridae / Q000276:immunology; D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics / Q000276:immunology; D016026:Bone Marrow Transplantation; D002648:Child; D003587:Cytomegalovirus / Q000276:immunology; D017353:Gene Deletion; D015870:Gene Expression; D020544:Graft vs Leukemia Effect; D006239:Haplotypes; D004854:Herpesvirus 4, Human / Q000276:immunology; D006801:Humans; D016219:Immunotherapy, Adoptive; D008297:Male; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013602:T-Lymphocytes, Cytotoxic / Q000166:cytology / Q000276:immunology / Q000637:transplantation*; D014184:Transplantation, Homologous
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; C407909:TCF3 protein, human