title: Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.
abstract: Viral infections are a leading fatal complication for patients with primary immunodeficiencies (PIDs) who require hematopoietic stem cell transplantation (HSCT). Use of virus-specific T lymphocytes (VSTs) has been successful for the treatment and prevention of viral infections after HSCT for malignant and nonmalignant conditions. Here we describe the clinical use of VSTs in patients with PIDs at 4 centers.
  
  
  
  We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.
  
  
  
  Patients with PIDs who have received VST therapy on previous or current protocols were reviewed in aggregate. Clinical information, including transplantation details, viral infections, and use of antiviral and immunosuppressive pharmacotherapy, were evaluated. Data regarding VST production, infusions, and adverse reactions were compared.
  
  
  
  Thirty-six patients with 12 classes of PID diagnoses received 37 VST products before or after HSCT. Twenty-six (72%) patients had received a diagnosis of infection with cytomegalovirus, EBV, adenovirus, BK virus, and/or human herpesvirus 6. Two patients were treated before HSCT because of EBV-associated lymphoproliferative disease. Partial or complete responses against targeted viruses occurred in 81% of patients overall. Time to response varied from 2 weeks to 3 months (median, 28 days). Overall survival at 6 months after therapy was 80%. Four patients had graft-versus-host disease in the 45 days after VST infusion, which in most cases was therapy responsive.
  
  
  
  VSTs derived from either stem cell donors or third-party donors are likely safe and effective for the treatment of viral infections in patients with PIDs.
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Tex; Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
authors.forename: Swati
authors.initials: S
authors.lastname: Naik
authors.affiliation: Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
authors.forename: Sarah K
authors.initials: SK
authors.lastname: Nicholas
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Tex; Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
authors.forename: Caridad A
authors.initials: CA
authors.lastname: Martinez
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Tex.
authors.forename: Ann M
authors.initials: AM
authors.lastname: Leen
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC; Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC.
authors.forename: Patrick J
authors.initials: PJ
authors.lastname: Hanley
authors.affiliation: Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
authors.forename: Steven M
authors.initials: SM
authors.lastname: Gottschalk
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Tex.
authors.forename: Cliona M
authors.initials: CM
authors.lastname: Rooney
authors.affiliation: Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, Tex.
authors.forename: I Celine
authors.initials: IC
authors.lastname: Hanson
authors.affiliation: Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Krance
authors.affiliation: Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Tex.
authors.forename: Elizabeth J
authors.initials: EJ
authors.lastname: Shpall
authors.affiliation: Sheikh Zayed Institute, Children's National Medical Center, Washington, DC.
authors.forename: Conrad R
authors.initials: CR
authors.lastname: Cruz
authors.affiliation: Bone Marrow Transplantation Department, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Persis
authors.initials: P
authors.lastname: Amrolia
authors.affiliation: Bone Marrow Transplantation Department, Great Ormond Street Hospital, London, United Kingdom.
authors.forename: Giovanna
authors.initials: G
authors.lastname: Lucchini
authors.affiliation: Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Nancy
authors.initials: N
authors.lastname: Bunin
authors.affiliation: Division of Allergy & Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa.
authors.forename: Jennifer
authors.initials: J
authors.lastname: Heimall
authors.affiliation: Department of Oncology, Division of Pediatric Hematology/Oncology, Johns Hopkins University School of Medicine, Baltimore, Md.
authors.forename: Orly R
authors.initials: OR
authors.lastname: Klein
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Andrew R
authors.initials: AR
authors.lastname: Gennery
authors.affiliation: Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
authors.forename: Mary A
authors.initials: MA
authors.lastname: Slatter
authors.affiliation: Scottish National Blood Transfusion Service, Aberdeen, United Kingdom; University of Aberdeen, Aberdeen, United Kingdom.
authors.forename: Mark A
authors.initials: MA
authors.lastname: Vickers
authors.affiliation: Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, Tex; Center for Human Immunobiology, Baylor College of Medicine and Texas Children's Hospital, Houston, Tex.
authors.forename: Jordan S
authors.initials: JS
authors.lastname: Orange
authors.affiliation: Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Tex; Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
authors.forename: Helen E
authors.initials: HE
authors.lastname: Heslop
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC; Division of Blood and Marrow Transplantation, Children's National Medical Center, Washington, DC.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Bollard
authors.affiliation: Center for Cancer and Immunology Research, Children's National Medical Center, Washington, DC; Division of Allergy and Immunology, Children's National Medical Center, Washington, DC. Electronic address: mkeller@cnmc.org.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Keller
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D006086:Graft vs Host Disease / Q000209:etiology / Q000821:virology; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007153:Immunologic Deficiency Syndromes / Q000628:therapy* / Q000821:virology; D016219:Immunotherapy, Adoptive; D007223:Infant; D013601:T-Lymphocytes / Q000637:transplantation*; D019562:Viral Load; D014777:Virus Diseases / Q000628:therapy* / Q000821:virology; D055815:Young Adult
keywords: Primary immunodeficiency; antiviral therapy; cytotoxic T lymphocytes; immunotherapy