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J Allergy Clin Immunol. 2016 May;137(5):1498-1505.e1. doi: 10.1016/j.jaci.2015.12.1311. Epub 2016 Feb 24.

Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes.

Author information

1
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.
2
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.
3
Center for Cell and Gene Therapy, Baylor College of Medicine, Texas Children's Hospital, Houston Methodist Hospital, Houston, Tex.
4
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.
5
Texas Children's Cancer Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Tex.
6
Department of Pediatrics, Section of Immunology, Allergy, and Rheumatology, Baylor College of Medicine, Houston, Tex.
7
Department of Stem Cell Transplantation, Division of Cancer Medicine, The University of Texas MD Anderson Cancer Center, Houston, Tex.
8
Sheikh Zayed Institute, Children's National Medical Center, Washington, DC.
9
Bone Marrow Transplantation Department, Great Ormond Street Hospital, London, United Kingdom.
10
Division of Oncology, Children's Hospital of Philadelphia, Philadelphia, Pa.
11
Division of Allergy & Immunology, Children's Hospital of Philadelphia, Philadelphia, Pa.
12
Department of Oncology, Division of Pediatric Hematology/Oncology, Johns Hopkins University School of Medicine, Baltimore, Md.
13
Institute of Cellular Medicine, Newcastle University, Newcastle upon Tyne, United Kingdom.
14
Scottish National Blood Transfusion Service, Aberdeen, United Kingdom; University of Aberdeen, Aberdeen, United Kingdom.
15
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.

Abstract

BACKGROUND:

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.

OBJECTIVE:

We sought to evaluate the safety and efficacy of VSTs for treatment of viral infections in patients with PIDs.

METHODS:

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.

RESULTS:

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.

CONCLUSION:

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.

KEYWORDS:

Primary immunodeficiency; antiviral therapy; cytotoxic T lymphocytes; immunotherapy

PMID:
26920464
PMCID:
PMC4860050
DOI:
10.1016/j.jaci.2015.12.1311
[Indexed for MEDLINE]
Free PMC Article

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