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

被引：94

作者：

Naik, Swati ^{[1
,2
]}

Nicholas, Sarah K. ^{[3
]}

Martinez, Caridad A. ^{[1
,2
]}

Leen, Ann M. ^{[1
]}

Hanley, Patrick J. ^{[4
,5
]}

Gottschalk, Steven M. ^{[2
]}

Rooney, Cliona M. ^{[1
]}

Hanson, I. Celine ^{[3
]}

Krance, Robert A. ^{[2
]}

Shpall, Elizabeth J. ^{[17
]}

Cruz, Conrad R. ^{[6
]}

Amrolia, Persis ^{[7
]}

Lucchini, Giovanna ^{[7
]}

Bunin, Nancy ^{[8
]}

Heimall, Jennifer ^{[9
]}

Klein, Orly R. ^{[10
]}

Gennery, Andrew R. ^{[11
]}

Slatter, Mary A. ^{[11
]}

Vickers, Mark A. ^{[12
,13
]}

Orange, Jordan S. ^{[3
,14
,15
]}

Heslop, Helen E. ^{[1
,2
]}

Bollard, Catherine M. ^{[4
,5
]}

Keller, Michael D. ^{[4
,16
]}

机构：

[1] Texas Childrens Hosp, Baylor Coll Med, Ctr Cell & Gene Therapy, Houston Methodist Hosp, Houston, TX 77030 USA

[2] Texas Childrens Hosp, Baylor Coll Med, Texas Childrens Canc Ctr, Houston, TX 77030 USA

[3] Baylor Coll Med, Sect Immunol Allergy & Rheumatol, Dept Pediat, Houston, TX 77030 USA

[4] Childrens Natl Med Ctr, Ctr Canc & Immunol Res, Washington, DC 20010 USA

[5] Childrens Natl Med Ctr, Div Blood & Marrow Transplantat, Washington, DC 20010 USA

[6] Childrens Natl Med Ctr, Sheikh Zayed Inst, Washington, DC 20010 USA

[7] Great Ormond St Hosp Sick Children, Bone Marrow Transplantat Dept, London, England

[8] Childrens Hosp Philadelphia, Div Oncol, Philadelphia, PA 19104 USA

[9] Childrens Hosp Philadelphia, Div Allergy& Immunol, Philadelphia, PA 19104 USA

[10] Johns Hopkins Univ, Sch Med, Dept Oncol, Div Pediat Hematol Oncol, Baltimore, MD 21205 USA

[11] Newcastle Univ, Inst Cellular Med, Newcastle Upon Tyne NE1 7RU, Tyne & Wear, England

[12] Scottish Natl Blood Transfus Serv, Glasgow, Lanark, Scotland

[13] Univ Aberdeen, Aberdeen AB9 1FX, Scotland

[14] Baylor Coll Med, Ctr Human Immunobiol, Houston, TX 77030 USA

[15] Texas Childrens Hosp, Houston, TX 77030 USA

[16] Childrens Natl Med Ctr, Div Allergy & Immunol, Washington, DC 20010 USA

[17] Univ Texas MD Anderson Canc Ctr, Dept Stem Cell Transplantat, Div Canc Med, Houston, TX 77030 USA

来源：

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY | 2016年 / 137卷 / 05期

基金：

美国国家卫生研究院;

关键词：

Primary immunodeficiency; immunotherapy; cytotoxic T lymphocytes; antiviral therapy; STEM-CELL TRANSPLANTATION; LYMPHOPROLIFERATIVE DISEASE; CORD BLOOD; VIRAL-INFECTIONS; EBV; CMV; MULTICENTER; ADENOVIRUS; THERAPIES; LYMPHOMA;

D O I：

10.1016/j.jaci.2015.12.1311

中图分类号：

R392 [医学免疫学];

学科分类号：

100102 ;

摘要：

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.

引用

页码：1498 / +

页数：9

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