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

Swati Naik, Sarah K Nicholas, Caridad A Martinez, Ann M Leen, Patrick J Hanley, Steven M Gottschalk, Cliona M Rooney, I Celine Hanson, Robert A Krance, Elizabeth J Shpall, Conrad R Cruz, Persis Amrolia, Giovanna Lucchini, Nancy Bunin, Jennifer Heimall, Orly R Klein, Andrew R Gennery, Mary A Slatter, Mark A Vickers, Jordan S OrangeHelen E Heslop, Catherine M Bollard, Michael D Keller

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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.

Original languageEnglish
Pages (from-to)1498-1505
Number of pages8
JournalJournal of Allergy and Clinical Immunology
Volume137
Issue number5
Early online date24 Feb 2016
DOIs
Publication statusPublished - May 2016

Keywords

  • primary immunodeficiency
  • immunotherapy
  • cytotoxic T lymphocytes
  • antiviral therapy

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    Naik, S., Nicholas, S. K., Martinez, C. A., Leen, A. M., Hanley, P. J., Gottschalk, S. M., Rooney, C. M., Hanson, I. C., Krance, R. A., Shpall, E. J., Cruz, C. R., Amrolia, P., Lucchini, G., Bunin, N., Heimall, J., Klein, O. R., Gennery, A. R., Slatter, M. A., Vickers, M. A., ... Keller, M. D. (2016). Adoptive immunotherapy for primary immunodeficiency disorders with virus-specific T lymphocytes. Journal of Allergy and Clinical Immunology, 137(5), 1498-1505. https://doi.org/10.1016/j.jaci.2015.12.1311