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Multicenter study of banked third party virus-specific T-cells to treat severe viral infections after hematopoietic stem cell transplantation

Ann M. Leen, Catherine M. Bollard, Adam M. Mendizabal, Elizabeth J. Shpall, Paul Szabolcs, Joseph H. Antin, Neena Kapoor, Sung-Yun Pai, Scott D. Rowley, Partow Kebriaei, Bimalangshu R. Dey, Bambi J. Grilley, Adrian P. Gee, Malcolm K. Brenner, Cliona M. Rooney, Helen E. Heslop

Key points

  • Banked third-party virus-specific T-cells can safely and rapidly treat severe or intractable viral infections post-HSCT

Abstract

Virus-specific T-cell lines could provide useful antiviral prophylaxis and treatment for immune-deficient patients if it were possible to avoid the necessity of generating a separate line for each patient, often on an emergency basis. We prepared a bank of 32 virus-specific lines from individuals with common HLA polymorphisms who were immune to Epstein-Barr virus, cytomegalovirus or adenovirus. Eighteen lines were administered to 50 patients with severe, refractory illness due to infection with one of these viruses after hematopoietic stem cell transplant. The cumulative rates of complete or partial responses at 6 weeks post-infusion were: 74.0% (95% CI: 58.5%-89.5%) for the entire group (n=50), 73.9% (51.2-96.6%) for cytomegalovirus (n=23), 77.8% for adenovirus (n=18), and 66.7% (36.9-96.5%) for Epstein-Barr virus (n=9). Only four responders had a recurrence or progression. There were no immediate infusion-related adverse events, and only two subjects developed de-novo graft-versus-host disease. Despite the disparity between the lines and their recipients, the mean frequency of virus-specific T-cells rose significantly post-infusion, coincident with striking decreases in viral DNA and resolution of clinical symptoms. The use of banked third-party virus-specific T-cells is a feasible and safe approach to rapidly treat severe or intractable viral infections after stem cell transplantation. (www.clinicaltrials.gov - NCT00711035)

  • Submitted February 22, 2013.
  • Accepted April 10, 2013.