Title

Scheduled Administration of Virus-Specific T cells for Viral Prophylaxis After Pediatric Allogeneic Stem Cell Transplant

Authors

Jeremy D. Rubinstein, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Carolyn Lutzko, Cincinnati Children's Hospital, Cincinnati, Ohio, United States.
Thomas Leemhuis, Hoxworth Blood Center; University of Cincinnati, Cincinnati, Ohio, United States.
Xiang Zhu, Cincinnati Children's Hospital, Cincinnati, Ohio, United States.
Giang Pham, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Lorraine M. Ray, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Shawn Thomas, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Celeste Dourson, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Jamie Wilhelm, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Adam Lane, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Jose A. Cancelas, Hoxworth Blood Center, Cincinnati, Ohio, United States.
Dakota Lipps, Cincinnati Children's Hospital, Cincinnati, Ohio, United States.
Justin Ferrell, Cincinnati Childrens Hospital Medical Center, Cincinnati, Ohio, United States.
Patrick J. Hanley, The George Washington University, United States.
Michael D. Keller, Childrens National Medical Center, Washington, District of Columbia, United States.
Catherine M. Bollard, The George Washington University, United States.
YunZu M. Wang, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Stella M. Davies, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Adam S. Nelson, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.
Michael Grimley, Cincinnati Children's Hospital Medical Center, Cincinnati, Ohio, United States.

Document Type

Journal Article

Publication Date

2-2-2022

Journal

Blood advances

DOI

10.1182/bloodadvances.2021006309

Abstract

Infections with double stranded DNA viruses are a significant cause of morbidity and mortality in pediatric patients following allogeneic hematopoietic stem cell transplantation (HSCT). Virus specific T-cell therapy (VSTs) have been shown to be effective treatment for infections with adenovirus, BK virus, cytomegalovirus (CMV), and Epstein-Barr virus (EBV). To date, prophylactic regimens to prevent or mitigate these infections using conventional anti-viral medications provide suboptimal response rates. Here we report on a clinical trial (NCT03883906) performed to assess the feasibility of rapid manufacturing and early infusion of quadrivalent VSTs generated from stem cell donors ("donor derived VSTs") into allogeneic HSCT recipients with minimal or absent viremia. Patients were eligible to receive scheduled VSTs as early as twenty-one days after stem cell infusion. Twenty-three patients received scheduled VSTs. 20/23 had no viremia at the time of infusion while three patients had very low-level BK viremia. Two developed clinically significant graft-versus-host disease, although this incidence was not outside of expected incidence early after HSCT and both were successfully treated with systemic corticosteroids (n=2). Five patients were deemed treatment failures. Three developed subsequent significant viremia/viral disease (n=3). Eighteen patients did not fail treatment, seven of whom did not develop any viremia while 11 developed low-level, self-limited viremia that resolved without further intervention. No infusion reactions occurred. In conclusion, scheduled VSTs appear to be safe and potentially effective at limiting serious complications from viral infections after allogeneic transplantation. A randomized study comparing this scheduled approach to the use of VSTs to treat active viremia is ongoing.

Department

Pediatrics

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