Scheduled Administration of Virus-Specific T cells for Viral Prophylaxis After Pediatric Allogeneic Stem Cell Transplant
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.
APA Citation
Rubinstein, Jeremy D.; Lutzko, Carolyn; Leemhuis, Thomas; Zhu, Xiang; Pham, Giang; Ray, Lorraine M.; Thomas, Shawn; Dourson, Celeste; Wilhelm, Jamie; Lane, Adam; Cancelas, Jose A.; Lipps, Dakota; Ferrell, Justin; Hanley, Patrick J.; Keller, Michael D.; Bollard, Catherine M.; Wang, YunZu M.; Davies, Stella M.; Nelson, Adam S.; and Grimley, Michael, "Scheduled Administration of Virus-Specific T cells for Viral Prophylaxis After Pediatric Allogeneic Stem Cell Transplant" (2022). GW Authored Works. Paper 331.
https://hsrc.himmelfarb.gwu.edu/gwhpubs/331
Department
Pediatrics