Viral Encephalitis after Hematopoietic Cell Transplantation: A Systematic Review

Danny Toomey; Tuan L Phan; Thommas Phan; Joshua A Hill; Danielle M Zerr

doi:10.1016/j.jtct.2023.06.022

Viral Encephalitis after Hematopoietic Cell Transplantation: A Systematic Review

Transplant Cell Ther. 2023 Oct;29(10):636.e1-636.e9. doi: 10.1016/j.jtct.2023.06.022. Epub 2023 Jul 6.

Authors

Danny Toomey¹, Tuan L Phan², Thommas Phan³, Joshua A Hill⁴, Danielle M Zerr⁵

Affiliations

¹ 1Day Sooner Research Team, Delaware; HHV-6 Foundation, Santa Barbara, California. Electronic address: dannytoomey1@gmail.com.
² HHV-6 Foundation, Santa Barbara, California; Department of Internal Medicine, The Ohio State University Wexner Medical Center, Columbus, Ohio.
³ Department of Statistics, University of California, Davis, California.
⁴ Department of Medicine, University of Washington, Seattle, Washington; Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center Seattle, Washington.
⁵ Department of Pediatrics, University of Washington, Seattle, Washington; Seattle Children's Hospital, Seattle, Washington.

PMID: 37422195
DOI: 10.1016/j.jtct.2023.06.022

Abstract

Viral encephalitis is a rare but serious complication after hematopoietic cell transplantation (HCT). The nonspecific early signs and symptoms and rapid progression can make it difficult to diagnose and treat in a timely fashion. To better inform clinical decision making in post-HCT viral encephalitis, a systematic review of prior studies of viral encephalitis was performed, with the goal of characterizing the frequency of various infectious etiologies and their clinical course, including treatments and outcomes. A systematic review of studies of viral encephalitis was performed. Studies were included if they described a cohort of HCT recipients who were tested for at least 1 pathogen. Of 1613 unique articles initially identified, 68 met the inclusion criteria, with a total of 72,423 patients studied. A total of 778 cases of encephalitis were reported (1.1%). Human herpesvirus 6 (HHV-6) (n = 596), Epstein-Barr virus (n = 76), and cytomegalovirus (n = 33) were the most commonly reported causes of encephalitis, and HHV-6 encephalitis tended to occur the earliest, accounting for most cases prior to day +100 post-transplantation. Of 29,671 patients with available transplantation data, encephalitis was diagnosed in 282 of 4707 (6.0%) cord blood transplantation (CBT) recipients, in 372 of 24,664 (1.5%) non-CBT allogeneic HCT recipients, and in 5 of 300 (1.7%) autologous HCT recipients. Of the 282 CBT encephalitis cases, 270 (95.7%) were caused by HHV-6. Overall, 288 (37.0%) of the 778 patients with encephalitis died, and 75 deaths were attributable to encephalitis, with the time between diagnosis and death ranging from 3 to 192 days. Viral encephalitis occurs in approximately 1% of HCT recipients, and HHV-6 is the most common cause. Mortality following encephalitis in HCT recipients is high, indicating an urgent need for advancement in preventive and therapeutic strategies.

Keywords: Hematopoietic cell transplantation; Systematic review; Viral encephalitis.