Association of Inherited Chromosomally Integrated Human Herpesvirus 6 with Neurologic Symptoms and Management after Allogeneic Hematopoietic Cell Transplantation

Reactivation of human herpesvirus 6 (HHV-6) after allogeneic hematopoietic cell transplantation (HCT) is associated with neurologic complications, but the impact of donor and/or recipient inherited chromosomally integrated HHV-6 (iciHHV-6) on post-HCT central nervous system (CNS) symptoms and diagnostic and therapeutic interventions is not well understood. The aims of the present study were (1) to compare the cumulative incidence of CNS symptoms in the first 100 days following allogeneic HCT among patients with donor and/or recipient iciHHV-6 (iciHHV-6(pos))with that of patients with neither donor nor recipient iciHHV-6 (iciHHV-6(neg)) and (2) to assess the role of HHV-6 detection in driving potentially unnecessary interventions in iciHHV-6(pos) patients. We performed a retrospective matched cohort study of 87 iciHHV-6(pos) and 174 iciHHV-6(neg) allogeneic HCT recipients. HHV-6 testing was performed at the discretion of healthcare providers, who were unaware of iciHHV-6 status. The cumulative incidence of CNS symptoms was similar in iciHHV-6(pos) (n = 37; 43%) and iciHHV-6(neg) HCT recipients (n = 81; 47%; P = .63). HHV-6 plasma testing was performed in similar proportions of iciHHV-6(pos) (n = 6; 7%) and iciHHV-6(neg) (9%) patients and was detected in all tested iciHHV-6(pos) HCTs and 2 (13%) iciHHV-6(neg) HCTs. This resulted in more frequent HHV-6-targeted antiviral therapy after iciHHV-6(pos) HCT (odds ratio, 12.8; 95% confidence interval, 1.5 to 108.2) with associated side effects. HHV-6 plasma detection in 2 iciHHV-6(pos) patients without active CNS symptoms prompted unnecessary lumbar punctures. The cumulative incidence of CNS symptoms was similar after allogeneic HCT involving recipients or donors with and without iciHHV-6. Misattribution of HHV-6 detection as infection after iciHHV-6(pos) HCT may lead to unnecessary interventions. Testing for iciHHV-6 may improve patient management. (C) 2021 The American Society for Transplantation and Cellular Therapy. Published by Elsevier Inc. All rights reserved.

Automated summary

This study aimed to compare the incidence of CNS symptoms after allogeneic HCT among patients with iciHHV-6(pos) and iciHHV-6(neg), and assess the impact of HHV-6 detection on unnecessary interventions. The cumulative incidence of CNS symptoms was similar between iciHHV-6(pos) and iciHHV-6(neg) HCT recipients, but HHV-6 detection in iciHHV-6(pos) patients led to more frequent antiviral therapy and unnecessary lumbar punctures. Testing for iciHHV-6 may improve patient management after allogeneic HCT.