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

Abstract

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.

Keywords: Hematopoietic cell transplantation; Human herpesvirus 6; Immunocompromised; Inherited chromosomally integrated human herpesvirus 6.