# Risk Factors and Outcome of HHV-6 Infections After Allogeneic Hematopoietic Cell Transplantation

## TL;DR

This study examines the risk factors and outcomes of HHV-6 infections in patients who received allogeneic hematopoietic cell transplants, finding that encephalitis from the virus is linked to higher mortality.

## Contribution

The study identifies specific risk factors and outcomes of clinically relevant HHV-6 infections after HCT, particularly the association with encephalitis and nonrelapse mortality.

## Key findings

- The cumulative incidence of clinically relevant HHV-6 infection was 3.7% by day 180 after transplantation.
- HHV-6 encephalitis was significantly associated with higher nonrelapse mortality (hazard ratio 3.821).
- Female sex, steroid use, and sirolimus use were identified as risk factors for HHV-6 infection.

## Abstract

Human herpesvirus 6 (HHV-6) reactivation is frequently seen in recipients of allogeneic hematopoietic cell (HCT) transplantation, but data on clinical outcomes and risk factors are scarce. We aimed to assess the epidemiological features and outcome of clinically relevant HHV-6 infections in the first 180 days after transplantation.

This was a single-center retrospective study of 405 consecutive allogeneic HCT recipients. We matched cases with a clinically relevant HHV-6 infection with control patients.

We found an cumulative incidence of 3.7% (95% confidence interval [CI], 1.9-5.5) and an overall incidence rate of 8.84 per 100 person-years (95% CI, 4.95-14.6) of clinically relevant HHV-6 infections during the study period. Adjusting for HCT-specific comorbidity index category, conditioning regimen, donor type, and acute graft-versus-host disease severity, the occurrence of HHV-6 encephalitis was significantly associated with a higher hazard of nonrelapse mortality (hazard ratio, 3.821; 95% CI, 1.437-10.155; P = .007). We observed a significantly higher mortality risk for cases compared to controls (P = .04) and found female sex (P = .017) and use of steroids (P = .023) or sirolimus (P = .006) as risk factors for HHV-6 infection. All cases had lymphopenia (<500/µL) at the day of diagnosis and 80% developed acute graft-versus-host disease around the HHV-6 infection.

HHV-6 encephalitis remains the most detrimental disease manifestation and posttransplant factors related to immune suppression are to be included in future epidemiological studies.

The estimated cumulative incidence of clinically relevant HHV-6 infection at day 180 after allogeneic hematopoietic cell transplantation was 3.7%. HHV-6 encephalitis was associated with a higher hazard of nonrelapse mortality.