HHV-6 reactivation associated with longer hospital stays, more readmissions in Memorial Sloan Kettering Trial

HHV-6 reactivation has previously been associated with poor outcomes following hematopoietic stem cell transplantation (HCT/HSCT). Ex vivo T-cell depleted (TCD) HCT is an alternative to conventional HCT that carries a lower risk of graft versus host disease (GVHD), a condition associated with HHV-6 reactivation. In the first such study on this type of HCT, 156 adult TCD HCT patients at Memorial Sloan Kettering Cancer Center were prospectively monitored to determine the rates of double-stranded DNA (dsDNA) virus reactivation and associated outcomes.

Overall, 85% of patients developed at least one viremia, and 33% of the patients had 2 or more viremias by day +180. HHV-6 was the most commonly reactivated virus, with 61% of patients affected. Patients with HHV-6 viremia, CMV viremia, and 2 or more viremias experienced longer hospital stays and were readmitted more often. In a similar study on conventional HCT, investigators detected 2 or more dsDNA viruses in the plasma of 62% of patients (Hill 2017).

All patients were treated prophylactically with acyclovir against HSV and VZV, and treatment of HHV-6 reactivation was at the clinician’s discretion. Of the 93 patients with HHV-6 viremia, only 9 were treated with antivirals to target this event (foscarnet (8) or valganciclovir (1)). HHV-6 reactivation had a median time to onset of 33 days post-transplant and a median duration of 7 days. Notably, 56% of patients with HHV-6 were readmitted to the hospital, compared to 29% of those without dsDNA viremia.

Treatment of HHV-6 was the specific reason for readmission in just 4 of the 50 patients with single HHV-6 viremia. The remaining patients in this group were hospitalized because of fever (11), pulmonary symptoms (11), other infections (7), and other miscellaneous reasons (17). Although the majority of readmissions in the HHV-6-only group were not for HHV-6-specific treatment, it is possible that the virus could have contributed to the onset of these symptomatic manifestations, although this relationship was not specifically analyzed as part of the study.

Of the 33 patients in the cohort who died, dsDNA viruses were described as the cause of death in 21% (7) of cases. In addition, one of the two patients who died of sepsis was found to have HHV-6 viremia. Overall survival at one year was similar among patients with and without dsDNA viremias. Likewise, there was no significant difference in GVHD between patients with and without viremia. As predicted for this type of HCT, GVHD rates were remarkably low; only one patient was readmitted due to GVHD, and no patients had grade 3-4 GVHD. While overall survival rates and development of GVHD were not found to be significantly higher in those with viremia, the authors note that the reactivation of dsDNA viruses still raised several clinical concerns.

The authors note that their approach to pre-emptive screening and treatment for virus reactivation was more cost-effective than treating viral disease in the absence of routine monitoring. They also call for cost-benefit analysis of prophylactic virus-specific cytotoxic T lymphocyte (CTL/VST) administration compared to PCR monitoring in the treatment of HCT patients, as CTLs have been shown to be safe and effective.

Read the full paper here: Huang 2017.