HHV-6 DNA in the CSF results in poor survival for HSCT patients

Over a period of 14 years, a group at the University of Washington (UW) and Fred Hutchinson Cancer Research Center tested 124 patients for HHV-6 DNA in the cerebrospinal fluid (CSF) and found 51 (41%) positive. Of the 51 HHV-6 positive CSF samples, 37 were positive for HHV-6 alone, while 14 were from patients with an additional diagnosis of a co-infection (5) or drug toxicity (3) or had transient symptoms (6).

Should physicians automatically discount HHV-6 if any other pathogen is found in the CSF? Should patients with both HHV-6 and EBV DNA in the CSF be treated only for EBV? Should a patient with disseminated fungal infection, CNS symptoms and 9,000 copies/ml of HHV-6 in the CSF be treated with ganciclovir— or just with an antifungal? These are the questions that UW group tried to answer with this study.

The UW group divided patients into one group with HHV-6 solo infections, and another group with both HHV-6 and other medical conditions. When they compared the two groups there was no significant difference and all patients with HHV-6 DNA in the CSF had poor survival (40-60% survival at 180 days), regardless of whether there was an alternate explanation for the CNS symptoms.

Why so much skepticism about HHV-6 as the cause of CNS disease in HSCT? One reason may be the tremendous confusion created by chromosomally integrated HHV-6 (ciHHV-6). Over the past 30 years, many high viral load cases were not recognized as ciHHV-6 and in some cases, symptoms were mistakenly attributed to HHV-6. Also, investigators were often baffled when high levels of HHV-6 DNA were found in asymptomatic patients.

The UW group led by Danielle Zerr concludes that there is not enough information to determine whether patients with a second diagnosis (eg. drug toxicity, other viral infection) should be treated with HHV-6 specific antivirals. They believe this question warrants further investigation.

HHV-6 CSF testing in the UW study was not performed routinely; it was done only at the request of the physician. Many centers are now moving toward routine testing of all HSCT/CBT patients for HHV-6 due to the high rate of limbic encephalitis at 1-3% for HSCT and 8-10% for CBT (Hill 2012, Scheurer 2013).

For the full paper, read Hill 2014.