Interview with Michael Boeckh and Joshua Hill on potential risks for ciHHV6 patients undergoing HCT

Expert Opinion: Drs. Joshua Hill and Michael Boeckh on the potential risks for ciHHV-6 patients undergoing HCT

The University of Washington and the Fred Hutchinson Cancer Research Center are at the forefront of studying the role of HHV-6 and ciHHV-6 in transplant patients. Michael Boeckh is Head of the Infectious Disease Sciences Program the Cancer Research Center. Joshua Hill is a senior fellow in infectious disease at both the medical and cancer centers.

Q: Are you considering screening HCT patients or donors for ciHHV-6?

Whether or not to screen HCT candidates and their donors for ciHHV-6 is a critical question that remains unclear. Given the findings of Endo et al, we are increasingly aware of the potential for HHV-6 reactivation and significant complications in immunocompromised patients with ciHHV-6. We hope more studies will be performed to guide the utility and necessity of screening in high-risk patients.

Q: Is there any concern by transplant specialists about the impact of steroids on patients with ciHHV-6 or reactivated HHV-6?

The strong association between increased risk for infections in HCT recipients and use of high-dose steroids, particularly for viral infections such as CMV, is well established. The association between HHV-6 reactivation and graft-versus-host disease has been demonstrated in many studies, and we suspect that the use of steroids is a co-factor in this process. High-risk HCT recipients who require >1 mg/kg of steroids a day may warrant monitoring for HHV-6, and perhaps especially those with ciHHV-6. Additional study in vivo will be important.

Q: Given the fact that HDAC inhibitors were shown to activate ciHHV-6A in vitro, should these medications be used with caution in ciHHV-6 patients?

Certainly, this is a reasonable concern. Given that these compounds have been used in HIV-infected patients to activate latently infected resting and memory T cells, they may be able to similarly affect ciHHV-6 cell lines. However, in vivo data is lacking and would be an interesting area of further investigation.

Q: Are there any plans to develop a mRNA assay to identify active infections in ciHHV-6 patients?

A clinically validated mRNA assay would be a great resource to help clinicians identify active HHV-6 transcription in patients with ciHHV-6. A number of recent publications have established sensitive and specific assays that could be used for this purpose. It will be important to study the utility of these assays to predict significant clinical endpoints and to ensure that positive findings in patients with ciHHV-6 represent lytic viral replication.

Q: What are your future plans for studying the consequences of ciHHV-6 reactivation in HCT patients?

We are excited to continue studying the implications of this interesting condition in larger cohorts of hematopoietic cell transplant (HCT) recipients to inform the importance of screening and monitoring strategies.

For more information, read Dr. Hill and Dr. Boeckh’s new publication which details the finding of HHV-6A reactivation in a ciHHV-6A transplant patient with encephalitis.