A large-scale multiplex PCR assay developed by a team in Japan was used to study 13 DNA viruses in 105 allogenic hematopoietic stem cell transplant patients. They found that patients treated with steroids had a significantly higher risk of HHV-6 reactivation (p=0.027), and that HHV-6 was the only virus tied to the onset of acute GVHD (p=0.016). Interestingly, HHV-6 reactivation was associated with a more severe stage of skin but not liver or gut aGVHD (P=0.005).
The authors also found that cord blood transplant patients were 10.4x more likely to reactivate with HHV-6. The authors looked at the association of HHV-6 reactivation in the absence of GVHD, and found that it was 3X greater in those treated with steroids (P=0.014). The authors point out that in cases of GVHD solely associated with HHV-6 reactivation, treatment with steroids might not be advised.
In addition to the nine herpesviruses, the group’s assay surveyed for adenovirus, BK virus, JC virus, parvovirus B-19 and hepatitis B. The patients were placed on acyclovir for prophylaxis against HSV and VZV reactivation, and whole blood was analyzed weekly from before the transplant to 42 days post-transplant.
The highest reactivation rate for HHV-6 was in the population of cord blood transplant patients (82.1%). No other virus showed a disproportionate rate of reactivation in patients receiving different stem cell sources.
Patients treated with anti-thymocyte globulin had a high risk of EBV reactivation (P= 0.10), and the rate of EBV reactivation was higher in children than in adults. There were no increased risks found for other drugs.
The authors point out that the study is in agreement with existing univariate and multivariate analyses that found an association between HHV-6 reactivation and the stage of GVHD, and that collectively these suggest that HHV-6 reactivation could precede GVHD and affect the development and/or severity of subsequent disease (Dulery 2012, Chevallier 2010). They also point out that HHV-6 induces the production of IL-1 and tumor necrosis factor, which are known to have the potential of worsening skin GVHD (Lusso 2006).
Previous studies have similarly found steroid use to be a risk factor for HHV-6 reactivation (Ogata 2006) and several studies have tied HHV-6 to GVHD.