HHV-6 reactivation leads to acute GVHD, increased mortality

HHV-6 reactivation: important predictor of poor outcome, acute GVHD after myeloablative transplantation

The results of a large-scale, comprehensive analysis of predictors and clinical outcomes for HHV-6 reactivation after allogeneic HSCT have just been released. Published in Bone Marrow Transplantation earlier this month, the study conducted by a research team based in the Netherlands demonstrates that the use of a myeloablative (MA) conditioning regimen during transplantation is a highly significant predictor of HHV-6 reactivation, and furthermore found HHV-6 reactivation to be heavily correlated with grades 2-4 acute GVHD as well as non-relapse mortality (NRM).

Overall, 108 patients who underwent HSCT were evaluated. HHV-6 DNA was detected in the plasma of 18 (17%) patients, HCMV DNA in 14 (13%) patients and EBV DNA in 5 (5%) patients. HHV-6 reactivation was observed in 16 of the 60 (27%) patients who were given a MA conditioning regimen, compared with 2/48 (4%) patients who received non-MA conditioning (P=0.02). Interestingly, this is not the first time that a transplant conditioning regimen has been correlated with increased risk of HHV-6 reactivation. Researchers have previously suggested a correlation with myeloablative conditioning (Ogata 2013, Chevallier 2010), as well as bortezomib (Velcade) (Horowitz 2013), alemtuzumab conditioning (Vu 2007), and ATG conditioning (Wang 2006). ATG conditioning has also been found to have no significant impact on HHV-6 reactivation in a recent study (Hill 2012)).

In addition, acute GVHD was observed in 40 out of 108 (37%) patients in the study. However, a staggering 14/18 patients with HHV-6 reactivation in the study developed severe aGVHD (grades 2-4). Of all clinical parameters analyzed, only HHV-6 reactivation remained statistically significant as an adverse prognostic factor for development of aGVHD (P<0.001). Furthermore, 25 of the original 108 patients who underwent HSCT in the study died, 8 of whom had HHV-6 reactivation. Thus, HHV-6 reactivation was also found to be highly correlated with non-relapse mortality (P=0.03).

In light of these significant findings, the group suggests that the development of HHV-6-specific prophylactic antiviral and/or cellular strategies may improve the outcomes of MA-treated HSCT patients, and that regular monitoring for HHV-6 reactivation after HSCT may be important to enable early initiation of antiviral treatment or to anticipate aGVHD in HSCT patients moving forward.

For more information, read the full paper and visit the Foundation webpage on HHV-6 & Transplant Complications.