A new meta-analysis published in Blood shows that transplant patients who reactivate with HHV-6 are 2-3 times more likely to develop acute GVHD.
German investigators conducted a broad scale analysis of CD8 T cell responses to HHV-6B, identifying novel epitopes with potential for immunotherapy or vaccines. The strongest responses were directed against an epitope from IE-2.
Investigators at the University of Minnesota found that cord blood transplant cancer patients with HHV-6B reactivation in the first 28 days are almost 4x more likely to relapse in the first two years compared to those with no early reactivation.
Late HHV-6B reactivation after 60 days was an independent risk factor for mortality in Japanese pediatric hematopoietic cell transplant recipients. Older children and those with hematologic malignancy were 10x more likely to develop late reactivation.
HHV-6B directly infects thymocytes, presumably affecting thymopoeisis. A review in Bone Marrow Transplantation explores the intriguing relationship between HHV-6B, T-cell reconstitution and aGVHD after allogenic hematopoietic cell transplantation.
Dutch investigators found that hematopoietic cell transplant patients with high levels of HHV-6 viremia have reduced late immune reconstitution while early reconstitution was not affected.
Stanford investigators found that high levels of HHV-6 viremia following allogeneic stem cell transplants were associated end organ disease and greater non-relapse mortality.
A Japanese trial of foscarnet prophylaxis in cord blood transplant patients was successful in reducing severity and mortality as well as suppressing high viral loads, but it failed to prevent encephalitis. The authors note that the blood brain barrier must be inflamed to allow effective penetration of the drug into the central nervous system and speculate that the prophylaxis may have protected the meninges.
HHV-6 is rarely identified as the cause of liver dysfunction in immunocompetent children, in part because HHV-6 is not included in routine testing, and HHV-6 infections can be highly localized to the liver. In this case, an alert team in Arizona identified HHV-6 by needle biopsy.
Japanese investigators described HHV-6 myelitis in patients who had received cord blood transplantations and report that where HHV-6 reactivation is suspected, early antiviral intervention can dramatically improve patient outcomes.
Investigators at Fred Hutch Cancer Research Center found that HHV-6B is the first DNA virus to reactivate at a median of 3 weeks, compared to CMV, EBV and Adenovirus at 5-6 weeks. HHV-6B also peaked rapidly, unlike other DNA viruses that took 3-6 weeks to reach peak viral load. HHV-6B reactivation resulted in increased mortality after 100 days.
Half of autologous hematopoietic cell transplant patients with HHV-6 reactivation exhibit fever plus a collection of symptoms that include diarrhea, rash and pneumonia.
HHV-6 infections in the liver transplant patients can’t be diagnosed in the blood. Ganciclovir prophylaxis for CMV cuts the rate of HHV-6 reactivation from 39% to 11%.
Investigators in Japan studied 145 patients who developed HHV-6 encephalitis. At 100 days after transplantation, the overall survival rate was just 58.3%, compared with 80.5% for patients who did not develop encephalitis. High-dose antiviral therapy was shown to mitigate high mortality rates in these patients.
T-cell depleted stem cell transplant patients at Memorial Sloan Kettering Cancer Center with HHV-6 viremia, CMV viremia, or 2 or more viremias experienced longer hospital stays and were readmitted more often. HHV-6 was the most commonly reactivated virus, with 61% of patients affected patients .