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.
Does HHV-6B reactivation impair thymic function leading to delayed immune reconstitution?
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.
HHV-6 viremia impairs late T-cell reconstitution in HCT
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.
High rate of HHV-6 end-organ disease and mortality in pediatric transplant patients
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.
Foscarnet prophylaxis reduces severity but does not prevent HHV-6 encephalitis
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 acute liver failure in an immunocompetent child: case report
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.
HHV-6 myelitis after cord blood transplantation
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.
HHV-6B reactivates first, proceeds to end organ disease faster in transplant patients
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.
HHV-6 reactivation associated with fever after autologous transplantation
Half of autologous hematopoietic cell transplant patients with HHV-6 reactivation exhibit fever plus a collection of symptoms that include diarrhea, rash and pneumonia.
Review of HHV-6 in Liver Transplantation
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%.
New study details devastating impact of HHV-6 encephalitis
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.
HHV-6 reactivation associated with longer hospital stays, more readmissions in Memorial Sloan Kettering Trial
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 .
Inherited ciHHV-6 increases risk of developing acute GVHD and CMV in transplant patients
A higher prevalence of inherited virus was found in patients
Investigators at Fred Hutchinson Cancer Center determined that transplant patients with inherited ciHHV-6 were twice as likely to develop acute graft vs host disease and three times more likely to develop high level CMV viremia. Transplant patients were also significantly more likely to have inherited ciHHV-6 than donors.
HHV-6 reactivation, monocytes and B cells are unusually elevated in cord blood transplant patients
CD8+ T cells recover but CD4+ T cells remain low
Investigators in France discovered that monocytes and B lymphocytes recover quickly and become abnormally elevated by day 75 in cord blood patients, while they remain below normal or normal in stem cell patients. Although CD8 T cells recover, CD4+ T cells remain below normal levels for six months in both groups.
Low sodium levels associated with HHV-6 encephalitis
Retrospective analysis of transplant patients revealed that low serum sodium levels are associated with HHV-6 encephalitis, but not HHV-6 myelitis. Low sodium is a possible marker for HHV-6 encephalitis post-transplantation.