A new study reports a surprisingly low rate of HHV-6 reactivation in recipients of half-matched bone marrow grafts using a reduced-intensity conditioning regimen. The authors speculate that the corticosteroid used for prophylaxis may have suppressed cytokine production which in turn limited reactivation of HHV-6.
Foscarnet approved for HHV-6 encephalitis in Japan
Although foscarnet is widely used for HHV-6 encephalitis, it has never been specifically approved for HHV-6. Japan’s Ministry of Health, Labor and Welfare was the first to approve foscarnet (Foscavir) for the treatment of HHV-6 encephalitis.
HHV-6 increases risk of an “idiopathic” pneumonia syndrome after HCT as does murine roseolovirus in a BMT mouse model. Early HHV-6 was also found to increase non-relapse mortality
Investigators from University of Michigan have demonstrated that murine roseolovirus is a useful homolog for the study of HHV-6 reactivation in lung disease. In a large retrospective study of HCT patients, they also found early HHV-6 reactivation to increase the risk of both idiopathic pneumonia syndrome and non-relapse mortality.
89% of the virus found in the spinal fluid of HCT patients in the first 60 days is HHV-6
An analysis of 165 central nervous system viral infections by the Center for International Blood and Bone Marrow Transplant Research found that most were positive for HHV-6. The outcome for patients with viral infection was poor with 50% mortality within 6 months and only 30% survival at 5 years.
HHV-6 is a greater risk than CMV for rejection in pediatric kidney transplantation
Investigators from the Children’s Hospital of Mexico found that although CMV caused the biggest increase in risk for liver rejection, HHV-6 was the more important infection associated with rejection of kidney transplants. A single HHV-6 infection resulted in an increased risk of over 5 fold, while a coinfection of EBV, HHV-6 and HHV-7 increased the risk of kidney rejection by over 17 fold.
Stanford finds high levels of HHV-6 in the tissues of children with liver failure
A team at Stanford reported that 48% of young children with “liver failure of unknown etiology” had high viral loads of HHV-6 in their liver tissues. As a result, Stanford has now instituted routine evaluation for HHV-6 in all children who present with liver failure.
RNA sequencing of HHV-6B transcriptome identifies U38 as the best target for HHV-6 RT-PCR testing
Investigators at University of Washington studied multiple samples to develop an assay that can detect active infection in patients with chromosomally integrated HHV-6. Current quantitative PCR DNA testing cannot determine whether a ciHHV6 patient has active replication.
Rapid lymphocyte expansion after HCT predicts increased HHV-6 reactivation
A team of researchers at Kyoto University in Japan reported that rapid lymphocyte expansion is a good predictive factor for increased HHV-6 reactivation, as well as reduced CMV antigenemia. Patients with aplastic anemia as a primary disease had a 5 fold increased risk of HHV-6 reactivation.
HHV-6 encephalitis in 32% of pediatric leukemia patients depleted of naïve T cells
Although depleting naïve T cells has been successful in preventing acute graft vs host disease in several studies, investigators from Spain reported an unexpectedly high incidence of HHV-6 encephalitis in a cohort of haploidentical transplant patients.
HHV-6 reactivation associated with unexplained fever and biliary atresia in pediatric liver transplant patients
A Japanese study found that unexplained fever and biliary atresia are associated with HHV-6B infection in pediatric transplant patients. 100% of seronegative infants developed a primary infection.
Meta-analysis shows strong association of HHV-6B reactivation and subsequent aGVHD
A new meta-analysis published in Biology of Blood and Marrow Transplantation shows that transplant patients who reactivate with HHV-6 are 2-3 times more likely to develop acute GVHD.
Cross-sectional analysis of CD8 T cell immunity to HHV-6B identifies new targets for adoptive T cell therapy
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.
Cord blood transplant patients with early HHV-6 reactivation have a 4x greater relapse rate
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 an independent risk factor for mortality in pediatric HCT
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.
