A hematology group in Australia reported a case of biopsy-proven HHV-6 myocarditis post-hematopoietic stem cell transplantation (HSCT). he post-mortem exam confirmed dilated cardiomyopathy and focal changes consistent with viral myocarditis and cardiac tissue was positive for HHV-6 DNA by nested and quantitative PCR. Separately, A Japanese group reported a worman who developed pericarditis with over 10,000 copies/ml of HHV-6 DNA in the pericardial fluid, after a cord blood transplant.
A group of researchers from Sao Paulo, Brazil reported the development of HHV-6 infection in the striatum of a 32-year-old man six weeks after allogeneic hematopoietic stem cell transplantation. This is the first reported case of HHV-6 infection affecting the striatum and presenting with Parkinsonism post-HSCT.
A group from Sapporo Medical University studied 105 post HSCT patients and determined that 7 developed CNS dysfunction in the first 42 days after transplant. Six out of the 7 were positive for HHV-6, but none of the other 12 pathogens tested. Four patients (3.8%) were diagnosed with HHV-6 encephalitis. The group used a qualitative multiplex PCR and then used a quantitative PCR to confirm the results.
A prospective study authored by Joshua Hill and Danielle Zerr determined that higher than average HHV-6B DNA levels increased the odds of developing delirium after cord blood transplantation (CBT) by almost three fold. Patients with DNA loads in the top quartile had a 4.5 fold increase in delirium.
HHV-6 may be the cause of “fever of unknown origin” in 30% of stem cell transplant (SCT) patients. By the third week after SCT, 70% of HHV-6 positive patients had a skin rash, compared to 39% of HHV-6 negative patients.
A group from Sapporo Medical University studied 105 post HSCT patients and determined that 7 developed CNS dysfunction in the first 42 days after transplant. Six out of the 7 were positive for HHV-6, but none of the other 12 pathogens tested. Four or 3.8% of the population were diagnosed with HHV-6 encephalitis.
In an article published in the Pediatric Infectious Disease Journal, Tetsushi Yoshikawa’s team from Fujita Health University School of Medicine determined that the severe neutropenia in primary HHV-6B infection is tied to reduced platelet counts, lower RANTES and higher levels of MCP-1, MIG and IP-10.
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).
Intensive care (ICU) patients with co-infections of HHV-6 and CMV are 7.5x more likely to die or have an extended stay in the hospital. On the other hand, single infections with either HHV-6 or CMV did not significantly impact outcome.
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. Their findings identify HHV-6 as the most common virus (found in 60% of all patients), and also as 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). In addition, patients treated with steroids had a significantly higher risk of HHV-6 reactivation (p=0.027) and 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 …
Dr. Flamand, a professor and molecular virologist at Université Laval in Quebec city, has written an editorial calling for screening of organ donors for ciHHV-6 status and careful monitoring of recipients of ciHHV-6 donor tissues for signs of active HHV-6 infection and HHV-6 antigen-induced immune rejection. Flamand also questions whether solid organs and stem cells derived from persons with ciHHV-6 should be used in transplantation.
Should physicians automatically discount HHV-6 if any other pathogen is found in the CSF? Should patients with both HHV-6 and EBV DNA in the CSF be treated only for EBV? These are the questions that UW group tried to sort out in this study.
The University of Washington and the Fred Hutchinson Cancer Research Center are at the forefront of studying the role of HHV-6 and ciHHV-6 in stem cell transplant patients. We asked their view on the implications immunocompromised patients with integrated HHV-6A reactivating with their own inherited virus.
HHV-6 reactivation before engraftment strongly predictive of graft failure
Trial explores immunotherapy for opportunistic viruses in transplantation