Over a dozen studies have now found HHV-6 to predict aGVHD, but this is the first to correlate viral reactivation with poor CD4+ cell immune reconstitution.
Opinion: call for ciHHV6 screening in transplantion
Two physicians from Texas propose that ciHHV6 status of donors and recipients be determined before solid organ transplantion, using a single pre-transplant qPCR test on whole blood, and that patients with ciHHV-6 or ciHHV-6 donors be carefully monitored for signs of active HHV-6 infection.
Multiple viral infections and HHV-6B increase risk of mortality in HSCT
A retrospective study of allogeneic hematopoietic stem cell transplant patients at University of Washington found that reactivation of several double stranded DNA viruses significantly increased the risk of overall mortality, as did an increased quantitative burden of viral exposure. HHV-6B conferred a significantly increased risk for overall mortality.
HHV-6 induced amnesia after rituximab therapy for autoimmune disease
A young woman on rituximab and two other immunomodulatory agents for the treatment of dermatomyositis developed encephalitis with severe anterograde amnesia. As the use of biologic treatments for refractory autoimmune disease has been increasing, physicians are advised to consider HHV-6 and offer prompt antiviral therapy to limit irreversible morbidity.
Immune reconstitution dramatically alters chance of survival in stem cell transplant patients with HHV-6 reactivation
Only 11% of HHV-6 reactivated patients with poor immune reconstitution survived compared to 63% in patients with higher levels of T cells (or over 200 CD3+ lymphocytes per microliter).
HHV-6 found to cause 35% of CNS infections in allo-HSCT transplantation
A retrospective analysis out of the Tokyo Metropolitan Cancer and Infectious Diseases Center reviewed 353 consecutive adult allogeneic hematopoietic stem cell transplant (allo-HSCT) cases and identified 17 cases of CNS infection post-transplant. As determined by PCR on cerebrospinal fluid, HHV-6 was found to be the causative agent in 6 cases, or 1.7% of all transplants.
New data on HHV-6B levels in CD134+ CD4+ cells
A group from the University of Minnesota studied the T cells of umbilical cord blood transplant patients and found that CD4+ T lymphocytes co-expressing CD134 contained more than twice the level of HHV-6B than cells without CD134 expression. Surprisingly, almost 70% of the CD134 negative cells contained HHV-6.
Does CD134 upregulation explain why HHV-6 reactivates preferentially in DRESS/ DIHS?
It has long been a mystery why HHV-6 is preferentially reactivated in drug reaction with eosinophilia and systemic symptoms (DRESS), also known as drug induced hypersensitivity syndrome (DIHS). HHV-6 reactivation occurs in over 60% of severe cases and is part of the definition of DIHS in Japan. Investigators in Japan suspect that the explanation may lie with the CD134 receptor on activated CD4 cells.
Drug-induced liver injury and HHV-6 reactivation without rash or fever
Another case of drug induced liver injury accompanied by HHV-6 reactivation has been reported in Japan, the second such case without exanthema to be described. An earlier case was reported last year (Fujita 2015). The authors suggest that drug-induced liver injury cases be investigated for HHV-6 reactivation when liver dysfunction begins several weeks after the initiation of a new drug typically associated with hypersensitivity syndromes.
Virus-specific immunotherapy for transplant patients with primary immune deficiencies
A group from Baylor College of Medicine reviewed the efficacy of treating viral infections in transplant patients with primary immunodeficiencies using their viral-specific T lymphocytes. A total of 36 patients were treated with these immunotherapy infusions before or after undergoing hematopoietic stem cell transplantation, and a complete or partial antiviral response were seen in 86% of patients with CMV, 76% of patients with EBV and all patients with adenovirus or HHV-6.
HHV-6 & 7 potentiate CMV infection in transplant patients
A new study suggests that HHV-6 and HHV-7 are important co-factors for the development of CMV infection post-transplant in allogeneic hematopoietic stem cell transplantation patients. Additionally, the presence of HHV-7 and CMV together may result in more severe infections than either virus alone.
HHV-6 reactivation reduces CD8+ T cell recovery with increased risk of infections and reduced survival
In a French study of 366 adult allogenic hematopeietic stem cell transplantation (aHSCT) recipients CD8+ T cell recovery was significantly reduced in patients with HHV-6 reactivation. HHV-6 reactivation was also associated with reduced survival and increased infections of CMV and BKV.
Stanford uses non-invasive new assay to detect occult infections including HHV-6 after lung transplantion
Researchers from Stanford University successfully used circulating cell-free DNA to identify infections in lung transplants that can often be found only with a more invasive transbronchial biopsy. This hypothesis free approach led to find HHV-6 & 7 at high levels in patients with infections, even though these viruses are not generally considered lung pathogens.
HHV-6 myocarditis, pericarditis following transplantation
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.
HHV-6 induced Parkinsonism post-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.