Human Herpesvirus 6 in Hematological Malignancies

Abstract

Pathogenetic roles of human herpesvirus (HHV)-6 in lymphoproliferative diseases have been of continued interest. Many molecular studies have tried to establish a pathogenic role for HHV-6 in lymphoid malignancies. However, whether HHV-6 plays a role in these pathologies remains unclear, as positive polymerase chain reaction results for HHV-6 in those studies may reflect latent infection or reactivation rather than presence of HHV-6 in neoplastic cells. A small number of studies have investigated HHV-6 antigen expression in pathologic specimens. As a result, the lack of HHV-6 antigen expression on neoplastic cells argues against any major pathogenic role of HHV-6. The role of HHV-6 in childhood acute lymphoblastic leukemia (ALL) has also been of interest but remains controversial, with 2 studies documenting higher levels of HHV-6 antibody in ALL patients, and another 2 large-scale studies finding no significant differences in HHV-6 seroprevalences between ALL patients and controls. Alternatively, HHV-6 is increasingly recognized as an important opportunistic pathogen. HHV-6 reactivation is common among recipients of allogeneic stem cell transplantation (SCT), and is linked to various clinical manifestations. In particular, HHV-6 encephalitis appears to be significant, life-threatening complication. Most HHV-6 encephalitis develops in patients receiving transplant from an unrelated donor, particularly cord blood, typically around the time of engraftment. Symptoms are characterized by short-term memory loss and seizures. Magnetic resonance imaging typically shows limbic encephalitis. Prognosis for HHV-6 encephalitis is poor, but appropriate prophylactic measures have not been established. Establishment of preventive strategies against HHV-6 encephalitis represents an important challenge for physicians involved with SCT.

Human herpes 6 virus encephalitis complicating allogeneic hematopoietic stem cell transplantation

“…9 In general, CNS infections post-alloHSCT have been associated with higher mortality and rejection rates, whereas long-term neurologic morbidity remains unknown. 5,6 Hence, in addition to characterizing the clinical presentation of encephalitis due to HHV-6 infection, we investigated whether early diagnosis and treatment influences mortality in alloHSCT recipients.…”

“…1,4 In approximately 2% of the population, viral DNA sequences are integrated into chromosomes. 5 Viral reactivation occurs in severely immune-compromised states such as hematopoietic stem cell transplantation, solid organ transplantation, and HIV/AIDS, causing diverse clinical manifestations including encephalitis, pneumonitis, thrombocytopenia, hepatitis, and fever. Interestingly, symptomatic reactivation is more frequently noted in patients receiving hematopoietic stem cell transplantation compared with patients with HIV/AIDS.…”

Foscarnet against human herpesvirus (HHV)-6 reactivation after allo-SCT: breakthrough HHV-6 encephalitis following antiviral prophylaxis

“…[1][2][3][4] HHV-6 reactivation is potentially associated with various post-transplant complications, including those affecting the skin, lung, gastrointestinal tract and central nervous system (CNS). 5,6 In particular, HHV-6 encephalitis has been recognized as a life-threatening complication associated with HHV-6 reactivation.…”

“…3,[7][8][9] The limbic system is a target of HHV-6. 3,[6][7][8][9][10] Recipients of unrelated transplants and cord blood (CB) display a high risk of HHV-6 encephalitis. 3,4,7,8 HHV-6 encephalitis develops concomitant to the appearance of a high-HHV-6 DNA load in plasma.…”

“…Several investigators have asserted that the establishment of methods to prevent HHV-6 encephalitis is needed for patients at high risk of this complication. 6,11,14,15,20,21 To prevent the development of HHV-6 encephalitis, we have attempted pre-emptive GCV therapy guided by plasma HHV-6 DNA load. 11 However, dynamic kinetics of plasma HHV-6 viral load make pre-emptive therapy difficult.…”