A Population-Based Study of Primary Human Herpesvirus 6 Infection

Hematopoietic SCT (HSCT) is often complicated by viral reactivations. In this retrospective cohort study (January 2004-August 2008, predictors for human herpes virus 6 (HHV6)-reactivation and associations between HHV6-reactivation and clinical outcomes after allogeneic HSCT were studied. HHV6 DNA load in plasma was monitored weekly by quantitative real-time PCR. Associations between the main end point HHV6-reactivation and other end points, that is, acute GVHD (aGVHD) and NRM were analyzed using Cox proportional hazard models. In total, 108 patients receiving either a myeloablative (MA; n ¼ 60) or non-myeloablative (NMA; n ¼ 48) conditioning regimen were included. Median age was 40 years (range 17-65); median follow-up was 20 months (range 3-36). In 16/60 (27%) patients with MA conditioning regimen, a HHV6 reactivation was observed (mean viral load 50 323 cp/mL) compared with 2/48 (4%) patients with a NMA conditioning regimen with low viral load (mean 1100 cp/mL). In multivariate analysis, MA conditioning was the only predictor for HHV6 reactivation (P ¼ 0.02). In addition, HHV6 reactivation was associated with grades 2-4 aGVHD (Po0.001) and NRM (P ¼ 0.03). Regular monitoring of HHV6 reactivation after HSCT might be important in MA HSCT patients to enable early initiation of antiviral treatment or to anticipate aGVHD, all of which may improve clinical outcome. Herpes virus reactivations, like human CMV (HCMV) and EBV, have been described to be associated with aGVHD, allograft rejections and increased NRM. 1-3 Human herpes virus 6 (HHV6), which reactivates early after HSCT, was found to be associated with aGVHD and increased NRM in children and, recently, in adults. [4][5][6][7] Predictors for the development of HHV6 reactivation are largely unknown. To date, only broad-spectrum and relatively toxic antiherpes virus drugs (for example, (val)ganciclovir and foscarnet-sodium) are used in the treatment of HHV6 disease or -reactivation. 8,9 With the progress in molecular diagnostics, better monitoring allows for further elucidation of the role of HHV6 reactivation and therapeutic protocols after HSCT. Therefore, we studied the predictors for HHV6 reactivation and the association of HHV6 reactivation with clinical outcome in adult allogeneic-HSCT recipients.

Section: Methodsmentioning

confidence: 99%

Human herpes virus 6 reactivation: important predictor for poor outcome after myeloablative, but not non-myeloablative allo-SCT

Pagter

Schuurman

Keukens

et al. 2013

“…HHV-6 comprises two closely related species, HHV-6A and -6B. 10 HHV-6B is a ubiquitous virus that infects virtually all children by 2 years of age 11 and is a causative agent for exanthema subitum. Less is known about the epidemiology and clinical significance of HHV-6A.…”

Section: Disease Associations: We Do Not Know the Precise Disease Assmentioning

confidence: 99%

Human herpesvirus-6 encephalitis after allogeneic hematopoietic cell transplantation: What we do and do not know

Ogata

Fukuda²,

Teshima

2015

104

Human herpesvirus-6 (HHV-6) encephalitis following allogeneic hematopoietic cell transplantation is a serious and often fatal complication accompanying reactivation of HHV-6B. Incidence varies among studies, but is reportedly 0-11.6% after bone marrow or PBSC transplantation and 4.9-21.4% after umbilical cord blood transplantation, typically around 2-6 weeks post transplant. Symptoms are characterized by memory loss, loss of consciousness and seizures. Magnetic resonance imaging (MRI) typically shows bilateral signal abnormalities in the limbic system. This complication is considered to represent acute encephalitis caused by direct virally induced damage to the central nervous system, but our understanding of the etiologies and pathogenesis is still limited. The mortality rate attributable to this pathology remains high, and survivors are often left with serious sequelae such as impaired memory and epilepsy. Despite the poor prognosis, no validated treatments or preventative measures have been established. Establishment of preventative strategies represents an important challenge. This article reviews the current knowledge of the clinical features, incidence, pathogenesis and treatment of HHV-6 encephalitis, and discusses issues needing clarification in the future to overcome this serious complication.

“…10,11 HHV-6 is the collective name for HHV-6A and HHV-6B, 12,13 two closely related beta-herpesviruses that establish primary infection in early childhood and maintain lifelong persistent infection with a combined seroprevalence of 490% in adults. [14][15][16][17] Of the two, HHV-6B is the variant implicated in nearly all documented cases of HHV-6 reactivation following HSCT, which typically occurs within 30 days of HSCT. 18 One of the most severe consequences of HHV-6 reactivation among post-transplant patients is infection of the central nervous system (CNS), which can lead to the development of HHV-6 encephalitis.…”

Section: Introductionmentioning

confidence: 99%

HHV-6 encephalitis in umbilical cord blood transplantation: a systematic review and meta-analysis

Scheurer

Pritchett

Amirian

et al. 2012

108

Reactivation of human herpesvirus-6 (HHV-6) frequently occurs following hematopoietic SCT (HSCT), and has been associated with clinical consequences in many patient populations. HHV-6 reactivation and HHV-6 encephalitis seem to occur more frequently in patients undergoing HSCT with cord blood (CB) as the stem cell source. We have conducted a systematic literature review and meta-analysis to investigate the clinical significance of this correlation. A systematic review of publications indexed in PubMed was performed for HSCT studies published over the past 10 years that fit inclusion criteria. Data on prevalences of HHV-6 reactivation and HHV-6 encephalitis post HSCT were abstracted from 19 papers. Meta-analyses were conducted to calculate combined prevalence estimates. The prevalences of HHV-6 reactivation and encephalitis were compared among CB vs non-CB HSCT. Prevalences of HHV-6 reactivation and HHV-6 encephalitis were significantly higher in patients receiving CB as the stem cell source than in patients receiving another stem cell source (72.0% vs 37.4%, Po0.0001; 8.3% vs 0.50%, Po0.0001, respectively). HHV-6 reactivation and HHV-6 encephalitis are significant complications in the post-HSCT setting, particularly in patients receiving CB as the stem cell source. Thus, patients undergoing umbilical CB transplantation should be closely monitored for HHV-6 reactivation.