High levels of human herpesvirus 6 DNA in peripheral blood leucocytes are correlated to platelet engraftment and disease in allogeneic stem cell transplant patients

Abstract

Summary. The aim of this study was to correlate human herpesvirus (HHV)-6 viral load with clinical symptoms in allogeneic stem cell transplant (SCT) patients. Seventy-four patients were monitored during the first 3 months after SCT using a qualitative polymerase chain reaction (PCR) for HHV-6 DNA. HHV-6 was detected in 181 out of 494 samples (36%) from 58 (78%) patients. These 181 samples were analysed using a quantitative competitive PCR. DNA could be quantified from 146 out of 181 samples (80´6%). The HHV-6 viral load was highest at 4 weeks compared with 8 weeks (P , 0´001) and 12 weeks (P 0´01) after SCT. Three patients had HHV-6 encephalitis and one patient had hepatitis. The HHV-6 DNA levels were higher in patients with HHV-6 than in those without HHV-6 (P 0´01). Patients who received grafts from unrelated or HLA-mismatched family donors had significantly higher HHV-6 DNA levels than patients who received grafts from matched sibling donors (P , 0´001). In a multiple regression model, unrelated donor grafts (P , 0´001) and use of intravenous immunoglobulin prophylaxis (P 0´04) influenced HHV-6 DNA levels. HHV-6 viral load was significantly correlated with delayed platelet engraftment in both univariate (P , 0´01) and multivariate analysis, and to the number of platelet transfusions.

Human herpes virus 6 infection is a hallmark of cord blood transplant in adults and may participate to delayed engraftment: a comparison with matched unrelated donors as stem cell source

“…In our study, along with others, we have already reported the main consequence of HHV6 infection was to delay neutrophil and plt recoveries, especially in early reactivating patients. 25,27,37 Delayed engraftment is a well-known complication of cord blood transplant occurring at a higher incidence when compared with other source of SCs. [1][2][3][4]6 The role of HHV6 in delayed engraftment raises logically the question of HHV6 prophylaxis in CB transplant.…”

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

“…4,5 HHV-6 encephalitis develops concomitant to peak blood HHV-6 DNA. 3,5,7,8 Some studies in which blood levels of HHV-6 DNA have been monitored have shown a correlation between HHV-6 reactivation and the development of HHV-6 encephalitis, 1,[3][4][5][6][7][8]56 but others have failed to demonstrate such associations. 2,57,58 The reasons for these divergent results may be because of the low incidence of HHV-6 encephalitis even in patients with HHV-6 reactivation.…”

“…[1][2][3][4][5][6] The duration of displaying positive HHV-6 DNA in plasma is only 1-2 weeks in most cases. 3,5,7,8 HHV-6B accounts for most reactivation events.…”

“…1,[3][4][5][6][7][8] The first case of HHV-6 encephalitis after allo-HCT was described in 1994 by Drobyski et al 9 Since then, a significant amount of information regarding the incidence, risk factors, therapy and outcomes has been reported. Over the past decade, HHV-6 encephalitis has become well known as a significant complication of allo-HCT.…”

Human herpesvirus-6 encephalitis followed by severe acute GVHD after a stem cell transplant from a microchimeric non-inherited maternal antigen (NIMA)-mismatched sibling

“…Among 338 recipients of bone marrow transplant, the incidence of central nervous system (CNS) symptoms associated with HHV-6 in the cerebrospinal fluid (CSF) was only 1.5% (five patients). 4 Recipients grafted with stem cells from HLA-mismatched donors have an increased risk of HHV-6 reactivation and disease, 4,5 which is also implicated as a cause of the initiation and exacerbation of graft-versus-host disease (GVHD). Here, we describe a patient who developed life-threatening acute GVHD following HHV-6 encephalitis after allogeneic peripheral blood stem cell transplantation (PBSCT) from an HLA-haploidentical sibling mismatched for noninherited maternal HLA antigens (NIMA).…”