Infections with human herpesvirus 6 variant B delay platelet engraftment after allogeneic haematopoietic stem cell transplantation

Abstract

Two variants of human herpesvirus 6 (HHV-6) have been described, variants A and B (Yoshikawa, 2004). The present study analysed cryo-conserved plasma samples of 82 patients after allogeneic stem cell transplantation (SCT) for HHV-6 DNA by specific quantitative real-time polymerase chain reaction (PCR) for variant A and variant B in order to answer three questions: is haematopoietic engraftment delayed in patients with HHV-6A or HHV-6B infections during marrow aplasia? Are HHV-6A or HHV-6B infections associated with an increased risk for graft-versus-host disease (GVHD)? Which risk factors for HHV-6A or HHV-6B reactivation after allogeneic SCT can be delineated? Patients and methodsA total of 82 consecutive patients who received an allogeneic SCT in our unit between January 1998 and March 2001 were included in the analysis. Their characteristics are summarised in Table I. Supportive care and treatment of cytomegalovirus (CMV) infections were carried out in a standardised manner as published (Schetelig et al, 2003). Samples of heparinised blood, which had originally been taken for monitoring CMV infections, were analysed retrospectively. The procedures for the separation of plasma, and for the identification and quantification of HHV-6A and HHV-6B DNA in the plasma have been described elsewhere (Wilborn et al, 1994;Nitsche et al, 2001). HHV-6 infection was defined as the detection of HHV-6 DNA in plasma, early HHV-6 infections were defined as those occurring before day 28. Platelet and neutrophil engraftment were defined as the first of three subsequent days with unsupported platelet counts >20 · 10 9 /l or with neutrophil counts >0AE5 · 10 9 /l after SCT. GVHD was classified according to common clinical criteria (Przepiorka et al, 1995 SummaryThe clinical significance of human herpesvirus (HHV-6) infections after allogeneic stem cell transplantation (SCT) remains controversial. We analysed cryoconserved plasma samples from 82 patients after allogeneic SCT by quantitative polymerase chain reaction for HHV-6 variants A and B. Platelet engraftment was delayed in patients with HHV-6B infections but not with HHV-6A infections detected before day +28. In multivariate analysis early HHV-6B infections and the type of conditioning were associated with platelet engraftment. In conclusion, the two variants of HHV-6 should be studied separately; early infections with HHV-6B may contribute to delayed platelet engraftment after allogeneic SCT.

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

“…[5][6][7][8][9][10][11][12][13][14][15][16][17][18][19]24,25,[28][29][30][31][33][34][35][36][37][38][39] Hentrich et al 25 reported a similar association between HHV6 reactivation and aGVHD, although no association was found between HHV6 reactivation and mortality. The association of HHV6 reactivation and aGVHD in the current study is comparable to the association found in other studies.…”

“…The association of HHV6 reactivation and aGVHD in the current study is comparable to the association found in other studies. 4,6,7,25,33,34 Although the exact mechanism of developing aGVHD is unknown, it is thought to be triggered by tissue damage due to previous therapy (toxicity) underlying disease and conditioning regimens. 35,36 HHV6 might be a factor in enhancing tissue damage by inflammatory responses, which is also suggested for other viruses.…”

Human herpesvirus type 6 reactivation after haematopoietic stem cell transplantation

“…Delayed platelet engraftment associated with HHV6 reactivation have been described in several studies, 4,13,15,[17][18][19][20] but this was not confirmed by others. [21][22][23] This is possibly caused by the low number of patients and variation in the conditioning regimens.…”

“…12 In other studies, high HHV6 reactivation rates (48-72%) were observed, but without any association with increased GvHD and non-relapse mortality. [13][14][15] This might be due to the fact that a majority of these patients received NMA conditioning (59%, 55% and 41%, respectively) and this might have lowered the risk of HHV6 reactivation. This is illustrated by our recent study in adult HSCT patients where MA conditioning appeared to be the only significant risk factor for the development of HHV6 DNA positive PCR observations following HSCT in a multivariate Cox proportional hazard model (HR 4.8; 95% CI 1.6-14.8, p = 0.006).…”

“…4,27 Only 2 studies reported HHV6 type A DNA viral loads after HSCT. 4,13 This might be due to geographical differences among populations or later acquisition of the more uncommon HHV6 type A variant. 28 With respect to disease, HHV6 encephalitis has been described in detail over 40 HSCT recipients 13,14,29,30 and central nervous system (CNS) dysfunction in patients with high HHV6 loads was reported in 2 studies.…”