Herpesvirus type 6 in patients undergoing bone marrow transplantation: serologic features and detection by polymerase chain reaction

Abstract

To evaluate the potential role of human herpesvirus type 6 (HHV-6) infection in patients after bone marrow transplantation (BMT) we sequentially analyzed buffy coat leukocytes, oral lavage fluid, and urine from 57 patients for the presence of HHV-6 DNA by polymerase chain reaction (PCR) before and after 60 BMTs. Twenty-four patients undergoing autologous BMT and 36 with allogeneic BMT were studied. Thirty-six patients (60%) were PCR positive in one or more tests. The majority of PCR-positive patients had positive results only sporadically, in 1 (n = 23) or 2 weeks (n = 5). Six patients were positive in 3 to 5 weeks. In 2 patients, we found a high frequency of positive tests, in 7 of 7 and 10 of 10 weeks analyzed. Twenty-four patients (40%) remained PCR negative throughout the post-BMT period. There was a significant correlation between the results of HHV-6 PCR and the occurrence of acute graft-versus-host disease (aGVHD). In grade II-IV, 6 of 8 (75%) patients had 2 or more positive PCR tests, compared with 5 of 25 (20%) patients without or with grade I aGVHD (P = .01). There was no difference in the outcome of PCR tests with respect to the type of BMT or pre-BMT HHV-6 enzyme-linked immunosorbent assay titers. Restriction enzyme analysis of PCR amplificates from 18 patients showed HHV-6 variant B in 16 (88.9%) and variant A in 2 cases (11.1%). We conclude that HHV-6 DNA can be detected in 60% of the patients after BMT. HHV-6 DNA can be detected more frequently in patients with moderate and severe aGVHD than in patients without aGVHD or with mild aGVHD.

Impact of human herpesvirus‐6 after haematopoietic stem cell transplantation

“…The frequency of HHV-6 reactivation in peripheral blood demonstrated in this study compares favourably with the 38-78% incidence rates reported previously (Wilborn et al, 1994;Kadakia et al, 1996;Imbert-Marcille et al, 2000;Ljungman et al, 2000). Of note, we found serology to be of limited diagnostic value.…”

Correlation between the detection of viral DNA by the polymerase chain reaction in peripheral blood leukocytes and serological responses to human herpesvirus 6, human herpesvirus 7, and cytomegalovirus in renal allograft recipients

“…Over 40% of patients who were DNAemia positive for CMV or HHV7 have consecutively positive PBL specimens in contrast to 10% for HHV6 DNAemia [Osman et al, 1996]. The observation that HHV6 positivity in PBL is often sporadic has been noted in other studies using PCR [Appleton et al, 1996;Wilborn et al, 1994] as well as viral culture [Yoshikawa et al, 1991]. The poor overall agreement between HHV6 DNAemia and a serological response to the virus is probably due to the sporadic nature of virus activity.…”

Monitoring of human herpesviruses after allogeneic peripheral blood stem cell transplantation and bone marrow transplantation

“…Although Epstein-Barr virus (EBV) is not a major cause of mortality after conventional allo-BMT, primary EBV infection and lymphoproliferative disorders can occur after T-cell-depleted BMT (Hanto et al, 1985). The herpesviruses are also reported to be associated with transplant-related complications, including acute graft-versus-host disease (GVHD) and delayed engraftment (Boström et al, 1990;Wilborn et al, 1994;Wang et al, 1996;Drobyski et al, 1993). over allo-BMT have been demonstrated; neutrophil and platelet engraftment is rapid (Bensinger et al, 1996) and immune reconstitution is probably improved (Ottinger et al, 1996;Storek et al, 1997).…”

“…It was reported that a high level of HHV-6 DNA in lung tissue and persistence of HHV-6 DNA in peripheral blood were significantly correlated with the development of acute GVHD (Cone et al, 1993;Wilborn et al, 1994). CMV infection is also associated with the development of acute and chronic GVHD (Lönnqvist et al, 1984;Söderberg et al, 1996).…”