Human Herpesvirus 6 in Lung Tissue from Patients with Pneumonitis after Bone Marrow Transplantation

Cone, Richard W.; Hackman, Robert C.; Huang, Meei‐Li; Bowden, Raleigh A.; Meyers, Joel D.; Metcalf, Mark A.; Zeh, Judith; Ashley, Rhoda; Corey, Lawrence

doi:10.1056/nejm199307153290302

Cited by 294 publications

(158 citation statements)

References 29 publications

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“…Furthermore, HHV-6 has been shown to be capable of causing interstitial pneumonitis in this group of patients, 33 and in previous studies it has been significantly associated with the occurrence of GVHD and concurrent EBV. 34 However, only 1/5 findings of HHV-6 and 2/3 findings of EBV were considered to be the cause of pneumonia.…”

Section: Discussionsupporting

confidence: 50%

The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia

Forslöw

Remberger

Nordlander

et al. 2009

Bone Marrow Transplant

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Section: Discussionsupporting

confidence: 50%

The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia

Forslöw

Remberger

Nordlander

et al. 2009

Bone Marrow Transplant

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“…1 Furthermore, there are reports that HHV-6 infection is associated with an increased incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection 3 and the occurrence of graft-versus-host disease (GVHD). 4 To date, there are only three reports of HHV-6-associated encephalitis in patients after bone marrow transplantation in the literature and two proved to be fatal, demonstrating the potential morbidity and mortality of this infection. [5][6][7] As HHV-6 is susceptible to ganciclovir and foscarnet but less sensitive to acyclovir, 1 clinical disease caused by this virus is potentially treatable.…”

Section: Discussionmentioning

confidence: 99%

Successful treatment of human herpesvirus-6 encephalitis after bone marrow transplantation

Bethge

Beck

Jahn

et al. 1999

Bone Marrow Transplant

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Summary:We report two cases of human herpesvirus-6 (HHV-6)-associated encephalitis in patients after BMT. Both patients reported distinct neurological symptoms with disorientation, sleepiness and loss of short-term memory. Diagnosis was based on PCR analysis of the cerebrospinal fluid (CSF) positive for HHV-6 variant B-DNA. After institution of therapy with foscarnet in both cases, neurological symptoms improved and in one patient clearance of HHV-6-DNA from CSF was demonstrated. These cases show that HHV-6 infection has to be considered in patients with neurological symptoms following BMT and effective treatment of HHV-6 encephalitis is possible if instituted early. Keywords: human herpesvirus-6; bone marrow transplantation; encephalitis; foscarnet Human herpesvirus-6 (HHV-6) is a member of the betaherpesvirus subfamily causing exanthem subitum in children. 1 Since its discovery in 1986, HHV-6 has been an emerging pathogen, especially in the immunocompromised host. In patients after BMT the reported incidence based on screening blood samples post transplant by polymerase chain reaction (PCR) is between 38-60%. 2 Infection occurs by reactivation of latent virus or exogenous infection. HHV-6 infection in transplant patients had been associated clinically with skin rash and fever, marrow suppression, interstitial pneumonitis and encephalitis. 1 Furthermore, there are reports that HHV-6 infection is associated with an increased incidence of cytomegalovirus (CMV) and Epstein-Barr virus (EBV) infection 3 and the occurrence of graft-versus-host disease (GVHD). 4 To date, there are only three reports of HHV-6-associated encephalitis in patients after bone marrow transplantation in the literature and two proved to be fatal, demonstrating the potential morbidity and mortality of this infection. [5][6][7] As HHV-6 is susceptible to ganciclovir and foscarnet but less sensitive to acyclovir, 1 clinical disease caused by this virus is potentially treatable. Here, we report two cases of HHV-6 encephalitis after allogeneic BMT successfully treated with foscarnet. Case reports Patient 1A 34-year-old man received an allogeneic unrelated BMT for relapsed acute lymphoblastic leukemia in January 1998. The conditioning regimen consisted of total body irradiation (12 Gy), etoposide 40 mg/kg and cyclophosphamide 120 mg/kg. GVHD prophylaxis consisted of antithymocyte globulin (ATG) (Thymoglobulin; Meriéux, Leimen, Germany) 3.5 mg/kg/day from day 4 (−4) before transplantation to day −1, cyclosporin A 5 mg/kg from day −1, prednisone 0.5 mg/kg from days +7 to 14, prednisone 1 mg/kg from days +14 to +28 and mycophenolate from day +0. The patient received ofloxacin, fluconazole and polyvalent immunoglobulin preparations every 3 weeks post BMT as antimicrobial prophylaxis. The recipient and donor were CMV seropositive. The patient was screened weekly by PCR for CMV-DNA. The early post-transplant period was without severe complications, in particular, no signs of GVHD. Two months after transplantation the patient developed CMV viremia and in ...

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“…Human herpesvirus-6 (HHV-6) shares many biological characteristics with CMV, including viral protein products (ෂ67% homology), 1 antigenic reactivity, and in vitro growth characteristics. 2 Several studies have suggested that HHV-6 is associated with fever, skin rash, 3 graft-versus-host disease (GVHD), 4 interstitial pneumonitis, 5 encephalitis, 6,7 thrombotic microangiopathy (TMA), 8 and suppression of engraftment, 9 in bone marrow transplant recipients.…”

mentioning

confidence: 99%

Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation

Tokimasa

Hara

Osugi

et al. 2002

Bone Marrow Transplant

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Summary:Human herpesvirus 6 (HHV-6) infection and disease are serious complications of allogeneic hematopoietic stem cell transplantation (allo-SCT). Ganciclovir (GCV) is effective against HHV-6 in vitro but the antiviral susceptibility of HHV-6 has not been well characterized in vivo. We retrospectively compared the HHV-6 reactivation rate in pediatric allo-SCT recipients with and without GCV prophylaxis. The HHV-6 reactivation rate at 3 weeks after allo-SCT in patients without prophylactic GCV administration was significantly higher than that in those receiving prophylactic GCV (11/28 vs 0/13, P Ͻ 0.01). Five of 36 patients without prophylactic GCV showed clinical manifestations including skin rash, interstitial pneumonitis, persistent thrombocytopenia, enterocolitis and thrombotic microangiopathy, respectively. HHV-6-associated symptoms were observed in one of the 13 patients receiving prophylactic GCV. This patient showed fever, diarrhea and graft rejection concomitantly with a sudden increase of HHV-6 DNA copy number. Patients who received GCV for treatment of HHV-6 infection showed an improvement in symptoms and/or decrease of HHV-6 copy number. Thus, GCV is effective for treating HHV-6 disease after allo-SCT in vivo.

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Human Herpesvirus 6 in Lung Tissue from Patients with Pneumonitis after Bone Marrow Transplantation

Abstract: The concentrations of HHV-6 genome in lung tissue and their relation to changes in serologic titers support an association between HHV-6 infection and idiopathic pneumonitis in immunocompromised hosts.

Cited by 294 publications

References 29 publications

The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia

The clinical importance of bronchoalveolar lavage in allogeneic SCT patients with pneumonia

Successful treatment of human herpesvirus-6 encephalitis after bone marrow transplantation

Ganciclovir is effective for prophylaxis and treatment of human herpesvirus-6 in allogeneic stem cell transplantation

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