Management of viral infections in bone marrow transplant recipients

Abstract

Following bone marrow transplantation (BMT), patients are at risk of viral infections because of prolonged and often profound immunosuppression. Specific viral pathogens that have been identified include members of the Herpesvirus family such as herpes simplex virus (HSV), cytomegalovirus (CMV), varicella zoster virus (VZV), Epstein-Barr virus (EBV), human herpes virus-6 (HHV-6) and adenovirus, as well as respiratory viruses including respiratory syncytial virus (RSV), influenza and parainfluenza. Infections caused by HSV occur most commonly during the pre-engraftment period following BMT. Both intravenous and oral aciclovir (acyclovir) have been effective in the treatment of mucocutaneous HSV infections following BMT. Additionally, prevention strategies using oral or intravenous aciclovir have been effective in decreasing the occurrence of HSV infection following BMT. Resistance of HSV strains to aciclovir is documented, although relatively infrequently. Foscarnet is a therapeutic alternative in patients with aciclovir-resistant HSV infections. CMV-associated infections, particularly CMV interstitial pneumonia (CMV-IP), remain a major cause of mortality following allogeneic BMT. Recipients of allogeneic BMT are more likely to develop significant CMV disease than those receiving autologous grafts. Ganciclovir plus intravenous immunoglobulin has substantially decreased the mortality associated with CMV-IP, although other, more effective strategies are still needed. Aciclovir, foscarnet and ganciclovir have been used to prevent infection and disease in patients who are seropositive or have seropositive donors. Ganciclovir given pre-emptively to patients with CMV infection has significantly decreased the incidence of disease and mortality following BMT. VZV infections occur 5 to 12 months after BMT, when immune reconstitution is still ongoing. Most VZV infections respond to high-dosage intravenous aciclovir. Until further data are available, oral antiviral agents should be used with caution. Prevention strategies are not required, as most patients respond to aciclovir therapy and suffer minimal morbidity from VZV infections. EBV infections may be asymptomatic, but have also been associated with serious complications including post-transplant lymphoproliferative disorders. Antiviral therapies have often been ineffective, but strategies involving adoptive transfer of donor leukocytes with function immunologic activity appear promising. The clinical significance of post-BMT HHV-6 infection remains to be determined. As the role of HHV-6 following BMT is unknown, treatment and prevention strategies are lacking. Reactivation of adenovirus infections typically occur 2 to 3 months following BMT. Infected BMT recipients infrequently develop disseminated infection, although, in those with disseminated infection mortality rates approach 50%. Adenovirus infections have also been associated with late onset haemorrhagic cystitis. No antiviral agents has been consistently effective against adenovirus. Respiratory viruses including RSV, influenza and parainfluenza can cause symptomatic infection following BMT and often occur in conjunction with community outbreaks. Early initiation of aerosolised ribavirin may be of benefit. Influenza vaccines are often ineffective in preventing infection when given early after BMT or in patients with graft-versus-host disease.