Management of Cytomegalovirus Infection after Solid-Organ or Stem-Cell Transplantation

Abstract

Recent developments in diagnosis and therapy of cytomegalovirus (CMV) infection have helped to reduce CMV-associated mortality following organ transplantation. However, CMV is still associated with significant morbidity in recipients of an allogeneic stem cell or solid-organ transplant. The clinical symptoms of active CMV infection per se and, most importantly, the prevalence of life-threatening CMV disease show broad variation between different patient populations depending on the type of transplant and the intensity of immunosuppression. Therefore, management of CMV infection must be stratified according to risk profiles of a given patient population. In the past decade, novel diagnostic assays (such as rapid shell-vial culture, polymerase chain reaction, pp65 antigen assay and sensitive hybridisation techniques) have been developed. Broad variations in the ability of a given test to predict a positive or negative risk of developing CMV disease have been observed between different transplant modalities. Highly effective therapeutic agents against CMV, such as ganciclovir and foscarnet, have become available, improving the outcome of patients with CMV disease. Moreover, antiviral prophylaxis with ganciclovir or aciclovir has been shown to reduce CMV infection and CMV disease following organ transplantation. However, these drugs are often associated with considerable toxicity. Moreover, antiviral resistance to ganciclovir and foscarnet has been observed in recipients of organ transplants and, even more frequently, in patients with AIDS. Short courses of pre-emptive antiviral therapy, administered after CMV infection has been documented by sensitive diagnostic techniques prior to the development of clinical symptoms, help to reduce duration and incidence of adverse effects associated with antiviral drugs and are thus an attractive alternative strategy compared with antiviral prophylaxis. Newer options, such as oral ganciclovir, cidofovir, benzimidavir (1263W94) and lobucavir, are currently under investigation and might further improve the management of CMV infection in recipients of solid-organ or stem-cell transplants.