ABSTRACT
Human cytomegalovirus (CMV) remains a significant cause of morbidity and mortality after hematopoietic stem cell transplantation (HSCT). Several important changes in the epidemiology of CMV infection and disease have occurred over the past decade, including an increase in late disease after day 100 and an increase in early disease in the setting of high posttransplant immunosuppression, as is seen with highdose steroids, the use of antithymocyte globulin (ATG) and CD34 depletion. Despite the introduction of multiple therapeutic agents such as ganciclovir, foscarnet, cidofovir, and immunotherapy, the mortality from CMV disease remains unacceptably high. This chapter discusses the epidemiology of, as well as treatment and prevention strategies for, CMV infection and disease. Aspects of the immunobiology of CMV and details of current diagnostic techniques, including methods of CMV quantitation, are reviewed elsewhere.1-3
Without antiviral prophylaxis, CMV infection and disease are more common after allogeneic transplant than after autologous transplant, with seropositive recipients being at highest risk for disease.4 Reactivation of CMV occurs approximately 70-80% of the time in seropositive recipients of allogeneic HSCT, and without prophylaxis 20-35% of these will progress to CMV disease.5 In contrast, 15-20% of seronegative individuals who receive a transplant from a seropositive donor will experience primary CMV infection.4,6 In autologous transplantation, 25-40% of seropositive patients will have reactivation, with disease following in only 1-6% of cases.7,8 Even in the era of ganciclovir
ient has remained significant with regard to the development of CMV disease and overall outcome after transplantation. Seronegative recipients have less risk of persistent pp65 antigenemia than do seropositive recipients, regardless of the donor serostatus. CMV interstitial pneumonitis is also seen less often in seronegative recipients when compared with seropositive recipients. Seropositive and seronegative recipients who receive products from seropositive donors also have worse overall survival when compared with seronegative donor/recipient pairs. Seropositivity has been identified as an independent risk factor for the development of acute graft-versus-host disease (GVHD) in T-celldepleted recipients,9,10 which adversely affects mortality. Therefore, although pre-emptive ganciclovir can effectively control CMV disease, seropositivity remains a risk factor for increased mortality following HSCT.
