Cytomegalovirus (CMV) is a significant cause of morbidity and mortality following
transplantation, especially in the pediatric population, who remain at high risk of primary
infection. The availability of effective
antiviral therapy has led to dramatic improvements in the outcome of CMV
infection in patients undergoing
transplantation. In recent years, three major strategies have been developed for the prevention of CMV disease in this population: reduction of risk of viral acquisition or reactivation by management of risk factors; prophylaxis of all 'at-risk' patients using prophylactic strategies for a defined period of time, initiated at or near the time of transplant; and pre-emptive treatment with
ganciclovir of selected 'at-risk' patients, guided by either
laboratory markers indicative of
subclinical infection or the presence of specific risk factors. In general, well designed comparative studies of one or more
antiviral agents for the prevention of CMV have not been carried out. While
ganciclovir appears to be more effective than
aciclovir, its tolerability profile is less optimal. The use of
foscarnet avoids myelosuppresions, but is associated with significant nephrotoxicity. Its use should be reserved for patients unable to tolerate
ganciclovir or with
ganciclovir-resistant CMV disease. Similar to
foscarnet, the high frequency of nephrotoxicity associated with the use of
cidofovir limits its use to clinical scenarios suggestive of
ganciclovir resistance. Newer options, such as
valaciclovir and
valganciclovir, are currently under investigation and preliminary experience has been promising. Finally, passive immunoprophylaxis has been shown to prevent CMV disease after solid
organ transplantation, but its use in
bone marrow transplantation is controversial. Essentially, pre-emptive strategies have relied on the quantitation in the peripheral blood of CMV
phosphoprotein pp65
antigen and/or the polymerase chain reaction assay. Strict guidelines for the use of those assays as a guide to pre-emptive
therapy have not been standardized. Prospective trials comparing pre-emptive
therapy using either intravenous or oral
ganciclovir, and now oral
valganciclovir or
valaciclovir, are necessary to determine the relative cost effectiveness and efficacy of these alternative strategies. Finally, it remains controversial as to whether prophylaxis or pre-emptive
therapy is the optimal strategy for preventing CMV disease. While a growing body of literature describes these approaches in adult transplant recipients, published experience in children has been much more limited.