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In the general population, cytomegalovirus (CMV) is a common infection that is frequently acquired at a young age; one in three children in the United States are infected with CMV. In patients undergoing transplantation, CMV most frequently presents as reactivation of a remotely acquired infection, whereas primary CMV infection in seronegative (−) recipients transmitted via allografts harvested from CMV-seropositive (+) donors poses the greatest threat of infection and viral end-organ disease. Naturally acquired CMV infection or infection via unscreened blood and blood products are seldom seen in this population. It is also important to note that in patients undergoing stem cell allograft transplantation, donor CMV (+) status is regarded as a more important prognosticator for complications and unfavorable outcome than transplantation with lesser human leukocyte antigen (HLA-C, HLA-DQ, or HLA-D) mismatch allografts or existence of acute or chronic graft-versus-host disease (GVHD). Similarly, in solid organ allograft recipients, CMV donor/recipient serologic discordance (D+/R−) has been the single most important determinant for post-transplant CMV viremia, CMV disease and survival of the allograft. Compared to other donor prognostic factors such as advance age or blood group type, graft from CMV (−) donor is preferable. HSCT after myeloablative conditioning, major HLA antigen mismatched and/or T cell-depleted grafts, and patients given cord blood stem cells with GVHD have higher susceptibility for CMV infection. Furthermore, CMV infections play an increasingly recognizable role in the incidence of GVHD, risk for invasive fungal disease, recurrence of malignancy, and non-cancer relapse mortality following allograft stem cell transplantation; even in the era of universal antiviral prophylaxis and/or preemptive therapy. Treatment with high-dose antirejection or anti-GVHD therapy with calcineurin inhibitors, corticosteroids, cytotoxic drugs, biologics like anti-CD52, anti-IL2, to a lesser extent, other anti-B cell antibodies that target CD20 and CD19 cell surface antigens are known to deplete hosts’ effective anti-CMV immune surveillance. Strategies to mitigate CMV risk in this population include identifying high-risk cohort prior to transplantation, antiviral drug and immunoprophylaxis for infection prevention, continued effective surveillance for sustained and rising viremia, and institution of preemptive therapy when appropriate. An overview of CMV risk and infection prevention, hosts' immunity -pathogen interaction, spectrum of clinical illness, diagnosis and management of CMV infection with an emphasis on new antiviral drugs, emerging strategies to modify patients' immune-inflammatory response to cytomegalovirus infection, ongoing research in vaccine development, and adaptive cellular immunotherapy are the focus of discussion in this chapter.

DOI: 10.1007/978-1-4939-9034-4_37