== Epidemiologic Risk-factors Associated with CMV Disease in Individuals Undergoing Hematopoietic Cell Transplantation Abbreviations: CMV, Cytomegalovirus; R+, recipient serpositive; D, Donor seronegative; R, recipient seronegative; D+, Donor positive; PBMC, peripheral blood mononuclear cells; GVHD, graft-versus-host disease; MMF, mycophenolate mofetil. significant mortality.3Prevention strategies aimed at limiting latent reactivation and viral replication have been successful in reducing the incidence of CMV pneumonia to approximately 4% in high-risk seropositive recipients4,5, but changes in transplant methods such as the expanded use of high-risk unrelated and wire blood donor grafts, have also defined new populations more likely to develop CMV invasive disease.6Unfortunately, even with potent antiviral therapy and Tepilamide fumarate advanced critical care and attention management, death from CMV pneumonia remains unacceptably high.3,7 With this review we address the epidemiology, pathogenesis, diagnostics, and evaluate up-to-date treatment and Tepilamide fumarate prevention Tepilamide fumarate strategies for CMV pneumonia in HCT individuals. We also discuss ongoing study focused on novel treatment and prevention options, including antivirals in development. With the continued growth of transplant programs throughout the world, an increased quantity of crucial care physicians will have exposure to and obligations for diagnosing and treating this major post-transplant infectious complication. We hope that this review will serve as a state-of-the-art upgrade on this infrequent yet important HCT complication for those with encounter in transplantation and provide a foundation for those new Tepilamide fumarate to this unique immunocompromised populace. == Epidemiology == == Incidence == The incidence of CMV pneumonia in the early years of HCT, prior to the intro of CMV prevention strategies, was around 1035% after allogeneic transplantation and 16% in autologous transplant recipients.8The institution of preemptive strategies used at most centers in the US (see prevention section below) have decreased the overall incidence of CMV disease in HCT recipients to around 58%.35The burden of disease has also shifted, as gastrointestinal (GI) disease is now considered the most common form of CMV disease in HCT; pneumonia is definitely estimated to make up about 1/3 of disease instances.5,9The majority of cases of CMV pneumonia still occur in the early post-transplant period ( day +100), but the number of those occurring in the late period (after day 100) have increased.3,10Late CMV disease occurs more frequently in subject matter who experienced CMV reactivation within the first 3 months after HCT (27), had graft-versus-host disease (GVHD), have prolonged lymphopenia at day time 100 (or low CD4 count) and in those seropositive recipients who received of a CMV-seronegative donor graft (28).912 == Outcomes == Outcomes in individuals who develop CMV pneumonia are generally very poor, even with the use of potent antiviral providers and aggressive critical care management. Rates of mortality associated with CMV pneumonia in the pre-treatment era were nearly 100%13, but with the introduction of ganciclovir (GCV) and additional antiviral therapy options, rates of death have fallen to approximately 3050%.1,3,14,15The need for respiratory and critical care support is strongly associated with increased mortality.16Interestingly, in some retrospective studies rare patients with proven CMV pneumonia survive actually without antiviral therapy1, suggesting different host factors may help determine survival post-infection. == Pre and Post-Transplant Risk Factors (Table 1) == == Table 1. == Epidemiologic Risk-factors Associated with CMV Disease in Individuals Undergoing Hematopoietic Cell Transplantation Abbreviations: CMV, Cytomegalovirus; R+, recipient serpositive; D, Donor seronegative; R, recipient seronegative; Tepilamide fumarate D+, Donor positive; PBMC, peripheral blood mononuclear cells; GVHD, graft-versus-host disease; MMF, mycophenolate mofetil. Strength of association shown by the number of arrows:shows increased rate; shows decreased rate; shows conflicting data. Detection in blood increases the risk for the development for both early and late CMV disease. Probably related to all lymphocyte subsets, but CD4 and CD8 probably most important. == Serologic status (Donor and Recipient) == Probably the most prominent risk element for CMV pneumonia is the transplant recipient’s CMV serologic status prior to transplantation (Table 1). Individuals who are known to be seropositive (R+) are at TRA1 the greatest risk for reactivation of latent computer virus through the transplant process and have the highest rates of subsequent CMV disease.3,1720The relationship of donor serostatus in R+ recipients remains controversial.2123In contrast to their high-risk counterparts, seronegative patients (R) who receive a positive donor graft (D+) have a much lower risk of CMV infection (1219%) and CMV disease (35%).20,24Less than half of the D+/R individuals that are found to have.