High risk of death due to bacterial and fungal infection among cytomegalovirus (CMV)-seronegative recipients of stem cell transplants from seropositive donors: Evidence for indirect effects of primary CMV infection

The impact of cytomegalovirus (CMV) serostatus (seropositive [(+)]or seronegative [(-)]) of the donor (D) and recipient (R) on mortality after allogeneic non-T cell-depleted stem cell transplantation (SCT) in the era of preemptive therapy was assessed among 1750 patients by means of multivariable Cox regression models. In an analysis that included only pre-SCT variables, D+/R+ and D+/R- patients had the highest risk for mortality. After neutropenia or the occurrence of CMV disease was controlled for only D+/R- patients remained at a significantly higher risk for mortality. Mortality due to bacteremia or invasive fungal infection was higher among D+/R- (18.3%) than D-/R- (9.7%) patients (P < .001). Thus, CMV serostatus remains associated with mortality; neutropenia due to ganciclovir administration and CMV disease explain the association with mortality among seropositive recipients. However, in D+/R- subjects, mortality appears to be associated with bacterial and fungal infection, indicating a possible immunomodulatory effect of primary CMV infection that was undetected despite intensive monitoring.