The Rate of Cytomegalovirus Infection and Disease in Correlation with the Type of Hematopoietic Stem Cell Transplantation in the Era of Preemptive Antiviral Therapy

Abstract

Background: Despite diagnostic and therapeutic advances, cytomegalovirus (CMV) has remained a significant complication after hematopoietic stem cell transplantation (HSCT). The widespread use of preemptive antiviral therapy has reduced the occurrence of early CMV disease and changed its epidemiology. In order to define the current trends and to establish future guidelines, we retrospectively analyzed the rate of CMV infection and disease in the following types of HSCT: autologous HSCT, fully matched-, mismatched- and haploidentical-allogeneic HSCT. Patients & Methods: Patients receiving HSCT in the Hadassah Hebrew University Medical Center over a 5-year period (April 2003-March 2008) were retrospectively reviewed for the occurrence of CMV infection and disease in relation to the 4 types of HSCT. Infection was defined by the presence of positive CMV antigenemia and/or real time PCR assays, and patients received preemptive antiviral treatment upon detection of CMV infection. Results: Of 634 patients who received HSCT in our center during the study period, 276 (43.5%) developed CMV infection and 16 (2.5%) had evidence for CMV disease, with the vast majority of disease occurring among haploidentical HSCT recipients. The occurrence of CMV infection and disease by transplant type is presented in the table: Type of HSCT Total Patients (tested patients) Number of patients with CMV infection (% of tested patients) CMV disease (% of tested patients; % of patients with CMV infection) (A.) autologous HSCT 240 (214) 55 (25.7%) 1 (0.5%; 1.8%) (B.) fully matched 289 (254) 145 (57.1%) 1 (0.4%; 0.7%) (C.) mismatched- 44 (38) 20 (52.6%)%) 0 (D.) haploidentical-allogeneic HSCT 113 (102) 56 (54.9%) 14 (13.7%; 25.0%) No statistically significant differences were found between the CMV-donor and recipient serostatus in the 3 categories of allogeneic HSCT. The rate of CMV infection was significantly higher in allogeneic compared to autologous HSCT (p < 0.001), with no significant differences between the 3 types of allogeneic HSCT. However, the rate of disease was significantly higher in haploidentical HSCT (p < 0.001). Fifteen of the 16 patients with CMV disease had a fatal outcome. We are presently analyzing the viral load kinetics and the associated risk factors in the different HSCT categories, Conclusions: Preemptive antiviral approach proved to be effective in the prevention of CMV disease in autologous and fully matched as well as mismatched allogeneic HSCT recipients. The increased rate of CMV disease and associated mortality in recipients of haploidentical HSCT despite preemptive antiviral therapy reflects their delayed immune reconstitution, and raises concern regarding the effectiveness of the current preemptive antiviral approach. Based on our findings, close monitoring and prophylactic antiviral treatment should be employed in this high-risk subgroup of HSCT recipients.