Cytomegalovirus Viral Load Continues to Predict Poor Outcomes in Adults and Children Despite Improved Hematopoietic Cell Transplantation Success

Background Recent advances of graft-versus-host disease prevention strategies have led to improved overall survival after hematopoietic cell transplantation (HCT). Whether cytomegalovirus (CMV) viral load continues to predict CMV disease, overall mortality and non-relapse mortality is poorly defined. Methods CMV seropositive patients undergoing allogeneic HCT between 2007-2017 with weekly CMV DNA PCR surveillance and preemptive therapy were analyzed. Multivariate Cox proportional hazards models were used to estimate the association between CMV viral load by day 100 at different thresholds with CMV disease, overall and non-relapse mortality up to one year post HCT. Results Of 1539 patients transplanted in the study period, 1349 survived >100 days after HCT and were included in the analyses. By day 100 post-HCT, CMV reactivation at any level was observed in 76% with the lowest incidence at all levels in young children. Pediatric patients had significantly less cytomegalovirus disease compared to the adult population. CMV reactivation was associated with a higher risk of CMV disease [aHR 6.8 (3.54-13)]; it was also associated with overall and non-relapse mortality among day 100 survivors, although the association was diminished recently. The strongest correlation was still apparent between viral load and mortality in patients with a viral load >3 log10 and lymphocyte counts <300 cells/mm3. Conclusions CMV viral load continued to be a strong predictor for CMV disease. With improved transplantation techniques, the association of viral load with overall and non-relapse mortality is diminished, but the effect was still present in patients with severe immunosuppression.