Cytomegalovirus Viral Load Continues to Predict Poor Outcomes in Adults and Children Despite Improved Hematopoietic Cell Transplantation Success.
Alicja Sadowska-Klasa, Hu Xie, Danniel Zamora, Alpana Waghmare, Joshua A Hill, Elizabeth R Duke, Margaret L Green, Masumi Ueda Oshima, Brenda M Sandmaier, Keith R Jerome, Wendy M Leisenring, Michael Boeckh
Abstract
Open AccessBackground: 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 nonrelapse mortality is poorly defined. Methods: CMV-seropositive patients undergoing allogeneic HCT between 2007 and 2017 with weekly CMV DNA polymerase chain reaction 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 and overall and nonrelapse mortality up to 1 year post-HCT. Results: Of 1539 patients who received a transplant 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 CMV disease compared to the adult population. CMV reactivation was associated with a higher risk of CMV disease (adjusted hazard ratio, 6.8 [95% confidence interval, 3.54-13]); it was also associated with overall and nonrelapse 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 count <300 cells/μL. 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 nonrelapse mortality is diminished, but the effect was still present in patients with severe immunosuppression.