Threshold of Quantitative Cytomegalovirus DNA PCR for Preemptive Treatment in Pediatric Hematopoietic Stem Cell Transplant Recipients

Abstract

Background: Consensus cytomegalovirus (CMV) DNA viral load thresholds for intervention in hematopoietic stem cell transplant (HSCT) recipients have not been established, especially in children. This study aimed at obtaining viral load thresholds of CMV DNA to guide preemptive management in pediatric HSCT recipients.

Materials and methods: A total of 465 blood samples from 177 children who received HSCT between 2015 and 2019 were included in a single center in Korea. The samples were analyzed for CMV infection by both antigenemia assay and quantitative DNA polymerase chain reaction. The 2 assay results were compared for the 233 samples which were collected when antiviral treatment has not been initiated. We determined the viral loads corresponding to the antigenemia of 5 pp65-positive cells/2×10 5 white blood cells (WBCs) as the level for initiating preemptive therapy.

Results: Sixty percent of the samples were collected within 100 days (39.7% in 0 to 50 d, 60.2% in 0 to 100 d) from the graft infusion. The correlation between CMV DNA viral load and CMV antigenemia level increased significantly after 50 days from the graft infusion ( r =0.71 vs. r =0.93, P <0.0001). The correlation was greater in the antiviral treatment-naive group than the treatment group ( r =0.75 vs. r =0.66, P <0.0001). Under receiver operating characteristic curve analysis of the treatment-naive group, the estimated threshold CMV DNA viral loads corresponding to 5 pp65-positive cells/2×10 5 WBCs was 898 IU/mL.

Conclusions: The CMV DNA levels that corresponded to 5 pp65-positive cells/2×10 5 WBCs was 900 IU/mL in the HSCT group. The proposed viral load thresholds can be used to guide preemptive therapy in pediatric HSCT recipients, especially in the preengraftment period.