Value of donor and recipient anti-CMV IgG titer in predicting CMV reactivation after allogeneic hematopoietic stem cell transplantation

Abstract

Despite advances in diagnosis and treatment, cytomegalovirus (CMV) reactivation remains a serious complication following allogeneic Hematopoietic Stem Cell Transplantation (allo-HSCT). Our objectives were to explore the impact of pre-transplant anti-CMV IgG titers in both donor and recipient on the occurrence of post-transplant CMV reactivation and to determine a threshold titer that would allow for better stratification of the post-transplant reactivation risk. We conducted a case-control study involving pediatric allo-HSCT recipients. We included 24 cases and 48 randomly selected controls. In univariate analysis, D-/R+ pre-transplant CMV serostatus (p=0.013), recipient anti-CMV IgG titer (p=0.012) and anti-CMV IgG titer R/D ratio (p=0.049) were associated with CMV reactivation. Donor anti-CMV IgG titer was a protective factor (p=0.046). Multivariate analysis showed that D-/R+ pre-transplant CMV serologic status (adjusted OR=6.874; 95% CI (1.37 – 34.4); p=0.019) and recipient anti-CMV IgG titer (adjusted OR=1.005; 95% CI (1.00 – 1.01); p=0.033) were independent risk factors. ROC curve analysis showed that optimal cut-off value to predict CMV reactivation was 113.75 AU/ml for the recipient anti-CMV IgG titer (Se=72.2%; Sp= 64.9%; AUC=0.701; p=0.016) and 1 for the anti-CMV IgG titer R/D ratio (Se=77.8%; Sp=78.4%; AUC=0.814; p<0.001). The prevalence of CMV reactivation was higher in patients with pre-transplant anti-CMV IgG titer >113.75 AU/mL (50% versus 16%; p= 0.002) and in those with anti-CMV IgG titer R/D ratio >1 (64% versus 15%; p<0.001). In summary, we have shown that both pre-transplant anti-CMV IgG titer in recipient and anti-CMV IgG titer R/D ratio were associated with the risk of CMV reactivation following allo-HSCT. Furthermore, a high pre-transplant anti-CMV IgG titer in the donor would be a protective factor. These findings would be useful for better risk stratification of CMV reactivation and adaptation of surveillance strategies.