RECIPIENT-TO-DONOR ANTI-CMV IGG RATIO AS A PREDICTOR OF CMV REACTIVATION AFTER ALLOGENEIC HEMATOPOIETIC STEM CELL TRANSPLANTATION: A CASE-CONTROL STUDY

Background: 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. Methods: We conducted a unicentric retrospective case-control study involving pediatric allo-HSCT recipients. All donors were related (genotypically identical or haploidentical). CMV reactivation was defined by a viral load ≥ 150 IU/ml in plasma. We included 24 cases (patients who had an episode of CMV reactivation in the first 100 days after HSCT) and 48 randomly selected controls (patients without CMV reactivation in the first 100 days after HSCT). Results: In univariate analysis, factors associated with CMV reactivation were D-/R+ pre-transplant CMV serostatus (p=0.013), recipient anti-CMV IgG titer (p=0.012), R/D anti-CMV IgG ratio (p=0.049), HLA haploidentical related donor (p=0.0001), GvHD prophylaxis with combination of cyclosporin A, cyclophosphamide and mycophenolate mofetil (p=0.0001), acute GvHD (p=0.001) and corticosteroids (p=0.0001). Donor anti-CMV IgG titer was a protective factor (p=0.046). Multivariate analysis showed that male donor gender (adjusted OR=4.919; 95% CI (1.103 – 21.942); p=0.037), D-/R+ pre-transplant CMV serologic status (adjusted OR=6.874; 95% CI (1.372 – 34.444); p=0.019), recipient anti-CMV IgG titer (adjusted OR=1.005; 95% CI (1.000 – 1.010); p=0.033), HLA haploidentical related donor (adjusted OR=5.472; 95% CI (1.334 – 22.453); p=0.018) and acute GvHD (OR=7.116; 95% CI (1.770 – 28.604) ; p=0.006) were independent risk factors for CMV reactivation after allo-HSCT. ROC curve analysis showed that the 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 R/D anti-CMV IgG 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 R/D anti-CMV IgG ratio >1 (64% versus 15%; p<0.001). Conclusion: In summary, we have shown that both pre-transplant anti-CMV IgG titer in the recipient and R/D anti-CMV IgG ratio were associated with the risk of CMV reactivation following allo-HSCT. Furthermore, a high pre-transplant anti-CMV IgG titer in the donor was associated with a lower incidence of reactivation. Our findings add to the published experiences that show that pre-HCT CMV serology titer impacts on post-HCT reactivation and warrants validation in larger multicenter cohorts.