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.

Background: Langerhans cell histiocytosis (LCH) is an inflammatory myeloid neoplasm characterized by clonal proliferation of CD1a+ and CD207+ dendritic cells, resulting from the constitutive activation of extracellular signal-regulated kinases.LCH is the most common histiocytic disorder in children. Clinical presentations vary widely, and treatment is tailored according to disease severity. Objective: We aimed to study the clinical characteristics, treatment response, and progression of LCH in children. Methods: A retrospective study was conducted including all patientsaged less than 18 years and diagnosed with LCH between January 2010 and July 2023 in two referral pediatric centers. Diagnosis of LCH was confirmed by DC1a expression. Patients were classified into single-system LCH and multisystem LCH (involving two or more organs).Patients were stratified into two groups: RO- and RO+ (with the involvement of one or more risk organs). The 2010 French guidelines and, more recently, the 2021 recommendations were adopted for LCH management. Results: Forty-three patients were enrolled in the study. The median age at diagnosis was three years, [IQR]: 1.5–6 years. Multisystem LCH withrisk organ (RO) involvement (MS RO+LCH) was the most prevalent group accounting for 44% of cases.Sixteenpatients(37%)were diagnosed with single-system (SS) LCH. The patients with multisystemic LCH were significantly younger than those with single-system LCH (p=0.003). Bone involvement was the most prevalent, occurring in 77% of patients, followed by skin involvement in 46% and liver involvement in 44%. Tumorous lesions in the central nervous system were observed in five patients.The BRAF-V600E mutation was identified in eight of the nine cases tested.Thirty-four patients received a vinblastine-based first-line therapy; six patients (18%) showednon-response after two courses of vinblastine induction. Two patients received Aracytine and Cladribine;a favorable outcome was observed in one case. BRAF inhibitorswere used in four cases; the responsewas favorable in two cases.The cumulative incidence ofreactivations at 5 years was 28%. Ten patients (23%) exhibited at least one permanent consequence including diabetes insipidus (n=8) and neurodegenerative LCH (n=1). The five-year overall survival (OS) and disease-free survival (DFS) rates were 93% and 63%, respectively. RO involvement and response to vinblastine induction influenced OS and DFS in univariate analysis. Conclusion: Although the improvement of overall survival in LCHthrough risk-adapted management, concerns persist regarding the potential risk for reactivation and the long-term consequences. The involvement of risk organs and non-response to vinblastine induction could worsen the prognosis.