Impact of CMV infection on pediatric allogeneic HSCT outcomes in a region of high CMV seroprevalence: a non-TBI cohort study.

Abstract

Cytomegalovirus (CMV) infection remains a major complication after allogeneic hematopoietic stem cell transplantation (allo-HSCT), particularly in regions with high CMV seroprevalence. Data regarding CMV outcomes in pediatric recipients receiving exclusively non-total body irradiation (non-TBI) conditioning are limited. In this single-center retrospective cohort study, we evaluated 514 pediatric patients (<18 years) who underwent first allo-HSCT with non-TBI conditioning between 2016 and 2022. Patients were categorized according to post-transplant CMV infection status. CMV surveillance was performed using quantitative PCR. Transplant outcomes, graft-versus-host disease (GVHD), survival, and relapse were analyzed using Kaplan-Meier and competing-risk models. Time-dependent Cox regression was used to evaluate the temporal association between CMV infection and severe acute GVHD (aGVHD). CMV infection developed in 293 patients (57%). CMV-positive patients had significantly higher rates of aGVHD (71.3% versus 50.7%, P < 0.001), severe grade III-IV aGVHD (36.9% versus 28.1%, P < 0.001), and hemorrhagic cystitis (28.3% versus 19.5%, P = 0.021). Competing-risk analysis demonstrated that CMV infection was independently associated with increased risk of any-grade aGVHD (sHR = 1.82, 95% CI: 1.45-2.28, P < 0.001) and severe aGVHD (sHR = 1.66, 95% CI: 1.23-2.26, P = 0.001). No significant differences were observed in neutrophil or platelet engraftment, chronic GVHD, relapse, overall survival (OS), or disease-free survival (DFS). However, among CMV-positive patients, CMV infection preceding aGVHD was associated with inferior 5-year OS compared with aGVHD preceding CMV infection (61.5% versus 73.9%, P = 0.03). CMV infection remains highly prevalent after pediatric non-TBI allo-HSCT in high-seroprevalence settings and is strongly associated with increased risk and severity of aGVHD. Early CMV infection may adversely influence survival by promoting subsequent alloimmune complications.