Adenovirus infection in adult allogeneic hematopoietic stem cell transplant recipients: Systematic review and meta-analysis.

Adenovirus (AdV) infection in adult patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) is associated with poor outcomes but management strategies differ among the centers. Data on incidence and risk factors for AdV infections in adult allo-HCT recipients are limited. Recommendations for routine monitoring for AdV are mainly based on data from pediatric cohorts, in which the incidence of AdV infection is much higher than in adults. The primary aim of this study was to report pooled incidence of AdV infections in adult allo-HCT recipients. Secondary aims were to report the incidence of AdV viremia, AdV high-level viremia (>1000 copies/ml), and AdV related mortality. The PRISMA system was used for systematic search. The Science Direct, and Scopus databases were searched for studies published between January 2000 and January 2025. In total, the meta-analysis included 25 studies reporting data on 61,832 patients, with 12 of them reporting regular AdV screening. The pooled incidence of any AdV infection was 7.3 % (95 % confidence interval CI, 6.2-8.4), the pooled incidence of AdV viremia was 7.2 % (95 % CI, 5.5-9.0), and the pooled incidence of high-level viremia was 3.4 % (95 % CI, 2.2-4.5). The overall mortality due to any AdV infection was 16.7 % (95 % CI, 12.1-21.3), mortality due to AdV in patients with viremia was 11.5 % (95 % CI, 7.3-15.7), and mortality due to AdV in patients with high-level viremia was 24.0 % (95 % CI, 11.1-36.9). The pooled incidence of AdV infection after HCT from different donors was: matched related donor 4.9 % (95 % CI, 3.0-6.9), matched unrelated donor 5.6 % (95 % CI, 2.9-8.2), and haploidentical donor 7.4 % (95 %CI, 5.3-9.5), with no statistically significant differences for donor type. When the incidence of AdV based on donor type was compared within the same study, in 3 among 7 studies, the incidence was higher in case of haploidentical donor (all 3 studies with post-transplant cyclophosphamide platform), while no difference in incidence was found in 4 studies. High AdV incidence was reported in 3 studies after transplant from cord blood (13-30 %). The subgroup analyses revealed that incidence of AdV infection and AdV viremia were higher in studies performing PCR screening and in studies with lower number of patients. No factors influencing AdV attributable mortality were identified. In conclusion, this meta-analysis identified the rate of AdV infection or viremia in adult allo-HCT recipients of over 7 %, and AdV-related mortality lower than previously reported, but as high as 24 % in patients with high level viremia. The role of routine screening and optimal pre-emptive management of AdV in adult patients require further studies.