Risk Factors for Posttransplant Lymphoproliferative Disorder in Children: A Systematic Review and Meta-analysis

Abstract.

Posttransplant lymphoproliferative disorder (PTLD) is the most frequent malignancy in pediatric patients following transplantation. This systematic review aimed to identify risk factors for PTLD in pediatric recipients of solid organ transplantation (SOT) and hematopoietic stem cell transplantation. Following PRISMA guidelines, a literature search was conducted in Medline, Embase, and Cochrane databases for studies published up to August 2025. Study characteristics were extracted, and data on potential risk factors were collected when available. Methodological quality was assessed using the Newcastle-Ottawa Scale for observational studies. Meta-analyses were performed when feasible. Of 4917 records identified, 80 studies were included. Among the investigated variables, negative recipient Epstein–Barr virus (EBV) serology before transplantation emerged as the most significant risk factor for PTLD. The pooled relative risk for PTLD in EBV-seronegative SOT recipients was 3.35 (95% confidence intervals, 2.43–4.60), and this association remained consistent across organ-specific subgroups. Additional variables, such as demographic characteristics, EBV viral load, immunosuppressive therapy, and rejection episodes, showed discordant results across studies, likely reflecting limited data and methodological heterogeneity. Negative pretransplant EBV serology is confirmed as a major risk factor for PTLD in pediatric transplant recipients. Moreover, the findings of this review provide a comprehensive synthesis of the available evidence regarding risk factors of PTLD in pediatric recipients of both SOT and hematopoietic stem cell transplantation, highlighting the need for further large-scale studies to clarify additional determinants.