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. 2025 Jul 17:13:1627990.
doi: 10.3389/fped.2025.1627990. eCollection 2025.

Analysis of risk factors for Epstein-Barr virus reactivation and progression to post-transplant lymphoproliferative disorder in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation

Lanzhou Jia  1   2   3 , Hui Yang  1   2   3 , Ya Zhou  1   2   3 , Yan Meng  1   2   3 , Luying Zhang  1   2   3 , Xiaoying Lei  1   2   3 , Xianming Guan  1   2   3 , Jie Yu  1   2   3 , Ying Dou  1   2   3
Affiliations

Analysis of risk factors for Epstein-Barr virus reactivation and progression to post-transplant lymphoproliferative disorder in pediatric patients undergoing allogeneic hematopoietic stem cell transplantation

Lanzhou Jia et al. Front Pediatr. .

Abstract

Background: Post-transplant infections are common complications, and the reasons are pre-transplant conditioning, time required for post-transplant immune reconstitution, and use of immunosuppressive agents. We aimed to analyze the risk factors for Epstein-Barr virus (EBV) reactivation and its progression to post-transplant lymphoproliferative disorder (PTLD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT) in children and to determine the EBV PCR diagnostic threshold for PTLD.

Methods: We retrospectively analyzed clinical data of 309 patients who underwent allo-HSCT without engraftment failure at the Children's Hospital of Chongqing Medical University from January 1, 2016, to December 21, 2021. The occurrences of EBV reactivation and PTLD were also recorded. The risk factors for EBV reactivation and progression to PTLD were analyzed, and the diagnostic threshold for PTLD was determined using whole-blood EBV PCR.

Results: Among 309 pediatric patients, 256 experienced EBV reactivation within one year and 12 progressed to PTLD. Univariate and multivariate analyses indicated that ATG was the independent risk factor for EBV reactivation. Grade III-IV acute graft-vs.-host disease (aGVHD) was the risk factor for PTLD after EBV reactivation.

Conclusions: Post-transplant EBV reactivation is a common complication after allo-HSCT, but rarely progresses to PTLD. Identification of the risk factors for PTLD and regular monitoring of the EBV-DNA load play important roles in prevention and cure of PTLD after HSCT.

Keywords: Epstein–Barr virus (EBV); allogeneic hematopoietic stem cell transplantation; pediatric; post-transplant lymphoproliferative disorder (PTLD); reactivation.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

Figure 1
Figure 1
Cumulative incidence of Epstein–Barr virus (EBV) reactivation within one year of allogeneic hematopoietic stem cell transplantation.
Figure 2
Figure 2
Monitoring of post-transplant whole blood EBV-DNA (natural logarithm) in patients diagnosed with PTLD (data points below the detection threshold are recorded as natural logarithm of 200 copies/ml. Different colored lines represent different patients, indicates the status of each monitoring point, ×indicates the death of the patient, ▴ represents the nearest monitoring point before Rituximab.
Figure 3
Figure 3
ROC curve analysis of sensitivity and specificity for diagnosing PTLD based on whole-blood EBV PCR.
Figure 4
Figure 4
Survival curves of 256 patients underwent allo-HSCT with EBV reactivation.
See this image and copyright information in PMC

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