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. 2023 Nov 7;24(22):16029.
doi: 10.3390/ijms242216029.

Pre-Emptive Use of Rituximab in Epstein-Barr Virus Reactivation: Incidence, Predictive Factors, Monitoring, and Outcomes

Apostolia Papalexandri  1 , Eleni Gavriilaki  2 , Anna Vardi  1 , Nikolaos Kotsiou  2 , Christos Demosthenous  1 , Natassa Constantinou  1 , Tasoula Touloumenidou  1 , Panagiota Zerva  1 , Fotini Kika  1 , Michalis Iskas  1 , Ioannis Batsis  1 , Despina Mallouri  1 , Evangelia Yannaki  1 , Achilles Anagnostopoulos  1 , Ioanna Sakellari  1
Affiliations

Pre-Emptive Use of Rituximab in Epstein-Barr Virus Reactivation: Incidence, Predictive Factors, Monitoring, and Outcomes

Apostolia Papalexandri et al. Int J Mol Sci. .

Abstract

Post-transplant lymphoproliferative disease (PTLD) is a fatal complication of hematopoietic cell transplantation (HCT) associated with the Epstein-Barr virus (EBV). Multiple factors such as transplant type, graft-versus-host disease (GVHD), human leukocyte antigens (HLA) mismatch, patient age, and T-lymphocyte-depleting treatments increase the risk of PTLD. EBV reactivation in hematopoietic cell transplant recipients is monitored through periodic quantitative polymerase chain reaction (Q-PCR) tests. However, substantial uncertainty persists regarding the clinically significant EBV levels for these patients. Guidelines recommend initiating EBV monitoring no later than four weeks post-HCT and conducting it weekly. Pre-emptive therapies, such as the reduction of immunosuppressive therapy and the administration of rituximab to treat EBV viral loads are also suggested. In this study, we investigated the occurrence of EBV-PTLD in 546 HCT recipients, focusing on the clinical manifestations and risk factors associated with the disease. We managed to identify 67,150 viral genomic copies/mL as the cutoff point for predicting PTLD, with 80% sensitivity and specificity. Among our cohort, only 1% of the patients presented PTLD. Anti-thymocyte globulin (ATG) and GVHD were independently associated with lower survival rates and higher treatment-related mortality. According to our findings, prophylactic measures including regular monitoring, pre-emptive therapy, and supportive treatment against infections can be effective in preventing EBV-related complications. This study also recommends conducting EBV monitoring at regular intervals, initiating pre-emptive therapy when viral load increases, and identifying factors that increase the risk of PTLD. Our study stresses the importance of frequent and careful follow-ups of post-transplant complications and early intervention in order to improve survival rates and reduce mortality.

Keywords: EBV reactivation; hematopoietic stem cell transplantation; post-transplant lymphoproliferative disease; retrospective studies; viral infection.

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Conflict of interest statement

E.G. is supported by the ASH Global Research Award and has consulted for Omeros Cooperation. The funder was not involved in the study design, collection, analysis, interpretation of data, the writing of this article, or the decision to submit it for publication.

Figures

Figure 1
Figure 1
Patient sampling scheme employed in the study.
Figure 2
Figure 2
A cutoff of 67,150 copies predicted post-transplant lymphoproliferative disease (PTLD) with 80% sensitivity and specificity.
See this image and copyright information in PMC

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