Contents lists available at ScienceDirect Journal of Clinical Virology journal homepage: www.elsevier.com/locate/jcv Full length article Epstein-Barr virus DNA load kinetics analysis in allogeneic hematopoietic stem cell transplant recipients: Is it of any clinical usefulness? Carlos Solano a,b , Eva María Mateo c , Ariadna Pérez a , Alberto Talaya d , María José Terol a , Eliseo Albert c , Estela Giménez c , Víctor Vinuesa c , José Luis Piñana a , Juan Carlos Hernández Boluda a , David Navarro c,d, ⁎ a Hematology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain b Department of Medicine, School of Medicine, University of Valencia, Valencia, Spain c Microbiology Service, Hospital Clínico Universitario, Institute for Research INCLIVA, Valencia, Spain d Department of Microbiology, School of Medicine, University of Valencia, Spain ARTICLE INFO Keywords: Epstein-Barr (EBV) Plasma EBV DNA-load EBV DNA doubling time EBV DNA half-life Allogeneic stem cell transplantation Post-transplant lymphoproliferative disease ABSTRACT Background: There is a lack of clinical information regarding the usefulness of plasma Epstein-Barr virus (EBV) DNA load kinetics analyses in the management of EBV infections in allogeneic hematopoietic stem cell trans- plantation (allo-HSCT) recipients. Namely, it remains unknown whether this type of analysis can help physicians to anticipate the development of high-level EBV DNAemia episodes requiring rituximab treatment or predict the risk of recurrent EBV DNAemia or post-transplant lymphoproliferative disorders (PTLDs). Study design: Unicentric, retrospective, observational study including 142 consecutive patients undergoing T-cell replete allo-HSCT. The plasma EBV DNA load was monitored on a weekly basis using the artus ® EBV PCR kit. Results: Fifty-five of the 142 patients (38.7%) developed at least one episode of EBV DNAemia; 13 of the 55 initial EBV DNAemia episodes (23.6%) were preemptively treated with rituximab, 7 patients had a recurrent episode of EBV DNAemia, and biopsy-proven PTLDs were diagnosed in 4 patients. The initial plasma EBV DNA load was not significantly different (P = 0.269) in episodes of self-resolving EBV DNAemia, those requiring rituximab treatment, or those leading to PTLDs. The plasma EBV DNA load doubling times were similar across all the groups (P = 0.799), and the EBV DNA-load half-life was not associated with the occurrence of recurrent EBV DNAemia (P = 0.550). Conclusion: Plasma EBV DNA-load kinetics analyses are unlikely to be useful in predicting the occurrence of high-level EBV DNAemia, PTLD, or recurrent EBV DNAemia. 1. Background Epstein-Barr virus (EBV)-related post-transplant lymphoprolifera- tive disorders (PTLDs) are a feared complication in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT) because of its severe clinical course and high mortality rate [1]. Monitoring EBV DNA load in blood by real-time PCR has become a mainstay practice for estimating the risk of an impending PTLD, triggering the implementa- tion of preventative strategies (such as a reduction in im- munosuppression or initiation of preemptive therapy with rituximab), and for assessing therapeutic responses in cases of high-level EBV DNAemia or PTLDs [2–4]. The European Conference on Infections in Leukemia (ECIL)-6 guidelines for EBV-PTLDs advise prospective screening for EBV DNAemia by quantitative PCR after allo-HSCT in patients at a high-risk of PTLDs [5]. Nevertheless, no specific re- commendation is given regarding the EBV DNA copy number that should trigger the initiation of preemptive therapy [5]. In addition, it states that the rate of EBV DNA-load increase is likely to be clinically relevant, but does not define what magnitude of increase should be considered important [5]. Viral DNA load kinetic parameters, such as the doubling time or half-life have been shown to be useful in the management of CMV infection in the allo-HSCT setting [6–10]. To our knowledge, no studies have specifically investigated whether the ana- lysis of EBV DNA-load dynamics is of any value in the clinical man- agement of EBV infection in allo-HSCT recipients. http://dx.doi.org/10.1016/j.jcv.2017.10.016 Received 21 September 2017; Accepted 24 October 2017 ⁎ Corresponding author at: Microbiology Service, Hospital Clínico Universitario, and Department of Microbiology, School of Medicine, Av. Blasco Ibáñez 17, 46010 Valencia, Spain. E-mail address: david.navarro@uv.es (D. Navarro). Abbreviations: aGvHD, acute graft versus host disease; allo-HSCT, allogeneic hematopoietic stem cell transplantation; ATG, anti-thymocyte globulin; dt, doubling time; EBV, Epstein- Barr virus; PTLD, post-transplant lymphoproliferative disorders Journal of Clinical Virology 97 (2017) 26–32 1386-6532/ © 2017 Elsevier B.V. All rights reserved. MARK