title: Dynamics of Epstein-Barr viral load after hematopoietic stem cell transplantation and effect of preemptive rituximab therapy.
abstract: BACKGROUND
  Epstein-Barr virus (EBV) displays oncogenic properties, particularly in the immunocompromised host. Notably, hematopoietic stem cell transplantation (HSCT) recipients with a detectable blood EBV viral load (BEBVL) are considered at higher risk of post-transplant lymphoproliferative diseases (PTLD). Therefore, BEBVL is monitored after HSCT, and preemptive rituximab may be used in patients with high values. However, little is known about post-HSCT BEBVL dynamics, and the threshold that should lead to anti-CD20 therapy is poorly defined.
  
  
  METHODS
  We retrospectively analyzed the post-HSCT BEBVL of 332 adult HSCT recipients in our center from 2005 to 2013, including the effect of rituximab.
  
  
  RESULTS
  Detection of BEBVL >100, 1000, 5000, 10 000, and 50 000 copies/mL occurred in, respectively, 77.7%, 69.6%, 37.0%, 27.1%, and 7.5% of the patients after a respective median time of 9, 14, 15, 16, and 14 weeks. No BEBVL threshold was associated with an overall survival difference. Seventy-eight patients received rituximab, with a BEBVL decrease in most. Among patients with detectable BEBVL, long-term survival did not differ in rituximab treated and non-treated, except for patients with BEBVL ≥50 000. Only one case of PTLD was observed.
  
  
  CONCLUSIONS
  BEBVL is frequently detectable after HSCT, but suggests no strong association with survival. Preemptive rituximab therapy threshold remains to be defined.
authors.affiliation: Infectious Disease Unit, University Hospital, Grenoble, France.|Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.|Infectious Disease Unit, University Hospital Joseph Raseta Befelatanana, Antananarivo, Madagascar.
authors.forename: Mihaja
authors.initials: M
authors.lastname: Raberahona
authors.affiliation: Infectious Disease Unit, University Hospital, Grenoble, France.|Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.
authors.forename: Chloe
authors.initials: C
authors.lastname: Wackenheim
authors.affiliation: Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.|Virology Laboratory, Infectious Agent Department, University Hospital, Grenoble, France.|HIV and Human Persistent Virus, Institut de Biologie Structurale, Grenoble, France.
authors.forename: Raphaele
authors.initials: R
authors.lastname: Germi
authors.affiliation: Cell Therapy Unit, Hematology Department, University Hospital, Grenoble, France.
authors.forename: Martin
authors.initials: M
authors.lastname: Carré
authors.affiliation: Cell Therapy Unit, Hematology Department, University Hospital, Grenoble, France.
authors.forename: Claude-Eric
authors.initials: CE
authors.lastname: Bulabois
authors.affiliation: Cell Therapy Unit, Hematology Department, University Hospital, Grenoble, France.|TIMC-TheREx - UMR 5525 CNRS-UGA, Grenoble, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Thiébaut
authors.affiliation: Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.|Virology Laboratory, Infectious Agent Department, University Hospital, Grenoble, France.|HIV and Human Persistent Virus, Institut de Biologie Structurale, Grenoble, France.
authors.forename: Julien
authors.initials: J
authors.lastname: Lupo
authors.affiliation: Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.|Virology Laboratory, Infectious Agent Department, University Hospital, Grenoble, France.
authors.forename: Touyana
authors.initials: T
authors.lastname: Semenova
authors.affiliation: Cell Therapy Unit, Hematology Department, University Hospital, Grenoble, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Cahn
authors.affiliation: Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.|Virology Laboratory, Infectious Agent Department, University Hospital, Grenoble, France.|HIV and Human Persistent Virus, Institut de Biologie Structurale, Grenoble, France.
authors.forename: Patrice
authors.initials: P
authors.lastname: Morand
authors.affiliation: Infectious Disease Unit, University Hospital, Grenoble, France.|Fédération d'Infectiologie Multidisciplinaire de l'Arc Alpin, Faculty of Medicine, Université Grenoble Alpes, Grenoble, France.|HIV and Human Persistent Virus, Institut de Biologie Structurale, Grenoble, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Epaulard
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000276:immunology* / Q000401:mortality / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects* / Q000401:mortality; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D016867:Immunocompromised Host / Q000276:immunology*; D007155:Immunologic Factors / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D008232:Lymphoproliferative Disorders / Q000276:immunology / Q000517:prevention & control* / Q000821:virology; D008297:Male; D008875:Middle Aged; D012189:Retrospective Studies; D000069283:Rituximab / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016019:Survival Analysis; D014184:Transplantation, Homologous / Q000009:adverse effects / Q000401:mortality; D016896:Treatment Outcome; D019562:Viral Load / Q000187:drug effects*; D014775:Virus Activation / Q000187:drug effects*; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D007155:Immunologic Factors; D000069283:Rituximab
keywords: Epstein-Barr virus; hematopoietic stem cell transplantation; preemptive therapy; rituximab; viral load