title: Epstein-Barr virus (EBV) load in cerebrospinal fluid and peripheral blood of patients with EBV-associated central nervous system diseases after allogeneic hematopoietic stem cell transplantation.
abstract: BACKGROUND
  To evaluate the diagnostic and prognostic utility of monitoring the Epstein-Barr virus (EBV) load in the cerebrospinal fluid (CSF) and peripheral blood for the patients with EBV-associated central nervous system (CNS) diseases after allogeneic hematopoietic stem cell transplantation (allo-HSCT), 172 patients undergoing allo-HSCT were enrolled in the study.
  
  
  METHODS
  The EBV DNA levels of blood were monitored regularly in recipients of transplants for 3 years post transplantation. The EBV DNA levels of CSF were monitored in patients with EBV-associated CNS diseases before the treatment and at different points following the treatment.
  
  
  RESULTS
  Post-transplant EBV-associated diseases developed in 27 patients, including 12 patients with EBV-associated CNS diseases. The 3-year cumulative incidences of EBV-associated diseases and EBV-associated CNS diseases were 19.5 ± 3.5% and 8.6 ± 2.4%, respectively. Patients with EBV-associated diseases showed higher loads of EBV DNA in their blood compared with patients with EBV DNA-emia. No difference was seen between the EBV DNA levels of blood in patients with CNS involvement and patients without CNS involvement. The EBV DNA loads of blood increased 3-14 days before the clinical manifestations of EBV-associated diseases emerged. The EBV DNA loads of CSF were higher than that of blood in patients with EBV-associated CNS diseases. In 12 patients with EBV-associated CNS diseases, EBV DNA levels were declining in both blood and CSF with the control of diseases, and the EBV DNA loads of CSF decreased faster than that of blood in 5 patients who responded to treatment, and the EBV DNA levels of CSF increased in 5 patients who were unresponsive to treatment. On multivariate analysis, the use of anti-thymocyte globulin and intensified conditioning regimens were independent risk factors for EBV-associated diseases and EBV-associated CNS diseases.
  
  
  CONCLUSIONS
  EBV-associated CNS diseases are not rare after allo-HSCT. The EBV DNA loads of CSF could act as an important indicator, but the EBV DNA loads of blood could not, for the diagnosis, prognosis, and therapeutic evaluation of EBV-associated CNS diseases.
authors.affiliation: Department of Hematology, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong, China. liuqifa628@163.com
authors.forename: Q-F
authors.initials: QF
authors.lastname: Liu
authors.forename: Y-W
authors.initials: YW
authors.lastname: Ling
authors.forename: Z-P
authors.initials: ZP
authors.lastname: Fan
authors.forename: Q-L
authors.initials: QL
authors.lastname: Jiang
authors.forename: J
authors.initials: J
authors.lastname: Sun
authors.forename: X-L
authors.initials: XL
authors.lastname: Wu
authors.forename: J
authors.initials: J
authors.lastname: Zhao
authors.forename: Q
authors.initials: Q
authors.lastname: Wei
authors.forename: Y
authors.initials: Y
authors.lastname: Zhang
authors.forename: G-P
authors.initials: GP
authors.lastname: Yu
authors.forename: M-Q
authors.initials: MQ
authors.lastname: Wu
authors.forename: R
authors.initials: R
authors.lastname: Feng
mesh_terms: D000293:Adolescent; D000328:Adult; D020805:Central Nervous System Viral Diseases / Q000097:blood* / Q000134:cerebrospinal fluid* / Q000453:epidemiology / Q000821:virology; D002648:Child; D004279:DNA, Viral / Q000097:blood / Q000134:cerebrospinal fluid; D020031:Epstein-Barr Virus Infections / Q000097:blood / Q000134:cerebrospinal fluid / Q000453:epidemiology / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000302:isolation & purification / Q000502:physiology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D014184:Transplantation, Homologous / Q000009:adverse effects; D019562:Viral Load; D055815:Young Adult
chemical_list: D004279:DNA, Viral
keywords: EBV-associated diseases; Epstein-Barr virus; allogeneic hematopoietic stem cell transplantation; central nervous system; cerebrospinal fluid