title: [Monitoring of early Epstein-Barr virus reactivation and preemptive therapy after allogeneic hematopoietic stem cell transplantation].
abstract: OBJECTIVE
  To investigate early Epstein-Barr virus (EBV) reactivation and the outcome of preemptive therapy after allogeneic hematopoietic stem cell transplantation (allo-HSCT).
  
  
  METHODS
  From January 2007 to January 2009, totally 277 patients after allo-HSCT were studied (haploidentical 116, unrelated 75, matched sibling 86). Conditioning regimens were mainly busulfan (BU) + cyclophosphamide (CY)/fludarabine (Flu) or total body irradiation (TBI) + CY/Flu. Antihuman thymocyte globulin (ATG) was added in haploidentical and unrelated transplants. Plasma EBV DNA was monitored once to twice weekly in the first 3 months after allo-HSCT with real time quantitative polymerase chain reaction (RQ-PCR). EBV viremia was diagnosed when EBV DNA was more than 5 × 10(2) copies/ml but without symptoms. Acyclovir (10 mg/kg, intravenous drip, 8 h) was used for preemptive therapy and immuno-suppressants were decreased if possible.
  
  
  RESULTS
  Totally 33 patients (11.9%) developed EBV viremia with a median time at day 44 (day 19 to day 84). The incidences of EBV viremia in the transplants from matched sibling, haploidentical, unrelated donors were 0, 15.5%, 20.0%, respectively. There was no significant difference between haploidentical and unrelated transplants (P = 0.09), but much less EBV viremia was seen in matched sibling transplant (P = 0.001). Twenty of 33 patients (60.6%) had complete response to preemptive therapy. The median time to reach EBV DNA negative in plasma was 11 (4 - 56) d. The median duration of preemptive therapy was 21 (14 - 60) d. Both univariate and multivariate analysis indicated that haploidentical and unrelated transplants, acute graft versus host disease (GVHD) were the risk factors for EBV viremia. Two-year overall survival in the patients with EBV viremia was significantly lower than that without EBV viremia (54.2% vs 72.1%, P = 0.006).
  
  
  CONCLUSIONS
  Our large clinical study has demonstrated that preemptive therapy with acyclovir that is guided by EBV viremia is effective in majority of the patients with high-risk for EBV reactivation after allo-HSCT, which may further decrease the risk for developing life-threatening EBV disease or post-transplantation lymphoproliferative disorder. Haploidentical and unrelated transplants, acute GVHD are the risk factors for EBV viremia which has negative impact on survival.
authors.affiliation: Department of Bone Marrow Transplantation, Beijing Daopei Hospital, Beijing 100049, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Tong
authors.initials: T
authors.lastname: Wu
authors.forename: Xing-yu
authors.initials: XY
authors.lastname: Cao
authors.forename: Jing-bo
authors.initials: JB
authors.lastname: Wang
authors.forename: Yuan
authors.initials: Y
authors.lastname: Sun
authors.forename: Yan-li
authors.initials: YL
authors.lastname: Zhao
authors.forename: Wan-ming
authors.initials: WM
authors.lastname: DA
authors.forename: Shu-quan
authors.initials: SQ
authors.lastname: Ji
authors.forename: Chun-rong
authors.initials: CR
authors.lastname: Tong
authors.forename: Dao-pei
authors.initials: DP
authors.lastname: Lu
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy*; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011184:Postoperative Period; D014184:Transplantation, Homologous; D019562:Viral Load; D014766:Viremia / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy*; D014775:Virus Activation; D055815:Young Adult
chemical_list: D004279:DNA, Viral; D000212:Acyclovir