title: Persistent Epstein-Barr viral load in Epstein-Barr viral naïve pediatric heart transplant recipients: Risk of late-onset post-transplant lymphoproliferative disease.
abstract: OBJECTIVE
  To examine the risk of late-onset post-transplant lymphoproliferative disorder (PTLD) in the presence of persisting high Epstein-Barr virus (EBV) in EBV naïve pediatric heart transplant (HT) recipients.
  
  
  METHODS
  A retrospective review of the medical records of the 145 pediatric HT recipients who had serial EBV viral load monitoring at our center was performed. We defined EBV naive patients whose EBV serology either IgM or IgG in the blood were negative at the time of HT and excluded passive transmission from mother to child in subjects less than 6 mo of age.
  
  
  RESULTS
  PTLD was diagnosed in 8 out of 145 patients (5.5%); 6/91 (6.5%) in those who were EBV seropositive and 2/54 (3.7%) in the EBV naïve group at the time of HT (P= 0.71). We found 32/145 (22%) patients with persistently high EBV load during continuing follow-up; 20/91 (22%) in EBV seropositive groupvs12/54 (22%) in EBV naïve group (P= 0.97). There was no significant association between pre-HT serostatus and EBV load after transplant (P> 0.05). In the EBV seropositive group, PTLD was diagnosed in 15% (3/20) of patients with high EBVvs4.2% (3/71) of patients with low or undetectable EBV load (P= 0.14) whereas in EBV naïve patients 8.3% (1/12) of those with high EBV load and 2.3% (1/42) with low or undetectable EBV load (P= 0.41). There was a highly significant association between occurrence of PTLD in those with high EBV load and duration of follow up (4.3 ± 3.9 years) after HT by Cochran-Armitage test for the entire cohort (P= 0.005). At least one episode of acute rejection occurred in 72% (23/32) of patients with high EBVvs36% (41/113) patients with low or undetectable EBV after HT (P< 0.05).
  
  
  CONCLUSIONS
  There is an association between persistently high EBV load during post-HT follow up and the occurrence of late-onset PTLD in pediatric HT recipients irrespective of serostatus at the time of transplant. The occurrence of allograft rejection increased in patients with high EBV load presumably due to reduction in immunosuppression.
authors.affiliation: Bibhuti Das, David Fixler, Deptartment of Pediatrics, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, United States.
authors.forename: Bibhuti
authors.initials: B
authors.lastname: Das
authors.affiliation: Bibhuti Das, David Fixler, Deptartment of Pediatrics, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, United States.
authors.forename: Robert
authors.initials: R
authors.lastname: Morrow
authors.affiliation: Bibhuti Das, David Fixler, Deptartment of Pediatrics, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, United States.
authors.forename: Rong
authors.initials: R
authors.lastname: Huang
authors.affiliation: Bibhuti Das, David Fixler, Deptartment of Pediatrics, Children's Medical Center, University of Texas Southwestern Medical Center, Dallas, TX 75235, United States.
authors.forename: David
authors.initials: D
authors.lastname: Fixler
keywords: Allograft rejection; Epstein-Barr virus; Immunosuppression; Pediatric heart transplantation; Post-transplant lymphoproliferative disorder