Published online Dec 24, 2016. doi: 10.5500/wjt.v6.i4.729
Peer-review started: July 12, 2016
First decision: September 12, 2016
Revised: October 5, 2016
Accepted: November 21, 2016
Article in press: November 23, 2016
Published online: December 24, 2016
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.
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.
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 group vs 12/54 (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 EBV vs 4.2% (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 EBV vs 36% (41/113) patients with low or undetectable EBV after HT (P < 0.05).
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.
Core tip: Post-transplant lymphoproliferative disorder (PTLD) after heart transplantation is a severe complication where there is still limited information is available. There are many publications on estimations of PTLD frequency in different settings and types of patient, as well as the factors associated with its appearance and prognosis. But, most studies do not take into account the length of follow-up which may be misleading given that patients are exposed to the risk of immunosuppression over a long period of follow-up. This study is unique that, it is a single center study span over a period of 18 years in which maintenance immunosuppression therapy and management of rejection episodes remained same throughout. Although, a single center study result cannot be generalized, however it adds to the existing literature for risk stratification of these patients based on whole blood Epstein-Barr virus (EBV) polymerase chain reaction (PCR) after accounting for the time since transplant and patients¡¯ pre-transplant EBV serostatus. This paper also highlights the risk of acute rejection after reduction or alteration in immunosuppression in patients with high EBV load by PCR without any effect on the occurrence of PTLD.