Persistent Epstein-Barr viral load in Epstein-Barr viral naïve pediatric heart transplant recipients: Risk of late-onset post-transplant lymphoproliferative disease

Abstract

AIMTo 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.METHODSA 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.RESULTSPTLD 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).CONCLUSIONThere 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.

Epstein‐Barr virus associated smooth muscle tumors in solid organ transplant recipients: Incidence over 31 years at a single institution and review of the literature

“…Persistently elevated high EBV viral loads measured in blood occurs commonly in solid organ transplant recipients, particularly those experiencing donor‐derived primary EBV infection; these patients are described as having a chronic EBV viral load phenotype . Interestingly, both immunocompetent and transplanted children infected with EBV at a very young age appear to have higher viral loads . This may make young children more vulnerable to concomitant or sequential PTLD and EBV‐SMT, as compared to their adult counterparts, which is also suggested by our review of the literature.…”

Epstein-Barr virus (EBV) reactivation and therapeutic inhibitors

“…49 50 Chronic uncontrolled EBV reactivation has been shown to be an important factor in the pathogenesis of NPC 51 and PTLD. 52 It has been shown that an NPC-associated BZLF1 variant is associated with the enhancement of lytic EBV infection. 53 PTLD has also been shown to be associated with detectable circulating EBV genome and ZEBRA, the gene product of BZLF1.…”

Hepatic Epstein-Barr Virus-Associated Smooth Muscle Tumor in a Heart and Liver Transplant Recipient

“…The chief risk factor for the development of EBV-SMT is believed to be high EBV viral load. 3 , 5 , 6 Although the mechanism of EBV-SMT is not known, one theory proposed that EBV entry into mesenchymal cells or their precursors may be mediated by high local levels of viremia without access to the B cell receptor CD21. 7 , 8 Once infected, EBV alters molecular signaling pathways, particularly the mechanistic target of rapamycin/Akt (also known as protein kinase B) pathway.…”