Introduction: Epstein-Barr virus (EBV)-associated post-transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, early detection is still challenging, which may result in a worse prognosis.
Methods: This prospective, multicenter, study enrolled 944 children (≤ 21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in 7 US centers between 2014, and 2019 (NCT02182986). Participants were followed for a minimum of 12 months and up to four years based on the time of enrollment. In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Sex, age, race, ethnicity, transplanted organ, EBV viral load, pre-transplant EBV serology of donor and recipient, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis were analyzed.
Results: Eighteen male and 16 female patients developed EBV+ PTLD, and the median ages at transplant and PTLD diagnosis were 4.3 years (IQR: 1.4–13.0) and 4.4 years (IQR: 2.6–12.8), respectively. The number of transplanted organs was 12 livers, 8 hearts, 7 kidneys, and 7 intestines including multiple organs. The 1-year, 2-year, and 3-year survival rates of patients after PTLD diagnosis were 90%, 83%, and 83%, respectively. The entire cohort was divided into two cohorts: 21 patients with destructive PTLD (monomorphic and polymorphic) and 13 patients with nondestructive PTLD (early lesion). Ages at transplant and PTLD diagnosis were significantly higher in destructive than in nondestructive PTLD patients (P = 0.03 and P = 0.04, respectively). Destructive PTLD patients had more extranodal lesions (P < 0.001) and were more frequently treated with chemotherapy or rituximab than nondestructive PTLD patients (P = 0.01). Destructive PTLD patients had detectable EBV by PCR more frequently than nondestructive PTLD patients within six months after transplant (P = 0.04, Figure 1-A), and EBV viral load at PTLD diagnosis was significantly higher in destructive than in nondestructive PTLD patients (P = 0.04). Pediatric recipients developed significantly more destructive PTLD than nondestructive PTLD within six months (P = 0.002, Figure 1-B). Patients ≥ 5 years of age at transplant had significantly more destructive than nondestructive PTLD (P = 0.047, Figure 2-A). Moreover, among patients with destructive PTLD, there were significantly more liver transplant recipients at age ≤ 5 years at transplant and non-transplant recipients at age ≥ 5 years at transplant (P = 0.02, Figure 2-B).
Conclusion: Destructive PTLD had significantly earlier onset and higher EBV viral load within six months post-transplant than nondestructive PTLD. Close follow-up of EBV within six months after transplant, especially in children ≤ 5 years at liver transplants or ≥ 5 years at non-liver transplants, may facilitate early detection of destructive PTLD.