Epstein–Barr virus‐associated post‐transplant lymphoproliferative disorders in pediatric transplantation: A prospective multicenter study in the United States

Abstract Background Epstein–Barr virus (EBV)‐associated post‐transplant lymphoproliferative disorders (PTLD) is the most common malignancy in children after transplant; however, difficulties for early detection may worsen the prognosis. Methods The prospective, multicenter, study enrolled 944 children (≤21 years of age). Of these, 872 received liver, heart, kidney, intestinal, or multivisceral transplants in seven US centers between 2014 and 2019 (NCT02182986). In total, 34 pediatric EBV+ PTLD (3.9%) were identified by biopsy. Variables included sex, age, race, ethnicity, transplanted organ, EBV viral load, pre‐transplant EBV serology, immunosuppression, response to chemotherapy and rituximab, and histopathological diagnosis. Results The uni−/multivariable competing risk analyses revealed the combination of EBV‐seropositive donor and EBV‐naïve recipient (D+R−) was a significant risk factor for PTLD development (sub‐hazard ratio: 2.79 [1.34–5.78], p = .006) and EBV DNAemia (2.65 [1.72–4.09], p < .001). Patients with D+R− were significantly more associated with monomorphic/polymorphic PTLD than those with the other combinations ( p = .02). Patients with monomorphic/polymorphic PTLD ( n = 21) had significantly more EBV DNAemia than non‐PTLD patients ( p < .001) and an earlier clinical presentation of PTLD than patients with hyperplasias ( p < .001), within 6‐month post‐transplant. Among non‐liver transplant recipients, monomorphic/polymorphic PTLD were significantly more frequent than hyperplasias in patients ≥5 years of age at transplant ( p = .01). Conclusions D+R− is a risk factor for PTLD and EBV DNAemia and associated with the incidence of monomorphic/polymorphic PTLD. Intensive follow‐up of EBV viral load within 6‐month post‐transplant, especially for patients with D+R− and/or non‐liver transplant recipients ≥5 years of age at transplant, may help detect monomorphic/polymorphic PTLD early in pediatric transplant.