Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients

: A major risk faced by bone‐marrow and solid organ transplant patients is the development of post‐transplant lymphoproliferative disease or post‐transplant lymphoma (PTLD). In pediatric transplantation, PTLD onset is often associated with a rapid rise in Epstein–Barr virus (EBV) load in peripheral blood mononuclear cells (PBMC). We have analyzed EBV viral loads in PBMC over time using real‐time quantitative PCR in 56 patients, 19 of which have been followed for more than 1 year. In nine patients; eight bone marrow (BMT) and one kidney transplant, PTLD was associated with a rapid rise in viral load, exceeding 1 × 105 EBV genomes/μg of PBMC‐derived DNA. Four of these patients exceeded 1 × 106 EBV genomes/μg PBMC DNA. All patients with viral loads exceeding 1 × 105 EBV genomes/μg PBMC DNA were clearly at high risk for transplant‐associated mortality, with only six of nine surviving. Importantly, only one of these deaths was directly attributable to EBV. A second elevated state of EBV load, defined as exceeding 2 × 104 EBV genomes/μg PBMC, was seen in a total of 12 BMT, kidney, heart, and liver transplant patients. These patients did not appear to be at immediate lethal risk for PTLD and one EBV‐attributable death was found in this group as well. Thirty‐four transplant patients whose EBV viral load oscillated from undetectable to 10 000 EBV genomes/μg PBMC DNA are reported as well. The threshold for normal EBV viral load based on our combined experience with viral load analysis is defined as 1 × 104 EBV genomes/μg PBMC DNA. The ability to rapidly analyze EBV load allows rapid changes in viral load, such as those that occur with PTLD onset, and the impact of anti‐CD20 antibody therapy to be rapidly detected.