title: Monitoring and modulation of Epstein-Barr virus loads in pediatric transplant patients.
abstract: 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 x 10(5) EBV genomes/microg of PBMC-derived DNA. Four of these patients exceeded 1 x 10(6) EBV genomes/microg PBMC DNA. All patients with viral loads exceeding 1 x 10(5) EBV genomes/microg 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 x 10(4) EBV genomes/microg 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/microg 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 x 10(4) EBV genomes/microg 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.
authors.affiliation: Department of Pediatrics, Section of Hematology-Oncology, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA. rorentas@mail.mcw.edu
authors.forename: Rimas J
authors.initials: RJ
authors.lastname: Orentas
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Schauer
authors.forename: Frederick W
authors.initials: FW
authors.lastname: Ellis
authors.forename: Joanna
authors.initials: J
authors.lastname: Walczak
authors.forename: James T
authors.initials: JT
authors.lastname: Casper
authors.forename: David A
authors.initials: DA
authors.lastname: Margolis
mesh_terms: D016026:Bone Marrow Transplantation; D004279:DNA, Viral / Q000032:analysis; D016679:Genome, Viral; D004854:Herpesvirus 4, Human / Q000235:genetics; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000821:virology*; D008223:Lymphoma / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000821:virology*; D008991:Monitoring, Physiologic; D016377:Organ Transplantation; D016133:Polymerase Chain Reaction / Q000379:methods; D011184:Postoperative Period; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D004279:DNA, Viral