title: Relationship of immunosuppression to Epstein-Barr viral load and lymphoproliferative disease in pediatric heart transplant patients.
abstract: BACKGROUND
  Post-transplant lymphoproliferative disease (PTLD) is a severe complication in transplant recipients. Detection of increased Epstein-Barr viral (EBV) load in the peripheral blood acts as a surrogate marker for increased risk of PTLD development. We prospectively monitored EBV load, immunosuppression and PTLD in pediatric heart transplant (HTx) patients to determine risk factors for an increased EBV load and risk of PTLD.
  
  
  METHODS
  Forty-one pediatric heart transplant recipients were included and underwent prospective monitoring of their immunosuppression and ethylene-diamine tetraacetic acid (EDTA) blood sampling for EBV load (copies/microg DNA) measurement using quantitative real-time polymerase chain reaction (PCR; TaqMan) during January 2001 to December 2006.
  
  
  RESULTS
  EBV load was measurable in 70% and was significantly increased (>2,000 copies/microg DNA) in 35% of the patients, with a median EBV load of 5,100 (range 0 to 50,665 copies/microg DNA). Increased EBV load was detected in patients receiving CsA-azathioprine or more than two doses of anti-thymocyte globulin (ATG) and in those <10 years of age, without any significant differences in CsA blood levels. Lowest or negative EBV load was measured in patients receiving CsA-mycophenolate mofetil (MMF) or CsA only. CsA blood levels were not predictable for increased EBV load or PTLD. Six patients developed a EBV-associated B-cell lymphoma (PTLD), among whom 4 (67%) were receiving CsA-azathioprine.
  
  
  CONCLUSIONS
  Frequent EBV load monitoring identifies patients at high risk for PTLD development. Azathioprine and ATG are major risk factors for increased EBV load and PTLD and patients may benefit from a change of immunosuppression in addition to pre-emptive anti-viral or anti-tumor strategies.
authors.affiliation: Department of Congenital Heart Defects/Pediatric Cardiology, Deutsches Herzzentrum Berlin, Germany. sschubert@dhzb.de
authors.forename: Stephan
authors.initials: S
authors.lastname: Schubert
authors.forename: Christiane
authors.initials: C
authors.lastname: Renner
authors.forename: Markus
authors.initials: M
authors.lastname: Hammer
authors.forename: Hashim
authors.initials: H
authors.lastname: Abdul-Khaliq
authors.forename: Hans Brendan
authors.initials: HB
authors.lastname: Lehmkuhl
authors.forename: Felix
authors.initials: F
authors.lastname: Berger
authors.forename: Roland
authors.initials: R
authors.lastname: Hetzer
authors.forename: Petra
authors.initials: P
authors.lastname: Reinke
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000032:analysis*; D020031:Epstein-Barr Virus Infections / Q000209:etiology / Q000821:virology*; D005260:Female; D005500:Follow-Up Studies; D006084:Graft Rejection / Q000150:complications / Q000517:prevention & control*; D016027:Heart Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000235:genetics*; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D007166:Immunosuppressive Agents / Q000009:adverse effects; D007223:Infant; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000821:virology*; D008297:Male; D011183:Postoperative Complications; D011379:Prognosis; D012189:Retrospective Studies; D019562:Viral Load
chemical_list: D004279:DNA, Viral; D007166:Immunosuppressive Agents