title: Prospective Epstein-Barr virus-related post-transplant lymphoproliferative disorder prevention program in pediatric allogeneic hematopoietic stem cell transplant: virological monitoring and first-line treatment.
abstract: BACKGROUND
  In 28 pediatric allogeneic hematopoietic stem cell transplant (allo-HSCT) recipients, we aimed to evaluate: (i) the impact of routine Epstein-Barr virus (EBV) DNA monitoring on the development of EBV-related post-transplant lymphoproliferative disorder (EBV-PTLD); (ii) the incidence of EBV infection and the potential risk factors; and (iii) the suitability of whole blood (WB) as clinical specimen to monitor the risk of patients to develop EBV-PTLD.
  
  
  METHODS
  Quantitative real-time polymerase chain reaction assay was performed on WB samples for all patients. EBV DNA quantification also in peripheral blood mononuclear cells (PBMCs) samples was adopted for the patients at higher risk of developing EBV-PTLD (≥ 10,000 copies/mL WB).
  
  
  RESULTS
  High EBV DNAemia levels were observed in 37.5% of the actively infected recipients (57.1%). Severe aplastic anemia, matched-unrelated donor transplant, the reduced-intensity conditioning regimen and, to a lesser extent, the in vivo T-cell depletion with anti-thymocyte immunoglobulin were associated with high viral load. A significant correlation between EBV DNA levels in WB and PBMC samples was obtained (r = 0.755, P < 0.001). A similar kinetics of EBV DNA in the 2 blood compartments was observed. Clinically, both specimen types appeared to be equally informative to assess the risk of patients to develop PTLD. On the basis of EBV DNAemia levels, in 3 patients (10.7%) immunosuppressive therapy was reduced and 1 patient (3.5%) received early treatment for probable EBV disease. No patients developed EBV-PTLD.
  
  
  CONCLUSIONS
  WB proved to be a suitable clinical specimen to monitor EBV DNA load after allo-HSCT for the management of EBV infection and PTLD prevention.
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Chiereghin
authors.affiliation: Pediatric Oncology and Haematology Unit "Lalla Seràgnoli", Department of Pediatrics, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Prete
authors.affiliation: Pediatric Oncology and Haematology Unit "Lalla Seràgnoli", Department of Pediatrics, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Belotti
authors.affiliation: Department of Biomedical and Neuromotor Sciences, Unit of Hygiene and Biostatistics, University of Bologna, Bologna, Italy.
authors.forename: D
authors.initials: D
authors.lastname: Gibertoni
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Piccirilli
authors.affiliation: Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: L
authors.initials: L
authors.lastname: Gabrielli
authors.affiliation: Pediatric Oncology and Haematology Unit "Lalla Seràgnoli", Department of Pediatrics, St. Orsola-Malpighi University Hospital, Bologna, Italy.
authors.forename: A
authors.initials: A
authors.lastname: Pession
authors.affiliation: Department of Specialised, Experimental, and Diagnostic Medicine, Operative Unit of Clinical Microbiology, Laboratory of Virology, St. Orsola-Malpighi University Hospital, University of Bologna, Bologna, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Lazzarotto
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D004279:DNA, Viral / Q000097:blood; D020031:Epstein-Barr Virus Infections / Q000150:complications / Q000188:drug therapy / Q000517:prevention & control* / Q000821:virology; D005260:Female; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects*; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D007165:Immunosuppression Therapy; D007223:Infant; D007558:Italy; D007963:Leukocytes, Mononuclear / Q000821:virology; D008232:Lymphoproliferative Disorders / Q000209:etiology / Q000517:prevention & control* / Q000628:therapy; D008297:Male; D010372:Pediatrics; D011183:Postoperative Complications; D011446:Prospective Studies; D019562:Viral Load
chemical_list: D004279:DNA, Viral
keywords: EBV-related post-transplant lymphoproliferative disorder; first-line treatment of PTLD; kinetics of EBV DNA load; pediatric allogeneic hematopoietic stem cell transplant; preemptive therapy; risk factors