title: Characteristics of early and late PTLD development in pediatric solid organ transplant recipients.
abstract: BACKGROUND
  Posttransplantation lymphoproliferative disorders (PTLD) present a major cause of mortality and morbidity after solid organ transplantation. The purpose of this study was to identify the factors associated with the development of early- and late-onset PTLD in pediatric solid organ transplant recipients.
  
  
  METHODS
  We examined the medical history, laboratory parameters, and pathology of 127 children with PTLD who were registered in the German multicenter pediatric PTLD registry. Data were collected retrospectively from 1991 to 2003 and prospectively from 2004 onward. We compared early (<1 year) and late (>1 year) PTLD using survival analysis.
  
  
  RESULTS
  The median time to PTLD was 3.00 (95% confidence interval, 2.12-3.26) years. Forty-two patients developed PTLD within the first year after transplantation (early PTLD) and 85 patients developed PTLD after 1 year (late PTLD). Early PTLD development was associated with younger age (P=0.0016), extranodal disease (P=0.019), graft organ involvement (P=0.0065), and immunosuppressive regimens including tacrolimus (P=0.001) or mycophenolate (P=0.0025). Most early PTLD patients experienced graft rejection before PTLD diagnosis (P=0.0081). Early PTLD was often of B-cell lymphoma histology (P=0.024) and tended to be Epstein-Barr virus positive (P=0.052). In contrast, Burkitt's lymphoma (P=0.0047) and Hodgkin's disease (P=0.016) were only observed in late PTLDs, which are more likely to present with nodal disease (P=0.019). Overall survival and event-free survival were not significantly different between early and late PTLD.
  
  
  CONCLUSIONS
  Early and late childhood PTLD have distinct characteristics. Whereas early PTLD appears mainly as an Epstein-Barr virus-driven disease especially favored by insufficient immunosurveillance, late PTLD often resembles tumors with distinct pathogenetic alterations and nodal appearance.
authors.affiliation: Department of Pediatric Hematology/Oncology, Hannover Medical School, Hannover, Germany.
authors.forename: Tilmann
authors.initials: T
authors.lastname: Schober
authors.forename: Theodor
authors.initials: T
authors.lastname: Framke
authors.forename: Hans
authors.initials: H
authors.lastname: Kreipe
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Schulz
authors.forename: Anika
authors.initials: A
authors.lastname: Großhennig
authors.forename: Kais
authors.initials: K
authors.lastname: Hussein
authors.forename: Ulrich
authors.initials: U
authors.lastname: Baumann
authors.forename: Lars
authors.initials: L
authors.lastname: Pape
authors.forename: Stephan
authors.initials: S
authors.lastname: Schubert
authors.forename: Anne-Margret
authors.initials: AM
authors.lastname: Wingen
authors.forename: Thomas
authors.initials: T
authors.lastname: Jack
authors.forename: Armin
authors.initials: A
authors.lastname: Koch
authors.forename: Christoph
authors.initials: C
authors.lastname: Klein
authors.forename: Britta
authors.initials: B
authors.lastname: Maecker-Kolhoff
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D005260:Female; D004854:Herpesvirus 4, Human / Q000302:isolation & purification; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000401:mortality; D008297:Male; D016377:Organ Transplantation / Q000009:adverse effects*; D012189:Retrospective Studies