title: Epstein-Barr virus-negative lymphoproliferate disorders in long-term survivors after heart, kidney, and liver transplant.
abstract: BACKGROUND
  Solid organ transplant patients undergoing long-term immunosuppression have high risk of developing lymphomas. The pathogenesis of the late-occurring posttransplantation lymphoproliferative disorders (PTLD) have not yet been extensively investigated.
  
  
  METHODS
  We studied 15 patients who developed PTLD after a median of 79 months (range 22-156 months) after organ transplant. Clonality, presence of Epstein-Barr virus (EBV) genome, and genetic lesions were evaluated by Southern blot analysis or polymerase chain reaction.
  
  
  RESULTS
  All monomorphic PTLD and two of three polymorphic PTLD showed a monoclonal pattern. Overall, 44% of samples demonstrated the presence of the EBV genome. Within monomorphic PTLD, the EBV-positive lymphomas were even lower (31%). A c-myc gene rearrangement was found in two cases (13%), whereas none of the 15 samples so far investigated showed bcl-1, bcl-2, or bcl-6 rearrangement. The modulation of immunosuppression was ineffective in all patients with monomorphic PTLD independent of the presence of the EBV genome. The clinical outcome after chemotherapy was poor because of infectious complications and resistant disease. With a median follow-up of 4 months, the median survival time of these patients was 7 months.
  
  
  CONCLUSIONS
  Late occurring lymphomas could be considered an entity distinct from PTLD, occurring within 1 year of transplant, because they show a histological and clinical presentation similar to lymphomas of immunocompetent subjects, are frequently negative for the EBV genome, are invariably clonal, and may rearrange the c-myc oncogene. New therapeutic strategies are required to reduce the mortality rate, and new modalities of long-lasting immunosuppression are called for.
authors.affiliation: Division of Hematology, Ospedali Riuniti di Bergamo, Largo Barozzi, Bergamo, Italy.
authors.forename: G
authors.initials: G
authors.lastname: Dotti
authors.forename: R
authors.initials: R
authors.lastname: Fiocchi
authors.forename: T
authors.initials: T
authors.lastname: Motta
authors.forename: A
authors.initials: A
authors.lastname: Gamba
authors.forename: E
authors.initials: E
authors.lastname: Gotti
authors.forename: B
authors.initials: B
authors.lastname: Gridelli
authors.forename: G
authors.initials: G
authors.lastname: Borleri
authors.forename: C
authors.initials: C
authors.lastname: Manzoni
authors.forename: P
authors.initials: P
authors.lastname: Viero
authors.forename: G
authors.initials: G
authors.lastname: Remuzzi
authors.forename: T
authors.initials: T
authors.lastname: Barbui
authors.forename: A
authors.initials: A
authors.lastname: Rambaldi
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002675:Child, Preschool; D005260:Female; D016679:Genome, Viral; D016027:Heart Transplantation; D004854:Herpesvirus 4, Human / Q000235:genetics / Q000302:isolation & purification*; D006801:Humans; D016030:Kidney Transplantation; D016031:Liver Transplantation; D008232:Lymphoproliferative Disorders / Q000209:etiology* / Q000473:pathology / Q000628:therapy / Q000821:virology*; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications; D011184:Postoperative Period; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome