title: A population-based study of 135 lymphomas after solid organ transplantation: The role of Epstein-Barr virus, hepatitis C and diffuse large B-cell lymphoma subtype in clinical presentation and survival.
abstract: BACKGROUND
  Epstein-Barr virus (EBV) plays a major role in the development of post-transplant lymphoproliferative disorder (PTLD), but there is an increasing awareness of EBV-negative PTLD. The clinical presentation of EBV-negative PTLD has not been as well characterised as EBV-positive cases. Further, there is limited knowledge on the clinical importance of diffuse large B-cell lymphoma (DLBCL) cell of origin subtype post-transplant.
  
  
  METHODS
  We studied the role of EBV, hepatitis C (HCV) and DLBCL subtype in clinical presentation and survival in 135 post-transplant lymphomas diagnosed 1980-2006 in a population-based cohort of 10 010 Swedish solid organ transplant recipients. The lymphomas were re-evaluated according to WHO 2008, examined for EBV, and clinical data were collected from medical records.
  
  
  RESULTS
  Lymphoma incidence rate was 159/100 000 person-years and is also reported by lymphoma subtype. EBV-negative lymphomas constituted 48% and were associated with HCV infection (p = 0.02), bone marrow involvement (p < 0.001), and T-cell phenotype (p = 0.002). Among DLBCL, 78% were of non-germinal centre subtype, which was associated with EBV-positivity (69%, p = 0.001), early occurrence (p = 0.03), heart/liver/lung/pancreas recipients (p = 0.02), anti-T-cell globulin (p = 0.001), and tacrolimus treatment (p = 0.02). DLBCL subtypes had similar overall survival. Five-year overall survival was 42% in all treated patients. Independent poor prognostic factors were older age, B symptoms, ECOG 2-4, kidney/pancreas/heart recipients, T-cell lymphoma, and HCV-infection.
  
  
  CONCLUSIONS
  With long follow-up, a large part of PTLD is EBV-negative, due to a high proportion of T-cell lymphomas and low of polymorphic PTLD. EBV-negative PTLD have a different clinical presentation. HCV may play an aetiological role in late-onset PTLD and was revealed as a new prognostic factor for inferior survival that needs to be confirmed in larger studies. The heavier immunosuppression in non-kidney transplantations seems to play a role in the development of non-germinal centre DLBCL. DLBCL cell of origin subtype lacks prognostic importance in the transplant setting.
authors.affiliation: Department of Medical Sciences, Section of Infectious Diseases, Uppsala University , Uppsala , Sweden.
authors.forename: Amelie
authors.initials: A
authors.lastname: Kinch
authors.forename: Eva
authors.initials: E
authors.lastname: Baecklund
authors.forename: Carin
authors.initials: C
authors.lastname: Backlin
authors.forename: Tor
authors.initials: T
authors.lastname: Ekman
authors.forename: Daniel
authors.initials: D
authors.lastname: Molin
authors.forename: Gunnar
authors.initials: G
authors.lastname: Tufveson
authors.forename: Pia
authors.initials: P
authors.lastname: Fernberg
authors.forename: Christer
authors.initials: C
authors.lastname: Sundström
authors.forename: Karlis
authors.initials: K
authors.lastname: Pauksens
authors.forename: Gunilla
authors.initials: G
authors.lastname: Enblad
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D020031:Epstein-Barr Virus Infections / Q000150:complications; D005260:Female; D006526:Hepatitis C / Q000150:complications; D006801:Humans; D015994:Incidence; D007223:Infant; D008223:Lymphoma / Q000453:epidemiology* / Q000209:etiology* / Q000473:pathology; D016403:Lymphoma, Large B-Cell, Diffuse / Q000473:pathology; D008297:Male; D008875:Middle Aged; D016377:Organ Transplantation / Q000009:adverse effects*; D055815:Young Adult