title: Influence of induction therapy, immunosuppressive regimen and anti-viral prophylaxis on development of lymphomas after heart transplantation: data from the Spanish Post-Heart Transplant Tumour Registry.
abstract: BACKGROUND
  Lymphoma after heart transplantation (HT) has been associated with induction therapy and herpesvirus infection. It is not known whether anti-viral agents administered immediately after HT can reduce the incidence of lymphoma.
  
  
  METHODS
  This study was a retrospective review of 3,393 patients who underwent HT in Spain between 1984 and December 2003. Variables examined included development of lymphoma and, as possible risk factors, recipient gender and age, induction therapies (anti-thymocyte globulin, OKT3 and anti-interleukin-2 receptor antibodies) and anti-viral prophylaxis (acyclovir or ganciclovir). To study the effect of evolving treatment strategy, three HT eras were considered: 1984 to 1995; 1996 to 2000; and 2001 to 2003.
  
  
  RESULTS
  Induction therapy was employed in >60% of HTs, and anti-viral prophylaxis in >50%. There were 62 cases of lymphoma (3.1 per 1,000 person-years, 95% confidence interval: 2.4 to 4.0). Univariate analyses showed no influence of gender, age at transplant, HT era, pre-HT smoking or the immunosuppressive maintenance drugs used in the first 3 months post-HT. The induction agent anti-thymocyte globulin (ATG) was associated with increased risk of lymphoma, and prophylaxis with acyclovir with decreased risk of lymphoma. Multivariate analyses (controlling for age group, gender, pre-HT smoking and immunosuppression in the first 3 months with mycophenolate mofetil and/or tacrolimus) showed that induction increased the risk of lymphoma if anti-viral prophylaxis was not used (regardless of induction agent and anti-viral agent), but did not increase the risk if anti-viral prophylaxis was used.
  
  
  CONCLUSIONS
  Induction therapies with ATG or OKT3 do or do not increase the risk of lymphoma depending on whether anti-viral prophylaxis with acyclovir or ganciclovir is or is not employed, respectively.
authors.affiliation: Complejo Hospitalario Universitario Juan Canalejo, La Coruña, Spain. mcrelei@canalejo.org
authors.forename: Maria G
authors.initials: MG
authors.lastname: Crespo-Leiro
authors.forename: Luis
authors.initials: L
authors.lastname: Alonso-Pulpón
authors.forename: José M
authors.initials: JM
authors.lastname: Arizón
authors.forename: Luis
authors.initials: L
authors.lastname: Almenar
authors.forename: Juan F
authors.initials: JF
authors.lastname: Delgado
authors.forename: Jesús
authors.initials: J
authors.lastname: Palomo
authors.forename: Nicolás
authors.initials: N
authors.lastname: Manito
authors.forename: Gregorio
authors.initials: G
authors.lastname: Rábago
authors.forename: Ernesto
authors.initials: E
authors.lastname: Lage
authors.forename: Beatriz
authors.initials: B
authors.lastname: Diaz
authors.forename: Eulalia
authors.initials: E
authors.lastname: Roig
authors.forename: Domingo
authors.initials: D
authors.lastname: Pascual
authors.forename: Teresa
authors.initials: T
authors.lastname: Blasco
authors.forename: Luis
authors.initials: L
authors.lastname: de la Fuente
authors.forename: Marta
authors.initials: M
authors.lastname: Campreciós
authors.forename: José A
authors.initials: JA
authors.lastname: Vázquez de Prada
authors.forename: Javier
authors.initials: J
authors.lastname: Muñiz
mesh_terms: D000212:Acyclovir / Q000627:therapeutic use; D000328:Adult; D000961:Antilymphocyte Serum / Q000009:adverse effects / Q000627:therapeutic use; D000998:Antiviral Agents / Q000627:therapeutic use*; D005260:Female; D015774:Ganciclovir / Q000627:therapeutic use; D016027:Heart Transplantation / Q000009:adverse effects*; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D008223:Lymphoma / Q000209:etiology / Q000517:prevention & control*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D016853:Muromonab-CD3 / Q000009:adverse effects / Q000627:therapeutic use; D012042:Registries / Q000706:statistics & numerical data*; D012189:Retrospective Studies; D012307:Risk Factors; D013030:Spain; D014777:Virus Diseases / Q000150:complications
chemical_list: D000961:Antilymphocyte Serum; D000998:Antiviral Agents; D007166:Immunosuppressive Agents; D016853:Muromonab-CD3; D015774:Ganciclovir; D000212:Acyclovir