title: Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation.
abstract: Non-Hodgkin lymphoma (NHL) incidence is greatly increased after kidney transplantation. NHL risk was investigated in a nationwide cohort of 8164 kidney transplant recipients registered on the Australia and New Zealand Dialysis and Transplant Registry. NHL diagnoses were ascertained using linkage with national cancer registry records. Multivariate Poisson regression was used to compute incidence rate ratios (IRRs) with 95% confidence intervals (CIs) comparing risk by transplant function, and risk factors for early (< 2 years) and late (>/= 2 years) NHL during the first transplantation. NHL occurred in 133 patients. Incidence was strikingly lower after transplant failure and cessation of immunosuppression than during transplant function (IRR, 0.25; 95% CI, 0.08-0.80; P = .019). Early NHL (n = 27) was associated with Epstein-Barr virus (EBV) seronegativity at transplantation (IRR, 4.66; 95% CI, 2.10-10.36, P < .001) and receipt of T cell-depleting antibodies (IRR, 2.39; 95% CI, 1.08-5.30; P = .031). Late NHL (n = 79) was associated with increasing year of age (IRR, 1.02; 95% CI, 1.01-1.04; P = .006), increasing time since transplantation (P < .001), and current use of calcineurin inhibitors (IRR, 3.13; 95% CI, 1.53-6.39; P = .002). These findings support 2 mechanisms of lymphomagenesis, one predominantly of primary EBV infection in the context of intense immunosuppression, and another of dysregulated lymphoid proliferation in a prolonged immunosuppressed state.
authors.affiliation: National Centre in HIV Epidemiology and Clinical Research, and School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia.
authors.forename: Marina T
authors.initials: MT
authors.lastname: van Leeuwen
authors.forename: Andrew E
authors.initials: AE
authors.lastname: Grulich
authors.forename: Angela C
authors.initials: AC
authors.lastname: Webster
authors.forename: Margaret R E
authors.initials: MR
authors.lastname: McCredie
authors.forename: John H
authors.initials: JH
authors.lastname: Stewart
authors.forename: Stephen P
authors.initials: SP
authors.lastname: McDonald
authors.forename: Janaki
authors.initials: J
authors.lastname: Amin
authors.forename: John M
authors.initials: JM
authors.lastname: Kaldor
authors.forename: Jeremy R
authors.initials: JR
authors.lastname: Chapman
authors.forename: Claire M
authors.initials: CM
authors.lastname: Vajdic
mesh_terms: D000328:Adult; D000367:Age Factors; D000368:Aged; D015331:Cohort Studies; D020031:Epstein-Barr Virus Infections; D005260:Female; D006801:Humans; D007165:Immunosuppression Therapy / Q000009:adverse effects*; D015994:Incidence; D016030:Kidney Transplantation / Q000009:adverse effects*; D008212:Lymphocyte Depletion; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000209:etiology*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D012042:Registries; D012189:Retrospective Studies; D012307:Risk Factors; D013997:Time Factors; D055815:Young Adult