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Blood, 16 July 2009, Vol. 114, No. 3, pp. 630-637.
Prepublished online as a Blood First Edition Paper on May 14, 2009; DOI 10.1182/blood-2009-02-202507.


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LYMPHOID NEOPLASIA

Immunosuppression and other risk factors for early and late non-Hodgkin lymphoma after kidney transplantation

Marina T. van Leeuwen1,2, Andrew E. Grulich1, Angela C. Webster35, Margaret R.E. McCredie6, John H. Stewart6, Stephen P. McDonald3,7, Janaki Amin1, John M. Kaldor1, Jeremy R. Chapman5, and Claire M. Vajdic8

1 National Centre in HIV Epidemiology and Clinical Research, and 2 School of Public Health and Community Medicine, University of New South Wales, Sydney, Australia; 3 Australia and New Zealand Dialysis and Transplant Registry, Queen Elizabeth Hospital, Adelaide, Australia; 4 School of Public Health, University of Sydney, Sydney, Australia; 5 Centre for Transplant and Renal Research, Millennium Institute, Westmead Hospital, University of Sydney, Sydney, Australia; 6 Department of Preventive and Social Medicine, University of Otago, Dunedin, New Zealand; 7 Disciplines of Medicine and Public Health, University of Adelaide, Adelaide, Australia; and 8 University of New South Wales Cancer Research Centre, Prince of Wales Clinical School, University of New South Wales, Sydney, Australia

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.


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