Risk of Early and Late Non-Hodgkin Lymphoma (NHL) in Australian Liver and Cardiothoracic Transplant Recipients.

Abstract

Aims: To determine whether risk of NHL is increased in cardiothoracic compared to liver transplant recipients, after adjustment for extent of immunosuppression and competing risk of death. Methods: A retrospective cohort study in Australia using population-based liver (n=1924) and cardiothoracic (n=2631) transplant registries (1984-2006). NHL incidence was ascertained by probabilistic record linkage with the Australian Cancer Database. Adult and pediatric transplant unit medical records were retrospectively reviewed to ascertain putative risk factor data, including demographics, co-morbid conditions, immunosuppressive agents received at transplantation and at regular intervals during follow-up, and serum viral antibody status at transplantation. Multiple imputation was used to impute missing Epstein-Barr virus (EBV) data. Adjusted hazard ratios (HR) for early (n=31) and late-onset (n=69) NHL were estimated using the Fine and Gray proportional subdistribution hazards model. Results: After imputation there were 22 early (<1yr) and 45 late (≥1yr) NHL cases available for multivariate analysis. Compared to liver recipients, lung recipients were at increased risk of early NHL (HR 5.18, 95%CI 1.39-19.3) after adjustment for recipient EBV seronegativity at transplantation (HR 3.33, 95%CI 1.08-10.4), receipt of OKT3 antibody (HR 10.0, 95%CI 2.50-40.0), male gender (HR 3.47, 95%CI 1.44-8.37), age, calendar year of transplant, receipt of ATG/ALG, and current dose of immunosuppressive agents. For late NHL, heart recipients were at increased risk compared to liver recipients (HR 3.66, 95%CI 1.33-10.0) after adjusting for EBV serostatus, age, sex, calendar year of transplant, time since transplantation, receipt of OKT3 and ATG/ALG, and the current dose and number of immunosuppressive agents. Imputed and non-imputed results were similar. Conclusions: Differences in immunosuppressive regimen do not appear to explain the excess risk of NHL in heart and lung compared to liver transplant recipients. There is growing evidence of heterogeneity in the risk factors for early and late NHL after solid organ transplantation.