Disassociation between risk of graft loss and risk of non-Hodgkin lymphoma with induction agents in renal transplant recipients

Background. It is widely assumed that the graft-enhancing properties of antilymphocyte induction agents and their lymphoma-inducing potential are intimately related. Methods. The Collaborative Transplant Study (CTS) database was used to evaluate graft survival and non-Hodgkin lymphoma at 3 years according to type of induction in 112,122 patients receiving a deceased-donor renal transplant during 1985 to 2004. Results. The relative risk of 3-year graft loss versus no induction was 1.07 (95% confidence interval [CI], 1.01-1.13; P= 0.016) with murine anti-CD3 monoclonal antibody (OKT3), 1.03 (95% Cl, 0.95-1.11; NS) with antithymocyte globulin (ATG)-Fresenius, 1.18 (95% Cl, 1.02-1.35; P=0.021) with ATGAM, 0.74 (95% Cl, 0.68-0.81; P < 0.001) with Thyrnoglobulin, and 0.78 (95% Cl, 0.72-0.84; P < 0.001) with interleukin (IL)-2RA induction. The standardized incidence ratio of lymphoma compared with a similar nontransplant population was 21.5 (95% Cl, 15.7-28.8; P < 0.001) with OKT3,4.9 (95% CI, 1.6-11.5; P=0.008) with ATG-Fresenius, 29.0 (95% Cl, 12.5-57.1; P < 0.001) with ATGAM, 21.6 (95% Cl, 14.3-31.2; P < 0.001) with Thymoglobulin, 7.8 (95% Cl, 4.4-12.9; P < 0.001) with IL-2RAs, and 9.4 (95% CI, 8.3-10.6 P < 0.001) with no induction. Conclusions. Those agents that offered the highest rates of graft survival were not necessarily associated with the highest risk of lymphoma. Graft survival was significantly improved with Thymoglobulin and IL-2RA induction, whereas lymphoma rates were highest with ATGAM, OKT3, and Thymoglobulin. IL-2RA agents seem to offer the best risk-to-benefit ratio for this patient population overall in terms of graft survival and lymphoma.