Thymic function, anti-thymocytes globulins, and cancer after renal transplantation

Background: Prolonged CD4 T cell lymphopenia after polyclonal antithymocyte globulins (ATG) is associated with an increased rate of cancers. Here, we examined whether pre-transplant thymic function estimated by TREC levels is predictive of cancer occurrence following ATG treatment. Patients and methods: The impact of TREC on cancer occurrence was analyzed in 115 consecutive incident renal transplant recipients having received ATG. Results: Mean follow-up was 7.5 +/- 2.6 years. After ATG induction, patients with the lowest pre-transplant TREC values had lower post-transplant CD4(+) and CD4(+) CD45RA(+) CD45RO(-) T cell counts, and a higher frequency of T cells with a regulatory phenotype (CD127(+)CD4(+)CD25(+)Foxp3(+)). Log-transformed pre-transplant TREC values were significantly lower in patients who developed cancer after transplantation (p<0.0001). The cumulative incidence of cancer was higher in patients having the lowest pre-transplant TREC values (Ti [low]: 47.4%, T2 [medium]: 12.5%, and T3 [high]: 2.7%; p<0.0001). In multivariate analysis, pre-transplant TREC value was the only predictive factor of cancer (HR, 0.39; 95% Cl, 0.16 to 0.97, for one log (TREC/10(6) PBMC); p=0.046). Conclusions: Pre-transplant thymic function is associated with an increased rate of post-transplant cancer in patients having received ATG. Omitting ATG in recipients with low pre-transplant TREC values should be considered. (C) 2011 Elsevier B.V. All rights reserved.