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±2.6years. 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 (T1 [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% CI, 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.
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±2.6years. 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 (T1 [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% CI, 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.
Authors: Felix Krenzien; Abdallah ElKhal; Markus Quante; Hector Rodriguez Cetina Biefer; Uehara Hirofumi; Steven Gabardi; Stefan G Tullius Journal: Transplantation Date: 2015-11 Impact factor: 4.939
Authors: Maria Cappuccilli; Gabriele Donati; Giorgia Comai; Olga Baraldi; Diletta Conte; Irene Capelli; Valeria Aiello; Andrea Pession; Gaetano La Manna Journal: J Inflamm Res Date: 2017-05-03