Relationship between rabbit anti-thymocyte globulin and development of PTLD and its aggressive form in renal transplant population (original) (raw)
Related papers
Transplant Immunology, 2011
Although antibody induction has gained in popularity, two agents are rarely combined. We retrospectively analyzed peripheral lymphocyte phenotypes of renal transplant recipients who received induction therapy with a different antibody/combination: alemtuzumab(C1H), Thymoglobulin(rATG), daclizumab(Dac), rATG + C1H, and rATG+ Dac. CD4+ T-cells were suppressed by C1H and rATG + C1H, as well as by rATG and rATG + Dac but to a lesser extent. The effect lasted for 3 years at around 40% of baseline values. CD8+ T-cells showed a similar trend but had a more rapid recovery to baseline. CD19+ B-cells were effectively suppressed for 2 months by C1H and rATG+ C1H, and abruptly returned to baseline afterwards; suppression by rATG(7 doses) was modest but lasted longer. A higher proportion of CD56+ CD16+ Natural Killer cells in C1H treated patients suggested a relatively spared effect of C1H on this cell type. Low CD25+ T-cells by 5-dose Dac returned to baseline around 6 months, whereas rATG + C1H and rATG+ Dac showed persistent effect. CD4+ CD25hi T-cells were suppressed by both rATG+ C1H and rATG + Dac, but the initial proportion of CD4 + CD25hi T-cells among CD4+ T-cells and CD4 + CD25hi/CD4+ CD25lo ratio were significantly higher in rATG + C1H. Overall, with extensive and persistent lymphocyte suppression by a simple administration of agents, single-dose rATG+ C1H induction can be an alternative in renal transplantation.
Rabbit anti-thymocyte globulin induction in renal transplantation: review of the literature
Transplant Research and Risk Management, 2014
Rabbit anti-thymocyte globulin (rATG) has proven benefit as induction therapy in renal transplant recipients, achieving reduced acute rejection rates and better short-term allograft function, with slightly higher rates of complications such as infections and malignancy. Compared with other agents, the most benefit from rATG induction has been observed in renal transplant recipients at high immunologic risk for rejection. However, in special populations, such as pediatrics, the elderly, and hepatitis C-positive and human immunodeficiency virus-positive renal transplant recipients, additional information is needed to delineate the absolute benefit of rATG induction compared with other induction agents. Selection of rATG as the choice of induction therapy in renal transplant recipients should be guided by a cost-effective approach in balancing efficacy, safety, and cost. This review summarizes the published literature on efficacy, safety, and cost of rATG induction in renal transplantation.
Urology & Nephrology Open Access Journal, 2017
High immunologic risk recipients pose a major challenge in transplantation. It is associated with early acute rejection post-transplantation and leads to decrease patient and graft survival. The need for effective immunosuppression early post-transplantation has resulted in emerging of induction protocols. Biologic agents used for induction are classified to monoclonal and polyclonal which are either depletive or non-depletive antibody therapies. Choosing the best agent and optimal dose remains a controversial issue and depends on many factors including the proper assessment of the immunologic risk, efficacy and safety of the used agent. There is no consensus for the optimal agent used as induction immunosuppression in kidney transplantation. rATG use is associated with decreased incidence of delayed graft function and acute rejection episodes.
Thymic function, anti-thymocytes globulins, and cancer after renal transplantation
Transplant Immunology, 2011
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 pretransplant TREC values were significantly lower in patients who developed cancer after transplantation (p b 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 b 0.0001). In multivariate analysis, pretransplant 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.
Hippokratia, 2012
Induction with anti-thymocyte globulin (ATG) during solid organ transplantation is associated with an improved clinical course and leads to prolonged lymphopenia. This study aims to investigate whether prolonged lymphopenia, caused by ATG induction, has an impact on patient and graft survival following liver and kidney transplantation. This was a single-center, retrospective study. A total of 292 liver and 417 kidney transplants were performed with ATG induction (6 mg/kgr, divided into four doses), and the transplant recipients were followed for at least three months. The average lymphocyte count for the first 30 days after the operation was calculated, and the cut-off value for defining lymphopenia was arbitrarily set to ≤ 500 cells/mm(3). There were 210 liver transplant recipients (71.9%) who achieved prolonged lymphopenia, whereas the remaining 82 recipients (28.1%) did not. The mean survival time of these patient groups was 10.27 and 12.71 years, respectively (p = 0.1217), and t...
Drugs, 2014
In the 30 years since the rabbit antithymocyte globulin (rATG) Thymoglobulin(®) was first licensed, its use in solid organ transplantation and hematology has expanded progressively. Although the evidence base is incomplete, specific roles for rATG in organ transplant recipients using contemporary dosing strategies are now relatively well-identified. The addition of rATG induction to a standard triple or dual regimen reduces acute cellular rejection, and possibly humoral rejection. It is an appropriate first choice in patients with moderate or high immunological risk, and may be used in low-risk patients receiving a calcineurin inhibitor (CNI)-sparing regimen from time of transplant, or if early steroid withdrawal is planned. Kidney transplant patients at risk of delayed graft function may also benefit from the use of rATG to facilitate delayed CNI introduction. In hematopoietic stem cell transplantation, rATG has become an important component of conventional myeloablative conditioni...
Transplantation proceedings
Efforts to improve long-term patient and allograft survival have included use of induction therapies as well as steroid and/or calcineurin inhibitor (CNI) avoidance/minimization. This is a retrospective review of kidney transplant recipients between September 2004 and July 2009. Immune minimization (group 1; n = 182) received alemtuzumab induction, low-dose CNI, and mycophenolic acid (MPA). Conventional immunosuppression (group 2; n = 232) received rabbit anti-thymocyte globulin, standard-dose CNI, MPA, and prednisone. Both groups were followed up for same length of time (49.4 ± 21.7 months; P = .12). Patient survival was also similar (90% vs 94%; P = .14). Death-censored graft survival was inferior in group 1 compared with group 2 (86% vs 96%, respectively; P = .003). On multivariate analysis, group 1 was an independent risk factor for graft loss (aHR = 2.63; 95% confidence interval [CI], 1.32-5.26; P = .006). Biopsy-proven acute rejection occurred more in group 1, due to late reje...