A prospective study (n=150) showed excellent results of Thymoglobulin induction in a CNICfree maintenance and steroid-tapering protocol. for confirmation.[38] GvHD prophylaxis with Thymoglobulin may result in less acute and chronic GvHD, lower TRM, improved survival and quality of life in myeloablative (S)-Mapracorat or reduced intensity conditioning protocols in patients receiving hematopoietic stem cells from related or unrelated donors. Attributable to its polyclonal nature, Thymoglobulin provides multifaceted immunomodulation suggesting that its use should be included in the immunosuppressant therapeutic armamentarium to help reduce the incidence of organ rejection and GvHD,[5] and for treatment of aplastic anemia. Introduction Immunosuppressive properties of polyclonal antithymocyte globulins (ATG) were first explained in the 1950s,[1] and ATG have been widely used for more than 30 years.[2] Recent findings demonstrate that ATG can provide a wide spectrum of immunomodulation, suggesting that their use in immunosuppression may help in reducing the incidence of organ rejection, improving patients end result after hematopoietic stem cell transplantation,[3] and treating autoimmune mediated disease, i.e. aplastic anemia. ATG is usually a mixture of different antibody specificities, which induces an extremely effective dose-dependent T-cell depletion in blood and lymphoid tissues via complement-dependent cytotoxicity, antibody dependent cellular cytotoxicity, and apoptosis.[4] Currently you will find three different ATGs commercially available: Human thymocytes are used as the immunogenic to produce Atgam? (Pharmacia & Upjohn, NY, USA) in horses and Thymoglobulin? (Genzyme Polyclonals, S.A.S. Marcy LEtoile, France) in rabbits, respectively; a Jurkat cell collection is used to produce ATG-Fresenius? (Fresenius Biotech GmbH, Graefelfing, Germany) in rabbits.[4] Despite sharing some common properties, the commercially available RAB21 ATG products are strictly different drugs.[5] Immunosuppressive (S)-Mapracorat activity varies significantly from one preparation to the other, resulting in quite different dosages. Among these products, Thymoglobulin is probably the most potent, and the most extensively analyzed ATG.[5,6] This review explains the clinical use of Thymoglobulin in organ transplantation and hematology/oncology. Mechanisms of action The role of Thymoglobulin in the prevention and treatment of allograft rejection, graft versus- host disease (GVHD), and treatment of aplastic anemia (AA) is usually well established. Recent investigations have shown that Thymoglobulin does not only deplete T-cells, but modulates numerous lymphocyte surface antigens and interferes with the function of a number of different immune effector cells, including B cells, dendritic cells, natural killer (NK) T cells, and regulatory T cells (Tregs).[7] Solid organ transplantation: Prevention of rejection (induction) The risk of organ rejection is bigger immediately (weeks to months) after transplantation. It declines during the first year and further on, but it is present through the whole life of the graft.[8] Thymoglobulin is indicated for prevention of graft rejection in organ transplantation (induction); dosage 1 to 1 1,5 mg/kg/day for 2 to 9 days (2 to 5 days in heart transplantation).[9] In the US, antibody induction is used in the majority ( 70%) of kidney and almost 50% of thoracic organ transplantations, and Thymoglobulin is the most frequently used induction agent.[10] It has the following roles in organ transplant recipients: reduction of the incidence of acute rejection, prevention of ischemia reperfusion injury and delayed graft function, and minimization of calcineurin inhibitors (CNIs) and/or corticosteroids.[13,18,23-25] Thymoglobulin induction versus no induction In two randomized, prospective trials Thymoglobulin was shown to decrease the rate of acute rejection in kidney transplant patients compared to no induction (15,1% vs. 25,4%; 15,2% vs. 30,4% respectively, p 0.001 in both studies). In these early studies, the incidences of leucopenia, thrombocytopenia, fever, and cytomegalovirus contamination were significantly higher in the Thymoglobulin groups.[11,12] A retrospective analysis in living donor kidney transplantation (n=214) in a single center versus a national cohort showed a significant benefit of Thymoglobulin induction vs. no antibody induction in a low risk patient populace. Five years individual survival was 96% vs. 90% (p=0,03), and acute rejection (S)-Mapracorat at one year was 2% vs. 21% (p 0,001). Thymoglobulin was well tolerated with very few infections, and a low incidence of malignancy.[13] Thymoglobulin induction versus other ATG induction In a prospective, double blind trial event free survival (defined as freedom (S)-Mapracorat from death, graft loss, or biopsy confirmed (S)-Mapracorat acute rejection – BPAR) after one (94% vs. 63% p=0,0005), five (73% vs. 33% p 0,001), and ten (48% vs. 29% p=0,011) years was significantly higher in Thymoglobulin treated patients (n=48) receiving a kidney transplant compared to Atgam (n=24). There were no post transplant lymphoproliferative disorder (PTLD) in the Thymoglobulin group and two cases in the Atgam group.[14] One prospective, randomized trial compared induction with Thymoglobulin (n=28) and ATG Fresenius (n=30) in kidney transplant recipients. Acute rejection after one year was numerically lower in the Thymoglobulin group (14,2% vs. 26,6%; ns). Thymoglobulin patients experienced a lower incidence of infections, lower white blood.
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