Results of the Double-Blind, Randomized, Multicenter, Phase Iii Clinical Trial of Thymoglobulin Versus Atgam in the Treatment of Acute Graft Rejection Episodes After Renal Transplantation1,2

Gaber, Osama O.; First, M. Roy; Tesi, Raymond J.; Gaston, Robert S.; Mendez, Robert; Mulloy, Laura L.; Light, Jimmy A.; Gaber, Lillian W.; Squiers, Elizabeth C.; Taylor, Rodney J.; Neylan, John F.; Steiner, Robert W.; Knechtle, Stuart J.; Norman, Douglas J.; Shihab, Fuad S.; Basadonna, Giacomo; Brennan, Daniel C.; Hodge, Ernest E.; Kahan, Barry D.; Kahana, Lawrence; Steinberg, Steven; Woodle, E. Steve; Chan, Laurence; Ham, J. M.; Stratta, Robert J.; Wahlström, Erik; Lamborn, Kathleen R.; Horn, H.R.; Moran, Hana Berger; Pouletty, Philippe; Schroeder, Timothy

doi:10.1097/00007890-199807150-00005

Cited by 279 publications

(127 citation statements)

References 18 publications

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“…In the transplantations from an unrelated donor, the addition of low-dose corticosteroid to the GVHD prophylactic regimen Table 2 Characteristics of the patients with post-transplant lymphoproliferative disorder (PTLD) PTLD after non-T-cell-depleted stem cell transplantation E Juvonen et al consisting of cyclosporine and methotrexate may have been a further contributing factor, although in our earlier study in the sibling transplantation setting there were fewer infections in the group of patients given the triple prophylaxis compared to patients given the combination of cyclosporine and methotrexate. 19 The present study also suggests a difference in the immunosuppressive effect between the different ATG products in the doses used, which is in accordance with the previous study by Gaber et al 23 They showed that after renal transplantation, the degree of T-cell depletion caused by Thymoglobuline s was significantly greater and longerlasting when compared to the effects of Atgam s . Thymoglobuline s was also more effective in the treatment of acute rejection.…”

Section: Discussionsupporting

confidence: 91%

High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment

Juvonen

Aalto

Tarkkanen

et al. 2003

Bone Marrow Transplant

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Section: Discussionsupporting

confidence: 91%

High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment

Juvonen

Aalto

Tarkkanen

et al. 2003

Bone Marrow Transplant

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“…Four female RMs 10-13 years old received a single dose of 2 Gy TBI, 3 mg/kg tacrolimus, 1 mg/kg prednisone and 1Á5 mg/kg anti-thymocyte globulin intravenously (thymoglobulin rabbit ATG; Genzyme, Cambridge, MA, USA). Preville et al calculated that a dose of 1 mg/kg in cynomolgus macaques was sufficient to induce borderline immunosuppressive effects, while a dose of 5 mg/kg reflects ATG used in organ transplantation [17,54,55].…”

Section: Animals and Sample Collectionmentioning

confidence: 99%

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

Meyer

Walker

Dewane

et al. 2015

Clinical and Experimental Immunology

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SummaryIn this study we examined the effects of non-myeloablative total body irradiation (TBI) in combination with immunosuppressive chemotherapy on immune homeostasis in rhesus macaques. Our results show that the administration of cyclosporin A or tacrolimus without radiotherapy did not result in lymphopenia. The addition of TBI to the regimen resulted in lymphopenia as well as alterations in the memory/naive ratio following reconstitution of lymphocyte populations. Dendritic cell (DC) numbers in whole blood were largely unaffected, while the monocyte population was altered by immunosuppressive treatment. Irradiation also resulted in increased levels of circulating cytokines and chemokines that correlated with T cell proliferative bursts and with the shift towards memory T cells. We also report that anti-thymocyte globulin (ATG) treatment and CD3 immunotoxin administration resulted in a selective and rapid depletion of naive CD4 and CD8 T cells and increased frequency of memory T cells. We also examined the impact of these treatments on reactivation of latent simian varicella virus (SVV) infection as a model of varicella zoster virus (VZV) infection of humans. None of the treatments resulted in overt SVV reactivation; however, select animals had transient increases in SVV-specific T cell responses following immunosuppression, suggestive of subclinical reactivation. Overall, we provide detailed observations into immune modulation by TBI and chemotherapeutic agents in rhesus macaques, an important research model of human disease.

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“…Early 7-to 10-d induction course with polyclonal antilymphocyte globulin or horsederived polyclonal anti-human thymocyte globulin has contributed to reduce the rate of acute rejection and improve early graft function in kidney transplant recipients (6,7). Even better results as far as frequency and severity of rejection episodes then were achieved with rabbit-derived polyclonal anti-human thymocyte globulin (RATG) (8), which thereafter became the standard biologic agent for induction therapy in kidney transplantation (9).…”

mentioning

confidence: 99%

Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

Ruggenenti

Codreanu²,

Cravedi³

et al. 2006

Clinical Journal of the American Society of Nephrology

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In high-risk kidney transplant recipients, induction therapy with rabbit anti-human thymocyte globulin (RATG) reduces the risk for acute rejection but is associated with significant toxicity, opportunistic infections, and cancer. Using reduced doses of RATG combined with anti-IL-2 antibodies may achieve the same antirejection activity of standard-dose RATG but with a better safety profile. This randomized, open-label study compared the efficacy, tolerability, and costs of low-dose RATG (0.5 mg/kg per d) plus basiliximab (20 mg 4 d apart) versus standard-dose RATG (2 mg/kg per d) in 33 consecutive high-risk renal transplant recipients (living-related transplant recipients, sensitized patients or patients who received another transplant, and patients with delayed graft function) over 6 mo of follow-up. All patients received concomitant therapy with steroids, cyclosporin A, and azathioprine or mycophenolate mofetil. Seventeen patients received low-dose RATG plus basiliximab, and 16 received standard-dose RATG. Patient (100 versus 100%) and graft (94 versus 100%) survival were comparable in the two groups, but the incidence of fever (17.6 versus 56.5%; P ‫؍‬ 0.01), leukopenia (23.5 versus 56.3%; P < 0.05), anemia (29.4 versus 62.5%; P < 0.05), cytomegalovirus reactivations (17.6 versus 56.5%; P ‫؍‬ 0.01), the number of transfused units (0.5 ؎ 0.9 versus 2.0 ؎ 2.4; P < 0.001), and treatment costs (3652 ؎ 704 versus 5400 ؎ 1960 euro; P ‫؍‬ 0.001) were lower with low-dose RATG plus basiliximab than with standard-dose RATG. There was one episode of biopsy-proven acute rejection on low-dose RATG plus basiliximab, and there were two on standard-dose RATG. In renal transplantation, induction therapy with basiliximab plus low-dose RATG effectively prevents acute rejection and is safer and more cost-effective than induction with standard-dose RATG.

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Results of the Double-Blind, Randomized, Multicenter, Phase Iii Clinical Trial of Thymoglobulin Versus Atgam in the Treatment of Acute Graft Rejection Episodes After Renal Transplantation1,2

Abstract: Thymoglobulin was found to be superior to Atgam in reversing acute rejection and preventing recurrent rejection after therapy in renal transplant recipients.

Cited by 279 publications

References 18 publications

High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment

High incidence of PTLD after non-T-cell-depleted allogeneic haematopoietic stem cell transplantation as a consequence of intensive immunosuppressive treatment

Impact of irradiation and immunosuppressive agents on immune system homeostasis in rhesus macaques

Basiliximab Combined with Low-Dose Rabbit Anti-Human Thymocyte Globulin

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