Browse
Submit Data
Databases
API
Help

Dataset Information

8 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Comparison of Basiliximab and Anti-Thymocyte Globulin as Induction Therapy in Pediatric Heart Transplantation: A Survival Analysis.

ABSTRACT: Basiliximab and anti-thymocyte globulin are widely used drugs for induction therapy after pediatric heart transplantation. The aim of this study was to determine whether any differences could be observed between basiliximab and anti-thymocyte globulin, with respect to long-term mortality, in a population of pediatric cardiac transplant recipients.An analysis of pediatric heart transplant patients (aged <18 years) from the United Network for Organ Sharing database was conducted that compared patients receiving basiliximab with those that received anti-thymocyte globulin for the risk of all-cause mortality. Secondary endpoints included death attributable to graft failure, cardiovascular causes, infection, or malignancy. Of the 2275 patients, 685 received basiliximab and 1590 anti-thymocyte globulin. One-year survival was similar for both groups; however, at 5 and 10 years, basiliximab was associated with poorer long-term survival (68% versus 76% at 5 years [P<0.001] and 49% versus 65% at 10 years [P<0.001], respectively). Basiliximab was associated with higher risk of death attributable to graft failure (P=0.013), but not death attributable to cardiovascular causes (P=0.444), infection (P=0.095), or malignancy (P=0.392). After multivariate analysis, use of basiliximab (versus use of anti-thymocyte globulin) remained significantly associated with all-cause mortality (hazard ratio, 1.27; 95% confidence interval, 1.02-1.57; P=0.030).In pediatric heart transplant patients, use of basiliximab for induction therapy was associated with an increased risk of mortality, when compared with those receiving anti-thymocyte globulin.

SUBMITTER: Ansari D

PROVIDER: S-EPMC4859398 | biostudies-other | 2015 Dec

REPOSITORIES: biostudies-other

ACCESS DATA

Json Xml

Similar Datasets

Immune reconstitution after anti-thymocyte globulin-conditioned hematopoietic cell transplantation.

Project description:Anti-thymocyte globulin (ATG) is being used increasingly to prevent graft-versus-host disease (GvHD); however, its impact on immune reconstitution is relatively unknown. We (i) studied immune reconstitution after ATG-conditioned hematopoietic cell transplantation (HCT), (ii) determined the factors influencing the reconstitution, and (iii) compared it with non-ATG-conditioned HCT.Immune cell subset counts were determined at 1-24 months post-transplant in 125 HCT recipients who received ATG during conditioning. Subset counts were also determined in 46 non-ATG-conditioned patients (similarly treated).(i) Reconstitution after ATG-conditioned HCT was fast for innate immune cells, intermediate for B cells and CD8 T cells, and very slow for CD4 T cells and invariant natural killer T (iNKT) (iNKT) cells. (ii) Faster reconstitution after ATG-conditioned HCT was associated with a higher number of cells of the same subset transferred with the graft in the case of memory B cells, naive CD4 T cells, naive CD8 T cells, iNKT cells and myeloid dendritic cells; lower recipient age in the case of naive CD4 T cells and naive CD8 T cells; cytomegalovirus recipient seropositivity in the case of memory/effector T cells; an absence of GvHD in the case of naive B cells; lower ATG serum levels in the case of most T-cell subsets, including iNKT cells; and higher ATG levels in the case of NK cells and B cells. (iii) Compared with non-ATG-conditioned HCT, reconstitution after ATG-conditioned HCT was slower for CD4 T cells, and faster for NK cells and B cells.ATG worsens the reconstitution of CD4 T cells but improves the reconstitution of NK and B cells.

| S-EPMC3681879 | biostudies-other

Rabbit anti-thymocyte globulin for the prevention of acute rejection in kidney transplantation.

Project description:This report describes the results of 2 international randomized trials (total of 508 kidney transplant recipients). The primary objective was to assess the noninferiority of rabbit anti-thymocyte globulin (rATG, Thymoglobulin® ) versus interleukin-2 receptor antagonists (IL2RAs) for the quadruple endpoint (treatment failure defined as biopsy-proven acute rejection, graft loss, death, or loss to follow-up) to serve as the pivotal data for United States (US) regulatory approval of rATG. The pooled analysis provided an incidence of treatment failure of 25.1% in the rATG and 36.0% in the IL2RA treatment groups, an absolute difference of -10.9% (95% confidence interval [CI] -18.8% to -2.9%) supporting noninferiority (noninferiority margin was 10%) and superiority of rATG to IL2RA. In a meta-analysis of 7 trials comparing rATG with an IL2RA, the difference in the proportion of patients with BPAR at 12 months was -4.8% (95% CI -8.6% to -0.9%) in favor of rATG. In conclusion, a rigorous reanalysis of patient-level data from 2 prior randomized, controlled trials comparing rATG versus IL-2R monoclonal antibodies provided support for regulatory approval for rATG for induction therapy in renal transplant, making it the first T cell-depleting therapy approved for the prophylaxis of acute rejection in patients receiving a kidney transplant in the United States.

| S-EPMC6767488 | biostudies-literature

Allogeneic hematopoietic cell transplantation after failed autologous transplant for lymphoma using TLI and anti-thymocyte globulin conditioning.

Project description:We describe 47 patients with lymphoma and failed prior autologous hematopoietic cell transplantation (HCT) who received TLI-ATG (anti-thymocyte globulin) conditioning followed by allogeneic HCT. Thirty-two patients had non-Hodgkin lymphoma (NHL; diffuse large B-cell lymphoma (n=19), T-cell NHL (n=6), mantle cell lymphoma (n=4) or other B-cell subtypes (n=3)), and 15 had Hodgkin lymphoma. The median follow-up was 4.9 (range, 2.1-11.9) years. The cumulative incidence of grade II-IV acute GvHD at day +100 was 12%, and the cumulative incidence of extensive chronic GvHD at 1 year was 36%. The 3-year cumulative incidences of overall survival (OS), PFS and non-relapse mortality (NRM) were 81%, 44% and 7%, respectively. Fifteen patients died (relapse, n=10; NRM, n=5). Among the 25 patients with relapse after allogeneic HCT, 11 (44%) achieved durable (>1 year) CRs following donor lymphocyte infusion or chemoradiotherapy. The majority of surviving patients (75%; n=24) were able to discontinue all immunosuppression. For patients with relapsed lymphoma after autologous HCT, allogeneic HCT using TLI-ATG conditioning is a well-tolerated, predominantly outpatient therapy with low NRM (7% at 3 years), a low incidence of GvHD, durable disease control and excellent OS (81% at 3 years).

| S-EPMC4699844 | biostudies-literature

A Double-Blind, Double-Dummy, Flexible-Design Randomized Multicenter Trial: Early Safety of Single- Versus Divided-Dose Rabbit Anti-Thymocyte Globulin Induction in Renal Transplantation.

Project description:A previous nonblinded, randomized, single-center renal transplantation trial of single-dose rabbit anti-thymocyte globulin induction (SD-rATG) showed improved efficacy compared with conventional divided-dose (DD-rATG) administration. The present multicenter, double-blind/double-dummy STAT trial (Single dose vs. Traditional Administration of Thymoglobulin) evaluated SD-rATG versus DD-rATG induction for noninferiority in early (7-day) safety and tolerability. Ninety-five patients (randomized 1:1) received 6 mg/kg SD-rATG or 1.5 mg/kg/dose DD-rATG, with tacrolimus-mycophenolate maintenance immunosuppression. The primary end point was a composite of fever, hypoxia, hypotension, cardiac complications, and delayed graft function. Secondary end points included 12-month patient survival, graft survival, and rejection. Target enrollment was 165 patients with an interim analysis scheduled after 80 patients. Interim analysis showed primary end point noninferiority of SD-rATG induction (p = 0.6), and a conditional probability of <1.73% of continued enrollment producing a significant difference (futility analysis), leading to early trial termination. Final analysis (95 patients) showed no differences in occurrence of primary end point events (p = 0.58) or patients with no, one, or more than one event (p = 0.81), or rejection, graft, or patient survival (p = 0.78, 0.47, and 0.35, respectively). In this rigorously blinded trial in adult renal transplantation, we have shown SD-rATG induction to be noninferior to DD-rATG induction in early tolerability and equivalent in 12-month safety. (Clinical Trials.gov #NCT00906204.).

| S-EPMC5069643 | biostudies-literature

Efficacy of rabbit anti-thymocyte globulin in severe aplastic anemia.

Project description:A combination of horse anti-thymocyte globulin and cyclosporine produces responses in 60-70% of patients with severe aplastic anemia. We performed a phase II study of rabbit anti-thymocyte globulin and cyclosporine as first-line therapy for severe aplastic anemia.Twenty patients with severe aplastic anemia treated with rabbit anti-thymocyte globulin were compared to 67 historical control cases with matched clinical characteristics treated with horse anti-thymocyte globulin.Response rates at 3, 6 and 12 months were similar for patients treated with rabbit anti-thymocyte globulin or horse anti-thymocyte globulin: 40% versus 55% (P=0.43), 45% versus 58% (P=0.44) and 50% versus 58% (P=0.61), respectively. No differences in early mortality rates or overall survival were observed. We then performed multivariable analyses of response at 6 months and overall survival and identified the presence of a paroxysmal nocturnal hemoglobinuria clone (P=0.01) and a pretreatment absolute reticulocyte count greater than 30×10(9)/L (P=0.007) as independent predictors of response and younger age (P=0.003), higher pretreatment absolute neutrophil (P=0.02) and absolute lymphocyte counts (P=0.03) as independent predictors of overall survival. None of the immunogenetic polymorphisms studied was predictive of response to immunosupressive therapy.Despite reports suggesting differences in biological activity of different anti-thymocyte globulin preparations, rabbit and horse anti-thymocyte globulin appear to have a similar efficacy for up-front treatment of severe aplastic anemia. Clinicaltrial.gov: NCT01231841).

| S-EPMC3166096 | biostudies-literature

Differential Elimination of Anti-Thymocyte Globulin of Fresenius and Genzyme Impacts T-Cell Reconstitution After Hematopoietic Stem Cell Transplantation.

Project description:Anti-thymocyte globulin (ATG) is a lymphocyte depleting agent applied in hematopoietic stem cell transplantation (HSCT) to prevent rejection and Graft-vs.-Host Disease (GvHD). In this study, we compared two rabbit ATG products, ATG-Genzyme (ATG-GENZ), and ATG-Fresenius (ATG-FRES), with respect to dosing, clearance of the active lymphocyte binding component, post-HSCT immune reconstitution and clinical outcome. Fifty-eigth pediatric acute leukemia patients (n = 42 ATG-GENZ, n = 16 ATG-FRES), who received a non-depleted bone marrow or peripheral blood stem cell graft from an unrelated donor were included. ATG-GENZ was given at a dosage of 6-10 mg/kg; ATG-FRES at 45-60 mg/kg. The active component of ATG from both products was cleared at different rates. Within the ATG-FRES dose range no differences were found in clearance of active ATG or T-cell re-appearance. However, the high dosage of ATG-GENZ (10 mg/kg), in contrast to the low dosage (6-8 mg/kg), correlated with prolonged persistence of active ATG and delayed T-cell reconstitution. Occurrence of serious acute GvHD (grade III-IV) was highest in the ATG-GENZ-low dosage group. These results imply that dosing of ATG-GENZ is more critical than dosing of ATG-FRES due to the difference in clearance of active ATG. This should be taken into account when designing clinical protocols.

| S-EPMC6414431 | biostudies-literature

Anti-Thymocyte Globulin Prophylaxis in Patients With Hematological Malignancies Undergoing Allogeneic Hematopoietic Stem Cell Transplantation: An Updated Meta-Analysis.

Project description:BackgroundAnti-thymocyte globulin (ATG) prophylaxis reduces graft-versus-host disease (GVHD) incidence. This meta-analysis aimed to explore the long-term efficacy of ATG and the influencing factors in patients undergoing allogeneic hematopoietic stem cell transplantation (allo-HSCT).MethodsPubMed, Embase, and Cochrane databases were searched for the relevant studies published up to August 2020. Data from randomized controlled trials (RCTs) on ATG prophylaxis for GVHD prevention in allo-HSCT patients were extracted.ResultsA total of eight relevant RCTs (1,348 patients) were included. ATG significantly reduced the incidence of grade III-IV aGVHD (P = 0.001) and cGVHD (P < 0.001). ATG significantly improved the GVHD relapse-free survival (GRFS) (P < 0.001). The immunosuppressive regimen (number and dose of immunosuppressants) was significantly reduced when using ATG (P = 0.005). Epstein-Barr virus (EBV) reactivation was high in patients receiving ATG (P = 0.003). No significant differences were detected in relapses, overall survival (OS), relapse-free survival (RFS), and non-relapse mortality (NRM) between the ATG and no ATG groups. Subgroup analyses revealed that the donor type and ATG formulation might be the possible sources of heterogeneity among the included studies. Meta-regression analysis showed that the cumulative dose of ATG did not affect GVHD, OS, relapse, RFS, and NRM.ConclusionAlthough ATG had no significant effect on relapse, RFS, and NRM, it significantly reduced the occurrence and severity of GVHD, improved the GRFS, and reduced the number and dose of immunosuppressants in patients undergoing allo-HSCT.

| S-EPMC8417733 | biostudies-literature

Anti-thymocyte globulin (thymoglobulin), tacrolimus, and sirolimus as acute graft-versus-host disease prophylaxis for unrelated hematopoietic stem cell transplantation.

Project description:Acute graft-versus-host disease (aGVHD) is a major cause of morbidity and mortality in patients undergoing unrelated hematopoietic stem cell transplantation. We prospectively evaluated the efficacy of intermediate-dose rabbit anti-thymocyte globulin (Thymoglobulin® a total of 4.5 mg/kg given over days -3, -2, and -1) in combination with tacrolimus and sirolimus for the prevention of aGVHD. We enrolled 47 recipients who underwent unrelated hematopoietic stem cell transplantation. Patients received daily granulocyte colony-stimulating factor starting on day +6 until neutrophil engraftment (median duration, 11 days; range, 9-15 days). Twenty-two patients received HLA 8/8 and 25 received 7/8 matched grafts, respectively. The median follow-up duration was 23.6 months (range, 18.8-27.9 months). The cumulative incidence of grade II to IV aGVHD was 23.4% (95% confidence interval, 12.4-36.3). At 2-year follow-up, the cumulative incidence of nonrelapse mortality was 31.9%, cumulative incidence of relapse was 24.6%, and cumulative incidence of chronic GVHD was 33%. Progression-free survival at 1 year was 54%, with a median of 17.7 months. Overall survival at 1 year was 65%, with no median reached. These results suggest that the combination of Thymoglobulin, tacrolimus, and sirolimus in patients undergoing unrelated hematopoietic stem cell transplantation is well tolerated and associated with a low incidence and severity of aGVHD and chronic graft-versus-host disease.

| S-EPMC3777606 | biostudies-literature

Myeloid-derived suppressor cells are bound and inhibited by anti-thymocyte globulin.

Project description:Myeloid-derived suppressor cells (MDSCs) inhibit T cell responses and are relevant to cancer, autoimmunity and transplant biology. Anti-thymocyte globulin (ATG) is a commonly used T cell depletion agent, yet the effect of ATG on MDSCs has not been investigated. MDSCs were generated in Lewis Lung Carcinoma 1 tumor-bearing mice. MDSC development and function were assessed in vivo and in vitro with and without ATG administration. T cell suppression assays, RT-PCR, flow cytometry and arginase activity assays were used to assess MDSC phenotype and function. MDSCs increased dramatically in tumor-bearing mice and the majority of splenic MDSCs were of the polymorphonuclear subset. MDSCs potently suppressed T cell proliferation. ATG-treated mice developed 50% fewer MDSCs and these MDSCs were significantly less suppressive of T cell proliferation. In vitro, ATG directly bound 99.6% of MDSCs. CCR7, L-selectin and LFA-1 were expressed by both T cells and MDSCs, and binding of LFA-1 was inhibited by ATG pre-treatment. Arg-1 and PD-L1 transcript expression were reduced 30-40% and arginase activity decreased in ATG-pretreated MDSCs. MDSCs were bound and functionally inhibited by ATG. T cells and MDSCs expressed common Ags which were also targets of ATG. ATG may be helpful in tumor models seeking to suppress MDSCs. Alternatively, ATG may inadvertently inhibit important T cell regulatory events in autoimmunity and transplantation.

| S-EPMC6830891 | biostudies-literature

Anti-thymocyte globulin could improve the outcome of allogeneic hematopoietic stem cell transplantation in patients with highly aggressive T-cell tumors.

Project description:The early experiment result in our hospital showed that anti-thymocyte globulin (ATG) inhibited the proliferation of lymphoid tumor cells in the T-cell tumors. We used the ATG as the part of the conditioning regimen and to evaluate the long-term anti-leukemia effect, the safety and complication in the patients with highly aggressive T-cell lymphomas. Twenty-three patients were enrolled into this study. At the time of transplant, six patients reached first or subsequent complete response, three patients had a partial remission and 14 patients had relapsed or primary refractory disease. The conditioning regimen consisted of ATG, total body irradiation, toposide and cyclophosphamide. The complete remission rate after transplant was 95.7%. At a median follow-up time of 25 months, 16 (69.6%) patients are alive and free from diseases, including nine patients in refractory and progressive disease. Seven patients died after transplant, five from relapse and two from treatment-related complications. The incidence of grades II-IV acute graft-vs-host disease (GvHD) was 39.1%. The maximum cumulative incidence of chronic GvHD was 30%. The most frequent and severe conditioning-related toxicities observed in 8 out of 23 patients were grades III/IV infections during cytopenia. Thus, ATG-based conditioning is a feasible and effective alternative for patients with highly aggressive T-cell tumors.

| S-EPMC4526780 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data