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Transplant International : Official... Jul 2013Strategies for induction in lung transplant recipients typically mirror those used in other solid organ transplant recipients. Polyclonal (Atgam, RATG) and monoclonal... (Review)
Review
Strategies for induction in lung transplant recipients typically mirror those used in other solid organ transplant recipients. Polyclonal (Atgam, RATG) and monoclonal (OKT3) T-cell depleting agents, IL-2 Receptor antagonists (basiliximab and daclizumab) have been used most commonly. In spite of evidence from ISHLT registry reports that induction reduces acute rejection and has a small benefit in freedom from bronchiolitis obliterans and long-term survival, other studies have been less convincing in terms of long-term benefit. Future iterations of induction strategy for lung transplant recipients will hopefully utilize tolerogenic approaches currently being tested in renal transplantation.
Topics: Alemtuzumab; Antibodies, Monoclonal, Humanized; Bronchiolitis Obliterans; Graft Rejection; Humans; Immunosuppressive Agents; Lung Transplantation; Lymphocyte Depletion; Receptors, Interleukin-2
PubMed: 23701023
DOI: 10.1111/tri.12115 -
Transplantation Reviews (Orlando, Fla.) Jan 2024Older liver transplant recipients have a lower risk of acute rejection than younger patients (9% for patients aged ≥65 years versus 23% for those aged 18-34 years)... (Review)
Review
Older liver transplant recipients have a lower risk of acute rejection than younger patients (9% for patients aged ≥65 years versus 23% for those aged 18-34 years) and are more vulnerable to immunosuppression-related complications. The number of liver transplant recipients ≥65 years has risen to 22% in Europe and the US, but limited information is available on the optimal immunosuppressive regimen for these patients. In this review, we discuss the appropriate management of immunosuppressive agents in older adults to minimize adverse events while avoiding acute rejection. The way the body processes drugs greatly depends on age. In the case of calcineurin inhibitor drugs, aging reduces hepatic metabolism, leading to changes in their pharmacokinetics. Corticosteroids also show decreased clearance as the patient ages. In severe cases of hypoalbuminemia, dose adjustment of mycophenolate acid derivatives may be necessary. However, the pharmacokinetic profiles of the mammalian target of rapamycin inhibitors, basiliximab, and rabbit anti-thymocyte globulin remain unaffected by age. Furthermore, age-related frailty may impact drug metabolism and require tailored interventions and closer follow-up. Although there is limited research, elderly liver transplant recipients require less immunosuppression with double or triple-agent regimens, lower exposure to calcineurin inhibitors, and a shorter course of corticosteroids. The usage of mammalian target of rapamycin inhibitors in older transplant populations has not been specifically investigated, and thus their usage should align with indications for younger patient groups.
Topics: Aged; Humans; Liver Transplantation; Graft Rejection; Immunosuppressive Agents; Immunosuppression Therapy; Calcineurin Inhibitors; Sirolimus; Adrenal Cortex Hormones; TOR Serine-Threonine Kinases
PubMed: 38128152
DOI: 10.1016/j.trre.2023.100817 -
American Journal of Transplantation :... Oct 2005This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a... (Clinical Trial)
Clinical Trial
This study examined alemtuzumab (anti-CD 52, Campath-1H) and basiliximab (anti-CD 25, Simulect) as induction immunosuppression in kidney transplantation. We used a single-center, nonrandomized, retrospective, sequential study design to evaluate outcomes in kidney transplant recipients given either alemtuzumab (n = 123) or basiliximab (n = 155) induction in combination with a prednisone-free maintenance protocol using tacrolimus and mycophenolate mofetil. Kaplan-Meier analyses of long-term patient and graft survivals and rejection rates were determined according to induction agent, donor source and recipient ethnicity. Secondary endpoints included the quality of renal allograft function and the etiology of infectious complications. Overall long-term patient and graft survival rates did not significantly differ between patients treated with alemtuzumab and basiliximab. A lower rate of early (<3 months) rejection was observed in the alemtuzumab (4.1%) versus the basiliximab (11.6%) group, but the rates for both groups were equivalent at 1 year. Patient and kidney survival and rejection rates were nearly identical between Caucasians and African Americans that received alemtuzumab. Quality of renal function and incidence of infectious complications were similar in the two groups. Alemtuzumab induction therapy was similar in efficacy to basiliximab in a prednisone-free maintenance immunosuppressive protocol for an ethnically diverse population of kidney transplant recipients.
Topics: Adolescent; Adult; Aged; Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antibodies, Neoplasm; Creatinine; Disease Progression; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Immunotherapy; Infant, Newborn; Kidney; Kidney Transplantation; Living Donors; Male; Middle Aged; Mycophenolic Acid; Prednisone; Proportional Hazards Models; Retrospective Studies; Tacrolimus; Time Factors; Treatment Outcome
PubMed: 16162205
DOI: 10.1111/j.1600-6143.2005.01067.x -
Liver Transplantation : Official... Apr 2008Corticosteroid-free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the...
Corticosteroid-free immunosuppression (IS) may be potentially beneficial for transplanted patients, particularly children. The purpose of this study was to evaluate the efficacy and cost of such strategy in primary pediatric liver transplantation (LT). Fifty pediatric LT recipients were prospectively treated with a steroid-free, tacrolimus-basiliximab-based IS (group TB). A group of 34 children transplanted under a conventional tacrolimus-steroids regimen served as control series (group TS). Groups TB and TS were compared regarding patient and graft survival, rejection incidence, infectious complications, and growth, as well as cost of the transplant procedure. Patient and graft survivals at 3 years were 96% and 94% in group TB, versus 91% and 88% in group TS (P = 0.380 and P = 0.370, respectively). Rejection-free graft survival at 3 years was 72% in group TB, versus 41% in group TS (P = 0.007). Patients in group TB had significantly less viral infections than patients in group TS (P = 0.045). Height standard deviation score was significantly enhanced in children from group TB, when compared to group TS. Medical care costs were similar in both groups. Steroid avoidance together with basiliximab immunoprophylaxis was not harmful in terms of allograft acceptance, and even seemed to be beneficial in the long term.
Topics: Adolescent; Adrenal Cortex Hormones; Antibodies, Monoclonal; Basiliximab; Belgium; Child; Child, Preschool; Costs and Cost Analysis; Humans; Immunosuppressive Agents; Infant; Liver Diseases; Liver Transplantation; Recombinant Fusion Proteins; Tacrolimus; Treatment Outcome
PubMed: 18383091
DOI: 10.1002/lt.21397 -
Journal of Hematology & Oncology Mar 2022Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR... (Randomized Controlled Trial)
Randomized Controlled Trial
Mesenchymal stromal cells plus basiliximab, calcineurin inhibitor as treatment of steroid-resistant acute graft-versus-host disease: a multicenter, randomized, phase 3, open-label trial.
BACKGROUND
Steroid-resistant (SR) acute graft-versus-host disease (aGVHD) lacks standard second-line treatment. Mesenchymal stromal cells (MSCs) have potential efficacy in SR aGVHD. We aimed to assess the efficacy and safety of MSCs combined with basiliximab and calcineurin inhibitor as second-line therapy for SR aGVHD.
METHODS
A randomized phase 3 trial involved 203 SR aGVHD patients at nine centers in China (September 2014-March 2019). Participants were randomized at a 1:1 ratio to receive second-line therapy with (n = 101) or without (n = 102) MSCs. The primary endpoint was the overall response (OR) at day 28. Secondary and safety endpoints included durable OR at day 56, failure-free survival, overall survival (OS), chronic GVHD (cGVHD), infection, hematological toxicity and relapse.
RESULTS
Of 203 patients, 198 (97.5%; mean age, 30.1 years; 40.4% women) completed the study. The OR at day 28 was higher in the MSC group than the control group (82.8% [82 patients] vs. 70.7% [70]; odds ratio, 2.00; 95% confidence interval [CI], 1.01-3.94; P = 0.043). The durable OR at day 56 was also higher in the MSC group (78.8% [78 patients] vs. 64.6% [64]; odds ratio, 2.02; 95% CI, 1.08-3.83; P = 0.027). The median failure-free survival was longer in the MSC group compared with control (11.3 months vs. 6.0 months; hazard ratio (HR) 0.68; 95% CI, 0.48-0.95, P = 0.024). The 2-year cumulative incidence of cGVHD was 39.5% (95% CI, 29.3-49.4%) and 62.7% (51.4-72.1%) in the MSC and control groups (HR 0.55, 95% CI, 0.36-0.84; P = 0.005). Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections (65 [65.7%] in the MSC group vs. 78 [78.8%] in the control group) and hematological toxicity (37 [37.4%] vs. 53 [53.5%]). The 3-year cumulative incidence of tumor relapse was 10.1% (95% CI, 5.2-17.1) and 13.5% (7.5-21.2%) in the MSC and control groups, respectively (HR 0.75, 95% CI, 0.34-1.67, P = 0.610).
CONCLUSIONS
MSCs plus second-line treatments increase the efficacy of SR aGVHD, decrease drug toxicity of second-line drugs and cGVHD without increasing relapse, and are well-tolerated. MSCs could be recommended as a second-line treatment option for aGVHD patients. Trial registration clinicaltrials.gov identifier: NCT02241018. Registration date: September 16, 2014, https://clinicaltrials.gov/ct2/show/NCT02241018 .
Topics: Acute Disease; Adult; Basiliximab; Calcineurin Inhibitors; Female; Graft vs Host Disease; Hematopoietic Stem Cell Transplantation; Humans; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Neoplasm Recurrence, Local; Steroids
PubMed: 35255929
DOI: 10.1186/s13045-022-01240-4 -
Experimental and Clinical... Apr 2024Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as... (Comparative Study)
Comparative Study
OBJECTIVES
Induction treatment in renal transplant is associated with better graft survival. However, intensified immunosuppression is known to cause unwanted side effects such as infection and malignancy. Furthermore, the effects of the routine use of immunosuppressants in low-risk kidney transplant recipients are still not clear. In this study, we assessed the first-year safety and efficacy of induction treatment.
MATERIALS AND METHODS
We examined first living donor kidney transplant patients who were on tacrolimus based immunosuppression therapy. We formed 3 groups according to the induction status: antithymocyte globulin induction, basiliximab induction, and no induction. We collected outcome data on delayed graft function, graft loss, creatinine levels, estimated glomerular filtration rates, acute rejection episodes, hospitalization episodes, and infection episodes, including cytomegalovirus infection and bacterial infections.
RESULTS
We examined a total of 126 patients (age 35 ± 12 years; 65% male). Of them, 25 received antithymocyte globulin, 52 received basiliximab, and 49 did notreceive any induction treatment. We did not observe any statistically significant difference among the 3 groups in terms of acute rejection episodes, delayed graft function, and first-year graft loss. The estimated glomerular filtration rates were similar among the groups. Overall bacterial infectious complications and cytomegalovirus infection showed similar prevalence among all groups. Hospitalization was less common in the induction-free group.
CONCLUSIONS
In low-risk patients, induction-free regimens could be associated with a better safety profile without compromising graft survival. Therefore, induction treatment may be disregarded in first living donor transplant patients who receive tacrolimusbased triple immunosuppression treatment.
Topics: Humans; Kidney Transplantation; Basiliximab; Immunosuppressive Agents; Female; Male; Tacrolimus; Living Donors; Adult; Antilymphocyte Serum; Middle Aged; Treatment Outcome; Time Factors; Graft Rejection; Graft Survival; Risk Factors; Retrospective Studies; Delayed Graft Function; Young Adult; Recombinant Fusion Proteins; Calcineurin Inhibitors; Drug Therapy, Combination
PubMed: 38742317
DOI: 10.6002/ect.2023.0010 -
Canadian Journal of Kidney Health and... 2020Kidney transplant recipients are given induction therapy to rapidly reduce the immune response and prevent rejection. Guidelines recommend that an interleukin-2 receptor...
BACKGROUND
Kidney transplant recipients are given induction therapy to rapidly reduce the immune response and prevent rejection. Guidelines recommend that an interleukin-2 receptor antibody (basiliximab) be the first-line agent and that a lymphocyte-depleting agent (antithymocyte globulin [ATG]) be reserved for those at high immunologic risk.
OBJECTIVE
To determine the incidence, risk factors, and outcomes for patients who receive both basiliximab and ATG for induction compared to either agent alone.
DESIGN
Retrospective cohort study.
SETTING
We used the transplant electronic medical record at the University of Alberta Hospital in Edmonton, Canada.
PATIENTS/SAMPLES/PARTICIPANTS
We included incident adult kidney transplant recipients from 2013 to 2018.
MEASUREMENTS
We measured baseline characteristics, type, and dose of induction therapy used, estimated glomerular filtration rate (eGFR) at 1-year posttransplant, and outcomes of all-cause graft failure, death-censored graft failure, all-cause mortality, and death with a functioning graft.
METHODS
Differences between induction groups were compared using chi-square test for categorical variables and Kruskal-Wallis tests for continuous variables. We performed multivariable logistic regression modeling with type of induction therapy as the dependent variable and the case-level factors as the predictors (adjusted odds ratio). We estimated the Kaplan-Meier failure functions and used log-rank tests to assess statistical significance of differences in unadjusted incidence across induction therapy types. We compared cumulative incidence functions using a Fine and Gray competing risk regression model.
RESULTS
In all, 430 kidney transplant recipients were followed for a mean of 3.9 years (standard deviation 1.5). Of these, 71% (n = 305) received basiliximab alone, 22% (n = 93) received ATG alone, and 7% (n = 32) received both basiliximab and ATG. After adjusting for age and sex, compared to the basiliximab alone group, patients were more likely to receive dual-induction therapy if they were sensitized (calculated panel reactive antibody ≥80%), had diabetes mellitus or peripheral vascular disease, or experienced delayed graft function. Compared to the ATG alone group, the dual-induction therapy group had worse graft function at 1 year (mean eGFR 42 vs. 59 mL/min/1.73 m, = .0008) and an increased risk of all-cause graft failure (31% vs. 13%, = .02) and death-censored graft failure (16% vs. 4%, = .03).
LIMITATIONS
There is a risk of confounding by indication, as patients who received dual-induction therapy likely had worse outcomes due to the indication for dual-induction therapy (such as delayed graft function).
CONCLUSIONS
In our study, 1 out of 10 recipients who were treated with basiliximab also received ATG for induction therapy. These patients experienced worse outcomes than those treated with ATG alone.
TRIAL REGISTRATION
Not applicable (cohort study).
PubMed: 33117549
DOI: 10.1177/2054358120964061 -
Immunotherapy Jul 2011Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection... (Review)
Review
Monoclonal antibodies are applied in various settings in renal transplantation. Depleting T-cell antibodies are used for treatment of steroid-resistant acute rejection and as induction therapy to reduce the intensity of concomitant immunosuppressive drug therapy. Induction therapy with the nondepleting IL-2 receptor antagonists basiliximab and daclizumab, added to cyclosporine-based regimens, reduces the incidence of acute rejection without side effects. However, an increase in long-term graft and patient survival has not been demonstrated yet. The B-cell-targeting antibody rituximab is used in blood group ABO-incompatible transplantation, in desensitization protocols, and for treatment of antibody-mediated rejection. Eculizumab interrupts the complement pathway and is a promising tool for the treatment of antibody-mediated rejection and post-transplant hemolytic-uremic syndrome. Future options are monoclonal antibodies with new molecular targets and antibodies that can be used for maintenance immunosuppression in order to avoid the toxicity of existing drugs. However, in several cases, the development of new monoclonal antibodies has been hampered by safety issues.
Topics: Animals; Antibodies, Monoclonal; Antilymphocyte Serum; B-Lymphocytes; Cyclosporine; Graft Rejection; Hemolytic-Uremic Syndrome; Humans; Immunoglobulin G; Immunosuppression Therapy; Immunosuppressive Agents; Kidney Transplantation; Mice; Rats; Receptors, Interleukin-2
PubMed: 21751955
DOI: 10.2217/imt.11.72 -
Transplant International : Official... Jul 2013Currently available immunosuppressive agents can be classified into three categories: induction agents, maintenance therapy, and treatment for rejection. This review... (Review)
Review
Currently available immunosuppressive agents can be classified into three categories: induction agents, maintenance therapy, and treatment for rejection. This review article will focus on induction immunosuppression. There are three antibodies which are used for induction therapy: the lymphocyte-depleting agents - anti-thymocyte globulin and alemtuzumab, and basiliximab which is nondepleting. Historically, immunosuppressant selection was solely based on efficacy for prevention of rejection. In the current era of transplantation, it is now common practice in the transplant community to select induction therapy on the basis of risk-benefit considerations for each patient. This article will focus on the efficacy of available induction agents and the selection of induction agent based on donor and recipient risk factors.
Topics: Alemtuzumab; Antibodies, Monoclonal; Antibodies, Monoclonal, Humanized; Antilymphocyte Serum; Basiliximab; Delayed Graft Function; Humans; Immunosuppressive Agents; Kidney Transplantation; Living Donors; Recombinant Fusion Proteins
PubMed: 23279211
DOI: 10.1111/tri.12043 -
Annals of Hepatology 2020The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their... (Comparative Study)
Comparative Study Randomized Controlled Trial
INTRODUCTION AND AIM
The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their renal insult. However, there is only little evidence for the safety and the efficacy of this regimen. This study aimed to evaluate the effectiveness and safety of basiliximab induction in liver transplantation.
MATERIALS AND METHODS
This study included 89 patients who were classified into two groups: standard triple immunosuppression (IS) regimen of steroid, tacrolimus (TAC) and mycophenolate mofetil (MMF) (n = 47) and induction IS regimen of basiliximab, low dose steroids and MMF with delayed introduction of CNI (n = 42). All patients were followed after liver transplantation for at least six months or until death.
RESULTS
There were no significant differences in patient survival, graft dysfunction, infection rate or type, or wound healing between both groups. The acute rejection rate was equivalent in both groups. Renal dysfunction in the first six months post-transplant was less in the basiliximab group in comparison to the other group (7.1% and 19.1% respectively).
CONCLUSION
Basiliximab-induced IS protocol is a safe regimen that reduces medium-term renal dysfunction and achieves similar survival without increasing the acute rejection or infection rate in liver transplantation recipients.
Topics: Adult; Basiliximab; Calcineurin Inhibitors; Drug Therapy, Combination; Egypt; Female; Graft Rejection; Graft Survival; Humans; Immunosuppressive Agents; Liver Transplantation; Male; Middle Aged; Mycophenolic Acid; Steroids; Tacrolimus; Time Factors; Treatment Outcome
PubMed: 32768592
DOI: 10.5604/01.3001.0012.2246