ABSTRACT
Background: Steroid-resistant (SR) lower gastrointestinal (LGI) tract graft-versus-host disease (GVHD) is the predominant cause of morbidity and mortality from GVHD after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The role of vedolizumab in the treatment of SR-LGI acute GVHD (aGVHD) remains uncertain. We aimed to assess the efficacy and safety of vedolizumab combined with basiliximab as second-line therapy for SR-LGI-aGVHD. Methods: This study aimed to explore the efficacy of vedolizumab combined with basiliximab for SR-LGI-aGVHD. The primary endpoint was the overall response (OR) on day 28. Secondary and safety endpoints included durable OR at day 56, overall survival (OS), chronic GVHD (cGVHD), non-relapse mortality (NRM), failure-free survival (FFS), and adverse events. Results: Twenty-eight patients with SR-LGI-aGVHD were included. The median time to start of combination therapy after SR-LGI-aGVHD diagnosis was 7 (range, 4-16) days. The overall response rate (ORR) at 28 days was 75.0% (95% CI: 54.8%-88.6%), and 18 achieved a complete response (CR) (64.3%, 95% CI: 44.1%-80.7%). The durable OR at day 56 was 64.3% (95% CI: 44.1%-80.7%). The 100-day, 6-month, and 12-month OS rates for the entire cohort of patients were 60.7% (95% CI: 45.1%-81.8%), 60.7% (95% CI: 45.1%-81.8%), and 47.6% (95% CI: 31.4%-72.1%), respectively. The median failure-free survival was 276 days; (95% CI: 50-not evaluable) 12-month NRM was 42.9% (95% CI: 24.1%-60.3%). The 1-year cumulative incidence of cGVHD was 35.7%. Within 180 days after study treatments, the most common grade 3 and 4 adverse events were infections. Nine (32.1%) patients developed cytomegalovirus (CMV) reactivation complicated with bacterial infections (25.0%, CMV infection; 7.1%, CMV viremia). Epstein-Barr virus (EBV) reactivation occurred in five patients (17.9%, 95% CI: 6.8%-37.6%). Only three patients (10.7%, 95% CI: 2.8%-29.4%) in our study developed pseudomembranous colitis. Conclusions: Vedolizumab plus basiliximab demonstrated efficacy in severe SR-LGI-aGVHD and was well-tolerated. Vedolizumab plus basiliximab may be considered a potential treatment option for patients with LGI-aGVHD.
Subject(s)
Antibodies, Monoclonal, Humanized , Basiliximab , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Humans , Graft vs Host Disease/drug therapy , Graft vs Host Disease/etiology , Antibodies, Monoclonal, Humanized/therapeutic use , Antibodies, Monoclonal, Humanized/adverse effects , Male , Female , Adult , Middle Aged , Basiliximab/therapeutic use , Hematopoietic Stem Cell Transplantation/adverse effects , Young Adult , Adolescent , Drug Therapy, Combination , Treatment Outcome , Gastrointestinal Diseases/etiology , Drug Resistance , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/adverse effects , Acute Disease , Steroids/therapeutic use , Aged , Retrospective StudiesABSTRACT
Basiliximab is an important treatment for steroid-refractory acute graft-versus-host disease (SR-aGVHD). We performed this retrospective study to evaluate the efficacy and safety of basiliximab treatment in SR-aGVHD patients following matched sibling donor hematopoietic stem cell transplantation (MSD-HSCT) (n = 63). Overall response rate (ORR) was 63.5% and 54% at any time and at day 28 after basiliximab treatment. Grade III-IV aGVHD before basiliximab treatment predicted a poor ORR after basiliximab treatment. The rates of virus, bacteria, and fungi infections were 54%, 23.8%, and 3.1%, respectively. With a median follow-up of 730 (range, 67-3,042) days, the 1-year probability of overall survival and disease-free survival after basiliximab treatment were 58.6% (95% confidence interval [CI] = 47.6%-72.2%) and 55.4% (95% CI = 44.3%-69.2%), respectively. The 3-year cumulative incidence of relapse and non-relapse mortality after basiliximab treatment were 18.9% (95% CI = 8.3%-29.5%) and 33.8% (95% CI = 21.8%-45.7%), respectively. Comorbidities burden before allo-HSCT, severity of aGVHD and liver aGVHD before basiliximab treatment showed negative influences on survival. Thus, basiliximab was safe and effective treatment for SR-aGVHD following MSD-HSCT.
Subject(s)
Antibodies, Monoclonal , Basiliximab , Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Recombinant Fusion Proteins , Humans , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Hematopoietic Stem Cell Transplantation/methods , Basiliximab/therapeutic use , Male , Female , Adult , Middle Aged , Recombinant Fusion Proteins/therapeutic use , Antibodies, Monoclonal/therapeutic use , Retrospective Studies , Adolescent , Siblings , Young Adult , Immunosuppressive Agents/therapeutic use , Steroids/therapeutic use , Acute Disease , Child , Treatment Outcome , Tissue DonorsABSTRACT
BACKGROUND: Patients undergoing heart transplants are at risk of rejection which can have significant morbidity and mortality. Induction immunosuppression at the time of transplant reduces the early risk and has additional benefits. The induction agent of choice within our program was changed from rabbit antithymocyte-globulin (rATG) to basiliximab, so it was necessary to evaluate whether this had any impact on patient outcomes. OBJECTIVES: Our primary objective was to describe rejection, infection, and other outcomes in adult heart transplant patients at the University of Alberta Hospital in Edmonton, Canada. METHODS: This study was a nonrandomized, retrospective cohort study. RESULTS: Sixty-three patients were included with median ages 50 years versus 54 years. More female patients received rATG (20% vs. 42.4%). The most common indication for transplant in both cohorts was ICM (63.3% vs. 57.6%). Patients who received rATG had significantly higher PRA (0% vs. 43%, p < .001). Acute rejection episodes were similar between basiliximab and rATG at 3 months (16.7% vs. 15.1%; p = 1.0) and 6-months (30.0% vs. 18.1%; p = .376). Infections were not statistically different with basiliximab compared to rATG at 3-months, 43.3% vs. 63.6% and at 6-months 60.0% vs. 66.7%). There were no fatalities in either group. CONCLUSIONS: Our study did not demonstrate differences in rejection with basiliximab compared to rATG. Mortality did not differ, but basiliximab-treated patients had fewer infections and infection-related hospitalizations than those treated with rATG. Larger studies with longer durations are needed to more completely describe the differences in rejection and infectious outcomes.
Subject(s)
Antibodies, Monoclonal , Antilymphocyte Serum , Basiliximab , Graft Rejection , Heart Transplantation , Immunosuppressive Agents , Recombinant Fusion Proteins , Humans , Basiliximab/therapeutic use , Female , Male , Heart Transplantation/adverse effects , Middle Aged , Retrospective Studies , Recombinant Fusion Proteins/therapeutic use , Graft Rejection/prevention & control , Graft Rejection/etiology , Graft Rejection/drug therapy , Graft Rejection/immunology , Antilymphocyte Serum/therapeutic use , Immunosuppressive Agents/therapeutic use , Adult , Follow-Up Studies , Antibodies, Monoclonal/therapeutic use , Graft Survival/drug effects , Graft Survival/immunology , Prognosis , Risk Factors , Postoperative Complications , Aged , Immunosuppression Therapy/methodsABSTRACT
BACKGROUND: We hypothesized that alemtuzumab use is safe in pediatric kidney transplant recipients (KTRs) with equivalent long-term outcomes compared to other induction agents. METHODS: Using pediatric kidney transplant recipient data in the UNOS database between January 1, 2000, and June 30, 2022, multivariate logistic regression, multivariable Cox regression, and survival analyses were utilized to estimate the likelihoods of 1st-year and all-time hospitalizations, acute rejection, CMV infection, delayed graft function (DGF), graft loss, and patient mortality among recipients of three common induction regimens (ATG, alemtuzumab, and basiliximab). RESULTS: There were no differences in acute rejection or graft failure among induction or maintenance regimens. Basiliximab was associated with lower odds of DGF in deceased donor recipients (OR 0.77 [0.60-0.99], p = .04). Mortality was increased in patients treated with steroid-containing maintenance (HR 1.3 [1.005-1.7] p = .045). Alemtuzumab induction correlated with less risk of CMV infection than ATG (OR 0.76 [0.59-0.99], p = .039). Steroid-containing maintenance conferred lower rate of PTLD compared to steroid-free maintenance (HR 0.59 [0.4-0.8] p = .001). Alemtuzumab was associated with less risk of hospitalization within 1 year (OR 0.79 [0.67-0.95] p = .012) and 5 years (HR 0.54 [0.46-0.65] p < .001) of transplantation. Steroid maintenance also decreased 5 years hospitalization risk (HR 0.78 [0.69-0.89] p < .001). CONCLUSIONS: Pediatric KTRs may be safely treated with alemtuzumab induction without increased risk of acute rejection, DGF, graft loss, or patient mortality. The decreased risk of CMV infections and lower hospitalization rates compared to other agents make alemtuzumab an attractive choice for induction in pediatric KTRs, especially in those who cannot tolerate ATG.
Subject(s)
Alemtuzumab , Basiliximab , Graft Rejection , Hospitalization , Immunosuppressive Agents , Kidney Transplantation , Humans , Alemtuzumab/therapeutic use , Child , Male , Hospitalization/statistics & numerical data , Female , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Adolescent , Child, Preschool , Basiliximab/therapeutic use , Infant , Graft Survival , Antilymphocyte Serum/therapeutic use , Treatment Outcome , Retrospective Studies , Delayed Graft Function/epidemiology , Cytomegalovirus InfectionsABSTRACT
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.
Subject(s)
Antilymphocyte Serum , Basiliximab , Immunosuppressive Agents , Kidney Transplantation , Living Donors , Tacrolimus , Adult , Female , Humans , Male , Middle Aged , Young Adult , Antilymphocyte Serum/adverse effects , Antilymphocyte Serum/therapeutic use , Basiliximab/adverse effects , Basiliximab/therapeutic use , Calcineurin Inhibitors/adverse effects , Calcineurin Inhibitors/administration & dosage , Delayed Graft Function/immunology , Drug Therapy, Combination , Graft Rejection/immunology , Graft Rejection/prevention & control , Graft Survival/drug effects , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Kidney Transplantation/adverse effects , Recombinant Fusion Proteins/adverse effects , Recombinant Fusion Proteins/therapeutic use , Retrospective Studies , Risk Factors , Tacrolimus/adverse effects , Tacrolimus/therapeutic use , Time Factors , Treatment OutcomeABSTRACT
BACKGROUND AND OBJECTIVES: The relative safety and efficacy of early steroid withdrawal in kidney transplant patients after basiliximab compared to anti-thymocyte globulin (ATG) induction therapy is unknown. We aimed to compare kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction from the United Network for Organ Sharing (UNOS) database. MATERIALS AND METHODS: We conducted a retrospective cohort analysis of the UNOS database and included first kidney transplant recipients who received ATG or basiliximab induction therapy. We compared graft and patient outcomes in those who received steroid maintenance and those who were discharged off steroids. RESULTS: Of 106,061 patients, 25,344 (86.7%) received basiliximab induction and were maintained on steroids (B-Sm), and 3,880 (13.3%) were on a steroid-free regimen (B-Sf). Graft failure rate was significantly higher in the B-Sf compared to B-Sm at 1-year (4.1 vs. 1.8%, p < 0.001), 3-year (6.0 vs. 4.3%, p < 0.001) and 5-year follow-up (7.7 vs. 6.4%, p = 0.0004). The mortality rate was significantly higher in B-Sf at 1-year (3.3 vs. 2.4%, p = 0.0005), 3-year (7.6 vs. 5.5%, p < 0.001) and 5-year follow-up (11.5 vs. 8.8%, p < 0.001) when compared to the B-Sm. 76,837 recipients received ATG induction therapy, 51,745 (72.4%) were on steroid maintenance therapy (A-Sm) and 25,092 (32.6%) were on a steroid-free regimen (A-Sf). The graft failure rate was significantly higher in A-Sf compared to A-Sm at 1-year follow-up (2.6 vs. 2.3%, p = 0.0006), however, there was no difference at 3-year (5.0 vs. 5.0%, p = 0.53) or 5-year follow-up (7.2 vs. 8.1%, p = 0.17). There was no difference in mortality rates between A-Sf vs. A-Sm at 1 year (2.5 vs. 2.4%, p = 0.98) and at 3 years (5.5 vs. 5.4%, p = 0.45), respectively. CONCLUSION: Patients who were maintained on steroids after basiliximab induction had better 5-year allograft survival and patient survival compared to those who were not maintained on steroids. However, steroid maintenance conferred no additional benefit after ATG induction and was associated with higher mortality.
Subject(s)
Antilymphocyte Serum , Basiliximab , Graft Rejection , Graft Survival , Immunosuppressive Agents , Kidney Transplantation , Humans , Basiliximab/therapeutic use , Basiliximab/administration & dosage , Male , Retrospective Studies , Antilymphocyte Serum/therapeutic use , Antilymphocyte Serum/administration & dosage , Female , Middle Aged , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/administration & dosage , Adult , Graft Rejection/prevention & control , Graft Survival/drug effects , Databases, Factual , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Treatment Outcome , Steroids/administration & dosage , Steroids/therapeutic use , Allografts , Time FactorsABSTRACT
Objectives: To investigate the efficacy of short-term substitution of recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as acute GVHD (aGVHD) prophylaxis in calcineurin inhibitors (CNI) intolerant patients following allogeneic hematopoietic stem cell transplantation (allo-HSCT) . Methods: This study included 17 patients with refractory malignant hematological disorders who underwent salvage allo-HSCT at the Bone Marrow Transplantation Department of Shanghai Zhaxin Traditional Chinese and Western Medicine Hospital from August 2021 to August 2022 and were treated with Baliximab to prevent aGVHD due to severe adverse reactions to CNI. There were seven men and ten women, with a median age of 43 years (18-67). Following the discontinuation of CNI, Basiliximab was administered at a dose of 1 mg/kg once weekly until CNI or mTOR inhibitors were resumed. Results: Basiliximab was started at an average of 5 (1-32) days after HSCT. The median duration of substitution was 20 (7-120) days. All had neutrophil engraftment within a median of 12 (10-17) days. Thirteen patients had platelet engraftment after a median of 13 (11-20) days. Four patients did not develop stable platelet engraftment. Eight patients (47.1% ) developed Grade â ¡-â £ aGVHD, while four (23.6% ) developed Grade â ¢/â £ aGVHD. Only one patient died from aGVHD. Before the end of the followup period, seven of 17 patients died. The longest followup period of the survivors was 347 days, and the median survival rate was not met. The overall survival (OS) rate at six months was 62.6%. Among the 17 patients, 13 (76.4% ) experienced cytomegalovirus reactivation, 7 (41.2% ) experienced EB virus activation, and no cytomegalovirus disease was observed. Conclusions: When CNI intolerance occurs during allo-HSCT, short-term replacement with Baliximab can be used as an alternative to prevent aGVHD.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Adolescent , Adult , Aged , Female , Humans , Male , Middle Aged , Young Adult , Antibodies, Monoclonal/therapeutic use , Basiliximab/therapeutic use , Calcineurin Inhibitors/therapeutic use , China , Graft vs Host Disease/prevention & control , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effectsABSTRACT
BACKGROUND: The use of induction immunosuppression for heart transplantation (HT) is debated given the uncertain benefit and potential risks of infection and malignancy. METHODS: This is a retrospective single-center analysis of 475 consecutive HT recipients from 2003 to 2020 grouped by use of induction with basiliximab group (BG) and the no basiliximab group (NBG). Subgroup analysis by era compared pre-2016 standard-basiliximab (BX) induction and 2016-2020 with selective-BX use as part of a calcineurin-inhibitor-sparing regimen. RESULTS: When adjusted for confounders (sex, age, PRA, eGFR), the BG was less likely to have acute cellular rejection (ACR) (OR.42, p < .001), but had more antibody mediated rejection (AMR) (OR 11.7, p < .001) and more cardiac allograft vasculopathy (CAV) (OR 3.8, p = .04). There was no difference between BG and NBG in the incidence of malignancies or infections. When stratified by era (pre-2016 vs. 2016-2020), ACR remained less common in the BG than the NBG (36% vs. 50%, p = .045) groups, while AMR remained more common (9.7 vs. 0% p = .005). There was no significant difference in conditional survival comparing pre-and post-2016 NBG (HR 2.20 (95% CI.75-6.43); however, both pre-2016 BG and post-2016 BG have significantly higher mortality (HR 2.37 [95% CI 1.02-5.50) and HR 2.69 (95% CI 1.08-6.71), p = .045 and.03, respectively]. CONCLUSION: Basiliximab reduces the incidence of ACR but increases the risk of AMR, CAV, and may be associated with increased mortality. Mechanistic studies are needed to describe a potential T-cell-escape mechanism with enhanced humoral immunity.
Subject(s)
Heart Transplantation , Neoplasms , Humans , Basiliximab/therapeutic use , Immunosuppressive Agents/therapeutic use , Immunosuppressive Agents/pharmacology , Antibodies, Monoclonal/therapeutic use , Retrospective Studies , Graft Rejection/drug therapy , Graft Rejection/etiology , Heart Transplantation/adverse effects , Recombinant Fusion Proteins/therapeutic useABSTRACT
BACKGROUND: This study aimed to compare the efficacy and safety of basiliximab (BAS) versus a single dose of anti-thymocyte globulin (r-ATG) induction therapy in pediatric kidney transplant recipients (KTRs). METHODS: This single-center retrospective comparative cohort study included all pediatric KTRs from May 2013 to April 2018 and followed up to 12 months. In the first period, all recipients received BAS, while from May 2016, a single 3 mg/kg dose of r-ATG was instituted. Maintenance therapy consisted of a calcineurin inhibitor plus prednisone plus azathioprine or mycophenolate. RESULTS: A total of 227 patients were included (BAS, n = 113; r-ATG, n = 114). The main combination of immunosuppressive drugs was tacrolimus, prednisone, and azathioprine in both groups (87% vs. 88%, p = .718). Patients receiving r-ATG showed superior survival-free of the composite endpoint (acute rejection, graft loss, or death; 76% vs. 61%, p = .003; HR 2.08, 1.29-3.34, p = .003) and lower incidence of biopsy-proven acute rejection (10% vs. 21%, p = .015). There was no difference in the overall incidence of CMV infection (33% vs. 37%, p = .457), PTLD (1% vs. 3%, p = .309), 30-day hospital readmissions (24% vs. 23%, p = .847), and kidney function at 12 months (86 ± 29 vs. 84 ± 30 mL/min/1.73m2, p = .614). CONCLUSIONS: These data suggest that induction therapy with a single 3 mg/kg dose of r-ATG is associated with higher efficacy for preventing acute rejection and similar safety profile compared to BAS.
Subject(s)
Antilymphocyte Serum , Kidney Transplantation , Humans , Child , Basiliximab/therapeutic use , Antilymphocyte Serum/therapeutic use , Antibodies, Monoclonal/therapeutic use , Prednisone/therapeutic use , Retrospective Studies , Cohort Studies , Azathioprine , Induction Chemotherapy , Graft Rejection/prevention & control , Graft Rejection/epidemiology , Immunosuppressive Agents/therapeutic use , Recombinant Fusion Proteins/therapeutic use , Transplant RecipientsABSTRACT
BACKGROUND: The use of induction therapy (IT) agents in the early post-heart transplant period remains controversial. The following recommendations aim to provide guidance on the use of IT agents, including Basiliximab and Thymoglobulin, as part of routine care in heart transplantation (HTx). METHODS: We recruited an international, multidisciplinary panel of 15 stakeholders, including patient partners, transplant cardiologists and surgeons, nurse practitioners, pharmacists, and methodologists. We commissioned a systematic review on benefits and harms of IT on patient-important outcomes, and another on patients' values and preferences to inform our recommendations. We used the GRADE framework to summarize our findings, rate certainty in the evidence, and develop recommendations. The panel considered the balance between benefits and harms, certainty in the evidence, and patient's values and preferences, to make recommendations for or against the routine post-operative use of Thymoglobulin or Basiliximab. RESULTS: The panel made recommendations on three major clinical problems in HTx: (1) We suggest against the routine post-operative use of Basiliximab compared to no IT, (2) we suggest against the routine use of Thymoglobulin compared to no IT, and (3) for those patients for whom IT is deemed desirable, we suggest for the use of Thymoglobulin as compared to Basiliximab. CONCLUSION: This report highlights gaps in current knowledge and provides directions for clinical research in the future to better understand the clinical utility of IT agents in the early post heart transplant period, leading to improved management and care.
Subject(s)
Heart Transplantation , Induction Chemotherapy , Humans , Network Meta-Analysis , Basiliximab , Heart Transplantation/adverse effects , HeartABSTRACT
BACKGROUND: Various induction regimens are available for kidney transplantation (KT); however, which is superior remains unclear. Moreover, although the induction regimens are effective and important for reducing side effects, their respective relationships with antibody-mediated rejection (AMR) after transplantation remain unclear. Therefore, this study aimed to elucidate the most effective induction regimen for AMR reduction through network analysis. METHODS: We performed a comprehensive search of databases, including basiliximab, alemtuzumab, antithymocyte globulin (ATG), and daclizumab as induction regimens for KT from inception to September 1, 2022. Using a network meta-analysis, we investigated the priorities of 5 induction regimens for patient survival, graft failure, and graft rejection after ABO-incompatible KT. RESULTS: In total, 25 studies comprising 1768 people were included in this network meta-analysis. The primary outcome was the AMR rate of other induction regimens compared with that of basiliximab, whereas the secondary outcomes were heart failure, stroke, hospitalization, peripheral artery disease, myocardial infarction, anemia, leukopenia, herpes zoster, or adverse events. Notably, ATG reduced the AMR rate by 59% (odds ratio, 0.41; 95% credible interval, 0.20-0.90), whereas the other drugs did not show statistical significance. Furthermore, secondary outcomes did not significantly differ between the induction regimens. CONCLUSION: ATG is widely used in KT induction regimens. Our results showed that ATG reduced the risk of AMR in KT recipients when compared with other induction drugs; therefore, it appears to be an efficient choice of induction regimen to reduce AMR after KT.
Subject(s)
Antilymphocyte Serum , Graft Rejection , Immunosuppressive Agents , Kidney Transplantation , Network Meta-Analysis , Humans , Graft Rejection/immunology , Graft Rejection/prevention & control , Immunosuppressive Agents/therapeutic use , Antilymphocyte Serum/therapeutic use , Basiliximab/therapeutic use , Graft Survival/drug effects , Alemtuzumab/therapeutic useABSTRACT
INTRODUCTION: Intestinal transplantation poses a unique challenge in the field of solid organ transplantation. The combination of tacrolimus and prednisone stands as the foundational cornerstone of maintenance immunosuppression in the field of intestinal transplantation. This case series aims to describe 1-year clinical outcomes of 5 intestinal transplant recipients who received a novel immunosuppression regimen consisting of monthly basiliximab, sublingual tacrolimus, and prednisone. METHODS: A retrospective analysis of patients who underwent intestinal transplantation in our center between January 01, 2020, and January 31, 2022, was conducted. Each recipient was followed for at least 1-year post-transplant. Recipient baseline demographics, clinical characteristics, and follow-up data were obtained from the electronic health records. Data collection included recipient demographics (age, sex, race/ethnicity, BMI), cause of intestinal failure, immunological data, infectiology data and treatment information. RESULTS: A total of five patients underwent intestinal transplantation, of which two males (40 %) and three females (60 %), with a median age of 20.1 years (17.4-28.8). The median (IQR) tacrolimus trough by month 1 was 10.4 (8.4-13.2) ng/mL. Subsequently, the median (IQR) tacrolimus troughs at specified periods are as follows, respectively: month 3: 10.2 (8.2-13.2) ng/mL; month 6: 8.4 (7.6-9.6) ng/mL; and month 12: 8.8 (6.2-9.8) ng/mL. Three patients (60.0 %) had biopsy proven rejection, but all of them had resolution after the optimization of immunosuppression. All patients were alive and had a functioning intestinal allograft at 1-year. CONCLUSION: The combination of monthly basiliximab, sublingual tacrolimus, and prednisone is an effective novel maintenance immunosuppression in intestinal transplantation. A larger and more extended study duration would be necessary to thoroughly assess the safety and sustained benefits of the novel maintenance immunosuppression regimen.
Subject(s)
Basiliximab , Graft Rejection , Immunosuppressive Agents , Prednisone , Tacrolimus , Humans , Tacrolimus/administration & dosage , Tacrolimus/therapeutic use , Basiliximab/administration & dosage , Basiliximab/therapeutic use , Male , Female , Prednisone/therapeutic use , Prednisone/administration & dosage , Adult , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/therapeutic use , Retrospective Studies , Graft Rejection/prevention & control , Graft Rejection/immunology , Young Adult , Adolescent , Treatment Outcome , Intestines/transplantation , Intestines/immunology , Graft Survival/drug effects , Transplant Recipients , Organ Transplantation , Drug Therapy, CombinationABSTRACT
Posttransplant lymphoproliferative disorder (PTLD) poses a significant concern in Epstein-Barr virus (EBV)-negative patients transplanted from EBV-positive donors (EBV R-/D+). Previous studies investigating the association between different induction agents and PTLD in these patients have yielded conflicting results. Using the Organ Procurement and Transplant Network database, we identified EBV R-/D+ patients >18 years of age who underwent kidney-alone transplants between 2016 and 2022 and compared the risk of PTLD with rabbit antithymocyte globulin (ATG), basiliximab, and alemtuzumab inductions. Among the 6620 patients included, 64.0% received ATG, 23.4% received basiliximab, and 12.6% received alemtuzumab. The overall incidence of PTLD was 2.5% over a median follow-up period of 2.9 years. Multivariable analysis demonstrated that the risk of PTLD was significantly higher with ATG and alemtuzumab compared with basiliximab (adjusted subdistribution hazard ratio [aSHR] = 1.98, 95% confidence interval [CI] 1.29-3.04, P = .002 for ATG and aSHR = 1.80, 95% CI 1.04-3.11, P = .04 for alemtuzumab). However, PTLD risk was comparable between ATG and alemtuzumab inductions (aSHR = 1.13, 95% CI 0.72-1.77, P = .61). Therefore, the risk of PTLD must be taken into consideration when selecting the most appropriate induction therapy for this patient population.
Subject(s)
Epstein-Barr Virus Infections , Graft Rejection , Graft Survival , Herpesvirus 4, Human , Immunosuppressive Agents , Kidney Transplantation , Lymphoproliferative Disorders , Postoperative Complications , Tissue Donors , Humans , Kidney Transplantation/adverse effects , Lymphoproliferative Disorders/etiology , Male , Female , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/etiology , Epstein-Barr Virus Infections/virology , Middle Aged , Adult , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Risk Factors , Follow-Up Studies , Prognosis , Graft Rejection/etiology , Antilymphocyte Serum/adverse effects , Retrospective Studies , Kidney Failure, Chronic/surgery , Transplant Recipients , Incidence , Induction Chemotherapy/adverse effects , Basiliximab , Alemtuzumab/adverse effects , Kidney Function TestsABSTRACT
BACKGROUND: For patients with steroid-refractory acute graft-versus-host disease (SR-aGVHD), effective second-line regimens are urgently needed. Mesenchymal stromal cells (MSCs) have been used as salvage regimens for SR-aGVHD in the past. However, clinical trials and an overall understanding of the molecular mechanisms of MSCs combined with basiliximab for SR-aGVHD are limited, especially in haploidentical haemopoietic stem cell transplantation (HID HSCT). METHODS: The primary endpoint of this multicentre, randomized, controlled trial was the 4-week complete response (CR) rate of SR-aGVHD. A total of 130 patients with SR-aGVHD were assigned in a 1:1 randomization schedule to the MSC group (receiving basiliximab plus MSCs) or control group (receiving basiliximab alone) (NCT04738981). RESULTS: Most enrolled patients (96.2%) received HID HSCT. The 4-week CR rate of SR-aGVHD in the MSC group was obviously better than that in the control group (83.1% vs. 55.4%, P = 0.001). However, for the overall response rates at week 4, the two groups were comparable. More patients in the control group used ≥ 6 doses of basiliximab (4.6% vs. 20%, P = 0.008). We collected blood samples from 19 consecutive patients and evaluated MSC-derived immunosuppressive cytokines, including HO1, GAL1, GAL9, TNFIA6, PGE2, PDL1, TGF-ß and HGF. Compared to the levels before MSC infusion, the HO1 (P = 0.0072) and TGF-ß (P = 0.0243) levels increased significantly 1 day after MSC infusion. At 7 days after MSC infusion, the levels of HO1, GAL1, TNFIA6 and TGF-ß tended to increase; however, the differences were not statistically significant. Although the 52-week cumulative incidence of cGVHD in the MSC group was comparable to that in the control group, fewer patients in the MSC group developed cGVHD involving ≥3 organs (14.3% vs. 43.6%, P = 0.006). MSCs were well tolerated, no infusion-related adverse events (AEs) occurred and other AEs were also comparable between the two groups. However, patients with malignant haematological diseases in the MSC group had a higher 52-week disease-free survival rate than those in the control group (84.8% vs. 65.9%, P = 0.031). CONCLUSIONS: For SR-aGVHD after allo-HSCT, especially HID HSCT, the combination of MSCs and basiliximab as the second-line therapy led to significantly better 4-week CR rates than basiliximab alone. The addition of MSCs not only did not increase toxicity but also provided a survival benefit.
Subject(s)
Graft vs Host Disease , Hematopoietic Stem Cell Transplantation , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Humans , Basiliximab/therapeutic use , Graft vs Host Disease/drug therapy , Hematopoietic Stem Cell Transplantation/adverse effects , Steroids/therapeutic use , Transforming Growth Factor beta/therapeutic use , Acute Disease , Mesenchymal Stem Cell Transplantation/adverse effectsABSTRACT
BACKGROUND: Optimizing the immunosuppressive regimen is essential to improve the long-term outcomes of pediatric liver transplant recipients. METHODS: We conducted a prospective, randomized, open-label study to compare the safety and efficacy of 2 treatment approaches during pediatric liver transplantation: tacrolimus monotherapy following basiliximab induction (the study group) and a dual regimen of tacrolimus plus steroids (the control group). A total of 150 patients were enrolled, with 75 patients allocated to each group. RESULTS: In both groups, recipients achieved graft and recipient overall survival rates exceeding 93%, with no statistically significant differences between them. However, the study group exhibited a significantly lower incidence of acute cellular rejection (ACR), delayed occurrence of ACR, and an improved ACR-free survival rate at 2 y compared with the control group. Notably, the study group also showed a significant reduction in the incidence of de novo donor-specific antibodies at 3-mo and 2-y posttransplant. Furthermore, 6 mo after the transplant, the study group demonstrated significant improvements in weight-for-age Z score and height-for-age Z score. No notable differences were observed in postoperative complications or the incidence of liver fibrosis between the 2 groups. CONCLUSIONS: Basiliximab induction combine with tacrolimus (TAC) monotherapy is a safe and effective immunosuppressive regimen to reduce the episodes of ACR without influencing the development of liver fibrosis and graft and recipient survival rate after pediatric liver transplantation.
Subject(s)
Basiliximab , Drug Therapy, Combination , Graft Rejection , Graft Survival , Immunosuppressive Agents , Liver Transplantation , Tacrolimus , Humans , Liver Transplantation/adverse effects , Liver Transplantation/mortality , Basiliximab/therapeutic use , Basiliximab/administration & dosage , Tacrolimus/administration & dosage , Tacrolimus/therapeutic use , Tacrolimus/adverse effects , Immunosuppressive Agents/administration & dosage , Immunosuppressive Agents/adverse effects , Immunosuppressive Agents/therapeutic use , Male , Female , Graft Rejection/prevention & control , Graft Rejection/immunology , Child , Prospective Studies , Child, Preschool , Graft Survival/drug effects , Infant , Treatment Outcome , Time Factors , Adolescent , Recombinant Fusion Proteins/administration & dosage , Recombinant Fusion Proteins/therapeutic use , Recombinant Fusion Proteins/adverse effectsABSTRACT
Steroid-free immunosuppression protocols gained popularity in pediatric liver transplantation (pLT) after the introduction of IL-2-receptor blockade for induction therapy. We analyzed the clinical and immunologic outcome data of the multicenter prospective observational ChilSFree study to compare the impact of steroid-free versus steroid-containing immunosuppressive therapy following pLT in a real-life scenario. Two hundred forty-six children [55.3% male, age at pLT median: 2.4 (range: 0.2-17.9) y] transplanted for biliary atresia (43%), metabolic liver disease (9%), acute liver failure (4%), hepatoblastoma (9%), and other chronic end-stage liver diseases (39%) underwent immune monitoring and clinical data documentation over the first year after pLT. Patient and graft survival at 1 year was 98.0% and 92.7%, respectively. Primary immunosuppression was basiliximab induction followed by tacrolimus (Tac) monotherapy (55%), Tac plus steroid tapering over 3 months (29%), or cyclosporine and steroid tapering (7%). One center used intraoperative steroids instead of basiliximab followed by Tac plus mycophenolate mofetil (7% of patients). N = 124 biopsy-proven T-cell-mediated rejections were documented in n = 82 (33.3%) patients. T-cell-mediated rejection occurred early (median: 41 d, range: 3-366 d) after pLT. Patients initially treated with Tac plus steroids experienced significantly fewer episodes of rejection than patients treated with Tac alone (chi-square p <0.01). The use of steroids was associated with earlier downregulation of proinflammatory cytokines interferon (IFN)-γ, Interleukin (IL)-6, CX motif chemokin ligand (CXCL)8, IL-7, and IL-12p70. Both primary immunosuppression with Tac plus steroids and living donor liver transplantation were independent predictors of rejection-free survival 1 year after pLT on logistic regression analysis. Adjunctive steroid therapy after pLT leads to earlier suppression of the post-pLT proinflammatory response and significantly reduced rejection rates during the first year after pLT (15.9%). Fifty-one percent of patients initially treated without steroids remain steroid-free over the first 12 months without rejection.
Subject(s)
Immunosuppressive Agents , Liver Transplantation , Humans , Male , Child , Female , Immunosuppressive Agents/adverse effects , Basiliximab , Liver Transplantation/adverse effects , Living Donors , Tacrolimus/therapeutic use , Steroids/therapeutic use , Mycophenolic Acid/therapeutic use , Graft Survival , Graft RejectionABSTRACT
BACKGROUND: To compare the safety and efficacy of once-daily tacrolimus (ODT) versus twice-daily tacrolimus (BDT) in adult live donor liver transplantation (LDLT). METHODS: In this open-labelled randomized trial, 174 adult patients undergoing LDLT were randomized into ODT or BDT, combined with basiliximab induction and mycophenolate mofetil (steroid-free regimen). Tacrolimus was started at a total dose of 1 mg and the trough level was aimed at 3-7 ng/ml. The primary endpoint was eGFR at 1,3- and 6 months post-transplant, using CKD- EPI equation. Secondary endpoints included biopsy-proven acute rejection (BPAR), metabolic complications, post-operative bilio-vascular complications and patient survival. RESULTS: There was no statistically significant difference in eGFR between the two groups at 6 months (ODT -96 ± 19, BDT -91 ± 21, p value-0.164). BPAR was comparable (18/84 in ODT, 19/88 in BDT, p value-0.981). For a similar dosage of tacrolimus, the median trough tacrolimus levels attained were significantly lower for ODT than BDT during the first-month post-transplant (p value-0.001). Metabolic complications due to immunosuppression, post-operative bilio-vascular complications and patient survival was similar between the two groups at 6 months. CONCLUSION: Once-daily tacrolimus has similar renal safety and efficacy as twice-daily tacrolimus when used in combination with basiliximab induction and mycophenolate in adult LDLT.
Subject(s)
Kidney Transplantation , Liver Transplantation , Adult , Humans , Tacrolimus/adverse effects , Liver Transplantation/adverse effects , Basiliximab , Living Donors , Delayed-Action Preparations , Immunosuppressive Agents/adverse effects , Graft Rejection/prevention & controlABSTRACT
High donor-derived cell-free DNA (dd-cfDNA) levels indicate transplant allograft injury and can identify graft rejection in kidney transplant recipients. Here, we evaluated the use of dd-cfDNA in pediatric kidney transplant rejection monitoring and treatment. METHODS: Forty-two pediatric kidney transplant patients were enrolled between February 2020 and August 2021. Dd-cfDNA was tested before and after biopsy/rejection treatment. There was a total of 61 allograft biopsies (44 for-cause, 17 surveillance). RESULTS: Graft rejection was found in 35/61 biopsies. Rejection was more common in basiliximab induction compared to rATG (77.1% vs. 22.9%, p = .0121). Median dd-cfDNA was higher in those with rejection (1.2% [0.34-3.12] vs. 0.24% [0.08-0.78], p < .0001). Dd-cfDNA was highest in biopsies with AMR and mixed AMR/TCMR. In addition, dd-cfDNA in basiliximab induction was higher compared to rATG (0.92% [0.27-1.8] vs. 0.26% [0.08-2], p = .0437). Median change in dd-cfDNA after rejection treatment was -0.57% (-1.67 to 0.05). Median time to dd-cfDNA <1% post-rejection treatment was 8.5 days (3.0-19.5). Dd-cfDNA in AMR was higher compared to TCMR or mixed rejection, and levels remained higher in AMR after treatment. In surveillance biopsies, 4/17 had rejection. Median dd-cfDNA was not different in those with versus without rejection (0.48% vs. 0.28%, p = .2342). Those without rejection all had dd-cfDNA <1%. In those with rejection, only one patient had dd-cfDNA >1%, and all had TCMR. CONCLUSIONS: Our findings support dd-cfDNA as a useful indicator of graft rejection and response to treatment. Additional studies are needed to determine the role of dd-cfDNA in graft health surveillance.
Subject(s)
Cell-Free Nucleic Acids , Kidney Transplantation , Humans , Child , Basiliximab , Tissue Donors , Transplantation, Homologous , Graft Rejection/etiology , Transplant RecipientsABSTRACT
Avoidance of steroids in pediatric liver transplantation may reduce toxicity and morbidity. The aim of this study was to analyze the feasibility of a steroid-free tacrolimus-basiliximab immunosuppression scheme, the risk factors associated with steroid requirement, and safety parameters. Patients who underwent liver transplantation for biliary atresia between 2011 and 2019 were included and followed for 6 months after transplantation. Immunosuppression consisted of tacrolimus-based treatment with basiliximab induction. Steroid-free survival was estimated, and risk factors for steroid requirement were evaluated using multivariate Cox regression analysis. A total of 76 patients were included, of whom 42 (55.3%) required steroids (>14 d) due to biopsy-proven acute rejection (47.6%, n = 20), instability in liver function tests (35.7%, n = 15), tacrolimus-related adverse drug reactions (14.3%, n = 6), or other reasons (bronchospasm episode, n = 1). Steroid-free survival was 45.9% (95% CI, 35.9-58.8). Independent factors associated with steroid requirement included tortuosity in tacrolimus trough levels (≥1.76 vs. <1.76: HR 5.8, 95% CI, 2.6-12.7; p < 0.001) and mean tacrolimus trough levels (≥ 6.4 ng/mL vs. < 6.4 ng/mL: HR 0.4, 95% CI, 0.2-0.7; p = 0.002). The rate of bacterial and viral infections was comparable between patients with and without steroids, although in the former group, cytomegalovirus infection developed earlier ( p = 0.03). Patients receiving steroids had higher total cholesterol, LDL, and HDL levels ( p < 0.05) during follow-up, but no changes in the height Z-score were observed 1 year after transplantation. Basiliximab induction in combination with tacrolimus-based treatment avoided steroid requirements in 45% of the patients. Tacrolimus variability and trough levels below 6.4 ng/mL independently increased the risk of steroid requirement. Further efforts should be focused on personalizing immunosuppressive treatment.
Subject(s)
Liver Transplantation , Tacrolimus , Humans , Child , Basiliximab/adverse effects , Tacrolimus/adverse effects , Liver Transplantation/adverse effects , Antibodies, Monoclonal/adverse effects , Feasibility Studies , Immunosuppressive Agents/adverse effects , Immunosuppression Therapy/adverse effects , Steroids/adverse effects , Graft Rejection/epidemiology , Graft Rejection/prevention & control , Graft Rejection/drug therapyABSTRACT
Heart transplantation (HT) has become the preferred treatment for end-stage heart disease, but postoperative complications such as infection still threaten the prognosis of HT patients. Basiliximab can help minimize immune rejection. However, there is a lack of relevant information to compare the prognosis of different immunosuppression regimens. This study aimed to investigate the risk factors associated with death and infection after HT surgery. We also provide some insightful information on the administration of basiliximab to improve the prognosis of HT patients. In total, 70 patients were included in this retrospective observational study. All participants underwent primary HT and were administered immunosuppressive agents postoperatively. Of these, 38 received additional basiliximab. There was a 6-month follow-up period after HT during which clinical outcomes were monitored. Logistic regression and cox-proportional hazard regression analyses were performed to determine the relationship between basiliximab use and the clinical outcomes of HT. Logistic regression analysis revealed that basiliximab use (odds ratio [OR]â =â 0.07, Pâ =â .014) was an independent risk factor for death after HT. d-Dimer (ORâ =â 9.05, Pâ =â .002) and basiliximab use (ORâ =â 0.15, Pâ =â .004) were independent risk factors for death after HT. Moreover, patients treated with basiliximab had shorter hospital lengths of stay (23.58â ±â 13.89 vs 39.41â ±â 24.43, Pâ =â .001) and intensive care unit lengths of stay (4.76â ±â 2.85 vs 11.25â ±â 5.79, Pâ <â .001). Furthermore, patients administered basiliximab had lower rates of death (1 [5.4%] vs 9 [28.1%], Pâ =â .007) and infection (6 [15.8%] vs 19 [59.4%], Pâ <â .001). The postoperative survival rate (hazard ratio 0.08, 95% confidence interval 0.01-0.65, Pâ =â .018) and survival against infection (hazard ratio 0.24, 95% confidence interval 0.09-0.64, Pâ =â .004) were significantly higher among patients receiving basiliximab treatment than among those not receiving treatment. Our study showed that basiliximab use was closely associated with the rate of postoperative death and infection after HT. HT patients with additional basiliximab administration as immunosuppressive treatment had a better clinical prognosis.