Basiliximab Treatment for Patients With Steroid-Refractory Acute Graft-Versus-Host Disease Following Matched Sibling Donor Hematopoietic Stem Cell Transplantation.

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.

Effects of Antithymocyte Globulin, Basiliximab, and Induction-Free Treatment in Living Donor Kidney Transplant Recipients on Tacrolimus-Based Immunosuppression.

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.

Alemtuzumab induction is associated with decreased hospitalization rates in pediatric kidney transplant: A UNOS data review for safety and outcomes with common induction regimens.

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.

Assessment of immunosuppression induction with basiliximab compared to antithymocyte-globulin in adult heart transplant patients.

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.

[Short-term substitution of calcineurin inhibitors (CNI) with recombinant humanized anti-CD25 monoclonal antibody (Basiliximab) as aGVHD prophylaxis in CNI intolerant patients after allogeneic hematopoietic stem cell transplantation].

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 Ⅱ-Ⅳ aGVHD, while four (23.6% ) developed Grade Ⅲ/Ⅳ 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.

A heart transplant center experience with basiliximab induction strategies: A double edged sword?

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.

Use of induction therapy post-heart transplantation: Clinical practice recommendations based on systematic review and network meta-analysis of evidence.

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.

Efficacy and safety of single-dose anti-thymocyte globulin versus basiliximab induction therapy in pediatric kidney transplant recipients: A retrospective comparative cohort study.

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.

Clinical outcomes of intestinal transplant recipients receiving maintenance basiliximab, sublingual tacrolimus and prednisone: A case series.

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.

The Effect of Induction Therapy on Antibody-Mediated Rejection in Kidney Transplantation: A Network Meta-Analysis Using Recent Data.

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.

Mesenchymal stromal cells plus basiliximab improve the response of steroid-refractory acute graft-versus-host disease as a second-line therapy: a multicentre, randomized, controlled trial.

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.

Feasibility of steroid-free tacrolimus-basiliximab immunosuppression in pediatric liver transplantation and predictors for steroid requirement.

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.

Utilization of donor-derived Cell-Free DNA in pediatric kidney transplant recipients: A single center study.

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.

Early steroids after pediatric liver transplantation protect against T-cell-mediated rejection: Results from the ChilSFree study.

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.

Randomized controlled trial of sustained release tacrolimus vs twice daily tacrolimus in adult living donor liver transplantation.

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.

Effect of basiliximab use on the risk of postoperative infection and death after heart transplantation: An observational study.

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] = 0.07, P = .014) was an independent risk factor for death after HT. d-Dimer (OR = 9.05, P = .002) and basiliximab use (OR = 0.15, P = .004) were independent risk factors for death after HT. Moreover, patients treated with basiliximab had shorter hospital lengths of stay (23.58 ±â€…13.89 vs 39.41 ±â€…24.43, P = .001) and intensive care unit lengths of stay (4.76 ±â€…2.85 vs 11.25 ±â€…5.79, P < .001). Furthermore, patients administered basiliximab had lower rates of death (1 [5.4%] vs 9 [28.1%], P = .007) and infection (6 [15.8%] vs 19 [59.4%], P < .001). The postoperative survival rate (hazard ratio 0.08, 95% confidence interval 0.01-0.65, P = .018) and survival against infection (hazard ratio 0.24, 95% confidence interval 0.09-0.64, P = .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.

Comparative analysis of Basiliximab and Alemtuzumab induction therapies in blood type A2-to-B kidney transplantation: Impact on kidney function and de novo donor-specific HLA antibodies.

PURPOSE: Blood group B kidney transplant candidates have lower transplantation rates and longer waiting times compared to other blood groups. Kidney transplantation from blood group A2-to-B has offered a solution for these patients. This study aimed to investigate the impact of Basiliximab and Alemtuzumab induction therapies on kidney function and de novo donor-specific antibodies (DSA) in blood type A2-to-B kidney transplant recipients within the first 12 months of post-transplant. METHODS: A retrospective analysis was conducted on 110 consecutive A2-to-B kidney transplant recipients between January 2015 and December 2022. Of these, 46 (41.8%) received Basiliximab, while 64 (58.2%) received Alemtuzumab as induction therapy. Demographics and comorbidities data were collected and compared between the two groups. Serum samples collected at 4- and 12-month intervals post-transplant were used to assess the presence of de novo DSA. Kidney allograft function was evaluated by monitoring serum creatinine levels and assessing Creatinine Clearance based on 24-h urine collection at various time points. RESULTS: During the follow-up period, 20.00% of patients who received Alemtuzumab developed de novo DSA, whereas none of the patients induced with Basiliximab developed de novo DSA (p = 0.038). Recipients who received Basiliximab were older (mean age = 72.00) and received higher Kidney Donor Profile Index (KDPI) kidneys (mean = 75) compared to those induced with Alemtuzumab (mean age = 58.00, mean KDPI = 49) (p < 0.001), with no significant difference observed in the last follow-up creatinine clearance or creatinine levels between the two groups (p = 0.28). CONCLUSION: The use of Basiliximab as induction immunosuppression in A2-to-B kidney transplant recipients is associated with a lower incidence of de novo HLA DSA formation without significant differences in overall renal function compared to Alemtuzumab.

The Impact of Basiliximab on Clinical Treg Detection through the Interference with CD25 Binding Site.

OBJECTIVE: Basiliximab (BXM) is commercial monoclonal antibody inhibitor of interleukin 2 receptor, which is widely used in the transplantation therapy for preventing acute rejection. However, we found BXM would interfere with the detection of Treg through flow cytometry in clinical practice. This study aimed to explore the interference caused by BXM in the clinical detection of Treg. METHODS: We compared the effects of BXM on two CD25 antibodies with different clone site, which are commonly used for Treg measurement. RESULTS: The result suggested CD25 (2A3) was inhibited by BXM, while CD25 (M-A251) was not affected. Moreover, we found 2A3/M-A251 Treg Ratio could reflect Treg cell activity and BXM blood concentration to some extent. CONCLUSION: BXM can effectively inhibit the binding of CD25 (2A3) antibody to its receptor on T cells membrane, which should be noted during Treg clinical detection.

Does the induction immunotherapy (basiliximab) influence the early acute cellular rejection index after orthotopic heart transplantation?- Preliminary assessment report.

The study aimed to determine the influence of induction therapy on the acute cellular rejection (ACR) index in adult heart transplant recipients during the one-year observation. The study population consisted of 256 consecutive adult patients (pts), aged 51.5 (±11.9) years, 199 (77%) men treated with orthotopic heart transplantation (OHT) in the period between 2015 and 2020 in a single high-volume heart transplant center. The endomyocardial biopsies (EMBs) were performed according to the protocol consisting of 7 protocolary EMBs for up to 3 months and 10 EMBs for up to one year after OHT. The rejection index (ACRI) was calculated as the number of scheduled EMBs with the ACR ≥ 2 divided by the total number of protocolary EMBs. The study population was divided into two groups according to the application of basiliximab. The total number of pts. who received basiliximab was 10 (3.9%). The main indications for the usage of the induction therapy were heart retransplantation, mechanical circulatory support (MCS), severe renal insufficiency (eGFR <30 mL/min/1.73 m2), and a panel of reactive antibody (PRA) > 10%. In the group with induction, the mean age was 49 (±14) years; 3 (30%) patients had the MCS prior to OHT, and 3 (30%) patients had heart retransplantation. Four (40%) patients had diabetes mellitus, and 4 (40%) patients had severe renal insufficiency. As maintenance therapy during the observation period, tacrolimus was given to 10 (100%) patients, everolimus to 2 (20%) patients, and MPA to 9 (90%) patients. In the group with no induction, the mean age was 51.8 (±12) years, MCS was used in 56 (23%) patients, 2 (0.8%) patients were retransplanted; 10 (4%) patients had eGFR <30 mL/min/1.73 m2 and 58 (24%) patients had diabetes. Tacrolimus was administered to 243 (99%) patients, cyclosporine to 3 (1%), everolimus to 40 (16%), and mycophenolate to 245 (99.6%) heart recipients. The median one-year ACRI was 0.0, IQR:0.0-0.08 in the group with induction vs. 0.077, IQR: 0.0-0.154 with no induction; p = 0.11. ACRI up to three months was significantly higher in the entire cohort in comparison to up to one year (P < 0.01). The multivariate analysis showed that only everolimus implementation and younger age at the time of transplant influenced patients' mortality rate (P < 0.01). Significant graft rejections (≥ 2R ISHLT) are most common in the first three months after OHT. Patients who are initially at high risk of significant cellular rejection may benefit from induction therapy.

Significant Increase in Cytomegalovirus (CMV) Infection in Solid Organ Transplants Associated With Increased Use of Thymoglobulin as Induction Therapy?

BACKGROUND: Cytomegalovirus (CMV) infection remains one of the most common viral pathogens affecting solid organ transplants (SOT). In 10 years of following the outcome of transplants, we noticed an increased incidence of CMV infection, along with increased use of rabbit anti-thymocyte globulin (rATG). The study aims to assess the incidence of active CMV infection and disease, response to treatment, and recurrence in a cohort of SOT. Furthermore, we look for correlating the CMV incidence with the type of induction therapy: r-ATG or interleukin 2 receptor-blocking antibody (basiliximab). METHODS: This was a single-center, retrospective 10-year study in patients submitted to kidney, kidney-liver, and kidney-pancreas transplants who used a preemptive therapy protocol for CMV. RESULTS: Among the 476 enrolled transplant recipients, 306 (64.2 %) had at least one episode of CMV infection (replication), and 71/306 patients (23.2 %) presented CMV-related disease. The most frequent clinical conditions associated with CMV disease were gastrointestinal. Among the 476 transplant patients, 333 received immunosuppressive induction with rATG (69.9 %); 140 (29.4 %) received induction with interleukin 2 receptor-blocking antibody (basiliximab). The initial maintenance immunosuppressive therapy in the patients who presented CMV infection was primarily performed with prednisone, tacrolimus, and sodium mycophenolate (91.7 %). The induction with rATG increased from 35.2%-94.6% in 10 years. The incidence of CMV infection was 20.7 % in the first year of observation and gradually increased to 87.3 % in the last year. CONCLUSIONS: The data suggest that the increase in the use of rATG in recent years could be responsible for the very expressive increase in the incidence of CMV infection/disease.