Vedolizumab plus basiliximab as second-line therapy for steroid-refractory lower gastrointestinal acute graft-versus-host disease.

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.

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.

A comparative analysis of kidney allograft outcomes in steroid use versus steroid discontinuation after basiliximab and ATG induction: A UNOS database study.

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.

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.

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.

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.

[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.

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.

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.

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.

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.

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.

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.

Ruxolitinib versus basiliximab for steroid-refractory acute graft-versus-host disease: a retrospective study.

Acute graft-versus-host disease (aGVHD) remains a major limitation of allogeneic hematopoietic stem cell transplantation; not all patients respond to standard glucocorticoids treatment. This study retrospectively evaluated the effects of ruxolitinib compared with basiliximab for steroid-refractory aGVHD (SR-aGVHD). One hundred and twenty-nine patients were enrolled, 81 in ruxolitinib and 48 in basiliximab group. The overall response (OR) at day 28 was higher in ruxolitinib group (72.8% vs. 54.2%, P = 0.031), as with complete response (CR) (58.0% vs. 35.4%, P = 0.013). Ruxolitinib led to significantly lower 1-year cumulative incidence of chronic GVHD (cGVHD) (29.6% vs. 43.8%, P = 0.021). Besides, ruxolitinib showed higher 1-year overall survival (OS) and 1-year cumulative incidence of failure-free survival (FFS) (OS: 72.8% vs. 50.0%, P = 0.008; FFS: 58.9% vs. 39.6%, P = 0.014). The 1-year cumulative incidence of non-relapse mortality (NRM) was lower in ruxolitinib group (16.1% vs. 37.5%, P = 0.005), and the 1-year relapse was not different. The 1-year cumulative incidence of cytomegalovirus (CMV) viremia, CMV-associated diseases and Epstein-Barr virus (EBV)-associated diseases was similar between the two groups, but EBV viremia was significantly lower in ruxolitinib group (6.2% vs. 29.2%, P < 0.001). Subgroup analyses revealed that OR and survival were similar in ruxolitinib 5 mg twice daily (bid) and 10 mg bid groups. However, ruxolitinib 10 mg bid treatment markedly reduced 1-year cumulative incidence of cGVHD compared with 5 mg bid (21.1% vs. 50.0%, P = 0.016). Our study demonstrated that ruxolitinib was superior to basiliximab in SR-aGVHD treatment and cGVHD prophylaxis, therefore should be recommended.

Impact of induction therapy on cytomegalovirus infection and post-transplant outcomes in pediatric heart transplant recipients receiving routine antiviral prophylaxis.

OBJECTIVES: Induction therapy has been increasingly used in pediatric heart transplantation. This study evaluated the impact of anti-thymocyte globulin (ATG) versus basiliximab as induction therapy on post-transplant cytomegalovirus (CMV) infection, rejection at 1 year, coronary allograft vasculopathy (CAV), and mortality in pediatric heart transplant recipients receiving antiviral prophylaxis. RESULTS: Of the 96 patients (age < 18 years) analyzed, 46 (47.9%) patients received basiliximab, and 50 (52.1%) received ATG. Median follow-up was 3.0 (IQR, 1.7-4.9) years with 32.3% reporting CMV infection. The ATG group, as compared with the basiliximab group, had similar incidences of CMV infection (36% vs. 28.3%, p = .418), CMV viremia (22% vs. 19.6%, p = .769), and CMV-positive tissue biopsy (30% vs. 22%, p = .486). The ATG group had lower incidences of rejection at 1 year (16% vs. 36.9%, p = .022) and CAV (4% vs. 23.9%, p = .006) with no difference in mortality (8% vs. 15.2%, p = .343), compared with the basiliximab group. Multivariate analysis showed that induction with ATG was associated with a lower risk of rejection at 1 year (OR, .31; 95% CI, .09-.94; p = .039) with no impact on the incidences of CMV infection (HR, 2.06; 95% CI, .54-7.89; p = .292), CAV (HR, .30; 95% CI, .04-2.58; p = .275), and mortality (HR, .39; 95% CI, .09-1.82; p = .233) compared to basiliximab induction. DISCUSSION AND CONCLUSIONS: In conclusion, induction with ATG was associated with reduction in risk of rejection at 1 year with no effects on CMV infection, CAV, and mortality in pediatric heart transplant recipients with universal antiviral prophylaxis compared with basiliximab induction therapy.

Basiliximab is associated with a lower incidence of De novo donor-specific HLA antibodies in kidney transplant recipients: A single-center experience.

PURPOSE: Induction immunosuppression has improved the long-term outcomes after kidney transplant. This study explores the association of different induction immunosuppression medications (Basiliximab vs. Alemtuzumab vs. rabbit Antithymocyte Globulin) used at the time of kidney transplant with the development of de novo donor-specific HLA antibodies (DSA) in the first 12 months post-transplant period. METHODS: A total of 390 consecutive kidney transplant recipients (KTR), between 2016 and 2018, were included in the analysis. A 104 (26.6%) received Basiliximab, 186 (47.6%) received Alemtuzumab, and 100 (25.6%) received rabbit Antithymocyte Globulin (rATG) for induction. All recipients had a negative flow cytometry crossmatch before transplant. Serum samples at 4- and 12-months post-transplant were assessed for the presence of de novo HLA DSA. kidney allograft function was compared among the three groups with calculated Creatinine Clearance on 24 h urine collection. RESULTS: De novo HLA DSA were detected in total of 81 (20.8%) patients within 12 months post-transplant. De novo HLA DSA were detected in 12/104 (11.5%), 43/186 (23.11%), and 26/100 (26%) KTR that received Basiliximab, Alemtuzumab, and rATG respectively (p = 0.006). KTR that received Basiliximab were significantly older, and the last follow-up creatinine clearance was significantly lower at 42 ml/min compared to KTR that received Alemtuzumab or rATG (p = 0.006). CONCLUSION: Induction immunosuppression utilizing Basiliximab is associated with significant reduction in development of de novo DSA within the first 12-months post kidney transplant but had lower creatinine clearance with long-term follow up.

Basiliximab therapy for immune-mediated bowel disease in a pediatric heart transplant patient.

In pediatric patients who undergo heart transplantation, severe immune-mediated bowel disease has been reported. Management is complex, and there are little data discussing the use of basiliximab for immune-mediated bowel disease. This case report discusses a pediatric patient who developed immune-mediated bowel disease following heart transplantation and was successfully managed with basiliximab.