Search

BackgroundSteroid-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.MethodsThis 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.ResultsTwenty-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.ConclusionsVedolizumab 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.

Intestinal steroid refractory acute graft-versus-host disease (SR-aGVHD) is the major cause of mortality in allogeneic hematopoietic stem cell transplantation (allo-HSCT). This retrospective cohort study aimed to identify the relationship between different steroid decreasing velocity and therapeutic response in patients with intestinal SR-aGVHD receiving basiliximab treatment, and also aimed to propose a reasonable steroid decreasing regimen for these patients. The median time for steroid dose decreasing to the 50% of initial dose and decreasing to the low-dose steroid for patients achieving ORR was 5 days and 12 days, respectively, which was both shorter than patients without achieving ORR. The ORR, NRM and survival in rapid and medium steroid decreasing group were all better than slow group. The cumulative incidence of ORR at any time was 90.4%, 78.1% and 62.3%, respectively, in rapid, medium, and slow group. The cumulative incidence of NRM at 1 year after basiliximab treatment was 18.7% (95% CI 11.3%–26.1%), 22.8% (95% CI 14.2%–31.4%) and 32.8% (95% CI 24.1%–41.5%), respectively, in rapid, medium, and slow group. The probability of OS at 1 year after basiliximab treatment was 76.9% (95% CI 68.9%–84.9%), 72.7% (95% CI 63.7%–81.7%), and 62.3% (95% CI 53.5%–71.1%), respectively, in rapid, medium, and slow group. Hence, it was helpful to decrease steroid to the 50% of initial dose ≤ 5 days and to the low-dose steroid ≤ 12 days after basiliximab treatment for intestinal SR-aGVHD patients, which may also be the reasonable steroid decrease protocol for these patients.

Background/Objectives: Potent immunosuppression lowers the incidence of acute graft rejection but increases the risk of infections. In order to decrease either infectious complications or acute rejection, it is necessary to identify risk groups of patients profiting from personalized induction immunosuppressive treatment. The aim of our analysis was to find whether there were higher incidences of infectious complications after kidney transplantation (KT) in groups with different induction immunosuppressive treatment and also to find independent risk factors for recurrent infections. Materials: We retrospectively evaluated all patients with induction treatment with basiliximab after kidney transplantation from 2014 to 2019 at our center relative to age- and sex-matched controls of patients with thymoglobulin induction immunosuppression. Results: Our study consisted of two groups: basiliximab (39) and thymoglobulin (39). In the thymoglobulin group we observed an increased incidence of recurrent infection in every observed interval; however, acute rejection was seen more often in the basiliximab group. A history of respiratory diseases and thrombocytopenia were identified as independent risk factors for recurrent bacterial infections from the first to sixth month after KT. Decreased eGFR from the first month, infections caused by multi-drug-resistant bacteria, and severe infections (reflected by the need for hospitalization) were identified as independent risk factors for recurrent bacterial infections from the first to the twelfth month after KT. Conclusions: We found that in the group of patients with thymoglobulin induction immunosuppressive treatment, infectious complications occurred significantly more often during the entire monitored period with decreased incidence of acute humoral and cellular rejection occurred more often.

Background: We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. Methods: Preemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000 copies/μl, they received valganciclovir adjusted for their renal function. Results: 132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p

Background: We performed a retrospective trial to determine asymptomatic CMV reactivation and CMV disease in kidney allograft recipients with positive CMV serostatus. Methods: Preemptive modified strategy under low dose thymoglobulin versus basiliximab induction was evaluated. Patients were monitored by CMV-polymerase chain reaction (PCR); if the viral load was >4000 copies/μl, they received valganciclovir adjusted for their renal function. Results: 132 recipients were included in the study, 84 and 48 receiving basiliximab and thymoglobulin induction respectively, and followed up for 12 months. Asymptomatic CMV reactivation was significantly higher for thymoglobulin (77.1% vs. 16.7%, p

Background Generally, an induction agent is chosen based on the conditions of the deceased donor and the recipient. Antithymocyte globulin (ATG) is preferred in relatively high-risk conditions. No clear evidence indicates which induction agent is safer or more efficient for deceased donor kidney transplantation (DDKT). This study compares the efficacy and safety of basiliximab (BSX) and ATG according to donor characteristics in DDKT. Methods A total of 724 kidney transplant recipients from three transplant centers were enrolled, and propensity score matching was performed. Based on a donor age of 60 years, donor kidney with acute kidney injury (AKI), and Kidney Donor Profile Index (KDPI) score of 65%, we investigated how the choice of induction therapy agent affected the posttransplant clinical outcomes of delayed graft function (DGF), acute rejection (AR), infectious complications, and allograft and patient survival. Results AR and DGF did not differ significantly according to induction agent in elderly/young donor, AKI/non-AKI, and high-KDPI/low-KDPI subgroups. The infection rate did not show meaningful differences. The differences in death-censored allograft survival and patient survival rates between induction agents were not statistically significant. Conclusion Our study suggests that BSX can produce clinical outcomes similarly favorable to those of ATG even in DDKT cases with relatively poor donor conditions. Nonetheless, the donor and recipient conditions, immunological risk, and infection risk must be all taken into consideration when choosing an induction agent. Therefore, clinicians should carefully select the induction therapy agent for DDKT based on the risks and benefits in each DDKT case.

Abstract Background Thrombotic microangiopathy is a syndrome characterized by microangiopathic hemolytic anemia and platelet aggregation, which is caused by endothelial injury, microcirculation thrombosis, and fibrin deposition. Transplant-associated thrombotic microangiopathy rarely occurs after lung transplantation and the onset is generally later than that after bone marrow or other solid organ transplantation. The treatment is to stop administration of the causal agent, which is often a calcineurin inhibitor, such as tacrolimus and cyclosporine. We herein report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation treated by introducing basiliximab and temporarily stopping any calcineurin inhibitors until resuming treatment with an alternative calcineurin inhibitor. Case presentation A 58-year-old Asian woman underwent bilateral lung transplantation for hypersensitivity pneumonitis caused by an avian antigen, or bird fancier’s lung disease. Postoperatively, she was started on triple immunosuppressive therapy, which included tacrolimus, mycophenolate mofetil, and steroids. On postoperative day 6, she developed thrombocytopenia followed by fever, hemolytic anemia, renal dysfunction, and purpura on her limbs and abdomen. She was diagnosed with transplant-associated thrombotic microangiopathy, and tacrolimus was thought to be the causal agent. We stopped tacrolimus and administered basiliximab. Then, she developed oliguria and needed continuous hemodiafiltration. On postoperative day 14, the platelet count recovered and she was switched from basiliximab to cyclosporine. Using this protocol, worsening thrombotic microangiopathy and acute rejection were avoided. Conclusions We report the case of a patient with early post-transplant thrombotic microangiopathy after lung transplantation that was treated with basiliximab. Switching from calcineurin inhibitors using basiliximab may be an option for treating thrombotic microangiopathy without increasing the risk of acute rejection.

Basiliximab (BAS) is an interleukin-2 monoclonal antibody initially used as induction therapy after liver and kidney transplantation. BAS use after lung transplantation (LTx) has supplanted antithymocyte globulin (ATG) as the main induction immunosuppression over the years, but few studies have compared them. In this study, we aimed to compare the efficacy and safety between BAS and ATG in LTx. We performed a retrospective analysis of all LTx done in Portugal between January 2016 and December 2019. Three groups were made according to the initial induction status: BAS, ATG or no induction (NI). The occurrences of cytomegalovirus (CMV) infection, pneumonia, side effects, primary graft dysfunction (PGD), acute rejection, chronic allograft disfunction (CLAD) and death episodes were assessed during two years after LTx. A total of 124 patients were divided in 3 groups: 61 (49.2%) BAS; 43 (34.7%) ATG; 20 (16.1%) NI. The incidences of pneumonia and CMV were similar between induction groups. Additionally, there was no difference between the induction groups in PGD, acute rejection, CLAD, deaths and two-year survival. Side effects were reported only in ATG group (n = 20; 46.5%). In our study, BAS had a better safety profile than ATG in LTx with a similar efficacy.

Background: With the rising incidence of diabetes and hypertension, the prevalence of end-stage renal disease has increased greatly so as the need for renal replacement therapy. Availability of suitable living-related donors is a major problem which increases the demand for deceased donor renal transplantation (DDRT), making it a lifeline for the patients on dialysis without any living donors. Methodology: This is a retrospective analysis of 118 DDRT done between 2012 and 2020, in a private quaternary care hospital in a south Indian state. All patients received basiliximab induction, with maintenance immunosuppression using steroids, mycophenolate mofetil (MMF) or mycophenolate sodium, and tacrolimus. Results: In our study, we report unadjusted graft survival of 93.2% and 81.3%, patient survival of 94.9% and 83.1% at the end of 1 and 5 years, respectively. The recipients with age < 60 years had 5 years graft survival of 87%. The study group consisted of 15.25% of the patients with panel reactive antibody (PRA) positive and 10.16% of them with donor-specific antibody (DSA) during renal transplantation, and there was only one allograft loss in this subset of the patients. Conclusion: This study confirms that human leukocyte antigen matching is not very important with the current immunosuppressive protocol using tacrolimus and MMF. Early initiations of tacrolimus do not increase the incidence of delayed graft function. We report 91.6% graft survival in the DSA-positive group, with basiliximab induction and desensitization protocol.

Introduction: Kidney transplantation is the renal replacement therapy (RRT) of choice for patients with end-stage renal disease. Although outcomes of deceased-donor kidney transplantation are inferior when compared to live donor kidney transplantation, they are still significantly better than being on chronic dialysis. There are very few studies comparing transplant outcomes between two kidneys obtained from the same donor. Aims: The aim of this study is to compare the graft and patient outcome of the kidneys of the same deceased donor transplanted into two different recipients. Materials and Methods: This is a prospective observational study done at the tertiary care center in South India over 2 years. A total of 29 pairs of deceased-donor transplants were followed up with one-half performed at donor institute (Group 1) and the same number performed at another network hospital (Group 2). Outcomes between the recipients of the two kidneys were compared. Data were statistically analyzed. Results: The majority of donors were relatively young (with a mean age of 37 years) and did not have multiple comorbidities. 1st kidney went to the donor hospital, whereas 2nd kidney was sent to other hospitals in the network. Cold ischemia times were higher (10.3 h vs. 6.5 h) for the 2nd kidneys. The majority of Group 1 patients did not receive induction, whereas 100% of Group 2 patients received basiliximab induction. The incidence of acute rejection (antibody plus cellular rejection) was numerically less in Group 2 compared to Group 1 but was not found to be statistically significant (P = 0.227). The incidence of acute cellular rejection in Group 1 was more compared to Group 2, and was found to be statistically significant (P = −0.038). Graft survival was similar in both groups (95.7 in Group 1 vs. 95.8 in Group 2). Patient survival was similar in both groups (P = −0.555) with a mean follow-up 25.9 months in Group 1 versus 24.6 months in Group 2. The choice of induction agent did not affect the graft or patient survival. In addition, there was no significant difference in the incidence of infections or mortality rate. Conclusion: Overall, the outcomes in the paired kidneys from the same donor transplanted to different recipients at different institutes had similar outcomes. The choice of induction agent did not have any influence on the overall graft and patient survival.

Introduction: Kidney transplant is a costly affair, especially in a developing country like India. The current study was carried out with the aim to analyze the clinical outcome retrospectively in terms of acute rejection (AR), graft survival, and patient survival in intermediate-risk recipients undergoing first renal transplant with Tacrolimus (TAC), Mycophenolic acid (MPA), and corticosteroid based triple maintenance immunosuppression in one of the most underprivileged population of the country who has to bear the cost of the induction agent not covered by any government scheme. Materials and Methods: It is a retrospective observational study. We included 101 patients, out of which 42 were in basiliximab group and 59 patients did not receive any induction agent. Apart from the induction, agent rest of the Immunosuppression protocol was same in all patients. The primary endpoint of the study was number of biopsy-proven AR within 1st year of transplantation. The secondary endpoints were patient and graft survival by 1 year. Results: Human leukocyte antigen mismatch and mean age of the patients in basiliximab group were significantly higher than noninduction group; otherwise, both groups were similar in all other baseline parameters. There was no significant difference between AR (21.43% v/s 18.64%), graft survival (97.30% v/s 98.15%), and patient survival (88.10% v/s 91.52%) at 1 year. Conclusion: Our study suggests that Induction immunosuppression may not be necessary for patients undergoing intermediate-risk living donor kidney transplant in the current scenario of TAC and MPA-based maintenance immunosuppression.

Introduction: The immunosuppressant regimen after kidney transplantation typically includes initial induction therapy followed by a maintenance regimen. The induction therapy was introduced with the aim of reducing acute rejections. A retrospective study was conducted to compare the outcomes in patients with different modalities of induction. Materials and Methods: This is a hospital-based retrospective study where 148 patients who have undergone live renal allograft transplantation at SCB Medical College and Hospital from March 2012 to February 2019 were included in the study. All cases included were crossmatch negative, ABO-compatible live renal allograft transplantations. All patients received tacrolimus, mycophenolate sodium, and steroids. Induction therapy varied depending on immunological risk and changes in protocol over time. Basiliximab, anti-T-lymphocyte globulin (ATLG), and anti-thymocyte globulin (ATG) were given in 56, 21, and 21 patients, respectively, and no induction therapy in 50 patients. All patients with an acute rise in serum creatinine and without an obvious cause of graft dysfunction were subjected to renal biopsy. The incidence of acute rejection, patient survival, and graft survival was calculated from the follow-up records and compared among patients receiving different induction therapies. Results: In the high-risk category patients, 31%, 20%, and 18.2% of patients (P = 0.6) and in the low risk category, 37%, 27.3%, and 20% of patients (P = 0.6) had acute rejections in basiliximab, ATLG, and ATG group, respectively. The patient survival at 1 year was 79.3%, 70%, and 81.8% in high-risk group patients (P = 0.84) and 88.9%, 81.8%, and 80% in low-risk group patients (P = 0.88) in the basiliximab, ATLG, and ATG groups, respectively. The graft survival at 2 years was 96.6%, 90%, and 90.9% in high-risk group patients (P = 0.32) and 88.9%, 90.9%, and 90% in low-risk group patients (P = 0.65) in the basiliximab, ATLG, and ATG groups, respectively. Conclusion: In the low-risk group, the use of different modalities of induction does not have any advantage over no induction therapy in reducing the incidence of acute rejection, or improving patient and graft survival. In the high-risk group, all the induction therapies used lead to similar outcomes and none show any advantage over the other in terms of statistical significance. However, patients who received ATLG or ATG have an increased incidence of septicemia as compared to basiliximab and no induction group.

Induction immunosuppressive therapy for kidney transplant recipients (KTRs) primarily includes interleukin-2 receptor antagonists, such as basiliximab (BXM) or lymphocyte-depleting agents, and anti-thymocyte globulin (ATG). This study aimed to investigate their effects on T cell dynamics during the early post-transplantation period. This prospective observational study included 157 KTRs. Peripheral blood samples were collected from each patient within 5 days before and 4 and 12 weeks after transplantation. Flow cytometric analysis was performed to assess various T cell subsets whose changes were then analyzed. In the ATG group, CD4+ T cell expression decreased significantly compared with that in the BXM group. However, CD4+CD161+ and CD4+CD25+CD127low T cell expression levels increased significantly. In the CD8+ T cell subset, a decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cell expression was observed in the ATG group. However, among patients diagnosed with biopsy-proven acute rejection, T cell subset expression did not significantly differ relative to non-rejection cases. In conclusion, ATG induction therapy resulted in more pronounced changes in T lymphocyte subsets than BXM induction, with increased CD4+CD161+ and CD4+CD25+CD127low T cells and an early decrease in CD8+CD28nullCD57+ and CD8+CCR7+ T cells, some of which are associated with acute rejection.

Coronavirus disease 2019 (COVID-19) has affected tens of millions of people globally since it was declared a pandemic by the World Health Organization on 11 March 2020. Since its outbreak in December 2019, the ongoing coronavirus COVID-19 pandemic has led to global social, economic and healthcare crises affecting millions of people and causing the death of hundreds of thousands of people worldwide. As with other fields of healthcare, the pandemic with its heavy workload imposed on hospital services and personnel significantly affected solid organ transplantation. Concerns for potential exposure to the virus and its related severe acute respiratory syndrome coronavirus type 2 (SARS-CoV2) have profoundly altered the process of organ donation and recovery, acceptance of organ offers, management of potential recipients and living donors, and above all transplanted and immunosuppressed patients. All those issues required prompt implementation of new practice measures and guidelines as well as continuous adaptations to the fluid and rapidly changing situation. Herein we describe a single transplant center experience with kidney transplantation during the COVID-19 pandemic; we review the national and institutional measures and restrictions undertaken in different phases of the ongoing event as well as the outcomes.

Currently, the graft-versus-host disease (GVHD) prophylaxis consists of an immunosuppressive therapy mainly based on antithymocyte globulin (ATG) or post-transplant cyclophosphamide (PTCy). GVHD remains a major complication and limitation to successful allogeneic haploidentical hematopoietic stem cell transplantation (haplo‐HSCT). We modified the ATG-based GVHD prophylaxis with the addition of basiliximab in the setting of haplo-HSCT and attempted to explore the appropriate dosages. We conducted a retrospective analysis of 239 patients with intermediate- or high-risk hematologic malignancies who received haplo-HSCT with unmanipulated peripheral blood stem cells combined or not with bone marrow. All patients received the same GVHD prophylaxis consisting of the combination of methotrexate, cyclosporine or tacrolimus, mycofenolate-mofetil, and basiliximab with different doses of ATG (5-9mg/kg). With a median time of 11 days (range, 7-40 days), the rate of neutrophil engraftment was 96.65%. The 100-day cumulative incidences (CIs) of grade II–IV and III–IV aGVHD were 15.8 ± 2.5% and 5.0 ± 1.5%, while the 2-year CIs of total cGVHD and extensive cGVHD were 9.8 ± 2.2% and 4.1 ± 1.5%, respectively. The 3-year CIs of treatment-related mortality (TRM), relapse, overall survival (OS), and disease-free survival (DFS) were 14.6 ± 2.6%, 28.1 ± 3.4%, 60.9 ± 3.4%, 57.3 ± 3.4%, respectively. Furthermore, the impact of the reduction of the ATG dose to 6 mg/kg or less in combination with basiliximab on GVHD prevention and transplant outcomes among patients was analyzed. Compared to higher dose of ATG(>6mg/kg), lower dose of ATG (≤6mg/kg) was associated with a significant reduced risk of CMV viremia (52.38% vs 79.35%, P

A 66-year-old Chinese man underwent a deceased donor kidney transplantation. Induction-immunosuppressive protocol consisted of basiliximab (BAS) and methyl prednisolone (MP), followed by maintenance immunosuppression with cyclosporin (CsA), mycophenolate mofetil (MMF), and prednisone (PED). The patient’s post-transplantation course was almost uneventful, and the graft was functioning well [serum creatinine (Scr) 2.15 mg/dL]. The MMF and CsA doses were decreased 1-month post-operative as the BK virus activation was serologically positive. His Scr was elevated to 2.45 mg/dL 45 days after the transplant. A graft biopsy showed BKV nephropathy (BKVN) and acute T cell–mediated rejection (TCMR) Banff grade IIA (I2, t2, ptc2, v1, c4d1, g0, and SV40 positive). The conventional anti-rejection therapy could deteriorate his BKVN, therefore, we administered BAS to eliminate activated graft-infiltrating T cells and combined with low-dose steroid. He responded well to the therapy after two doses of BAS were given, and the kidney graft status has been stable (recent Scr 2.1 mg/dL).

We aimed to identify the characteristics of immune reconstitution (IR) in patients who recovered from steroid-refractory acute graft-versus-host disease (SR-aGVHD) after basiliximab treatment. A total of 179, 124, 80, and 92 patients were included in the analysis for IR at 3, 6, 9, and 12 months, respectively, after haploidentical donor hematopoietic stem cell transplantation (HID HSCT). We observed that IR was fastest for monocytes and CD8+ T cells, followed by lymphocytes, CD3+ T cells, and CD19+ B cells and slowest for CD4+ T cells. Almost all immune cell subsets recovered comparably between patients receiving

BackgroundInduction therapy is used in about 80% of lung transplant centers and is increasing globally. Currently, there are no standards or guidelines for the use of induction therapy. At our institution, we have two induction strategies, basiliximab, and alemtuzumab. The goal of this manuscript is to share our experience and practice since this is an area of controversy.MethodsWe retrospectively reviewed 807 lung transplants performed at our institution between 2011 and 2020. Indications for the use of the basiliximab protocol were as follows: patients over the age of 70 years, history of cancer, hepatitis C virus or human immunodeficiency virus infection history, and cytomegalovirus or Epstein-Barr virus (donor positive/ recipient negative). In the absence of these clinical factors, the alemtuzumab protocol was used.Results453 patients underwent alemtuzumab induction and 354 patients underwent basiliximab. There were significant differences in delayed chest closure (24.7% alemtuzumab vs 31.4% basiliximab, p = 0.037), grade 3 primary graft dysfunction observed within 72 hours (19.9% alemtuzumab vs 29.9% basiliximab, p = 0.002), postoperative hepatic dysfunction (8.8% alemtuzumab vs 14.7% basiliximab, p = 0.009), acute cellular rejection in first year (39.1% alemtuzumab vs 53.4% basiliximab, p < 0.001). The overall survival rate of the patients with alemtuzumab induction was significantly higher than those of the patients with basiliximab induction (5 years survival rate: 64.1% alemtuzumab vs 52.3%, basiliximab, p < 0.001). Multivariate Cox regression analysis confirmed lower 5-year survival for basiliximab induction (HR = 1.41, p = 0.02), recipient cytomegalovirus positive (HR = 1.49, p = 0.01), postoperative hepatic dysfunction (HR = 2.20, p < 0.001), and acute kidney injury requiring renal replacement therapy (HR = 2.27, p < 0.001).ConclusionsIn this single center retrospective review, there was a significant difference in survival rates between induction strategies. This outcome may be attributable to differences in recipient characteristics between the groups. However, the Alemtuzumab group experienced less episodes of acute cellular rejection within the first year.

Introduction and aim: The interleukin-2 receptor antagonist; basiliximab is used to allow delayed introduction of Calcineurin inhibitors (CNI) after liver transplantation and thus delay their renal insult. However, there is only little evidence for the safety and the efficacy of this regimen. This study aimed to evaluate the effectiveness and safety of basiliximab induction in liver transplantation. Materials and methods: This study included 89 patients who were classified into two groups: standard triple immunosuppression (IS) regimen of steroid, tacrolimus (TAC) and mycophenolate mofetil (MMF) (n = 47) and induction IS regimen of basiliximab, low dose steroids and MMF with delayed introduction of CNI (n = 42). All patients were followed after liver transplantation for at least six months or until death. Results: There were no significant differences in patient survival, graft dysfunction, infection rate or type, or wound healing between both groups. The acute rejection rate was equivalent in both groups. Renal dysfunction in the first six months post-transplant was less in the basiliximab group in comparison to the other group (7.1% and 19.1% respectively). Conclusion: Basiliximab-induced IS protocol is a safe regimen that reduces medium-term renal dysfunction and achieves similar survival without increasing the acute rejection or infection rate in liver transplantation recipients.

Abstract Background The efficacy and safety of minimisation of immunosuppression including early steroid withdrawal in kidney transplant recipients treated with Basiliximab induction remains unclear. Methods This retrospective cohort study reports the outcomes from 298 consecutive renal transplants performed since 1st July 2010–June 2013 treated with Basiliximab induction and early steroid withdrawal in low immunological risk patients using a simple immunological risk stratification and 3-month protocol biopsy to optimise therapy. The cohort comprised 225 low-risk patients (first transplant or HLA antibody calculated reaction frequency (CRF ≤50% with no donor specific HLA antibodies) who underwent basiliximab induction, steroid withdrawal on day 7 and maintenance with tacrolimus and mycophenolate mofetil (MMF), and 73 high-risk patients who received tacrolimus, MMF and prednisolone for the first 3 months followed by long term maintenance immunosuppression with tacrolimus and prednisolone. High-risk patients not undergoing 3-month protocol biopsy were continued on triple immunosuppression. Results Steroid withdrawal could be safely achieved in low immunological risk recipients with IL2 receptor antibody induction. The incidence of biopsy-proven acute rejection was 15.1% in the low-risk and 13.9% in the high-risk group (including sub-clinical rejection detected at protocol biopsy). One- year graft survival was 93.3% and patient survival 98.5% in the low-risk group, and 97.3 and 100% respectively in the high-risk group. Graft function was similar in each group at 1 year (mean eGFR 61.2 ± 23.4 mL/min low-risk and 64.6 ± 19.2 mL/min high-risk). Conclusions Immunosuppression regimen comprising basiliximab induction, tacrolimus, MMF and prednisolone with early steroid withdrawal in low risk patients and MMF withdrawal in high risk patients following a normal 3-month protocol biopsy is effective in limiting acute rejection episodes and produces excellent rates of patient survival, graft function and complications.

Introduction: Interleukin-2 receptor antagonists are recommended to reduce the risk of acute rejection (AR) in kidney transplant. This prospective study was undertaken to compare the incidence of AR with basiliximab induction as compared to no induction in first kidney recipients of living donors with tacrolimus (TAC)- and mycophenolate mofetil-based triple immunosuppression at 6 months. Methods: Two hundred and sixty patients were included in the study, 202 in the basiliximab group and 58 in the no induction group. Patients in the basiliximab group received two doses of 20 mg each on day 0 and day 4. The primary outcome was biopsy-proven AR at 6 months, and the secondary outcomes were incidence of infections and other adverse events along with graft and patient survival at the end of follow-up. All patients were followed up for a period of minimum 6 months. Results: There was no difference in baseline characteristics between the groups except higher human leukocyte antigen mismatch in the basiliximab group (3.80 ± 1.50 vs. 2.81 ± 1.53, P = 0.002). Forty-two (20.8%) patients in the basiliximab group developed AR at 6 months as compared to 10 (17.2%) in the no induction group (P = 0.55). There was no difference in adverse events between the groups. At a median follow-up of 1 year, graft survival (97% vs. 98.3%, P = 0.60) and patient survival (99% vs. 98.2%, P = 0.87) were also similar between the basiliximab and no induction groups, respectively. Conclusions: This study suggests that there is no advantage of using basiliximab induction in reducing AR in first kidney recipients of living donors in TAC-based triple immunosuppression.

Aim: The outcome and long-term adverse events associated with induction agent use for living donor (LD) kidney transplantation (KT) in India were studied. Materials and Methods: Consecutive LD kidney transplant recipients (KTRs) from 2005 to 2013 were studied. They were divided based on induction agent use, into induction group and no induction group. The induction group was further subdivided into those receiving antithymocyte globulin (ATG group) and those receiving basiliximab (IL-2RB group). Study subjects were also classified into high and low immunological risk groups. Outcomes evaluated were patient and graft survival, acute rejections, infections, leucopenia, malignancy, new-onset diabetes mellitus, antibody-mediated rejections, and 1-year serum creatinine. Results: Of 605 LD-KTRs, 445 (73.6%) received induction. 403 (90.6%) received basiliximab induction. There was significant improvement in patient and graft survival in induction group (log rank P = 0.041 and 0.024, respectively), but this benefit disappeared when adjusting for immunosuppressive regimen as well as when only patients on tacrolimus-mycophenolate (Tac-MPA) were considered. There was significant reduction in acute rejections, tuberculosis (TB), and BK viremia in the induction group even in patients receiving Tac-MPA. There was no significant difference between basiliximab and ATG except for increased risk of BK viremia with ATG. Conclusions: The use of induction agents is associated with reduced incidence of acute rejections and serious infections (TB and BK viremia). The survival benefit of induction agent use is lost with the Tac-MPA-based immunosuppression. Thus, induction agent use is not essential for better survival if using Tac-MPA-based regimen.

The objective of this study was to compare outcomes between basiliximab and low-dose r-ATG in living donor kidney transplantation recipients with low immunological risk. Patients in the low-dose r-ATG group received 1.5 mg/kg of r-ATG for 3 days (total 4.5 mg/kg). Graft survival, patient survival, acute rejection, de novo donor specific antibody (DSA), estimated glomerular filtration rate (e-GFR) changes, and infection status were compared. Among 268 patients, 37 received r-ATG, and 231 received basiliximab. There was no noticeable difference in the graft failure rate (r-ATG vs. basiliximab: 2.7% vs. 4.8%) or rejection (51.4% vs. 45.9%). de novo DSA was more frequent in the r-ATG group (11.4% vs. 2.4%, p = 0.017). e-GFR changes did not differ noticeably between groups. Although most infections showed no noticeable differences between groups, more patients in the r-ATG group had cytomegalovirus (CMV) antigenemia and serum polyomavirus (BK virus) (73.0% vs. 51.9%, p = 0.032 in CMV; 37.8% vs. 15.6%, p = 0.002 in BK), which did not aggravate graft failure. Living donor kidney transplantation patients who received low-dose r-ATG and patients who received basiliximab showed comparable outcomes in terms of graft survival, function, and overall infections. Although CMV antigenemia, BK viremia were more frequent in the r-ATG group, those factors didn’t change the graft outcomes.

Background Acute renal dysfunction (ARD) may appear in heart transplant (HTx) patients both in the early postoperative period and during follow-up, even after several years. CD25 is a subunit of the interleukin-2 receptor which is found exclusively on activated CD4 T lymphocytes. CD25 is crucial for clonal expansion of anti-allograft host lymphocytes that mediate in acute rejection. There are experiences supporting the use of Anti-CD25 monoclonal antibodies (MAb) immediately after HTx in patients with ARD as a bridge to renal function recovery, allowing the temporary suspension of treatment with CNI. Methods In this study we report two cases of successful use of weekly MAb (basiliximab) in HTx patients who developed late ARD after HTx. Conclusions In coclusion, we think that in cases of ARD where CNI therapy plays a key role, the use of weekly doses of basiliximab allows CNI discontinuation until the restoration of renal function is achieved.

Acute graft versus host disease (aGVHD) remains a major problem after allogeneic hematopoietic stem cell transplantation. Standard frontline therapy for aGVHD involves corticosteroids. However, fewer than half of patients have a lasting complete response. The long-term mortality rate of steroid-refractory aGVHD (SR-aGVHD) remains around 70%. To date, no consensus has been reached regarding the optimal salvage treatment for SR-aGVHD. We performed the first prospective, multi-center clinical trial to assess the efficacy and safety of a novel approach to treat severe (grades III–IV) SR-aGVHD with the combination of basiliximab and etanercept. Sixty-five patients with severe SR-aGVHD from six centers were included. The median number of basiliximab infusions was 4 (range 2–11) and of etanercept was 9 (range 2–12). At day 28 after starting the combination treatment, overall response (complete and partial response: CR+PR) to second-line treatment was 90.8% with 75.4% being CR. The incidences of CR per organ were 100%, 73.8%, and 79.7% for skin, liver, and gut involvement, respectively. Patients >30-y old (p = 0.043, RR = 3.169), development of grades III–IV liver aGVHD (p = 0.007, RR = 5.034) and cytomegalovirus (CMV) reactivation (p = 0.035, RR = 4.02) were independent predictors for incomplete response. Combined treatment with basiliximab and etanercept resulted in improved CR to visceral aGVHD and significantly superior 2-y overall survival (54.7% vs. 14.8%, p

Background/AimsThe most commonly used immunosuppressant therapy after liver transplantation (LT) is a combination of tacrolimus and steroid. Basiliximab induction has recently been introduced; however, the most appropriate immunosuppression for hepatocellular carcinoma (HCC) patients after LT is still debated.MethodsNinety-three LT recipients with HCC who took tacrolimus and steroids as major immunosuppressants were included. Induction with basiliximab was implemented in 43 patients (46.2%). Mycophenolate mofetil (MMF) was added to reduce the tacrolimus dosage (n=28, 30.1%). The 1-year tacrolimus exposure level was 7.2 ± 1.3 ng/mL (mean ± SD).ResultsThe 1- and 3-year recurrence rates of HCC were 12.9% and 19.4%, respectively. Tacrolimus exposure, cumulative steroid dosages, and MMF dosages had no impact on HCC recurrence. Induction therapy with basiliximab, high alpha fetoprotein (AFP; >400 ng/mL) and protein induced by vitamin K absence/antagonist-II (PIVKA-II; >100 mAU/mL) levels, and microvascular invasion were significant risk factors for 1-year recurrence (P

A series of monoclonal antibodies (mAbs) are commonly utilized in renal transplantation as induction therapy (a period of intense immunosuppression immediately before and following the implant of the allograft), to treat steroid-resistant acute rejections, to decrease the incidence and mitigate effects of delayed graft function, and to allow immunosuppressive minimization. Additionally, in the last few years, their use has been proposed for the treatment of chronic antibody-mediated rejection, a major cause of late renal allograft loss. Although the exact mechanism of immunosuppression and allograft tolerance with any of the currently used induction agents is not completely defined, the majority of these medications are targeted against specific CD proteins on the T or B cells surface (e.g., CD3, CD25, CD52). Moreover, some of them have different mechanisms of action. In particular, eculizumab, interrupting the complement pathway, is a new promising treatment tool for acute graft complications and for post-transplant hemolytic uremic syndrome. While it is clear their utility in renal transplantation, it is also unquestionable that by using these highly potent immunosuppressive agents, the body loses much of its innate ability to mount an adequate immune response, thereby increasing the risk of severe adverse effects (e.g., infections, malignancies, haematological complications). Therefore, it is extremely important for clinicians involved in renal transplantation to know the potential side effects of monoclonal antibodies in order to plan a correct therapeutic strategy minimizing/avoiding the onset and development of severe clinical complications.

Background: Antibodies (ABs) against the 65 kDa isoform of the intracellular enzyme glutamate decarboxylase (GAD65) have been found in limbic encephalitis (LE) and other neurological conditions. The direct significance of anti-GAD65-ABs for epilepsy is unclear. However, in histological preparations from biopsies of resective epilepsy surgeries, predominantly cytotoxic T-lymphocytes were detected making close contacts to neurons. Activated T-lymphocytes can, in turn, be selectively controlled by therapeutic interleukin-2 receptor ABs such as Basiliximab.Case Presentation: We report of a 25 year-old male patient with epilepsy since the age of 18 and displaying clinical signs of LE and a high titer of GAD65 ABs in cerebrospinal fluid (CSF) and serum. Monthly, repetitive, intravenous Cortisone pulse therapies that were initially administered for six months failed to improve his condition. Subsequent flow-cytometry analysis of CSF showed especially an increased fraction of activated HLADR+ CD8+ T-Lymphocytes (fCD8+TL) when compared to controls. Thus, a second, intravenous Cortisone pulse therapy with an additional Basiliximab dose of 20mg/month was started. After three months, the fCD8+TL in the CSF normalized; after six months, the psychological impulse-control deficits normalized; and after eleven months the patient was seizure free. However, seven weeks later, seizures and, later on, psychological deficits recurred and fCD8+TL were once again present in the CSF. Flumazenil-PET, MRI-volumetry and neuropsychological changes during therapy are described.Conclusion: The correlation of the fCD8+TL in the CSF with clinical and paraclinical measures of disease activity combined with the unambiguous response to Basiliximab strongly argues in favor of the putative pathogenic role fCD8+TL in anti-GAD65 LE. The clinical relapse at the end of the observation period might be due to the formation of human anti-drug ABs, a well-known complication of therapy with chimeric ABs.

Antecedentes El rechazo agudo del injerto es unacomplicación importante en pacientes sometidosa trasplante renal. El presente estudio buscacomparar el porcentaje de rechazo agudo delinjerto en el primer año del trasplante renal alhaber recibido daclizumab o basiliximab comoinductor de inmunosupresión. Métodos Es un estudio observacional de cohorteretrospectivo y comprende el período de enero de2000 hasta diciembre de 2008. Fue realizado enel Servicio de Nefrología del Hospital Calderón Guardia. La población fue aquellos pacientestrasplantados renales en el Hospital Calderón Guardia y que recibieron basiliximab o daclizumab como inductor de inmunosupresión. Resultados La presencia de rechazo agudo delinjerto se presentó con mayor frecuencia en el grupo que recibió basiliximab comparado con elde daclizumab. Discusión La proporción de rechazo agudo delinjerto renal durante el primer año del trasplanteen el Hospital Calderón Guardia presentó diferencias entre los pacientes tratados con daclizumab y los tratados con basiliximab. En esteúltimo grupo hubo más rechazo.

Objetivos: Avaliar a eficácia e a segurança do uso de Basiliximab, anticorpo monoclonal quimérico que atua bloqueando o receptor de interleucina-2, na profilaxia de rejeição aguda em transplantes renais de alto risco realizados entre agosto/1999 e agosto/2002. Métodos: Foram analisados 75 receptores de transplante renal, considerados de alto risco para rejeição, que receberam Basiliximab como terapia de indução, na dose de 20mg no dia zero e no quarto dia após o transplante, com exceção das crianças com menos de 40kg de peso que tiveram a dose reduzida à metade. Os pacientes foram avaliados quanto ao sexo, idade, raça, doença de base, tipo de doador, tempo em diálise, tempo de isquemia fria, reação ao medicamento, incidência de rejeição e de infecção, sobrevida do paciente, causas de perda do enxerto e óbitos. Resultados: Episódios de infecção ocorreram em 70,6% dos casos, sendo o sítio mais freqüente o trato urinário (38,7%). O tempo de aparecimento foi em média 2,27 ± 1,8 meses. Rejeição ocorreu em 17,6% dos pacientes, sendo que nenhuma córtico-resistente. Apenas um paciente (criança) apresentou efeito colateral (crise convulsiva). Um paciente perdeu o enxerto por problema técnico e dois foram ao óbito com rim funcionante. A sobrevida do paciente em seis meses foi de 97,6%. Conclusão: O uso de Basiliximab foi seguro e eficaz na profilaxia da rejeição neste grupo de pacientes de alto risco.

Abstract Background Nowadays, better immunosuppressors have decreased the rates of acute rejection in kidney transplantation, but have also led to the emergence of BKV-associated nephropathy (BKVAN). Therefore, we prospectively investigated BKV load in plasma and urine samples in a cohort of kidney transplants, receiving basiliximab combined with a mycophenolate mofetil-based triple immunotherapy, to evaluate the difference between BKV replication during the first 3 months post-transplantation, characterized by the non-depleting action of basiliximab, versus the second 3 months, in which the maintenance therapy acts alone. We also performed sequencing analysis to assess whether a particular BKV subtype/subgroup or transcriptional control region (TCR) variants were present. Methods We monitored BK viruria and viremia by quantitative polymerase chain reaction (Q-PCR) at 12 hours (Tx), 1 (T1), 3 (T2) and 6 (T3) months post-transplantation among 60 kidney transplant patients. Sequencing analysis was performed by nested-PCR with specific primers for TCR and VP1 regions. Data were statistically analyzed using χ2 test and Student's t-test. Results BKV was detected at Tx in 4/60 urine and in 16/60 plasma, with median viral loads of 3,70 log GEq/mL and 3,79 log GEq/mL, respectively, followed by a significant increase of both BKV-positive transplants (32/60) and median values of viruria (5,78 log GEq/mL) and viremia (4,52 log GEq/mL) at T2. Conversely, a significantly decrease of patients with viruria and viremia (17/60) was observed at T3, together with a reduction of the median urinary and plasma viral loads (4,09 log GEq/mL and 4,00 log GEq/mL, respectively). BKV TCR sequence analysis always showed the presence of archetypal sequences, with a few single-nucleotide substitutions and one nucleotide insertion that, interestingly, were all representative of the particular subtypes/subgroups we identified by VP1 sequencing analysis: I/b-2 and IV/c-2. Conclusions Our results confirm previous studies indicating that BKV replication may occur during the early hours after kidney transplantation, reaches the highest incidence in the third post-transplantation month and then decreases within the sixth month, maybe due to induction therapy. Moreover, it might become clinically useful whether specific BKV subtypes or rearrangements could be linked to a particular disease state in order to detect them before BKVAN onset.