Combination Of Basiliximab Research Articles

MO948: Impact of DE Novo Immunosuppression in The Covid-19 Serological Status at Kidney Transplantation

BACKGROUND AND AIMSCOVID-19 infection has heavily impacted our national health system since March-2020. Although the kidney transplant (KT) activity was strongly reduced initially, nowadays it is partially recovered by using ‘COVID-clean’ pathways and vaccination of KT candidates since February-2021. However, scarce information is available regarding how de novo KT immunosuppression influences the serological status of vaccinated recipients.METHODWe reviewed the course of 38 de novo KT recipients transplanted between March-September 2021 fully vaccinated before KT. SARS-CoV-2 IgG antibodies against Spike (IgG-S) before and after KT (median: 32 days) were quantified with a serological assay (positive ≥13.0 AU/mL).RESULTSOf 38 recipients, 35 showed positive IgG-S at KT (92%). We exclude from the analysis, 4 recipients with COVID infection which interfered the analysis and 5 with inappropriate samples. The remaining 26 recipients had received the second dose of the mRNA vaccine a median time of 48 days before the pre-KT IgG determination. All patients maintained IgG-S over the cut-off after KT, but we observed that half de novo recipients (53.8%) showed a 50% reduction in the level of IgG-S at 1 month: 12/20 (60%) of those who received induction with basiliximab and 2/6 (33%) who received thymoglobulin. Regarding the impact of maintenance immunosuppression under induction with basiliximab, the IgG-S levels halved in 50% of those with tacrolimus-mycophenolate and 67% with tacrolimus-everolimus.The restricted analysis of IgG-S levels excluding five outliers before KT (>800 AU/mL) showed the most intense reduction in three KT recipients who received thymoglobulin-tacrolimus- mycophenolate (263.8 versus 68.8, 74%) compared with seven basiliximab-tacrolimus-mycophenolate cases (494.4 versus 359.8, 27%) and eleven basiliximab-tacrolimus-everolimus (344.0 versus 306.4, 11%) KT recipients.CONCLUSIONImmunosuppression in de novo KT recipients reduces significantly the seroprotective levels of antibodies anti-Spike induced by COVID m-RNA vaccines in more than half the recipients. In our experience, the combination of thymoglobulin, tacrolimus and mycophenolate produces a more intense reduction than the combination of basiliximab with tacrolimus and mycophenolate or everolimus.

Early efficacy of islet transplantation in the treatment of adult advanced diabetes

Objective: To evaluate the safety and efficacy of islet transplantation for patients with advanced diabetes. Methods: Five cases of islet allotransplantation were performed on 4 adult recipients. The same blood type adult brain-dead pancreas donors were selected and the islets were prepared in GMP laboratory. The prepared islet suspension was slowly injected into the liver of the recipients within 30-60 minutes. The immunosuppressive regimen was a combination of basiliximab, tacrolimus and mycophenolate mofetil and TNF-alpha monoclonal antibody was used to reduce the post-transplant inflammatory response. Insulin was temporarily applied to control blood glucose after surgery, and the dosage of insulin was adjusted to decrease according to the blood glucose level until it was discontinued. Results: A total of 5 islet transplants were performed in 4 patients, including 1 patient who received the second islet transplantations. All operations were succeed and the blood glucose and portal pressure were stable during the operation. Exogenous insulin was continued to keep blood glucose level stable (4-12 mmol/L) after surgery. Four cases (including the one who received two islet transplantation) started to stop using insulin at the third to fourth week, and the insulin dosage of the other case was 74% lower than that before the operation, and no hypoglycemic reaction occurred in all patients after islet transplantation. The C-peptide level in 3 patients reached the normal range, and the level in one patient with type I diabetes (without insulin release) remained at 0.45-0.6 μg/L (0.15-0.2 nmol/L). In addition, one patient showed a rise in blood glucose again and continued to use insulin half a year after insulin discontinuation. Then, he was performed the second islet transplantation which showed good effect and stopped taking insulin in 10 days after surgery. There were 3 cases of liver puncture bleeding after opeation, of which 2 cases were treated with ultrasound radiofrequency ablation to stop bleeding, 1 case stopped spontaneously, and no other complications were found. Conclusions: Islet transplantation is effective in the treatment of advanced diabetes patients with small trauma and high safety, which is worthy of more promotion. Long-term efficacy and maintenance therapy still need further investigation.

Basiliximab application on liver recipients: a meta-analysis of randomized controlled trials

The benefits of the application of basiliximab induction therapy in liver transplantation are not clear. The present meta-analysis was to evaluate the pros and cons of basiliximab use in liver transplantation. We searched the associated publications in English from July 1998 to December 2015 in the following databases: MEDLINE, PubMed, Ovid, EMBASE, Web of Science and Cochrane Library. Basiliximab significantly decreased the incidence of de novo diabetes mellitus after liver transplantation (RR=0.56; 95% CI: 0.34-0.91; P=0.02). Subgroup analysis showed that basiliximab in combination with steroids-free immunosuppressant significantly decreased the incidence of biopsy-proven acute rejection (RR=0.62; 95% CI: 0.39-0.97; P=0.04) and new-onset hypertension (RR=0.62; 95% CI: 0.42-0.93; P=0.02). Basiliximab may be effective in reducing de novo diabetes mellitus. What is more, basiliximab in combination with steroids-free immunosuppressant shows statistical benefit to reduce biopsy-proven acute rejection and de novo hypertension.

Combining therapeutic antibodies using basiliximab and etanercept for severe steroid-refractory acute graft-versus-host disease: A multi-center prospective study

ABSTRACTAcute 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 <0.001) compared with classical salvage treatments. Our data suggest that the combination of basiliximab and etanercept may constitute a promising new treatment option for SR-aGVHD.

Excellent Therapeutic Results Achieved in Salvage Therapy for Steroid-Refractory Grades III-IV Acute Gvhd with Basiliximab and Etanercept: A Multicenter Prospective Study

Introduction: Standard first-line therapy for the treatment of acute graft-versus-host disease (aGVHD) involves corticosteroids. However, fewer than half of patients have durable complete response. Steroid refractory aGVHD (SR-aGVHD) is associated with increased mortality, and long-term mortality rate remains around 70%. Second-line treatments included antithymoglobulin (ATG), mycophenolate mofetil (MMF), tacrolimus (FK), IL-2R antibodies, alemtuzumab, etanercept, infliximab, sirolimus and others. The overall complete remission (CR) rate from the 28 published retrospective studies that evaluating agents for second-line therapy of SR-aGVHD was 32%, the median survival was only about 6 months and no agent was clearly superior. To date, no consensus has been reached regarding the optimal secondary treatment of SR-aGVHD. Based on the pivotal roles of T cells and inflammatory cascade in aGVHD induction, since 2009 we performed a multicenter prospective study to assess the efficacy and safety of an approach to treat severe (grades III-IV) SR-aGVHD by the combination of basiliximab (anti-IL2-R) and etanercept (anti-TNFα).Methods: We conducted an open-label, non-randomized, phase II study at three centers, Bone Marrow Transplantation Center, the First Affiliated Hospital, Zhejiang University School of Medicine (Hangzhou), Department of Hematology, Zhejiang Provincial People's Hospital (Hangzhou), and Department of Hematology, Guangzhou General Hospital of Guangzhou Military Command (Guangzhou), between January 2009 and October 2013. Patients fulfilled one of the following criteria were included: (1)when newly diagnosed with grades III-IV aGVHD or overlap syndrome and showed progression after 3 days, or no improvement after at least 7 days of treatment or partial response at 14 days with 2 mg/kg per day prednisolone; or (2) de novo grades I-II aGVHD but eventually evolved into grades III-IV during treatment with prednisolone. Basiliximab was given intravenously at 20mg/d on days 1, 4, 8, 15, 22, 29, 36 (if necessary). Etanercept was given subcutaneously at 25mg per dose twice a week for 4 weeks and then pursued at 25mg once a week for another 4 weeks. During combined therapy all patients received cyclosporine and maintained on therapeutic level. Prednisolone was tapered by 10% of the total dose twice weekly.Results: (1) Forty-one patients with steroid-refractory grades III-IV aGVHD were included. Acute GVHD occurred at a median time of 13 days post-transplantation (range: 5-85). First-line treatment with 2 mg/kg/day steroids was initiated at GVHD diagnosis. Thirty patients (73.2%) were diagnosed as grade II aGVHD but evolved into severe aGVHD during treatment with prednisolone, and 11 patients (26.8%) were severe aGVHD at onset. Median time from diagnosis of aGVHD to study enrollment was 12 days (range 3-49). Fifteen patients (36.6%) presented with overall grade III aGVHD and 63.4% with grade IV. (2) Median number of infusions of basiliximab was 4 (range 2-7) and median number of etanercept was 8 (range 1-11). At day 28 after treatment by the combination therapy of basiliximab and etanercept was initiated, overall response (CR+PR) to second-line treatment was 92.7% with 78% of CR. The incidences of CR per organ was 100%, 80.5% and 85.4% for skin, gut and liver involvement, respectively. Nine of 24 evaluable patients developed chronic GVHD (cGVHD), in which 4 cases were with mild cGVHD and 5 with extensive cGVHD. (3)The cumulative incidence of a invasive pulmonary fungal infection at 12 months post-transplantation was 42.4%. Although twenty-eight patients (69.3%) experienced at least 1 cytomegalovirus (CMV) reactivation, all patients developed CMV-positive antigenemia without CMV disease. One patient developed viral encephalitis by human herpesvirus 6 (HHV6). No case of Epstein-Barr virus (EBV) reactivation was reported. Five-year overall survival (OS) rate after the combination therapy was 55.2% . A total of 17 patients died and causes of death ordered by the number of patients were invasive pulmonary fungal infection, (n=8, 47.1%), relapse (n=4, 23.5%), aGVHD (n=4, 23.5%), and arrhythmia (n=1, 5.9%).Conclusions: Here we developed a novel salvage treatment approach for grades III-IV SR-aGVHD by using the combination of basiliximab and etanercept, which achieved a clinically meaningful response in approximately more than 90% of patients and 55.2% of 5-year OS. DisclosuresNo relevant conflicts of interest to declare.

Renal Transplantation in HIV-positive Renal Transplant Recipients: Experience at the Mannheim University Hospital

Renal transplantation in HIV-positive patients with end-stage renal disease has in recent years become a successful treatment option. We report two patients who underwent renal transplantation using a combination of basiliximab, calcineurin inhibitors, mycophenolate mofetil (MMF), and steroids with a “non-interacting” antiretroviral combination therapy consisting of stavudine or abacavir, lamivudine, and nevirapine. We observed no acute rejection but a BK polyomavirus infection in both patients. In conclusion, a quadruple immunosuppression with an interleukin 2 receptor antagonist, a calcineurin inhibitor, MMF, and steroids appears to be advisable to prevent high rates of acute rejection, but if possible thereafter immunosuppression should be tapered rapidly (eg, MMF stop, prednisolone dose 5 mg/d). The selection of antiretroviral agents should avoid compounds that interact severely with the immunosuppression used.

Early Steroid Withdrawal Regimen Prevents New‐Onset Diabetes Mellitus in Old‐Age Recipients After Living Donor Liver Transplantation

Steroid use after liver transplantation is known to increase the risk of new-onset diabetes mellitus (NODM). In this study, we tried to identify a patient subgroup who would benefit with regard to NODM by an early steroid withdrawal regimen (ESWR) after living donor liver transplantation (LDLT) METHODS: Among 100 adult LDLT patients, 65 were on a conventional immunosuppressive regimen (CIR), and 35 were on an ESWR. With the ESWR, the steroid was tapered off mostly within 7 days with induction of basiliximab in combination with tacrolimus and mycophenolate mofetil (MMF). The CIR was a combination of tacrolimus and steroid. MMF was added in selected patients. Steroid was tapered off 2-6 months after LT. The presence of NODM was investigated cross-sectionally 6 months after LT. There was no significant difference in terms of acute cellular rejection, sepsis, or death during follow-up. NODM had developed in 13 patients (13 %). Old recipient age (≥ 55) and pretransplant history of hypertension were significant risk factors for NODM. The type of immunosuppression was the single risk factor for NODM in subgroup of old-age recipients (≥ 55 years) on the CIR (hazard ratio 13.34, p = 0.04). ESWR can safely reduce the incidence of NODM after LDLT in old-age recipients. Therefore, ESWR should be considered first in old-age recipients undergoing LDLT.

Induction With Basiliximab Plus Thymoglobulin Is Effective and Safe in Old-for-Old Renal Transplantation: Six-Month Results of a Prospective Clinical Study

Old-for-old renal transplantation is becoming more frequent, but the optimal immunosuppressive regimens for this transplant population are still unclear. The aim of this pilot prospective study was to evaluate the efficacy and safety of the combination of basiliximab with a short course of low-dose thymoglobulin induction therapy among a group of patients receiving kidneys from donors >60 years (OLD), compared with those receiving organs from donors <60 years (YNG). Forty-six consecutive deceased donor kidney transplant patients received induction therapy with a combination of basiliximab (20 mg IV on days 0 and 4) and thymoglobulin (200 mg total dose IV on days 0–3). As maintenance immunosuppression starting on day 4, patients received a low dose of calcineurin inhibitor and steroids. Demographic characteristics at baseline were not significantly different between the 2 groups. At 6 months, patient survival, graft survival, and acute rejection rates were similar between the YNG and OLD groups: 100% and 95%, 96% and 95%, and 8% and 0%, respectively. Patients in the OLD group showed higher serum creatinine concentrations (YNG 1.5 ± 0.3 vs OLD 1.9 ± 0.3 mg/dL; P = .0002) but not proteinuria (YNG 0.11 ± 0.11 vs OLD 0.15 ± 0.14 g/24 h; P = ns). No significant difference was evident between the 2 groups regarding infectious, hematologic, or posttransplantation lymphoproliferative disorder complications. This study showed that a combination of basiliximab and a short course of low-dose thymoglobulin provided effective and safe immunosuppression, in old-for-old renal transplantation, with good renal function without an increased risk of posttransplantation infectious or hematologic complications.

Basiliximab induced non-cardiogenic pulmonary edema in two pediatric renal transplant recipients

We report two cases of non-cardiogenic pulmonary edema as a complication of basiliximab induction therapy in young pediatric renal transplant patients identified following a retrospective review of all pediatric renal transplant cases performed in the National Paediatric Transplant Centre, Childrens University Hospital, Temple Street, Dublin, Ireland. Twenty-eight renal transplantations, of which five were living-related (LRD) and 23 were from deceased donors (DD), were performed in 28 children between 2003 and 2006. In six cases, transplantations were pre-emptive. Immunosuppression was induced pre-operatively using a combination of basiliximab, tacrolimus and methylprednisolone in all patients. Basiliximab induction was initiated 2 h prior to surgery in all cases and, in 26 patients, basiliximab was re-administered on post-operative day 4. Two patients, one LRD and one DD, aged 6 and 11 years, respectively, developed acute non-cardiogenic pulmonary edema within 36 h of surgery. Renal dysplasia was identified as the primary etiological factor for renal failure in both cases. Both children required assisted ventilation for between 4 and 6 days. While both grafts had primary function, the DD transplant patient subsequently developed acute tubular necrosis and was eventually lost within 3 weeks due to thrombotic microangiopathy and severe acute antibody-mediated rejection despite adequate immunosuppression. Non-cardiogenic pulmonary edema is a potentially devastating post-operative complication of basiliximab induction therapy in young pediatric patients following renal transplantation. Early recognition and appropriate supportive therapy is vital for patient and, where possible, graft survival.

Basiliximab and Infliximab for the Treatment of Steroid-Refractory Crohn's Disease

Price, Michelle M.B., B.S.; Probert, Christopher S. J. M.D.; Creed, Tom M.D. Author Information

Incidence of PTLD in Pediatric Renal Transplant Recipients Receiving Basiliximab, Calcineurin Inhibitor, Sirolimus and Steroids

Pediatric renal transplant recipients were enrolled in a multicenter, randomized, double-blind trial of steroid withdrawal. Subjects received basiliximab, calcineurin inhibitor, sirolimus and steroids. Of 274 subjects enrolled, 19 (6.9%) subjects developed posttransplant lymphoproliferative disorder (PTLD). The relative hazard (RH) for PTLD was 5.3-fold higher in children aged < or =5 versus those >12 years (p = 0.0017). EBV seronegative subjects had a 4.7-fold higher RH compared to EBV positive subjects (p = 0.02). Among EBV donor+/recipient- (D+/R-) subjects, the RH increased by 6.1-fold (p = 0.0001). In a multivariate model, risk factors included recipient age < or =5 years (RH 3.2, 95% CI: 1.1-9.6, p = 0.034) and EBV D+/R- status (RH 7.7, 95% CI: 1.6-35.9, p = 0.010). Of 19 patients with PTLD, 17 are alive with functioning grafts and 2 lost their grafts, 1 of whom subsequently died of recurrent PTLD. This 'robust' immunosuppression protocol was associated with low rejection rates but an unacceptably high incidence of PTLD. The combination of basiliximab, calcineurin inhibitor, sirolimus and steroids resulted in over-immunosuppression in a high-risk pediatric population and we do not recommend its use. Future studies must include routine viral monitoring to permit early identification of viral activity and a protocol driven reduction of immunosuppression aimed at avoiding complications.

Report of the Experience With Enteric-Coated Sodium Mycophenolate in a De Novo Population of Kidney Transplant Recipients at High Risk for Delayed Graft Function

The introduction of mycophenolate as an adjuvant in immunosuppressive regimes has improved clinical outcomes of transplant patients due to a reduced incidence of acute rejection episodes. Nevertheless, the need for dose adjustments or therapy discontinuations (up to 45% in some series), have downgraded the efficacy of mycophenolate mofetil (MMF). From October 2003 to April 2005, 36 kidney transplantations were performed at our site. The immunosuppressive protocol included induction with basiliximab, administered on days 0 and 4 posttransplantation, cyclosporine microemulsion (CsA-ME) monitored by concentrations at 2 hours (C2), enteric-coated sodium mycophenolate (EC-MPS; 720 ± 180 mg bid), and steroids. Mean follow-up time was 7.3 ± 4.4 months. Fourteen patients (38.9%) experienced delayed graft function (DGF). Seven (19%) episodes of acute rejection included 5 graded as I-A, 1 as grade I-B, and 1 as grade II-A. There were discontinuations of EC-MPS. Regarding gastrointestinal (GI) adverse events, there were 2 episodes of noninfectious diarrhea, 1 gastritis, and 1 upper GI hemorrhage. There were 11 infections: 4 in the urinary tract; 3 in the lung; 3 in the GI tract; and 1 CMV infection. There were no hematological adverse events. Two (6%) graft losses were reported to be due to sepsis. In this group of patients who experienced a high incidence of DGF, the combination of basiliximab, CsA-ME (monitored by C2), and EC-MPS resulted in low Banff grade acute rejection episodes which were all responsive to steroids. The incidence of GI adverse events was only 11%.

Basiliximab Induction in Adult Liver Transplant Recipients With 93% Rejection-Free Patient and Graft Survival at 24 Months

Induction with the use of interleukin-2 receptor monoclonal antibodies may avoid many of the adverse events associated with polyclonal antibodies and significantly impact on rejection-free long-term survival in orthotopic liver transplantation (OLTx). We describe our experience with the use of basiliximab induction therapy in adult OLTx recipients on tacrolimus-based immunosuppression. Forty-six consecutive deceased donor primary OLTx were analyzed. All patients received standard doses of basiliximab, tacrolimus, and steroids. Mycophenolate mofetil was also used as indicated. The mean follow-up period was 17.9 months. Forty-three patients remained rejection-free during follow-up. The actuarial patient and graft survival rate at 2 years was 93%. The rate of histology-proven hepatitis C virus (HCV) recurrence was 24%, with two progressing to severe cholestatic recurrent HCV. None of the study patients developed (cytomegalovirus (CMV) infection or posttransplant lymphoproliferative disease (PTLD). Results were compared to a historical group of 46 OLTx recipients on tacrolimus-based immunosuppression without basiliximab induction. The historical group had a rejection rate of 34% with lower patient and graft survival rates of 71.74% and 69.5%, respectively, at 24 months as well as a higher histological HCV recurrence rate of 77% (17/22), with three patients progressing to graft failure within 2 years. CMV infection and disease developed in 4.5% of the patients. Although PTLD was not observed, three recipients with hepatocellular carcinoma (HCC) developed and died of metastatic HCC. Induction with basiliximab in combination with tacrolimus-based immunosuppressive regimen reduces the incidence of rejection and improves rejection-free survival rate after OLTx without increasing the incidence of CMV, PTLD, or HCV recurrence.

A Safe Immunosuppressive Protocol in Adult-to-Adult Living Related Liver Transplantation

Background In this series of 32 adult-to-adult living related liver transplantations, we assessed the efficacy and safety of basiliximab in combination with a tacrolimus-based regimen. Basiliximab, a chimeric monoclonal antibody directed against the alpha chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for cadaveric liver transplant recipients. Patients and Methods Thirty-two adult-to-adult living related liver transplantations were performed in the last 3 years. All patients received two 20 mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10–15 ng/mL target trough levels) and steroids (starting with 20 mg IV switched to PO as soon as the patient was able to eat and weaned within 1–2 months). The average follow-up was 395 days after transplantation. Results Of the patients, 93.75% remained rejection-free during follow-up with an actuarial rejection-free probability of 92.59% within 3 months. Two patients (6%) had one episode of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.85% and 81.25%. One patient (3%) experienced one episode of sepsis. There was no evidence of cytomegalovirus infections or side effects related to the basiliximab. We found zero de novo malignancy but we observed two patients with metastatic spread of their primary malignancy during the follow-up. Conclusion Basiliximab in association with tacrolimus and steroids is effective as prophylaxis of ACR among adult living related liver transplant recipients.

Basiliximab in a Triple-Drug Regimen With Tacrolimus and Steroids in Liver Transplantation

Background Basiliximab, a chimeric monoclonal antibody (mAb) directed against the α chain of the interleukin-2 (IL-2) receptor (CD25), has been extensively evaluated as induction therapy for kidney transplant recipients, more frequently in combination with a cyclosporine-based regimen. In this study, we assessed the efficacy and safety of basiliximab in combination with tacrolimus and steroids following liver transplantation. Methods One hundred fifty-two liver transplant recipients (141 cadaveric donors and 11 living donors [LRLT]) in the last 4 years were treated with 2 20-mg doses of basiliximab (days 0 and 4 posttransplantation) followed by tacrolimus (0.15 mg/kg/d; 10–15 ng/mL target trough levels) and steroids (500 mg intravenous [IV] bolus at the reperfusion followed by 20 mg orally daily and weaning off in 1 or 2 months). Follow-up ranged from 104 to 1630 days after transplantation (mean, 665 days; SD ± 442.65; median, 509 days). Results Eighty-five percent of patients remained rejection-free during follow-up with an actuarial rejection-free probability of 78% within 3 months. Nineteen patients had 22 episodes of biopsy-proven acute cellular rejection (ACR). Actuarial patient and graft survival rates at 3 years were 86.7% and 75.8%, respectively. Twenty-seven patients (20.6%) experienced 1 episode of sepsis, requiring temporary reduction of immunosuppressive therapy. There was no evidence of CMV infections or side effects related to basiliximab. We observed 2 de novo malignancies, 1 recurrence from an ileal carcinoid tumor and 1 pulmonary recurrence of hepatocellular carcinoma (HCC) in 1 recipient of LRLT. Conclusions Basiliximab in association with tacrolimus and steroids is effective prophylaxis of ACR in liver transplant recipients and does not increase the incidence of infections or adverse effects.

Steroid Withdrawal or Steroid Avoidance in Renal Transplant Recipients: Focus on Tacrolimus-Based Immunosuppressive Regimens

Steroid-induced adverse effects after transplantation include cosmetic, metabolic, and cardiovascular complications. Steroid withdrawal or avoidance with cyclosporine-based regimens have been hampered by an unacceptably high rate of acute rejections and increased rates of graft loss. Recently the results of several large, randomized trials of steroid withdrawal/avoidance with tacrolimus-based immunosuppression in renal transplant recipients became available. A review of these trials appeared to be of clinical interest. Data from the THOMAS trial clearly indicate that steroid withdrawal from a regimen of tacrolimus, mycophenolate mofetil (MMF), steroids after 3 months after transplantation is safe with regard to acute rejection rate and graft survival. If an induction therapy with daclizumab is used in combination with tacrolimus and MMF (CARMEN trial), even steroid avoidance is safe with regard to acute rejection rate and graft survival. Finally, in the ATLAS trial, steroid avoidance with basiliximab in combination with tacrolimus (resulting in tacrolimus monotherapy) or alternatively with tacrolimus and MMF both resulted in similar graft survival, but higher rates of acute rejection. In conclusion, steroid withdrawal is safe from a triple-drug regimen of tacrolimus, MMF, and steroids after 3 months after transplantation, and steroid use may completely be avoided with tacrolimus, and MMF combined with daclizumab induction. Tacrolimus monotherapy may be achieved using basiliximab induction at the price of higher rates of acute rejection, but with unaffected graft survival. Thus tacrolimus-based immunosuppression with or without interleukin-2 receptor antagonist induction has made steroid withdrawal or avoidance a realistic option in renal transplantation.

Anti-Interleukin-2 Receptor Antibodies for the Prevention of Rejection in Pediatric Renal Transplant Patients

The anti-interleukin-2 receptor (anti-IL-2R) antibody therapy is an exciting approach to the prevention of acute rejection after renal allograft transplantation whereby immunosuppression is exerted by a selective and competitive inhibition of IL-2-induced T cell proliferation, a critical pathway of allorecognition. The anti-IL-2R antibodies specifically block the alpha-subunit of the IL-2R on activated T cells, and prevent T cell proliferation and activation of the effector arms of the immune system. The anti-IL-2R antibodies are used as induction therapy, immediately after renal transplantation, for prevention of acute cellular rejection in children and adults. During acute rejection, the IL-2Ralpha chain is no longer expressed on T cells; thus, the antibodies cannot be used to treat an existing acute rejection. Two anti-IL-2R monoclonal antibodies are currently in clinical use: daclizumab and basiliximab. In placebo-controlled phase III clinical trials in adults, daclizumab and basiliximab in combination with calcineurin inhibitor-based immunosuppression, significantly reduced the incidence of acute rejection and corticosteroid-resistant acute rejection without increasing the risk of infectious or malignant complications, and neither antibody was associated with the cytokine-release syndrome. Children who receive calcineurin inhibitors and corticosteroids for maintenance immunosuppression, as well as children who receive augmented immunosuppression to treat acute rejection, are at increased risk of growth impairment, hypertension, hyperlipidemia, lymphoproliferative disorders, diabetes mellitus, and cosmetic changes. In older children, the cosmetic adverse effects frequently reduce compliance with the treatment, and subsequently increase the risk of allograft loss. Being effective and well tolerated in children, the anti-IL-2R antibodies reduce the need for calcineurin inhibitors while maintaining the overall efficacy of the regimen; thus, the anti-IL-2R antibodies increase the safety margin (less toxicity, fewer adverse effects) of the baseline immunosuppression. Secondly, the anti-IL-2R antibodies decrease the need for corticosteroids and muromonab CD3 (OKT3) in children as a result of decreased incidence of acute rejection. The recommended pediatric dose of daclizumab is 1 mg/kg intravenously every 14 days for five doses, with the first dose administered within 24 hours pre-transplantation. This administration regimen maintains daclizumab levels necessary to completely saturate the IL-2Ralpha (5-10 microg/mL) in children for at least 12 weeks.The recommended pediatric dose of basiliximab for recipients <35 kg is 10 mg, and 20 mg for recipients > or =35 kg, intravenously on days 0 and 4 post-transplantation. This administration regimen maintains basiliximab levels necessary to completely saturate the IL-2Ralpha (>0.2 microg/mL) in children for at least 3 weeks.

First experience with basiliximab in pediatric liver graft recipients.

Several studies have shown a significant reduction of acute cellular graft rejection in adult liver and kidney graft recipients treated with monoclonal anti-interleukin-2 (IL-2)-receptor antibodies. The mechanism was inhibition of activated T-helper cells by blocking the alpha-chain (CD25) of the IL-2 receptor. The pilot study described here evaluated the use of basiliximab in pediatric liver transplantation (LTx), which is the first report on its use in children. Fifty-two liver-transplanted children were analyzed in this study. A matched-pair historical control group (n = 26) received cyclosporin A (CsA) and prednisolone, and patients in the basiliximab group (n = 26) were treated with low-dose CsA and basiliximab (after reperfusion and on day 4 post-transplant). The incidences were compared of acute graft rejections, infectious complications, and the adverse effects of immunosuppressive medication within the first 6 months post-transplant. The incidence of acute rejection was significantly higher in the control group (61.5% vs. 11.5%, p = 0.0004). The frequency of infectious complications was similar (46.1% vs. 53.8%). Patients in the basiliximab group showed less arterial hypertension; however, the differences were not statistically significant (30.7% vs. 7.7%, p = 0.07). Nephrotoxicity, hepatotoxicity or neurotoxicity were only seen in the control group (7.7%; 3.8%; 3.8%, respectively). Hence, the use of basiliximab in combination with CsA and steroids in pediatric liver transplant recipients is safe and reduces the incidence of acute graft rejection. Further studies are needed to confirm our preliminary results and to analyze long-term effects on post-transplant lymphoproliferative disease, chronic rejection, and patient survival.