Induction immunosuppression strategies and long-term outcomes after heart transplantation

Although the use of induction therapy has reduced the risk of acute rejection after heart transplantation, its use may be associated with other adverse outcomes. We aimed to examine the effect of no induction (NoInd), induction with basiliximab (BAS), or induction with antithymocyte globulin (ATG) on outcome after heart transplantation. We analyzed data from the International Society for Heart and Lung Transplantation (ISHLT) registry for adult heart transplants performed between 2000 and 2013. The primary outcome was cumulative all-cause mortality, and the secondary outcome was cause-specific death. We identified 27 369 transplants whose recipients received NoInd (n = 15 688), ATG (n = 6830), or BAS (n = 4851). Over a median follow-up of 1497 days, overall 30-day mortality was 5% and 1-year mortality was 11%. Survival after transplant was similar in patients treated with NoInd compared with ATG. The survival was improved using NoInd compared with BAS (log-rank P = .040), adjustment HR = 1.11 (95% CI, 1.04-1.19). Compared to NoInd, BAS was associated with higher risk of graft failure-related deaths, HR = 1.27 (95% CI, 1.02-1.58), and ATG was associated with higher risk of malignancy-related deaths, HR = 1.18 (95% CI, 1.01-1.39). Survival of patients who received NoInd was similar to ATG and better compared with BAS. Further, the use of ATG may be associated with increased malignancy-related mortality, compared with NoInd.     

Basiliximab treatment for steroid‐resistant rejection in pediatric patients following liver transplantation for acute liver failure

An IL‐2 receptor antagonist, basiliximab, decreases the frequency of ACR in liver transplant (LT) recipients as induction therapy. The aim of this study was to evaluate the effectiveness of basiliximab against SRR as rescue therapy in pediatric LT patients with ALF. Forty pediatric ALF patients underwent LT between November 2005 and July 2013. Among them, seven patients suffering from SRR were enrolled in this study. The median age at LT was 10 months (6–12 months). SRR was defined as the occurrence of refractory rejection after more than two courses of steroid pulse therapy. Basiliximab was administered to all patients. The withdrawal of steroids without deterioration of the liver function was achieved in six patients treated with basiliximab therapy without patient mortality, although one patient developed graft loss and required retransplantation for veno‐occlusive disease. The pathological examinations of liver biopsies in the patients suffering from SRR revealed severe centrilobular injuries, particularly fibrosis within one month after LT. We demonstrated the effectiveness and safety of rescue therapy consisting of basiliximab for SRR in pediatric LT recipients with ALF.     

Choice of induction regimens on the risk of cytomegalovirus infection in donor‐positive and recipient‐negative kidney transplant recipients

F.L. Luan, M. Samaniego, M. Kommareddi, J.M. Park, A.O. Ojo. Choice of induction regimens on the risk of cytomegalovirus infection in donor‐positive and recipient‐negative kidney transplant recipients.
Transpl Infect Dis 2010: 12: 473–479. All rights reserved Background. Late occurrence of cytomegalovirus (CMV) infection remains a concern in CMV‐seronegative kidney and/or pancreas transplant recipients of CMV‐seropositive organs (donor positive/recipient negative, D+/R?) despite the use of prophylaxis. We investigated the impact of various antibody induction regimens on CMV infection in this group of patients. Methods. A total of 254 consecutive D+/R? kidney and/or pancreas transplant patients were studied. The induction agents rabbit anti‐thymocyte globulin (rATG) or basiliximab were used according to the center practice. All patients received prophylaxis with valganciclovir (VGCV) for either 3 or 6 months. The occurrence of CMV infection was confirmed by positive DNA viremia. Multivariate Cox regression analyses were performed to determine risk factors for CMV infection. Results. The cumulative incidence of CMV infection was 58, 112, and 59 cases per 1000 patient‐years for patients who received no antibody induction, induction with rATG, or basiliximab induction, respectively (P=0.02). The use of rATG but not basiliximab was associated with an increased risk for CMV infection (adjusted hazard ratio [AHR] 2.13, 95% confidence interval [CI] 1.24–3.54, P=0.006). Acute rejection and its treatment with rATG were not associated with an increased risk for CMV infection when an additional course of VGCV was given following the treatment. Longer duration of prophylaxis was associated with a reduced risk for CMV infection (AHR 0.54, 95% CI 0.33–0.87, P=0.011). Conclusions. Induction with rATG is associated with increased risk of CMV infection. Longer duration of prophylaxis is beneficial.     

Treatment of a patient with myasthenia gravis using antibodies against CD25

Objectives –  To measure clinical and immunological parameters in a patient with myasthenia gravis (MG) treated with antibodies against CD25 (basiliximab, Simulect^®).
Patient and methods –  Injections of basiliximab were given repeatedly together with cyclosporin A and corticosteroids for 9 months to a patient with severe MG. Her muscle function score was monitored and the immunological parameters were followed using ELISA, flow cytometry and radioimmunoassay.
Results –  The patient improved moderately and corticosteroid treatment could be withdrawn. The percentage of activated CD4⁺ T cells decreased during treatment, while that of 'naïve' T cells increased. The serum levels of sCD28, sCD152, sCD80, sCD86 and IL-10 decreased. The treatment was stopped due to repeated infections.
Conclusion –  Treatment with basiliximab appears to be suitable only for severely ill patients who do not respond to conventional treatments. However, careful monitoring of side effects is necessary.     

One-year results of basiliximab induction and tacrolimus associated with sequential steroid and MMF treatment in pediatric kidney transplant recipient

We report the 1-year results with a triple immunosuppressive regimen in pediatric recipients of a first kidney transplant, in order to evaluate its safety and efficacy in the prevention of acute rejection and in the reduction of steroid side effects. The immunosuppression is as follows: (i) basiliximab (20 mg if body weight >30 kg; 10 mg if < 30 kg) is given pretransplant and at day 4; (ii) tacrolimus (Tac) is administered in order to obtain blood trough levels of 10-20 and 5-10 ng/ml during and after the first 2 months post-transplant, respectively; (iii) steroids are tapered during the first 6 months and then replaced by mycophenolate mofetil (depending on previous rejection episodes, infection status and the result of a routine biopsy) at a dosage of 4-600 mg/m(2) body surface area. Fifty-three children (median age 13 years, range 2-20) have entered this protocol. One-year patient and kidney survival are 100% and 94% respectively. During the first year a total of nine rejections in seven patients (13% of the cohort study) occurred, all but one responsive to steroids. Renal function was satisfactory throughout the first year (mean CrCl was 63.8 +/- 18 and 60.9 +/- 15.5 ml/min/1.73 m(2) at 6 and 12 months respectively). Subclinical signs of rejection were absent in more than 80% of biopsies (grade I Banff) at 6 months (n = 47); at the 12th month biopsy (n = 42) score I was stable in 20 patients (16 after stopping steroids) and had worsened in eight biopsies (six after stopping steroids). Major complications were insulin-dependent diabetes in three (5.6%) children with the need of insulin for a mean of 3 months; transient hyperglycemia (11 patients), treated with a dietary regimen, symptomatic viral infections (in 11 patients: two parvovirus B19, three cytomegalovirus and two Epstein-Barr virus systemic infections, three interstitial pneumonia, two BK nephritis). Tac doses more than 0.3-0.4 mg/kg/day are at significantly higher risk of viral infection. In conclusion, this immunosuppressive regimen is associated with a low percentage of clinical (13%) and subclinical rejections, but with a relatively high number of infections, prevented by a reduction in Tac doses (<0.3 mg/kg/day) during the first 2 months after transplantation. The assessment of steroid withdrawal needs a longer follow-up.     

Two-dose basiliximab compared with two-dose daclizumab in renal transplantation: a clinical study

BACKGROUND: Addition of the interleukin-2 receptor (IL-2R) antagonists basiliximab or daclizumab to a calcineurin inhibitor-based regimen significantly reduces risk of acute rejection with a tolerability profile similar to a placebo. Use of a truncated two-dose regimen of daclizumab has been reported, but till date, there has been no controlled study of two-dose daclizumab vs. two-dose basiliximab. METHODS: Deceased-donor renal transplant recipients were randomized to basiliximab (20 mg on days 0 and 4) or daclizumab (50 mg on days 1 and 14) with cyclosporine, mycophenolate mofetil and corticosteroids. Flow cytometry was used to calculate the proportion of CD25(+) T cells in peripheral blood. RESULTS: Thirty patients were randomized to basiliximab and 28 to daclizumab. There was one patient death in each group, with no other graft losses. By six months, the incidence of biopsy-proven acute rejection was 0% with basiliximab vs. 21.4% with daclizumab (p < 0.05). Three patients in the daclizumab group required OKT3 for steroid-resistant rejection. There were no between-group differences in the incidence of infection. The proportion of CD25(+) T cells declined markedly during the first two wk in both groups, but was significantly lower in the basiliximab group during weeks six to eight. CONCLUSION: Two doses of basiliximab are more effective than two 1 mg/kg doses of daclizumab in preventing acute rejection in de novo renal transplant patients receiving cyclosporine, mycophenolate mofetil and corticosteroid maintenance therapy. In patients receiving relatively low-level immunosuppression in order to minimize toxicity, basiliximab may be preferable to a truncated daclizumab regimen.