抗CD25单克隆抗体治疗耐激素的急性移植物抗宿主病疗效分析

本研究探讨抗CD25单克隆抗体在单倍体相合骨髓移植术（hiBMT）后耐激素的急性移植物抗宿主病（aGVHD）治疗中的作用。对15例单倍体相合BMT后出现耐激素的Ⅱ-Ⅳ度aGVHD的患者给予巴利昔单克隆抗体20mg，第1、4天静脉点滴，未达到疗效的病人间隔1周后重复本治疗。结果显示：完全有效8例（53．33％），其中4例无病生存，2例生存伴局限性cGVHD，2例死于肺部感染；3例部分有效（20％），其中1例无病生存，1例死于aGVHD及感染，1例死于肺部感染；4例无效（26．67％）死亡，死亡原因有GVHD、肺部感染、心力衰竭。总有效率73．33％，总生存率46．67％。该药应用安全，未发现输注相关的毒副作用。结论：抗CD25单克隆抗体对单倍体相合BMT后耐激素的Ⅱ-Ⅳ度aGVHD具有较好的疗效，但总的生存率仍然较低，感染仍然是导致该类患者死亡的主要原因，因此加强环境保护，预防感染极为重要。     

The long-term survival of simultaneous pancreas and kidney transplant with basiliximab induction therapy

Interleukin-2 receptor (IL2R) antibody has emerged as an attractive induction therapy for organ transplant. However, the long-term outcome of basiliximab induction in simultaneous pancreas and kidney (SPK) transplant remains speculative. We retrospectively analyzed the long-term survivals of 91 consecutive SPK recipients with basiliximab as induction, combination of steroid, tacrolimus (TAC) and mycophenolate acid (MFA)--either mycophenolate mofetil (MMF) or sodium mycophenolate (myfortic) as maintenance. At one, three, five, and seven-yr, the actual patient survival rate were 91.2%, 90.3%, 88.1%, and 88.2%, respectively; kidney graft survivals were 90.1%, 84.7%, 78.6%, and 70.6%, respectively; and pancreas graft survivals were 86.8%, 80.6%, 71.4%, and 58.8% respectively. There was a low incidence of rejection and CMV infection. Basiliximab induction with TAC, MFA, and steroid maintenance therapy can provide excellent long-term outcome for SPK recipients.     

Use of IL-2 receptor antagonists to reduce delayed graft function following renal transplantation: a review

Delayed graft function (DGF) occurs in approximately 30% of renal transplant patients, and significantly increases risk of long-term graft loss. This article reviews the potential for use of interleukin-2 receptor (IL-2R) antagonists to reduce the burden of DGF. IL-2R antagonists decrease incidence of acute rejection without increasing risk of cytomegalovirus infection or malignancy, and show equivalent efficacy to lymphocyte-depleting antibody agents in standard risk patients with immediate graft function. The nephrotoxicity associated with calcineurin inhibitors (CNIs) has led to use of delayed or low-dose CNI regimens with induction therapy in patients with DGF. In this setting, use of an IL-2R antagonist with mycophenolate mofetil and steroids with delayed cyclosporine appears to be associated with a low incidence of biopsy-proven rejection and comparable renal function to patients with immediate function. Additionally, there is intriguing evidence to suggests that IL-2R antagonists may reduce risk of DGF occurring. A number of large-scale and smaller studies have reported a trend to reduced incidence of DGF or improved early renal function using IL-2R antagonists compared with placebo, although data are not entirely consistent. In conclusion, the ability of IL-2R antagonists to reduce acute rejection with no additional safety concerns makes them an attractive option for patients with DGF.     

Basiliximab in association with tacrolimus and steroids in caucasian cadaveric renal transplanted patients: significant decrease in early acute rejection rate and hospitalization time

Safety and tolerability of basiliximab in renal transplantation have been proven in different immunosuppressive regimens. Few informations are available about the association of basiliximab with tacrolimus and steroids. We present a retrospective analysis performed in Caucasian cadaveric renal transplant recipients, comparing a basiliximab, tacrolimus and steroids induction protocol (GrA: 51 patients) with a tacrolimus and steroids protocol (GrB: 46 patients). A significant decrease in acute rejection rate in the first 3 months (2.0% vs. 17.4%; p < 0.01) was noted. Interestingly, the recipients in GrA were at major immunologic risk for the younger age of recipients, the greater number of mismatches and the higher rate of second transplants. The hospitalization times resulted reduced of 5.3 d in GrA vs. GrB (20.8 d vs. 26.1 d; p < 0.05). The adverse events patterns and profiles were similar in the two treatments groups. One patient in each group had a post-transplant lymphoprolipherative disorder. No significant difference was found in patient and graft survival. According to the results of this study, in a Caucasian adult population, basiliximab in association with tacrolimus and steroids is a safe and efficacious tool for acute rejection prevention and it is cost saving by reducing the hospitalization times.     

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.     

Induction therapy with rabbit antithymocyte globulin versus basiliximab after kidney transplantation: a health economic analysis from a German perspective

A health economic analysis was undertaken based on the 1‐year database from a randomized study of rabbit anti‐human thymocyte immunoglobulin (rATG) versus basiliximab, in kidney transplantation using resource utilization data and cost estimates from three German hospitals. A three‐state Markov model was applied to estimate cost‐effectiveness to 10 years post‐transplant. Total mean treatment cost per patient to year 1 post‐transplant was €62 075 vs. €59 767 for rATG versus basiliximab (P < 0.01). rATG therapy was associated with similar treatment costs to basiliximab by year 2, and a predicted cumulative treatment cost saving of €4 259 under rATG versus basiliximab by year 10 post‐transplant. The mean number of quality‐adjusted life years (QALYs) per patient by year 1 was 0.809 vs. 0.802 in the rATG and basiliximab cohorts, respectively (P = 0.38), with cumulative QALYs of 6.161 and 6.065 per patient by year 10. By year 2, the cumulative cost per QALY was slightly lower under rATG (€35 378) than basiliximab (€35 885), progressing to a saving of €1 041 under rATG for the cumulative cost per QALY by year 10. In conclusion, this model indicates that rATG induction provides a modest increase in QALYs with lower long‐term costs than basiliximab in deceased‐donor high‐risk kidney transplant patients.     

Low‐dose basiliximab induction therapy in heart transplantation

We prospectively studied efficacy and safety outcomes of two 10‐mg doses of intravenous basiliximab on day 0 and day 4 for induction therapy in 17 consecutive de novo heart transplant recipients. By the 2‐week assessment post‐transplant, there were no deaths, graft failures, or acute cellular rejections (ACRs) ISHLT grade ≥ 2R. By the 1‐year assessment post‐transplant, there were 1 (6%) infectious death, no graft failures, 2 (12%) grade 2R ACRs, 6 (35%) asymptomatic cytomegalovirus (CMV) infections, and 4 (25%) treated infections. Our study was the first to show that low‐dose basiliximab induction in heart transplant resulted in favorable efficacy and safety outcomes. Additionally, calcineurin inhibitor (CNI) initiation in a low‐risk population could be safely delayed using the strategy of modified low‐dose postoperative basiliximab. This strategy also appears to allow subsequent early corticosteroid wean, although with the concomitant maintenance of higher CNI levels and higher dosing of mycophenolate.     

The Impact of Alemtuzumab and Basiliximab Induction on Patient Survival and Time to Bronchiolitis Obliterans Syndrome in Double Lung Transplantation Recipients

We examined the effect of alemtuzumab and basiliximab induction therapy on patient survival and freedom from bronchiolitis obliterans syndrome (BOS) in double lung transplantation. The United Network for Organ Sharing database was reviewed for adult double lung transplant recipients from 2006 to 2013. The primary outcome was risk‐adjusted all‐cause mortality. Secondary outcomes included time to BOS. There were 6117 patients were identified, of whom 738 received alemtuzumab, 2804 received basiliximab, and 2575 received no induction. Alemtuzumab recipients had higher lung allocation scores compared with basiliximab and no‐induction recipients (41.4 versus 37.9 versus 40.7, p < 0.001) and were more likely to require mechanical ventilation before to transplantation (21.7% versus 6.5% versus 6.2%, p < 0.001). Median survival was longer for alemtuzumab and basiliximab recipients compared with patients who received no induction (2321 versus 2352 versus 1967 days, p = 0.001). Alemtuzumab (hazard ratio 0.80, 95% confidence interval 0.67–0.95, p = 0.009) and basiliximab induction (0.88, 0.80–0.98, p = 0.015) were independently associated with survival on multivariate analysis. At 5 years, alemtuzumab recipients had a lower incidence of BOS (22.7% versus 55.4 versus 55.9%), and its use was independently associated with lower risk of developing BOS on multivariate analysis. While both induction therapies were associated with improved survival, patients who received alemtuzumab had greater median freedom from BOS.     

Tacrolimus-induced cholestatic syndrome following pediatric liver transplantation and steroid-resistant graft rejection

Several factors may contribute to post-transplant cholestatic complications after liver transplantation. These include ischemic reperfusion injury, hypoperfusion, bile duct strictures, and hepatotoxic drugs. Up to now, there have been no publications on tacrolimus cholestatic toxicity in clinical transplantation when the drug was used in therapeutic doses. We describe six pediatric liver graft recipients in whom cholestatic complications developed under a tacrolimus-based immunosuppression following liver transplantation and all of them suffered from previous steroid-resistant graft rejection. The overall incidence of cholestatic syndrome was 5.4% in children receiving tacrolimus. The immunosuppression was switched back to cyclosporine and prednisolone in all six patients resulting in completely resolved clinical signs and laboratory findings. We conclude from our observations that a cholestatic syndrome following pediatric liver transplantation may be caused by tacrolimus therapy following steroid-resistant graft rejection, even if given in therapeutic doses.