两种生物免疫诱导方案对肾移植受者的影响

目的评估肾移植受者中应用两种不同生物制剂进行免疫诱导治疗的疗效和安全性。方法回顾性分析2008年6月至2013年4月,在解放军第452医院泌尿外科暨成都军区泌尿外科中心应用生物制剂进行免疫诱导治疗的78例尸体肾移植受者的临床资料。根据应用免疫诱导方案不同分为两组,单克隆抗体组(A组,35例,接受巴利昔单抗治疗)和多克隆抗体组[B组,43例,接受抗胸腺细胞球蛋白(ATG)治疗]。另以同期在该院未接受免疫诱导治疗的肾移植受者作为对照组(C组,32例)。分析3组受者术后12周内的人、肾存活情况。监测3组受者术后7、14、30、60 d血清肌酐(Scr)水平变化。比较3组受者急性排斥反应、移植肾功能延迟恢复、感染等并发症的发生率。结果术后12周,3组受体人、肾存活率分别为A组100%和100%,B组97.7%和97.7%,C组100%和96.9%,各组间比较差异无统计学意义(均为P0.05)。术后7、14 d,与C组比较,A组和B组的Scr水平明显下降,差异均有统计学意义(均为P0.05)。与C组比较,A、B两组受者急性排斥反应发生率均降低,差异有统计学意义(均为P0.05);3组受者移植肾功能延迟恢复发生率比较,差异无统计学意义(均为P0.05)。B组受者术后感染发生率高于A组和C组,差异均有统计学意义(均为P0.05)。结论免疫诱导治疗在肾移植受者中应用安全有效。     

Impact of immunosuppressant therapy on early recurrence of hepatocellular carcinoma after liver transplantation

Background/Aims

The 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.

Methods

Ninety-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).

Results

The 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<0.05). High AFP and PIVKA-II levels, and positive ¹⁸fluoro-2-deoxy-d-glucose positron-emission tomography findings were significantly associated with 3-year recurrence (P<0.05).

Conclusions

Induction therapy with basiliximab, a strong immunosuppressant, may have a negative impact with respect to early HCC recurrence (i.e., within 1 year) in high-risk patients.     

Basiliximab induction improves the outcome of renal transplants in children and adolescents

Thirty-two children and adolescents received their renal transplant at the Montefiore Medical Center, in New York, between October 1996 and May 2000. Twenty-four patients received basiliximab, in addition to tacrolimus and steroids (basiliximab group). The remaining eight patients received only tacrolimus and steroids (non-basiliximab group). The 1-year patient survival rate was 100% in both groups. The 1-year graft survival rate was 87.5% for the basiliximab group and 75% for the non-basiliximab group (P=0.45). The rates of acute rejection in the basiliximab and non-basiliximab groups were 26% and 43%, respectively (P=0.36). However, in recipients with ≤3 HLA mismatches, the rate of acute rejection was zero in the basiliximab group, and 40% in the non-basiliximab group (P=0.04). The beneficial effect occurred despite the fact that tacrolimus was maintained at below the target levels. There were no adverse events directly attributable to the administration of basiliximab. There were no cases of opportunistic infections or post-transplant lymphoproliferative disease. In summary, addition of basiliximab to tacrolimus and prednisone significantly decreased the rate of acute rejection in well-matched patients. Moreover, this effect was manifest at lower, and therefore less toxic, tacrolimus levels. Received: 19 December 2000 / Revised: 23 April 2001 / Accepted: 24 April 2001     

Myeloablative haploidentical hematopoietic stem cell transplantation using basiliximab for graft-versus-host disease prophylaxis

Abstract

Objectives

We retrospectively compared the prophylactic effect of basiliximab and antithymocyte globulin (ATG) after haploidentical hematopoietic stem cell transplantation (HSCT) in patients with leukemia.

Methods

Haploidentical HSCT using basiliximab for graft-versus-host disease (GVHD) prophylaxis in 10 patients with leukemia was retrospectively compared to ATG for GVHD prophylaxis in 24 patients.

Results

All the patients achieved neutrophil engraftment. One patient in the ATG group did not achieve platelet engraftment. The incidence of grade II–IV and grade III–IV acute GVHD was 30 and 20%, respectively, in the basiliximab group and 16.7 and 4.2%, respectively, in the ATG group (P > 0.05). Extensive cGVHD developed in 40 and 22.2% of patients in the basiliximab group and ATG group, respectively (P > 0.05). Basiliximab resulted in mild infection and a low incidence (10%) of infection-related mortality; ATG resulted in relative severe infection with 29.2% infection-related mortality (P > 0.05). During the follow-up period, 20% of the basiliximab group and 22.7% of the ATG group relapsed (P > 0.05). In the basiliximab group and the ATG group, the 3-year accumulative overall survival rate was, respectively, 80 and 52.5% and the 3-year leukemia-free survival, respectively, was 60 and 49.6% (P > 0.05).

Discussion

The incidences of grade II–IV and grade III–IV aGVHD in the basiliximab group were similar to those in halpoidentical HSCT containing ATG. Compared to the ATG group, the basiliximab group had a lower rate of transplantation-related mortality and better long-term survival, but without statistical significance.

Conclusion

The prophylactic regimen of basiliximab with haploidentical HSCT against GVHD seems safe and promising. More studies needed to verify this.     

The Effect of Costimulatory and Interleukin 2 Receptor Blockade on Regulatory T Cells in Renal Transplantation

Regulatory T cells (Treg) are critical regulators of immune tolerance. Both IL‐2 and CD28‐CD80/CD86 signaling are critical for CD4⁺CD25⁺FOXP3⁺ Treg survival in mice. Yet, both belatacept (a second‐generation CTLA‐4Ig) and basiliximab (an anti‐CD25 monoclonal antibody) are among the arsenal of current immunotherapies being used in kidney transplant patients. In this study, we explored the direct effect of basiliximab and belatacept on the Tregs in peripheral blood both in the short term and long term and in kidney biopsies of patients with acute rejection. We report that the combined belatacept/basiliximab therapy has no long‐term effect on circulating Tregs when compared to a calcineurin inhibitor (CNI)‐treated group. Moreover, belatacept‐treated patients had a significantly greater number of FOXP3⁺ T cells in graft biopsies during acute rejection as compared to CNI‐treated patients. Finally, it appears that the basiliximab caused a transient loss of both FOXP3⁺ and FOXP3^? CD25⁺ T cells in the circulation in both treatment groups raising important questions about the use of this therapy in tolerance promoting therapeutic protocols.     

巴利昔单抗作为免疫诱导剂预防国人心脏移植术后早期急性排斥反应的疗效和安全性的观察

目的观察国人心脏移植用巴利昔单抗作为免疫诱导剂与传统的三联免疫抑制剂合用的耐受性和预防术后早期急性排斥反应的效果。方法心脏移植患者47例,男38例,女9例,平均年龄(44.9±13.4)岁,包括扩张型心肌病20例(42.5%),缺血性心肌病12例(25.5%),致右室心律失常性心肌病8例(17.0%),肥厚型心肌病2例(4.2%),心脏肿瘤2例(4.2%),瓣膜性心肌病1例(2.1%),高血压心脏病1例(2.1%),巨细胞性心肌炎1例(2.1%)。术前淋巴细胞群体反应抗体(PRA)>10%者4例,交叉配型均<5%。用巴利昔单抗诱导治疗20mg×2次。三联免疫抑制剂用法:术中给予甲基强的松龙500mg×2次,术后125mg每8h1次;拔除气管插管后给予强的松1mg.kg-1.d-1,以后每3天减量10mg,至总量10mg/d维持。环孢素A(CsA)于术后血肌酐<150μmol/L开始服用,剂量3～6mg.kg-1.d-1,分2次服用,血药谷值浓度维持在180～300ng/ml。术后3周作1次心内膜活检。霉酚酸酯(MMF)1.0～2.0mg/d,分2次服用。急性排斥反应分级按照国际心肺移植协会(ISHLT)的标准。巨细胞病毒感染的监测用PP65抗原血症试验,EB病毒感染用ELISA方法查抗体。结果47例患者全部存活。急性排斥反应分级结果:0级30(63.8%)人,ⅠA级11(23.4%)人,ⅠB级3(6.3%)人,Ⅱ级3(6.3%)人。MMF平均剂量(1.2±0.3)g/d。CsA于术后平均(3.4±2.1)d开始服用,平均累积剂量(4.1±1.2)mg.kg-1.d-1,平均谷值浓度(237.0±76.2)ng/ml。术后1个月内感染5人,但无巨细胞病毒和EB病毒感染。结论国人心脏移植用巴利昔单抗作为免疫诱导剂与传统的三联免疫抑制剂合用的耐受性良好,预防术后早期急性排斥反应有效。     

巴利昔单抗预防肾移植术后急性排斥反应的临床分析

目的:探讨巴利昔单抗(舒莱)诱导治疗联合其他免疫抑制剂在预防肾移植术后急性排斥反应的临床疗效.方法:回顾分析我院2007年6月到2009年9月%例肾移植患者的临床资料,其中54例患者接受舒莱诱导治疗联合三联免疫抑制剂吗替麦考酚(骁悉,MMF)+他克莫司(普乐可复,FK506 )或环孢素A(CsA)+皮质激素治疗(诱导组...     

A single center's clinical experience with quadruple immunosuppression including ATG or IL2 antibodies and mycophenolate mofetil in simultaneous pancreas–kidney transplants

Acute rejection remains a major problem in simultaneous pancreas–kidney (SPK) transplant and occurs in 60–100% of the cases.
With the introduction of mycophenolate mofetil (MMF) replacing azathioprine (AZA) as a basis immunosuppressant, reduced rates of rejection have been reported. This study investigates the frequency and clinical relevance of allograft rejection in SPK patients receiving anti‐thymocyte globulin (ATG) or Basiliximab® induction therapy and cyclosporine Neoral® (CyA), MMF, steroid basis immunosuppression.
Between December 1996 and October 1999, 21 consecutive patients (15 males, 6 females) received a SPK transplant at our institution with a mean±standard deviation (SD) age of 42±6 yr. Of these, 14 patients were treated with anti‐thymocyte globulin (ATG) Fresenius® (rabbit) 3–5 mg/kg for 6±2 d, cyclosporine Neoral (CyA) (trough levels 350–400 ng/mL), MMF 3 g/d and low dose steroid therapy. Seven SPK patients were treated with Basiliximab (Simulect®, Novartis 20 mg on d 0 and d 4 post‐transplant) instead of ATG. The patients had an average human leucocyte antigen (HLA) mismatch of 3.9/6 and a negative cross match. All patients remained on triple drug therapy. Three patients were switched to tacrolimus instead of Neoral for CyA intolerance. The mean±SD cold ischemia time (CIT) of the organs was 10.1±2.4 h for the pancreas and 10.5±2.6 h for the kidney.
Results: Biopsy‐proven rejection occurred in the kidney of 1 ATG patient (8%), which responded to steroid bolus therapy. One of the patients (14%) with Basiliximab induction developed renal allograft rejection, which was resolved after a 6‐d course of anti‐CD3 mAb (OKT3) treatment. All patients (100%) were free from rejection in the pancreas, as measured by urine amylase levels and glycemic control without the need for exogenous insulin with a mean glycosylated hemoglobin (HBA₁C) of 5.1±0.7% and serum creatinine with a mean of 1.24±0.24 mg/dL in a mean follow‐up period of 17±15 months (median 12, range 2–37).
Conclusion: Triple drug immunosuppression including cyclosporine, MMF and low dose steroids with ATG or interleukin 2 (IL2) receptor antibodies induction therapy appears to be a very suitable immunosuppressive regimen for combined pancreas–kidney transplant (PKT) with a marked reduction in the incidence of rejection.     

肾移植中2剂舒莱和2剂赛尼哌对外周血可溶性白细胞介素-2受体水平的影响及意义

目的:探讨2剂舒莱和2剂赛尼哌在尸体肾移植中对外周血可溶性白细胞介素2受体(sIL2R)水平的影响及意义。方法:105例首次接受尸体肾移植的受者随机分为舒莱组、赛尼哌组和对照组,所有受者术后均接受普乐可复或环孢素A加骁悉加泼尼松三联疗法。另外舒莱组在术前2h、术后4天静脉滴注20mg舒莱,赛尼哌组在前24h、术后7天静脉滴注50mg赛尼哌。检测各组术前及术后每周共8周外周血中sIL2R水平变化,记录2个月内急性排斥(AR)的例数。结果:舒莱和赛尼哌组外周血中sIL2R水平分别在术后8周和3周内比对照组低(P<0.05)。术后第4～6周舒莱组比赛尼哌组低(P<0.05)。在术后2个月内,舒莱组、赛尼哌组和对照组发生急性排斥反应的例次分别为1、9、17例,各组比较差异有统计学意义(P<0.05)。结论:2剂舒莱对外周血中sIL2R的抑制及抗急性排斥反应效果比2剂赛尼哌好。     

标准双剂与单剂巴利昔单抗用于肾移植的对比研究

目的比较标准双剂巴利昔单抗与单剂巴利昔单抗在肾移植中的作用及安全性。方法研究对象为2008年1月至2011年5月在武汉大学人民医院泌尿外科接受同种异体尸体肾移植的121例患者。按接受巴利昔单抗的方式分为两组。标准双剂巴利昔单抗组(双剂组),53例,按产品说明书分别于术前和术后第4日静脉注射巴利昔单抗20 mg;单剂巴利昔单抗组(单剂组),68例,术前应用巴利昔单抗20 mg。监测两组患者围手术期免疫功能的变化。比较两组患者不良反应发生情况[移植物功能延迟恢复(DGF)、急性排斥反应、肺部感染]和人、肾存活情况。结果两组患者术前体液免疫和细胞免疫功能比较,差异无统计学意义。与术前相比,术后第5日两组患者的细胞免疫和体液免疫功能受到不同程度的抑制(均为P0.05),同时与单剂组相比,双剂组的细胞免疫功能和体液免疫功能均明显受抑制(均为P0.05);与术后第5日相比,术后第15日两组患者的细胞免疫和体液免疫功能均不同程度恢复,但仍较术前明显降低(CD3、CD4、Ig M、Ig A),部分指标显示持续抑制水平,较术后第5日仍持续下降(CD8、Ig G)。双剂组和单剂组患者的DGF发生率分别为8%、7%,随访1年内排斥反应发生率分别为13%、12%,肺部感染发生率分别为9%、10%,两组比较差异均无统计学意义(均为P0.05)。双剂组和单剂组患者的1年人存活率分别为94%、98%,移植肾存活率分别为93%、96%,两组比较差异均无统计学意义(均为P0.05)。结论肾移植中应用单剂或双剂巴利昔单抗同样有效,不增加不良反应发生率,1年人、肾存活率相当。围手术期检测免疫功能可以有效指导个体化免疫诱导治疗。