巴利昔单抗对肾移植受者白细胞介素2和可溶性白介素2受体的影响

目的:分析巴利昔单抗和抗CD3单克隆抗体(OKT3)对肾移植受者白细胞介素2(IL2)和可溶性白细胞介素2受体(sIL2R)的影响,评价其治疗的有效性及安全性。方法:将74例肾移植受者随机分为巴利昔单抗组(n=39)和OKT3组(n=35)。所有病人均采用环孢素+霉酚酸酯+泼尼松三联免疫抑制维持治疗。巴利昔单抗组:分别于术前2h和术后d4使用巴利昔单抗20mg,静脉滴注;OKT3组:从术后d1开始,给OKT35mg静脉滴注,qd,共7～10d。检测术后2mo内IL2和sIL2R浓度,观察急性排斥反应(AR)、肌酐恢复时间、不良反应、受者和移植肾存活情况。结果:巴利昔单抗组IL2和sIL2R浓度明显低于OKT3组(P<0.05)。有12例病人发生AR,巴利昔单抗组3例,OKT3组9例(P<0.05)。巴利昔单抗组肌酐恢复时间(4.7±s2.1)d,明显短于OKT3组(9±5)d(P<0.05)。巴利昔单抗组感染7例,细胞因子释放综合征0例,过敏反应0例,明显低于OKT3组(P<0.05)。结论:巴利昔单抗明显降低IL2和sIL2R浓度和AR发生率,不良反应少,是一种强效安全的免疫抑制剂。     

撤除激素的肾移植免疫抑制方案研究

目的观察在应用巴利昔单抗的基础上,早期撤除激素的免疫抑制剂方案临床效果。方法21例肾移植患者在应用巴利昔单抗的同时联合他克莫司(FK506)和霉酚酸酯(MMF),早期撤除激素,随访观察急性排斥发生情况,以及对血糖血脂代谢的影响等。结果巴利昔单抗联合FK506和MMF,早期撤除激素,使急性排斥发生率明显降低同时,也降低高血糖、高血脂等代谢紊乱发生率。结论应用巴利昔单抗同时联合强有力的免疫抑制剂FK506和MMF,调整药物FK506浓度于治疗窗范围,早期撤除激素,是安全有效的方案。     

霉酚酸酯在肾移植术后的临床应用

目的:建立霉酚酸酯(MMF)与环孢素A(CsA)及皮质激素(Pred)合用时CsA的治疗窗,分析霉酚酸酯在肾移植术后的临床疗效.方法:对临床164份病例资料进行回顾性分析.结呆:MMF方案CsA的治疗窗为:1mo内为150～300ng/ml,1～3mo 120～260ng/ml,3～6mo 110～225ng/ml;MMF方案中毒反应、排异反应发生均低于经典三联方案(CsA 硫唑嘌呤Aza Pred).结论:MMF方案优于经典三联方案,可安全、有效地预防肾移植术后急慢性排斥及中毒反应的发生率.     

硫唑嘌呤与霉酚酸酯在预防肾移植急性排斥反应的疗效对比

目的对比观察肾移植患者服用硫唑嘌呤与霉酚酸酯的临床疗效。方法32例肾移植患者随机分成硫唑嘌呤组和霉酚酸酯组,两组基本条件相同。对患者肾移植术后移植肾功能恢复时间、感染及急性排斥反应发生率等项目进行临床观察。结果硫唑嘌呤组和霉酚酸酯组分别有9例和8例患者于术后第四天Scr完全恢复正常,硫唑嘌呤组患者1例出现肾小管坏死,术后1个月肾功能恢复正常。两组均有1例发生急性排斥反应,霉酚酸酯组1例急性排斥患者,Scr水平停留在189μmol.L-1水平。同一患者不同时间段服用硫唑嘌呤及霉酚酸酯后Tmax、C2、CO及AUC各数据比较无显著性差异。两组患者服用环孢素后毒副作用相当。结论硫唑嘌呤和霉酚酸酯联合环孢素使用方案在临床应用过程中,对肾移植的预后无显著性差异。     

免疫抑制剂Belatacept获准用于预防肾移植排斥反应

百时美施贵宝(Bristol-Myers Squibb)公司开发的选择性免疫抑制剂belatacept(商品名为Nulojix)于2011年6月15日获美国FDA批准用于预防成年肾移植病人的急性排斥反应。此外,本品也获准与其他免疫抑制剂如巴利昔单抗、吗替麦考酚酯和皮质类固醇联用。     

巴利昔单抗联合鼠抗人CD3单克隆抗体在高致敏受者肾移植中的临床应用

目的:探讨巴利昔单抗与鼠抗人CD3单克隆抗体(OKT3)联合诱导在高致敏受者肾移植临床应用中的有效性及安全性。方法:术前2个月内群体反应性抗体(PRA)检测值均>50%的尸体供肾肾移植受者20例,其中9例受者接受巴利昔单抗联合OKT3免疫诱导(联合诱导组),11例受者接受OKT3常规免疫诱导(OKT3诱导组),均以他克莫司(Tac)+吗替麦考酚酯(MMF)+泼尼松(Pred)为基础免疫抑制方案,评估术后移植肾功能恢复情况、3个月内急性排斥反应发生率、1年内肺部感染发生率、1年人/肾存活率及移植肾功能。结果:联合诱导组、OKT3诱导组肾移植术后3个月内急性排斥反应发生率及术后1年内肺部感染发生率分别为11.1%vs.36.4%(P=0.319),11.1%vs.63.6%(P=0.028);联合诱导组患者术后1周内移植肾功能恢复正常比例明显高于OKT3诱导组(88.9%vs.27.3%,P=0.010);联合诱导组术后1年人/肾存活率均为100%,与OKT3诱导组(分别为90.9%、81.8%)比较,差异不显著(P=1.00和P=0.100);术后1年联合诱导组、OKT3诱导组血肌酐值分别为(105±24)、(97±22)μmol·L-1(P=0.437)。结论:巴利昔单抗联合OKT3进行免疫诱导,在预防高致敏受者术后早期排斥反应的同时,缩短了移植肾功能的恢复时间,是一种安全、有效的防治策略。     

抗CD25单克隆抗体治疗非血缘脐血移植后激素耐药的急性GVHD的疗效分析

目的观察抗CD25单克隆抗体（巴利昔单抗）治疗非血缘脐带血造血干细胞移植（UCBT）后糖皮质激素耐药的急性移植物抗宿主病（aGVHD）的疗效。方法 2010年8月—2013年3月21例恶性血液病患者在安徽省立医院接受UCBT后发生中重度急性GVHD（其中Ⅱ度4例、Ⅲ度6例、Ⅳ度11例）,男11例,女10例,中位年龄12（3-33）岁,其中急性淋巴细胞白血病11例,急性髓细胞白血病10例。全部患者均接受环孢素（3 mg·kg^-1·d^-1,静脉滴注）和霉酚酸脂（30 mg·kg^-1·d^-1）并甲基强的松龙1-2 mg·kg^-1·d^-1无效后,加用巴利昔单抗每次20 mg,每周2次静脉点滴,连用3-4次,观察急性GVHD控制情况。结果 21例患者中完全缓解10例,部分缓解为7例,无效4例,总有效率81%。有效患者使用巴利昔单抗后平均起效的时间为6 d,巴利昔单抗开始使用时间和症状缓解开始时间存在相关性。结论抗CD25单抗对UCBT后发生的激素耐药的急性GVHD具有显著的疗效,无明显毒副作用,且应用时间越早,急性GVHD症状缓解越早。     

霉酚酸酯治疗过敏性紫癜肾炎疗效和安全性的系统评价

目的：探讨霉酚酸酯治疗过敏性紫癜肾炎的疗效,系统评价治疗过程中及恢复后的安全性。方法：我院随机调查56例过敏性紫癜肾炎患者,随机分为两组,试验组和对照组,试验组28例,对照组28例。试验组采用激素治疗搭配霉酚酸酯治疗;对照组采用激素治疗搭配环孢素A、硫唑嘌呤治疗或者单纯的激素治疗。结果：与单纯激素治疗相比霉酚酸酯的治疗效果较好,与激素治疗搭配环孢素A相比,6个月时霉酚酸酯治疗过敏性紫癜肾炎的疗效无明显差异,但在治疗12个月时霉酚酸酯的治疗效果明显优于激素治疗搭配环孢素A。与硫唑嘌呤相比,霉酚酸酯治疗效果更有优势。在不良反应方面,霉酚酸酯的不良反应发生率低于硫唑嘌呤,但与激素治疗搭配环孢素A相比差异无统计学意义。结论：现有数据表明,霉酚酸酯治疗过敏性紫癜肾炎的疗效优于硫唑嘌呤,霉酚酸酯较激素治疗搭配环孢素A和硫唑嘌呤治疗不良反应发生率低。     

达利珠单抗在预防同种肾移植急性排斥反应中的临床应用(英文)

目的 :探讨达利珠单抗在预防同种肾异体移植术后急性排斥反应的作用。方法 :回顾分析了已随访 1a的 2 8例 (男性 2 4例 ,女性 4例 ,年龄 32a±s 5a)应用 2剂达利珠单抗的病人的临床效果 ,并以同期肾移植 80例 (男性 6 8例 ,女性 12例 ,年龄34a± 11a)作为对照组。所有病人均给予以麦考酚酸酯 (mycophenolatemofetil,MMF) ,环孢素 (ci closporin ,CsA) ,甲基强的松龙 (methylprednisolone ,MPD)和泼尼松 (prednisone ,Pred)为基础的免疫抑制方案 ;达利珠单抗在基础治疗方案上 ,分别于手术前 2 4h内和手术后d 14按照剂量为 1mg·kg- 1通过静脉注射给药。观察急性排斥反应发生率、药物不良反应、感染发生率、病人和移植物的 1a存活率。所有病人均随访 1a以上。结果 :达利珠单抗组在 3mo内急性排斥反应发生率 (4% )显著低于对照组 (2 5 % ) ,差异有显著意义 (P <0 .0 5 ) ;达利珠单抗具有良好的耐受性 ,无细胞因子释放综合征的发生 ;在感染及不良反应方面与对照组比较无显著性差异 ;2组比较病人 1a的存活率 (达利珠单抗组为 89% ,对照组为 96 % )和移植肾存活率 (达利珠单抗组 89% ,对照组 94 % )无显著性差异 (P >0 .0 5 )。结论 :2剂达利珠单抗加上MMF ,CsA ,MPD ,Pred联合应用的免疫抑制方案对预防同种异     

巴利昔单抗免疫诱导在肝移植术中的临床研究

目的探索巴利昔单抗免疫诱导治疗在预防肝移植术后急性排斥反应发生中的临床价值及可行性。方法选择2011年2月至2013年2月于我院就诊的肝移植术患者49例,随机将患者分为治疗组与对照组,对照组采用常规(FK506+GCS)二联免疫治疗法,治疗组(术前2 h和术后第4天应用巴利昔单抗免疫诱导),以后采用常规三联预防移植术后排斥反应,比较两组患者的临床疗效。结果治疗组与对照组相比,首次发生急性排斥反应的时间明显延长,P<0.05,差异具有统计学意义;治疗组患者的急性排斥反应的发生率明显低于对照组,P<0.05,差异具有统计学意义;治疗组患者与对照组患者的术后感染及不良反应的发生率差异不明显,P>0.5,无统计学意义;治疗组患者1年后死亡2例,对照组1年后患者死亡3例。结论巴利昔单抗免疫诱导治疗对于预防肝移植术后急性排斥反应发生具有积极意义。     

The use of mycophenolate mofetil in transplant recipients

With the development of new immunosuppressive agents, the focus of anti-rejection therapy has shifted from prevention of acute allograft rejection to an emphasis on sufficient immunosuppression with minimal toxicity. Mycophenolate mofetil (MMF) is a recently developed immunosuppressive drug, which acts to inhibit T and B cell proliferation by blocking the production of guanosine nucleotides required for DNA synthesis. It also prevents the glycosylation of adhesion molecules that are involved in attachment of lymphocytes to endothelium and potentially in leukocyte infiltration of an allograft during an immune response. High-quality randomized clinical trials have demonstrated that MMF, when used with cyclosporine (CsA) and steroids, reduces the frequency and severity of acute rejection episodes in kidney and heart transplants, improves patient and graft survival in heart allograft recipients and increases renal allograft survival at 3 years. It has also been effective in reversing acute and resistant rejection episodes in heart, kidney and liver recipients. The ability of MMF to facilitate sparing of other immunosuppressive agents, particularly in CsA-related nephrotoxicity, is also promising. By permitting reduction in CsA doses, MMF may stabilize or improve renal graft function in patients with CsA-related nephrotoxicity or chronic allograft nephropathy. Early results of phase I and II trials evaluating MMF therapy in liver and combined pancreas/kidney transplant recipients are encouraging. The main adverse effects associated with oral or intravenous MMF are gastrointestinal and hematologic in nature. Although the direct costs of using MMF vs. azathioprine (AZA) are higher, the decreased incidence and treatment of acute rejection in patients treated with MMF supports its use as a cost-effective option during the first year following transplantation.Thus, MMF has become an important therapeutic tool in the transplant clinician's armamentarium. Ongoing issues to be resolved in clinical trials include the role of MMF in the absence of other potent agents, e.g., as monotherapy or with a steroid but without calcineurin inhibitor; whether MMF will have an impact on chronic allograft dysfunction; and the cost-effectiveness of treatment following the first year of transplantation.     

Early steroid withdrawal protocol with basiliximab, cyclosporine and mycophenolate mofetil in renal-transplant recipients

OBJECTIVE: Adverse effects of steroids have led to efforts to minimize their use in recipients of organ transplants. This study evaluated an early steroid withdrawal protocol including basiliximab, cyclosporine (CsA) and mycophenolate mofetil (MMF) in renal-transplant recipients. METHODS: Between January 2001 and April 2005, our early steroid withdrawal protocol was used in 130 patients who underwent renal transplantation. Immunosuppression consisted of CsA (6-8 mg/kg), MMF (2 g/kg) and methylprednisolone (MP); basiliximab was given as induction therapy (steroid withdrawal group). MP was administered in a dose of 500 mg or 250 mg at renal transplantation; thereafter, the dose was rapidly tapered and MP was withdrawn on day 14 post-transplant. RESULTS: The incidence of acute rejection in the steroid withdrawal group was similar to that in the conventional steroid treatment group (without basiliximab) (18% vs. 21%). The severity of rejection episodes was similar in the two groups. Patient and graft survivals were 100% and 97% in the steroid withdrawal group. In 80 of the 130 patients (62%) in the steroid withdrawal group, MP was successfully withdrawn, with good allograft function during follow-up. In the other 50 patients (38%), MP was reinitiated because of acute rejection or other reasons. The success rate of steroid withdrawal 12 months after transplantation in recipients of ABO-compatible grafts was significantly higher than that in recipients of ABO-incompatible grafts (66% vs. 44%). The dose of MMF during the 12 months after renal transplantation was significantly lower in steroid reinitiated group than in the successful withdrawn group (p<0.05). Patients in the successful withdrawn group showed metabolic benefits such as lower cholesterol levels as compared with the steroid reinitiated group. CONCLUSION: Although further follow-up is necessary to confirm our results, our protocol successfully permitted the early withdrawal of steroids in 62% of renal-transplant recipients, with no resumption of steroid treatment during 3 years of follow-up.     

Mycophenolate mofetil (Cellcept)

Mycophenolate mofetil (MMF) is a new immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the purine synthesis pathway of lymphocytes. IMPDH is crucially important for the proliferative responses of human T- and B-lymphocytes. Therefore, inhibition of IMPDH leads to selective lymphocyte suppression. Following successful testing in different in vitro and animal models, MMF entered clinical trials, where it has been used in combination with cyclosporin and steroids. MMF has rapid and complete absorption following oral administration. Pilot studies suggested a significant reduction in the incidence of rejection at doses of 1 - 3 g/day. These data led to the initiation of 3 pivotal trials, in which MMF was compared against different standard immunosuppressive protocols. Nearly 1500 patients were enrolled in these 3 randomised, double-blind, multicentre studies of the addition of MMF to standard immunosuppressive protocols for the prevention of acute renal allograft rejection. After six months, the rate of biopsy-proven rejection was significantly reduced. The adverse event profile resembles that of triple therapy with azathioprine: primarily involving the gastrointestinal (GI) tract, the haematopoietic system and the occurrence of opportunistic infections. MMF affords improved immunosuppressive therapy following renal, and probably other solid organ, transplantation. It is licensed for the prevention of acute renal allograft rejection in most countries around the world.     

Mycophenolate mofetil (Cellcept)

Mycophenolate mofetil (MMF) is a new immunosuppressive drug designed to inhibit inosine monophosphate dehydrogenase (IMPDH). IMPDH is a key enzyme in the purine synthesis pathway of lymphocytes. IMPDH is crucially important for the proliferative responses of human T- and B-lymphocytes. Therefore, inhibition of IMPDH leads to selective lymphocyte suppression. Following successful testing in different in vitro and animal models, MMF entered clinical trials, where it has been used in combination with cyclosporin and steroids. MMF has rapid and complete absorption following oral administration. Pilot studies suggested a significant reduction in the incidence of rejection at doses of 1-3 g/day. These data led to the initiation of 3 pivotal trials, in which MMF was compared against different standard immunosuppressive protocols. Nearly 1500 patients were enrolled in these 3 randomised, double-blind, multicentre studies of the addition of MMF to standard immunosuppressive protocols for the prevention of acute renal allograft rejection. After six months, the rate of biopsy-proven rejection was significantly reduced. The adverse event profile resembles that of triple therapy with azathioprine: primarily involving the gastrointestinal (GI) tract, the haematopoietic system and the occurrence of opportunistic infections. MMF affords improved immunosuppressive therapy following renal, and probably other solid organ, transplantation. It is licensed for the prevention of acute renal allograft rejection in most countries around the world.     

肺移植受者应用巴利昔单抗诱导治疗的回顾性分析

目的:探讨肺移植受者应用巴利昔单抗诱导治疗的免疫抑制方案疗效。方法:回顾性分析101例肺移植患者,依照入选/排除标准筛选出有效病例73例。其中30例为诱导组,即分别在术中、术后给予两剂巴利昔单抗诱导治疗;另43例为对照组,即不接受诱导治疗。所有患者术后均采用他克莫司、吗替麦考酚酯和泼尼松三联免疫抑制方案预防排斥反应。2组患者均随访12个月,观察排斥反应、代谢并发症的发生以及患者的存活情况。结果:术后1年内,诱导组的急性排斥反应发生率为10%,对照组为33%,两组间差异有统计学意义(P<0.05)。诱导组并发症的发生率为63%,对照组为47%,两组间差异有统计学意义(P<0.05)。生存分析提示2组患者的半数生存期无统计学差异(P>0.05)。结论:以他克莫司为基础的免疫抑制方案中应用巴利昔单抗诱导治疗可以明显降低肺移植术后急性排斥反应发生率,但对肺移植患者的长期存活率没有显著性影响。     

Basiliximab: a review of its use as induction therapy in renal transplantation

Basiliximab (Simulect), a chimeric (human/murine) monoclonal antibody, is indicated for the prevention of acute organ rejection in adult and paediatric renal transplant recipients in combination with other immunosuppressive agents.Basiliximab significantly reduced acute rejection compared with placebo in renal transplant recipients receiving dual- (cyclosporin microemulsion and corticosteroids) or triple-immunotherapy (azathioprine- or mycophenolate mofetil-based); graft and patient survival rates at 12 months were similar. Significantly more basiliximab than placebo recipients were free from the combined endpoint of death, graft loss or acute rejection 3 years, but not 5 years, after transplantation.The incidence of adverse events was similar in basiliximab and placebo recipients, with no increase in the incidence of infection, including cytomegalovirus (CMV) infection. Malignancies or post-transplant lymphoproliferative disorders after treatment with basiliximab were rare, with a similar incidence to that seen with placebo at 12 months or 5 years post-transplantation. Rare cases of hypersensitivity reactions to basiliximab have been reported.The efficacy of basiliximab was similar to that of equine antithymocyte globulin (ATG) and daclizumab, and similar to or greater than that of muromonab CD3. Basiliximab was as effective as rabbit antithymocyte globulin (RATG) in patients at relatively low risk of acute rejection, but less effective in high-risk patients. Numerically or significantly fewer patients receiving basiliximab experienced adverse events considered to be related to the study drug than ATG or RATG recipients. The incidence of infection, including CMV infection, was similar with basiliximab and ATG or RATG.Basiliximab plus baseline immunosuppression resulted in no significant differences in acute rejection rates compared with baseline immunosuppression with or without ATG or antilymphocyte globulin in retrospective analyses conducted for small numbers of paediatric patients. Limited data from paediatric renal transplant recipients suggest a similar tolerability profile to that in adults. Basiliximab appears to allow the withdrawal of corticosteroids or the use of corticosteroid-free or calcineurin inhibitor-sparing regimens in renal transplant recipients.Basiliximab did not increase the overall costs of therapy in pharmacoeconomic studies.CONCLUSION: Basiliximab reduces acute rejection without increasing the incidence of adverse events, including infection and malignancy, in renal transplant recipients when combined with standard dual- or triple-immunotherapy. The overall incidence of death, graft loss or acute rejection was significantly reduced at 3 years; there was no significant difference for this endpoint 5 years after transplantation. Malignancy was not increased at 5 years. The overall efficacy, tolerability, ease of administration and cost effectiveness of basiliximab make it an attractive option for the prophylaxis of acute renal transplant rejection.     

麦考酚酸酯在肾移植中的应用

目的：观察麦考酚酸酯（ ｍｙｍcoｐｈｅｎｏｌａｔｅｍｏｆｅｔｉｌ,ＭＭＦ）预防移植肾急性排斥的安全性及有效性。方法：４０例肾移植病人分为２组,２０例［男性１２例,女性 ８例,年龄（４３ ± ｓ １０） ａ］为治疗组,给予ＭＭＦ1ｇ, ｐｏ, ｂｉｄ;另 ２０例［男性 １３例,女性 ７例,年龄（４５±１１） ａ］为对照组,给予硫唑嘌呤（Ａｚａ） １５０ｍｐ,ｐｏ, ｑｎ。共 ６ ｍｏ。结果： ＭＭＦ组急性排斥反应发生率为０,Ａｚａ组为２例,２组间差异无显著意义（Ｐ＞０．０５）。２组病人的消化道反应、肝中毒、感染等并发症的发生率的差异无显著意义（Ｐ＞０．０５）。结论：ＭＭＦ是一种能预防移植肾急性排斥反应的安全、有效的免疫抑制剂。