抗胸腺细胞球蛋白在肾移植中的应用

自1993年6月～1996年2月应用抗胸腺细胞球蛋白（ATG）预防或治疗各种排斥反应86例，结果7例超急性排斥反应者仍有4例再次发生超急性排斥反应，43例术中及术后加用ATG者仅有5例发生急性排斥反应，14例难治性急性排斥反应者有13例得以逆转，17例肾小管坏死者有16例安全度过急性肾小管坏死期，5例慢性排斥反应者肾功能明显好转。认为ATG能有效地预防急性排斥反应，可使绝大多数耐激素难治性急性排斥反应逆转，而且是急性肾小管坏死过渡期最理想的免疫抑制剂，但不能预防超急性排斥反应及慢性排斥反应。所有患者对ATG耐受良好，少数患者可出现一过性白细胞和血小板减少，短期内适量使用ATG不增加患者的感染机会。     

Antithymocyte globulin induction therapy improves survival in lung transplantation for cystic fibrosis

Cystic fibrosis (CF) is an inherited condition that leads to respiratory failure and is the third most common indication for adult bilateral lung transplantation (LuTX). In contrast to other lung diseases, the immune system of CF patients is up‐regulated and we therefore hypothesized that these patients would benefit from induction therapy. In the current study, we investigated the impact of antithymocyte globulin (ATG) induction therapy in CF patients after LuTX. One hundred and forty six patients who underwent LuTX for CF at our centre between January 1999 and December 2010 were included in the study and retrospectively analysed. They were divided into two groups according to the immunosuppressive protocol: group‐A (n = 103) with and group‐B (n = 43) without induction therapy on top of the basic calcineurin inhibitor based triple immunosuppression with mycophenolate mofetil and steroids. Perioperative survival was significantly better in the ATG group, a benefit sustained for the entire follow‐up. ATG induction resulted in a significantly lower incidence of acute rejections without an increase in infectious complications. Taken together, our results indicate that ATG induction therapy confers a significant survival benefit in CF patients undergoing LuTX and reduces rejection. We advocate the use of induction therapy in this patient cohort.     

Antilymphocyte globulin versus OKT3 induction therapy in cadaveric kidney transplantation: a prospective randomized study.

Different induction therapies have been used in renal transplantation to avoid cyclosporine (CsA) nephrotoxicity and early acute graft rejection. This study compares the efficacy of a short course of prophylactic OKT3 to that of antilymphocyte globulin (ALG) in preventing acute renal allograft rejection when administered concomitantly with CsA and steroids. Between March 1988 and December 1990, 140 first-cadaver renal transplant recipients were randomly allocated to two immunosuppression groups--ALG group (n = 68): ALG 15 mg/kg just before transplant surgery, ALG 12 mg/kg the first day after transplant, followed by four doses of 10 mg/kg on alternate days; and OKT3 group (n = 72): OKT3 5 mg just before transplant, followed by four doses of 5 mg/d. Both groups included low-dose CsA and steroids. The incidence of rejection during the first 3 months after transplantation was 15% in the ALG group and 19% in the OKT3 group (NS). Kaplan-Meier estimates of patients free of rejection at 2 years was 85% in the ALG group and 77% in the OKT3 group (NS). The 3-year actuarial graft survival was 82% and 85% (NS), and 3-year patient survival was 97% and 98% (NS), in the ALG and OKT3 groups, respectively. These results indicate that the concomitant association of CsA and ALG or OKT3 constitutes a safe and effective therapeutic strategy that provides a low incidence of rejection and gives good results for patient and graft survival.     

Antithymocyte globulin induction therapy in hepatitis c-positive liver transplant recipients

It is unclear whether antithymocyte globulin (ATG) induction therapy in hepatitis C-positive (HCVpositive) liver transplant recipients influences the risk of developing recurrent HCV disease. Multiple acute rejection episodes and high-dose steroids and/or OKT3 used to treat acute rejection increase the risk of graft loss from HCV. We studied the impact of ATG induction on graft and patient survival in HCVpositive liver transplants performed since 1990. Recipients who died or lost their grafts within 1 month of transplantation were excluded. Second, third, and fourth grafts were excluded, as were patients with stage III or IV hepatocellular carcinoma. There were 443 cadaveric liver transplants in adult recipients, of whom 142 (32%) were HCV positive. The incidence of biopsy-proven acute rejection was less in patients who received ATG induction, 34.2% (ATG induction) versus 66.6% (no ATG induction) (P = .01). ATG induction did not influence the risk of graft loss from HCV-related disease (P ≤ .75). When only HCV-related graft loss was considered, 10-year graft survival for HCV-positive recipients was 74% (ATG induction) versus 68.2% (no ATG induction). Whether ATG induction was given or not had no significant impact on either overall graft survival (P = .39) or patient survival (P = .11) in HCVpositive recipients. Presented at the Fifth Biennial Meeting of the American Hepato-Pancreato-Biliary Association, Fort Lauderdale, Florida, April 14–17, 2005     

Midterm results of a prospective randomized comparison of two different rabbit-antithymocyte globulin induction therapies after heart transplantation

This prospective randomized study compared the effects in heart transplant recipients of thymoglobulin and ATG, two rabbit polyclonal antithymocyte antibodies available for induction therapy. Among 40 patients (29 men and 11 women, mean age: 40.7 +/- 14 years) undergoing orthotopic heart transplantation, 20 were randomly allocated to receive induction with thymoglobulin (group A) and 20 to ATG-fresenius (group B). Comparisons between the two groups included early posttransplant (6 months) incidence of acute rejection episodes (grade >/= 1B), bouts of steroid-resistant rejection, time to first rejection, survival, graft atherosclerosis, infections, and malignancies. The study groups displayed similar preoperative and demographic variables. No significant difference was found with regard to actuarial survival (P =.98), freedom from rejection (P =.68), number of early rejections > 1B (P =.67), mean time to first early cardiac rejection (P =.13), number of steroid-resistant rejections (P =.69). Cytomegalovirus reactivations were more frequent among group A (65%) than group B (30%; P =.028). New infections due to cytomegalovirus occurred only in group A (four patients; 20%; P =.05). No cases of malignancies were observed at a mean follow-up of 32.8 +/- 8.9 months. Although thymoglobulin and ATG showed equivalent efficacy for rejection prevention, they have different immunological properties. In particular, thymoglobulin seems to be associated with a significantly higher incidence of cytomegalovirus disease/reactivation.     

A randomized trial of alemtuzumab vs. anti-thymocyte globulin induction in renal and pancreas transplantation

Abstract:  The role of alemtuzumab as an immunosuppressive agent is evolving. We conducted a prospective randomized trial comparing alemtuzumab and rabbit anti-thymocyte globulin (rATG) induction in adult kidney and pancreas transplantation using similar maintenance immunosuppression. Between February 1, 2005 and June 15, 2006 (median follow-up six months), 98 patients were randomized either to alemtuzumab (n = 48) or to rATG (n = 50) induction; 77 (79%) underwent kidney alone (KA) transplant, 17 (17%) pancreas–kidney transplant, and four (4%) pancreas after kidney transplant. Of 77 KA transplants, 66 (86%) were from deceased donors and 31 (40%) from expanded criteria donors (ECD). Re-transplantation, HLA-match, antibody titer, ECD, race, cytomegalovirus status, steroid use, delayed graft function, preservation time, and immunological risk were similar between the two induction groups. Patient, kidney, and pancreas graft survival rates were 100%, 96%, and 95%, respectively. Survival, initial length of stay, delayed graft function, and overall acute rejection rates were similar between alemtuzumab and rATG groups, but acute rejection occurred in nine (20%) rATG patients compared with zero (0%) alemtuzumab patients who received KA transplants (p = 0.007). Mean induction costs differed in the alemtuzumab ($1474) and rATG ($4996, p < 0.001) groups. In the short term after kidney and pancreas transplantation, alemtuzumab and rATG induction therapies are similarly safe and effective.     

Long-term evaluation of basiliximab induction therapy in live donor kidney transplantation: a five-year prospective randomized study

BACKGROUND/AIMS: The long-term evaluation of basiliximab induction therapy has not been addressed yet. We aim to evaluate its long-term effects in living related donor kidney transplantation. METHODS: 100 adult recipients with their first kidney allograft were randomized into two treatment groups--one group received basiliximab and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine microemulsion and azathioprine) and were closely followed for 5 years. RESULTS: Basiliximab significantly reduced the proportion of patients who experienced an acute rejection in the first year (18/50) when compared to the control group (31/50) and in 5 years (27/50) when compared to (36/50) the controls. The cumulative steroid dose used throughout the study was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable between the two treatment groups. There was no significant difference in patients and graft survival; 5-year patient and graft survival were 100 and 86% for basiliximab, and 96 and 88% for the control group respectively. CONCLUSION: Although routine basiliximab induction significantly reduces the incidence of acute rejection, its beneficial long-term effects on graft function and patient and graft survival are not yet evident.     

Antithymocyte globulin in renal transplant recipients. Report of a prospective randomized controlled trial.

Horse antihuman thymocyte globulin (HAHTG) combined with prednisone and azathioprine (lmuran) was used as immunosuppressive therapy in a randomized controlled sutdy in 50 renal allograft recipients. Side effects of HAHTG administration given intravenously were mostly mild. In the treated group, four patients out of 26 died of infectious complications, whereas in the control group, three patients out of 24 died of infectious complications (chi2 = .01,P greater than .05). The graft survival at 18 months was ten of 24 in the control group and ten of 26 in the treated group (chi2 = 1.26, P greater than .05). Cumulative graft survival was 58.3% in the control group and 38.1% in the treated group at 18 months. However, if we consider the people who died with a functioning graft not as graft failure but as if they left the study, then the cumulative graft survival is 64.5% in the control group and 65.9% in the treated group. Thus, the mortality from infective causes and graft survival were not significantly different between the two groups. Hence, we draw the conclusion that use of HAHTG did not exert a beneficial effect on the ultimate outcome.     

Basiliximab induction therapy for live donor kidney transplantation: a long-term follow-up of prospective randomized controlled study

Background/Aims  The effect of basiliximab induction therapy on long-term patient and graft survival is not yet clear. We aimed to evaluate if there is any advantage of routine basiliximab induction on the long-term outcome of living related donor kidney transplantation. Methods  One hundred adult recipients with their first kidney allograft were randomized into two treatment groups, one group received basiliximab and the second served as a control. All patients received a maintenance triple immunosuppressive therapy (steroids, cyclosporine (CsA) micro-emulsion and azathioprinep) and were followed up thoroughly for 7 years. Results  Basiliximab significantly reduced the proportion of patients who experienced acute rejection in the first year (18/50) when compared to the control group (31/50), and in 7 years (28/50) when compared to (37/50) in controls. The cumulative steroid dose used throughout the whole study period was significantly lower in the basiliximab group. The overall incidence of post-transplant complications was comparable among the two treatment groups. There was no significant difference in patient or graft survival; 7 years patient and graft survival were 92, 76% for basiliximab and 92, 80% for the control group, respectively. Conclusion  Routine basiliximab induction significantly reduced the incidence of acute rejection without any noticeble beneficial effect on the long-term renal transplantation outcome.     

Rabbit antithymocyte globulin as induction immunotherapy in pediatric heart transplantation

BACKGROUND: There is little published data on the use of antithymocyte globulins in children. This retrospective study describes the use of Thymoglobulin (Imtix, SangStat, Lyon, France) in pediatric cardiac transplantation over a 13-year period in a single center that adjusted the dose of Thymoglobulin according to platelet count monitoring and examines the short-term hematological effects as well as longer-term outcomes. METHODS: Data for all children who received a heart transplant at the H?pital Cardiologique at Lyon from 1984 to 2001 and who were given Thymoglobulin as part of their immunosuppressive protocol were extracted. The dose of Thymoglobulin given depended on baseline platelet count and was 2, 1.5, or 1 mg/kg per day over 5 days for the following platelet count groups: greater than 150,000/mm (normal group), 100 to 150,000/mm (mild thrombocytopenia group), and 50 to 100,000/mm (moderate thrombocytopenia group). RESULTS: Thirty children of median age 14.2 years were given a median cumulative dose of Thymoglobulin of 8 mg/kg per patient; the moderate thrombocytopenia subgroup was given significantly less (6.4 mg/kg) ( P=0.032). Immediate tolerability of Thymoglobulin was good, with no cases of first-dose syndrome, anaphylaxis, or serum sickness. The platelet count decreased at the start of therapy, but recovered after discontinuation, and did not give rise to clinical concern. Patients were followed up for a median of 6.3 years (7 days-15.5 years); actuarial survival was 90%, 86%, and 74.5%, respectively, at 1, 5, and 10 years. In the first year, 50% of patients suffered an episode of rejection. The overall incidence of infection in the month following transplantation was 40%. One lymphoma occurred at 5 months. CONCLUSIONS: The use of Thymoglobulin in pediatric heart-transplant patients as part of an immunosuppressive protocol, with dose adjustment according to platelet levels, has been shown to be effective in terms of rejection rate and patient survival and safe in terms of the incidence of infections and malignancy.     

肾移植中应用IL-2受体拮抗剂与抗胸腺细胞球蛋白行免疫诱导的长期疗效比较

目的 比较肾移植中应用白细胞介素2受体拮抗剂(IL2Ra)与抗胸腺细胞球蛋白(rATG)行免疫诱导的长期疗效.方法 回顾性分析2006年至2010年间的371例肾移植受者,其中使用IL2Ra诱导治疗者261例(IL2Ra组),使用rATG诱导治疗者110例(rATG组).所有受者术后采用钙调磷酸酶抑制剂+吗替麦考酚酯+皮质激素的三联免疫抑制方案,并使用更昔洛韦预防巨细胞病毒感染,使用复方磺胺甲(恶)唑预防卡氏肺孢子虫感染.术后对所有受者随访了1～5年,观察和比较移植肾功能恢复延迟(DGF)、1年内急性排斥反应和感染的发生率,以及受者和移植肾长期存活率等.结果 两组间受者性别、年龄、原发病等资料的差异均无统计学意义(P＞0.05),但与IL2Ra组比较,rATG组受者接受的供肾更多来源于尸体供肾(P＜0.01),且供肾冷缺血时间较长(P＜0.01).IL2Ra组和rATG组术后DGF发生率分别为3.1％和1.8％(P＞0.05),术后1年内急性排斥反应发生率分别为10.7％和2.7％ (P＜0.05),感染发生率分别为14.9％和21.8％ (P＞0.05).术后1、2和3年,IL2Ra组受者存活率分别为98.9％、98.9％和98.5％,rATG组均为98.2％ (P＞0.05);IL2Ra组移植肾存活率分别为98.5％、98.1％和97.7％,rATG组均为97.3％(P＞0.05).结论 在临床肾移植中,经rATG诱导治疗较IL2Ra有更低的急性排斥反应发生率,并且不增加发生感染的风险.     

Selective versus standard hyperalimentation: A randomized prospective study

Fifty consecutive surgical patients were included in a randomized prospective study to determine the relative advantages and disadvantages of two types of nutritional support systems: one, selective hyperalimentation, relies on a balanced substrate formula, while the other, standard hyperalimentation, depends on carbohydrate and protein to satisfy the energy requirements of the patient. The patients who received the balanced substrate formula had significantly fewer complications than those receiving standard hyperalimentation, even though both groups achieved positive energy and nitrogen balance. The enhanced safety of selective hyperalimentation suggests its therapeutic superiority as a basic nutritional support system for a busy surgical service.     

A randomized trial of everolimus‐based quadruple therapy vs standard triple therapy early after lung transplantation

Calcineurin inhibitor (CNI) therapy after lung transplantation increases risk of kidney failure. Early everolimus‐based quadruple low CNI immunosuppression may improve renal function without compromising efficacy or safety. A prospective, randomized, open‐label, 12‐month multicenter trial was conducted at 8 German sites. Patients 3‐18 months after lung transplantation were randomized (1:1), stratified by baseline estimated glomerular filtration rate (eGFR). In the quadruple low CNI regimen, patients received everolimus (target trough level 3‐5 ng/mL) with reduced CNI (tacrolimus 3‐5 ng/mL or cyclosporine 25‐75 ng/mL) and a cell cycle inhibitor plus prednisone. In the standard triple CNI regimen, patients received tacrolimus (target trough level >5 ng/mL) or cyclosporine (>100 ng/mL) and a cell cycle inhibitor plus prednisone. Of the 180 patients screened, 130 were randomized: 67 in the quadruple low CNI group and 63 in the standard triple CNI group. The primary endpoint (eGFR after 12 months) demonstrated superiority of the quadruple low CNI regimen: 64.5 mL/min vs 54.6 mL/min for the standard triple group (least squares mean, analysis of covariance; P < .001). Key efficacy parameters (biopsy‐proven acute rejection, chronic lung allograft dysfunction, and death) and safety endpoints were similar between both groups. Quadruple low CNI immunosuppression early after lung transplantation was demonstrated to be efficacious and safe. Clinical trials registry: ClinicalTrials.gov NCT01404325.