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1.
BACKGROUND/AIMS: Induction with rabbit antithymocyte globulin (RATG) has been reported to be effective in cadaveric liver transplantation. The aim of this study was to compare two immunosuppressive protocols in adult living-related liver transplantation (LRLT). METHODOLOGY: From May 2001 through May 2003, 34 LRLT were performed. The first 17 patients (group 1) were treated with tacrolimus (TAC) and steroids. The next 17 patients (group 2) were treated with a steroid-sparing protocol using RATG. RESULTS: The one-year patient and graft survival was respectively 76.5% and 64.7% for group 1 and 88.2 and 76.5% for group 2 (p = 0.037 and p = NS, respectively). Incidence of acute cellular rejection was 41.2% in group 1 compared to 47% in group 2 (p = NS). Mean daily TAC dose at 6 months was 6.5 +/- 1.1 mg/day in group 1 and 3.2 +/- 0.9 mg/day in group 2 (p < 0.001). In group 1, 41.1% experienced CMV infection compared to 11.7% in group 2 (p = NS). CONCLUSIONS: These results suggest that this approach of RATG induction followed by postoperative, steroid-free, and low-dose TAC is safe and provides for adequate immunosuppression and similar outcome when compared to controls treated with standard TAC and steroid immunosuppression.  相似文献   

2.
Using cyclosporine A (CyA), long-term results after heart-lung transplantation became possible. Since 1981, 761 clinical heart lung transplantations have been registered at the International Society for Heart Transplantation. Candidates for this operation reveal signs of irreversible heart and lung diseases which are caused by cardiac lesions (e.g. valvular disease, Eisenmenger reaction due to congenital malformation) or pulmonary disorders (e.g. primary pulmonary hypertension, emphysema, fibrosis). The standard surgical procedure necessitates three anastomoses which combine donor and recipient tracheae, right atria and aortae. Immunosuppression consists of CyA (blood levels of 300-500 ng/ml), azathioprine (1-2 mg/kg/d) and rabbit antithymocyte globuline (RATG) (IgG: 2-4 mg/kg/d). After the first 2 postoperative weeks, RATG is replaced by low dose methylprednisolone (0.3-0.1 mg/kg/d). As an alternative, RATG may be omitted completely. Postoperatively, a variety of complications may evolve. Early problems (within the first month) comprise acute pulmonary rejection, bacterial pneumoniae, and multiorgan failure. Diagnosis of acute lung rejection proves difficult; it includes clinical signs, chest radiographic appearances and cytoimmunological monitoring of the peripheral blood. Transbronchial lung biopsies are for precise diagnosis of similar value to endomyocardial biopsies after heart transplantation. Late postoperative complications comprise viral, bacterial, fungal, and protozoal infections and chronic obliterative bronchiolitis. With increasing experience, the 30 day mortality fell to below 20% according to the International Society for Heart Transplantation. The one-year survival rate between 1986 und 1988 was reported to be 61%. The results of some individual groups are even better.  相似文献   

3.
AIM: To investigate the efficacy and safety of a single-dose daclizumab induction therapy in orthotopic liver transplantation (OLTx). METHODS: A retrospective study was made for 54 cases of OLTx in recent three years. The daclizumab group consisted of 23 cases of OLTx who received single-dose of 2 mg/kg intravenously after postoperative 24 hours. The control group consisted of the remaining 31 patients. Additional immunosuppressors included steroids, mycomphenolate mofetil, facrolimus or microemulsion cyclosporine used in all patients. Meta-statistical analysis was made for general data, incidence of acute rejection and infection, postoperative clinical course, complications and prognosis between two groups. RESULTS: Pretransplant demographies were not significantly different between two groups. In the induction group there were significantly less acute rejection episodes (5 of 23, 21.74 %) than those in the control group (12 of 31, 38.71 %), which were proved by pathologic diagnosis (P<0.05). The incidence of infection at the early stage was not significantly different between two groups. CONCLUSION: Induction therapy with single-dose of daclizumab is safe and effective and appears to be able to reduce the incidence of acute rejection.  相似文献   

4.
Lung transplantation can be a life-saving procedure for those with end-stage lung diseases. Unfortunately, long term graft and patient survival are limited by both acute and chronic allograft rejection, with a median survival of just over 6 years. Immunosuppressive regimens are employed to reduce the rate of rejection, and while protocols vary from center to center, conventional maintenance therapy consists of triple drug therapy with a calcineurin inhibitor (cyclosporine or tacrolimus), antiproliferative agents [azathioprine (AZA), mycophenolate, sirolimus (srl), everolimus (evl)], and corticosteroids (CS). Roughly 50% of lung transplant centers also utilize induction therapy, with polyclonal antibody preparations [equine or rabbit anti-thymocyte globulin (ATG)], interleukin 2 receptor antagonists (IL2RAs) (daclizumab or basiliximab), or alemtuzumab. This review summarizes these agents and the data surrounding their use in lung transplantation, as well as additional common and novel therapies in lung transplantation. Despite the progression of the management of lung transplant recipients, they continue to be at high risk of treatment-related complications, and poor graft and patient survival. Randomized clinical trials are needed to allow for the development of better agents, regimens and techniques to address above mentioned issues and reduce morbidity and mortality among lung transplant recipients.  相似文献   

5.
Interleukin 2 receptor antagonists (IL-2Ra) are frequently used as induction therapy in liver transplant recipients to decrease the risk of acute rejection while allowing the reduction of concomitant immunosuppression. We conducted a systematic review of prospective, controlled studies to test the hypothesis that the use of IL-2Ra is associated with a decrease in acute rejection and/or a decrease in the side effects of concomitant medication. We performed a search of all major databases and secondary sources from inception to December 2010. Random effects models were used to assess the incidence of acute rejection, graft loss, patient death, and adverse side effects, with or without IL-2Ra. Subgroup analysis and meta-regression were used to explore differences in effect and sources of heterogeneity. Eighteen studies (13 randomized and 5 nonrandomized) met the inclusion and exclusion criteria. Acute rejection at 12 months or later favored the use of IL-2Ra (relative risk [RR] 0.83; 95% confidence interval [CI] 0.76-0.94) and steroid-resistant rejection was also less frequent in patients receiving IL-2Ra (RR 0.66; CI 0.48-0.91). Graft loss and patient death did not differ significantly between treatments. Patients who received IL-2Ra in addition to reduced or delayed calcineurin inhibitors had better renal function (mean difference of estimated glomerular filtration rate: 6.29 mL/min; CI 1.66-10.91) and a lower incidence of renal dysfunction (RR 0.46; CI 0.27-0.78). The use of IL-2Ra was also associated with a lower incidence of posttransplant diabetes mellitus, whereas the incidence of other adverse events was similar. CONCLUSION: The use of IL-2Ra is associated with a lower incidence of acute rejection after transplantation. Concomitant immunosuppression can be reduced, avoiding long-term side effects of immunosuppression.  相似文献   

6.
Although usually reversible, acute rejection of kidney graft is a negative factor in long-term graft survival. Commonly used in pediatric renal transplantation, immunosuppresive induction therapy is established to prevent it. New immunosuppressive agents have been developed in recent years and among them anti-CD25 monoclonal antibody appears to be specially interesting. AIM: To evaluate efficacy and safety of anti-CD325 monoclonal antibody (basiliximab) versus polyclonal antibodies as induction therapy in renal transplantation. MATHERIAL Y METHODS: Thirty consecutive kidney transplants performed in children 4-16 years age in Hospital Infantil La Fe through 1997-2000. The first 15 patients received polyclonal antibodies as induction therapy, and 15 consecutive ones received monoclonal anti-CD25 antibodies. Receptor, donor and graft characteristics were similar in both groups. Also, maintenance immunosuppression was the same. RESULTS: The follow-up was over one year in all patients. Four patients in the polyclonal antibody group suffered one acute rejection episode and four other patients had some drug reaction. In the anti-CD25 treatment group there was one episode of acute graft rejection and no collateral effects were observed. Glomerular filtration rate, proteinuria, hypertension, infection episodes, graft and patient survival were similar in both groups. CONCLUSIONES: Induction therapy for pediatric renal transplantation with anti-CD25 antibody has been effective and safe. Compared with polyclonal antibodies as standard treatment, basiliximab reduced acute rejection episodes and had no collateral side effects. Graft and patient one year survival were identical in the two groups.  相似文献   

7.
Common variable immune deficiency and lung transplantation   总被引:1,自引:0,他引:1  
We report on a male patient with bronchiectasis secondary to common variable immune deficiency (CVID) receiving lung transplantation. The patient had been diagnosed with CVID many y prior to right-sided single lung transplantation and was receiving appropriate immunoglobulin substitution therapy. He received antithymocyte globulin induction and maintenance triple therapy with cyclosporine, azathioprine and prednisolone. The early post-operative course was complicated by the development of severe acute cellular rejection and organizing pneumonia. Despite immunoglobulin replacement and antifungal prophylaxis and treatment, Aspergillus fumigatus was repeatedly cultured from bronchoalveolar lavage fluid, 18 months after transplantation. The patient died following a protracted period of repeated hospital admissions, 46 months after transplantation. A review of the literature suggests that many CVID patients appear to have had a complicated post-operative course after lung- and other solid-organ transplantation, and highlights the need for the establishment of international registries for transplanted patients with uncommon conditions.  相似文献   

8.
Maintenance immunosuppression for lung transplantation includes cyclosporine or tacrolimus, mycophenolate mofetil or azathioprine, and prednisone. Some centers rely on induction agents including OKT3 (murine monoclonal antibody, OKT3), ATG (antithymocyte globulin), or thymoglobulin. In addition, a number of new agents including sirolimus (SRL) and the interleukin (IL)-2 receptor antagonists, daclizumab and basiliximab, have become available. Management of chronic rejection typically consists of augmented immunosuppression using many of the standard agents, and other potent agents such as methotrexate or cytoxan or more novel strategies including photopheresis, radiation, and total lymphoid irradiation (TLI).  相似文献   

9.
This report details a single center's experience with OKT3 induction immunosuppression for liver transplantation. One hundred ninety-nine consecutive, unselected adult liver recipients received OKT3 therapy for 9–10 days combined with low-dose steroids and azathioprine. Cyclosporine was begun to overlap with the last few days of OKT3 therapy. The average dose of OKT3 was 45 mg. Fifty-two patients (26.1%) experienced 57 episodes of acute rejection. The median time of onset of rejection was 18 days after grafting. Seventy-eight percent of the rejection episodes were steroid-sensitive. Recurrent rejection was uncommon and the need for OKT3 retreatment was infrequent. One year actuarial graft and patient survival was 79.7% and 82.3% respectively. Based on this evidence, it appears that OKT3 prophylaxis provides good control of acute rejection with a very low incidence of recurrent rejection.  相似文献   

10.
Renal transplantation represents a method of choice in irreversible renal failure. The outcome of renal transplantation is affected by acute or chronic rejection and long-term evaluation also suggest a role of adverse effects of immunosuppressive therapy, mainly the incidence of cardiovascular complications and tumours. Immunosuppressive therapy with biologic agents aims to reduce the incidence of acute rejections, prolong allograft survival and, consequently, patient survival. Apart from a reduction in acute rejection incidence, biological agents are used in a selected group of patients to eliminate the need for an adjunctive treatment with steroids and to reduce consequences of ischemic-reperfusion damage in older donors who suffer from a range ofco-morbidities. The most frequently used therapies include induction and anti-rejection therapy with a rabbit polyclonal anti-human thymocyte globulin (rATG) or an induction therapy with monoclonal anti-interleukin-2 receptor antibody (anti-IL2R), basiliximab. Considering the high immunosuppressive effect of rATG, adverse effects, mainly opportunistic infections and more frequent delayed tumourigenesis, have to be taken into account.  相似文献   

11.
We analyzed the outcome of 537 adolescents (age 12–18 years) with idiopathic aplastic anemia included in the database of the Severe Aplastic Anemia Working Party of the European Group for Blood and Marrow Transplantation comparing: i) matched family donor hematopoietic stem cell transplantation performed as first-line treatment with ii) front-line immunosuppressive therapy not followed by subsequent transplant given for failure and with iii) hematopoietic stem cell transplantation performed after failed front-line immunosuppressive therapy. Overall survival was 86% in the matched family donor hematopoietic stem cell transplantation group, 90% in patients given front-line immunosuppressive alone (those who did not fail this treatment and who did not receive subsequent rescue with hematopoietic stem cell transplantation) and 78% in subjects who underwent hematopoietic stem cell transplantation post failed front-line immunosuppressive therapy (P=0.14). Event-free survival in the same groups was respectively 83%, 64% and 71% (P=0.04). Cumulative incidence of rejection was 8% in matched family donor hematopoietic stem cell transplantation and 9% in transplants post failed front-line immunosuppression (P=0.62). Cumulative incidence of acute graft-versus-host disease was 12% in matched family donor transplants and 18% in transplants post failed immunosuppression (P=0.18). Chronic graft-versus-host disease was higher in matched family donor hematopoietic stem cell transplantation (8%) than in transplants post failed immunosuppressive therapy (20%) (P=0.0009). Cumulative incidence of post-therapy malignancies was 0.7% in matched family donor transplantations, 7% in transplantations post failed immunosuppression and 21% after front-line immunosuppression (P=0.0017). In the whole cohort, under multivariate analysis, the diagnosis to treatment interval of two months or under positively affected overall survival whereas up-front immunosuppression alone (with no subsequent rescue transplants) negatively affected event-free survival. In transplanted patients an interval from diagnosis to treatment of 2 months or under, bone marrow as source of cells and first-line matched family donor transplants provided a significant advantage in overall and event-free survival. Aplastic anemia in adolescents has a very good outcome. If a matched family donor is available, hematopoietic stem cell transplantation using bone marrow cells is the first choice treatment. If such a donor is not available, immunosuppressive treatment may still be an acceptable second choice, also because, in case of failure, hematopoietic stem cell transplantation is a very good rescue option.  相似文献   

12.
Sixty-two patients underwent cardiac transplantation at the University of Arizona from March 1979 to March 1985. Thirteen patients (11 men and 2 women) were over 50 years of age at the time of transplantation and 49 were under the age of 50. The mean age (+/- SEM) of the patients over 50 was 53 +/- 1 years. Eight of these patients were treated with conventional immunosuppressive therapy (azathioprine, prednisone and rabbit antithymocyte globulin) and five, beginning in January 1983, were treated with cyclosporine, prednisone and rabbit antithymocyte globulin. Early mortality (0 to 90 days) was 16% in the group over 50 versus 18% for those under 50. The late mortality (greater than 90 days) was 36 and 33%, respectively. In both groups, rejection and infection were the principal causes of death. The incidence of infection was 1.9 +/- 0.5 episodes per patient in those patients over 50 and 1.9 +/- 0.4 in those under 50. The incidence of rejection was 1.3 episodes per patient-year in patients over 50 and 1.7 episodes per patient-year in those under 50. Actuarial survival at 1 year was 72 +/- 14% in the group over 50 and 66 +/- 7% in the group under 50 years of age. These data indicate that the results of cardiac transplantation for patients over 50 do not differ significantly from those for patients under 50. Therefore, it is concluded that a rigidly defined age criterion for cardiac transplant recipients is not acceptable. Each potential recipient must be evaluated in terms of individual risk and benefit from the procedure.  相似文献   

13.
Over the last decade, improvements in surgical techniques, lung preservation, immunosuppression, and management of ischemia-reperfusion injury and infections have contributed to increase the 1 year patient survival after lung transplantation to 70 to 80%. However, the incidence of acute rejection remains higher than after other types of solid organ transplantation, and long-term survival is threatened by bronchiolitis obliterans, which is thought to be a form of chronic allograft rejection. This article reviews major aspects of clinical presentation, risk factors, diagnosis, and management of acute and chronic rejection after lung transplantation.  相似文献   

14.
Between February 1983 and July 1987, twelve patients underwent heart-lung transplantation at the University of Cape Town and the University of Munich. The patients included eight men and four women, whose ages ranged from 15 to 49 years (mean, 27 years). The underlying pathologic condition was idiopathic primary pulmonary hypertension in five cases, Eisenmenger's syndrome in four cases, idiopathic pulmonary fibrosis in one case, diffuse fibrosing alveolitis in one case, and chronic emphysema in one case. The immunosuppressive regimen consisted of cyclosporine A, azathioprine, and rabbit antithymocyte globulin (RATG) during the first 2 postoperative weeks; RATG was subsequently replaced by methylprednisolone. Pulmonary rejection frequently occurred in the absence of cardiac rejection; in one case, however, this situation was reversed. Two patients required retransplantation, which was undertaken for caseating pulmonary tuberculosis with obliterative bronchiolitis after 1 year in one case and for early pulmonary insufficiency after 2 days in the other case. There were no operative deaths, but three early deaths occurred, owing to respiratory insufficiency of unknown origin (10 days postoperatively), multiorgan failure (10 days postoperatively), and acute liver dystrophy (11 days postoperatively). Five weeks after operation, a fourth patient died of multi-organ failure. There were five late deaths, all of which resulted from infectious complications. Three patients, including one who underwent retransplantation, remain alive and well, 10 to 36 months postoperatively.  相似文献   

15.
肺移植是肺脏疾病终末期的治疗选择,闭塞性细支气管炎、巨细胞病毒感染都是移植后第1年常见的慢性排斥反应。所有的肺移植患者终生服用3种免疫抑制药物,包括钙调神经磷酸酶抑制剂、抗代谢药物及小剂量激素。不同的医疗机构使用的免疫抑制剂的方案存在差异,肺移植使用免疫抑制剂的共识尚未形成。本综述主要探讨肺移植术后诱导和维持免疫抑制治疗药物与方案,为规范治疗提供参考。  相似文献   

16.
The results of pancreatic transplantation could be improved markedly since using the bladder drainage technique. The best function rates can be achieved when transplanting simultaneously a kidney from the same donor. In our own series of 50 combined pancreas-/kidney transplantations (CPKT) the 1-year-graft function rate for both organs reaches 88%. The drainage of the exocrine pancreatic secretions into the urinary tract leads, however, to a high incidence of recurrent urinary tract infections. Diagnosis of rejections after combined pancreas-/kidney transplantation is mainly based on the function of the simultaneously transplanted kidney and the exocrine secretion of the pancreatic graft. In spite of triple drug therapy (prednisolone, azathioprine, cyclosporine A) and ATG (antithymocyte globulin) prophylaxis the incidence of acute rejection episodes is initially high. For rejection therapy monoclonal antibodies, such as OKT3, are most effective. Glucose metabolism is almost completely normalized after successful pancreatic transplantation. Considering late diabetic complications, however, only positive effects on diabetic neuropathy are confirmed. This is probably due to the very late onset of therapy by pancreatic transplantation. A significant improvement in other late diabetic complications can only be expected in long term follow up studies. The positive effect on physical and psychological rehabilitation, however, improves the quality of life in most of the patients after CPKT substantially. Even though the results of isolated pancreatic transplantation reaches 1-year-graft function rates of approximately 60% in single centers, the indication to this treatment should consider the disadvantages of long term immunosuppression and the uncertain results considering secondary complications.(ABSTRACT TRUNCATED AT 250 WORDS)  相似文献   

17.
Levine SM  Angel L  Anzueto A  Susanto I  Peters JI  Sako EY  Bryan CL 《Chest》1999,116(5):1273-1277
STUDY OBJECTIVES: The incidence of posttransplant lymphoproliferative disorder (PTLD) has been reported to range from 6.4 to 20% in lung transplant (LT) recipients. Postulated contributing factors include Epstein-Barr virus (EBV) infection and the use of immunosuppression, particularly muromonab-CD3 (OKT3)(Orthoclone OKT-3; Ortho Biotech; Raritan, NJ). We sought to examine these PTLD risk factors in 109 LT recipients at our institution who survived > 1 month. DESIGN: Retrospective review of EBV serology of all LT recipients at our institution. Our standard transplant protocol includes OKT3 for induction and refractory rejection, as well as lifelong acyclovir for herpes prophylaxis. We do not perform EBV donor-recipient matching. SETTING: A university-based LT center. RESULTS: We found that 5 of 109 patients were serologically negative for EBV prior to lung transplantation, and all of these patients converted following lung transplantation. The mean time to conversion was 151 days (range, 11 to 365 days). One fatal case of PTLD was documented in an EBV seroconverter (one of five patients) 12 weeks status posttransplantation for lymphangioleiomyomatosis. One nonfatal extrathoracic PTLD was documented in a seropositive patient (1 of 104 patients) 33 months posttransplantation. CONCLUSIONS: We conclude the following: (1) PTLD in LT recipients may have a lower incidence (2 of 109 patients; 1.8%) than previously reported, despite an aggressive immunosuppressive regimen; and (2) the incidence of PTLD is higher in patients with primary EBV infection (20% vs 1%).  相似文献   

18.
心脏移植围术期处理经验   总被引:5,自引:0,他引:5  
目的:总结8例心脏移植围术期处理的临床经验.方法:8例晚期心肌病患者接受同种异体原位心脏移植术,围术期免疫抑制剂采用两剂赛尼哌加环磷酰胺诱导方案,维持治疗为环孢素A 霉酚酸酯(或硫唑嘌呤) 泼尼松三联方案,术后72 h内保持低水平的中心静脉压.结果:8例受者均存活,围术期及随访期间受者均无急性排斥反应、移植物功能不全、肝肾功能不全、严重机会性感染等并发症.结论:围术期适当强度的免疫抑制治疗,合理应用强心利尿和抗生素预防治疗是防治心脏移植术后并发症的有效方法.  相似文献   

19.
Antithymocyte globulin (ATG) preparations in allogeneic stem cell transplantation are used in various conditioning regimens both to prevent graft rejection and reduce the incidence and severity of graft-versus-host disease. Tecelac (RATG) is a highly purified ATG preparation with high specific activity. The high specific antibody content implies the need for lower doses, with reduced side-effects in comparison to other ATGs. Here, we report on the first 10 patients worldwide who received RATG as part of conditioning. Patients were heterogeneous with regard to diagnoses and graft characteristics. RATG was given in cases of matched unrelated donors, mismatched family donors, reduced conditioning, or high risk for graft failure. Mostly mild allergic reactions toward RATG were seen. All of the patients engrafted in due time. Two died within 2 months of transplant of pulmonary complications not related to RATG. Two developed GVHD grade I, no chronic GVHD was seen to date. Viremia occurred in two, with no viral disease developed. Of the eight patients surviving, one suffered relapse of acute leukemia, one shows impending graft failure. The others are well. Using RATG in conditioning is feasible.  相似文献   

20.
OBJECTIVE: Corticosteroids play a key role in immunosuppression after transplantation. However, because chronic steroid treatment may cause significant morbidity and mortality, steroid-free immunosuppression remains a desirable goal. To the best of our knowledge, there are no reports on successful steroid withdrawal (SW) in lung transplant recipients. METHODS: The study group included 35 patients who underwent heart-lung, double-lung or single-lung transplantation. Criteria for initiation of SW were stable pulmonary function tests and absence of clinical or bronchoscopic evidence of acute or chronic rejection in the last 6 months. Pulmonary function, blood pressure and metabolic parameters were compared between the patients who underwent SW and those who did not. RESULTS: Eight patients (23%) underwent SW. Median follow-up was 19 months (range 11-23 months). Compared to the non-withdrawal group, the withdrawal group was older (60+/-6 vs. 52+/-13 years, P=0.01, r=0.49), had higher rates of emphysema (88% vs. 18%, P=0.01) and use of a cyclosporine-based regimen (62% vs. 26%, P=0.0001), and had longer time from transplantation to the withdrawal attempt (70+/-13 vs. 29+/-26 months, P=0.0002). The SW group showed no adverse effects in graft function and no deterioration on pulmonary function tests. SW had a beneficial metabolic effect, with a decrease in mean cholesterol level from 229+/-45 to 194+/-25 mg/dl (P=0.02) and no significant change in weight, systolic blood pressure or glucose level. In the non-withdrawal group, mean cholesterol levels increased from 175+/-34 to 209+/-57 mg/dl (P=0.0005), weight increased from 72+/-15 to 80+/-14 kg (P=0.0001), and systolic blood pressure increased from 125+/-15 to 139+/-16 mmHg (P=0.001); glucose levels did not change. There was a significant correlation between total cholesterol level and weight in both groups (P=0.0006, r=-0.56 and P=0.01, r=-0.46, respectively). CONCLUSIONS: Late SW is safe in stable patients after lung transplantation. There was no evidence of rejection or a deterioration in pulmonary function. Lipid profile improvement and blood pressure stabilization accompanied the termination of steroid therapy.  相似文献   

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