Renal transplantation without steroids

Cyclosporin has been in use in our unit since 1982 to treat renal transplant recipients. In two controlled clinical trials cyclosporin monotherapy was compared with cyclosporin with steroids, and with cyclosporin with azathioprine. The addition of steroids did not improve graft survival but did increase the incidence of infection. The addition of azathioprine also had no effect upon graft outcome. We conclude that cyclosporin monotherapy provides very adequate immunosuppression in the majority of cases giving an 80% survival rate for cadaveric kidney transplants at 1 year. Triple therapy has been used successfully by other centres although graft survival rates are no different from our own. Such treatment does, however, provide more powerful immunosuppression and is appropriate for previously sensitised patients and for children. Under this regimen steroids can be withdrawn at a later date. Sequential therapy with four agents is highly immunosuppressive. The long-term results are uncertain at the present time, and this expensive treatment needs careful evaluation. In our experience it is perfectly possible to undertake cadaveric renal transplantation without having to prescribe regular steroid therapy for the majority of patients. We have been impressed by the lack of serious side effects with this treatment and would still regard cyclosporin monotherapy as the treatment of choice for unsensitised renal transplant patients.     

Pediatric renal transplantation without steroids

Pediatric renal transplant patients present a number of challenges and problems, especially the inhibited post-transplant growth seen in children receiving standard immunosuppressive triple therapy that includes steroids. We report the successful use of steroid-free immunosuppression since 1990 in 14 pediatric renal allograft recipients who received a 10-day initial course of antilymphocyte globulin and surface area-adjusted doses of cyclosporine, 7 of whom also received mycophenolate mofetil (MMF) as maintenance immunosuppression. Only 1 patient died (3 months after transplantation as a result of a primary Epstein-Barr virus infection-induced lymphoproliferative disorder), 1 patient’s graft never functioned, and another patient lost his graft after 3 years because of chronic rejection. Three patients experienced early acute cellular rejection, which resolved in 2 cases with OKT3, and in the 3rd with MMF. There were no late acute rejections. All patients evidenced growth and a growth spurt under this regimen. We conclude that all the pediatric patients benefited from our steroid-free protocol and that this protocol is superior to conventional triple therapies, which entail the eventual reduction and discontinuation of steroids, a procedure that not only inhibits growth but also carries an additional risk of acute rejection due to a steroid-adapted immune response. Received April 16, 1997; received in revised form September 8, 1997; accepted September 10, 1997     

不用体外循环的异位并列心脏移植实验研究

１９８８年７月至１９９１年７月，我们在不用体外循环情况下做了７０条犬胸内异位并列心脏移植实验。术后供心总复跳率９１．４２％，犬最长存活１３天。供心植入２８ｈ后，以多普勒相控阵超声显象诊断仪检查，可见自体心与供心功能均正常。８ｋｇ重犬的供心植入后，每分钟排血１．２Ｌ，左室收缩增厚率２０％。移植后存活１３天的供心组织学检查见有明显急性排斥反应改变。     

ABO Incompatible High-Titer Renal Transplantation without Splenectomy or Anti-CD20 Treatment

Most successful protocols for renal transplantation across ABO incompatible (ABOi) barriers have utilized splenectomy as part of the pre-conditioning process. We recently described successful ABOi transplantation using anti-CD20 monoclonal antibody in lieu of splenectomy. In the current study, we hypothesized that plasmapheresis (PP) and low dose CMV hyper-immunoglobulin (CMVIg) alone would be sufficient to achieve successful engraftment of ABOi kidneys. We describe four blood type incompatible patients who received live donor renal transplants from A1 (two patients), A2 (one patient), and B (one patient) donors. All patients started with antihuman globulin (AHG) phase titers of 64 or higher and were pre-conditioned with PP/CMVIg but not splenectomy or anti-CD20. All 4 patients underwent successful transplantation and have a mean current serum creatinine of 1.1 (range: 0.9-1.2). There were no episodes of antibody mediated rejection. Rapid allograft accommodation may limit the need for long-term antibody suppression provided by splenectomy or anti-CD20, thereby eliminating the added infectious risk of these modalities and removing another disincentive to ABOi transplantation.     

Results of orthotopic heart transplantation with and without the use of maintenance steroids

From March 1984 to June 1987, 51 patients underwent primary orthotopic heart transplantation at the Second University Department of Surgery, Vienna. Recipients were immunosuppressed with a combination of either ciclosporine and azathioprin (double drug regimen = DD, 10 patients), or ciclosporine, azathioprin and low-dose steroids (triple drug regimen = TD, 33 patients). Four patients who died intra- or perioperatively and 4 who were switched to conventional therapy were excluded from analysis. In both groups, ciclosporine was administered to obtain whole blood HPLC trough levels of 200-400 ng/ml in the 1st month, 150-250 ng/ml from the 2nd to the 6th and 100-150 ng/ml after the 6th month. Azathioprin 2 mg/kg per day was given, and in TD patients, an additional 0.2 mg/kg per day of prednisolon: all patients received prophylactic antithymocyte globulin for 7-10 days postoperatively. Five deaths from acute rejection in the DD group contrasted with none in the TD group. The high incidence of fatal rejection episodes was reflected in a 40% Kaplan-Meier 1-year survival for DD vs 84% for TD (p less than 0.0001). Analysis of endomyocardial biopsies (DD vs TD) demonstrated 20.4% vs 57.0% absent, 46.0% vs 29.5% mild, 31.2% vs 12.4% moderate and 2.4% vs 1.1% severe rejection. Fatal and nonfatal infections and toxic side effects occurred with the same frequency in both protocols. Calculation of mean ciclosporine levels resulted in 249.7 ng/ml (TD) and 206.0 ng/ml (DD) in the 1st month (p less than 0.05). Consequently, adjunctive maintenance low-dose steroids combined with increased ciclosporine levels in the early posttransplant course are considered responsible for the improved results.     

自制无滤网输血器在骨髓移植中的应用

目的避免回输骨髓时聚集的小细胞团或破损细胞粘附堵塞滤网,确保输髓通畅.方法用无滤网的输液滴管替代有滤网的输血滴管,并保留输血器的瓶塞穿刺针及与头皮针相连的接管.结果自制无滤网输血器应用25例次骨髓回输中,无1例发生堵塞、吸附凝集现象.结论用无滤网输血器行骨髓回输,能确保造血干细胞有效、快速地回输给患者.     

Transplantation of the bone marrow microenvironment leads to hematopoietic chimerism without cytoreductive conditioning

BACKGROUND: It has been hypothesized that regimens to induce transplantation tolerance and long-term hematopoietic chimerism require recipient conditioning with whole body irradiation or a cytoablative regimen to create space within the marrow microenvironment to permit pluripotent stem cell engraftment. The purpose of this study was to determine if transplantation of an intact bone marrow microenvironment in the form of a bone graft would permit stable hematopoietic stem cell engraftment, shape the repertoire of developing T cells, and induce donor-specific unresponsiveness in the absence of a conditioning regimen. METHODS: Fragments of femur were transplanted under the kidney capsule of recipient mice. At defined time points after bone graft transplantation recipients were assayed for chimerism, bone graft viability, and responses to donor and third party alloantigens in vitro and in vivo. RESULTS: In the absence of an immunological barrier, bone graft transplantation resulted in long-term multi-lineage hematopoietic chimerism in the peripheral blood. Nude bone graft transplantation into SCID recipients resulted in development of donor- derived T cells that underwent negative selection on bone graft derived I-E+ cells within the thymus. Across a fully allogeneic barrier in immunocompetent recipients treated with combined blockade of the CD40 and CD28 pathways bone graft transplantation resulted in long-term donor-specific hyporesponsiveness in vitro and acceptance of donor specific skin grafts. CONCLUSIONS: Transplantation of bone marrow in the form of a bone graft may facilitate the production of hematopoietic chimerism and lead to long-term donor-specific hyporesponsiveness in the absence of a cytoreductive conditioning regimen.     

自制无滤网输血器在骨髓移植中的应用

目的避免回输骨髓时聚集的小细胞团或破损细胞粘附堵塞滤网，确保输髓通畅。方法用无滤网的输液滴管替代有滤网的输血滴管，并保留输血器的瓶塞穿刺针及与头皮针相连的接管。结果自制无滤网输血器应用25例次骨髓回输中，无1例发生堵塞、吸附凝集现象。结论用无滤网输血器行骨髓回输，能确保造血干细胞有效、快速地回输给患者。     

非转流原位肝移植不同术式对麻醉管理的影响

目的比较非转流背驮式与经典式原位肝移植术(orthotopic liver transplantation,OLT)对麻醉管理的影响。方法回顾性分析2003年11月~2006年12月我院50例非转流OLT的临床资料,其中背驮式(A组)和经典式(B组)各25例,比较2组患者在围术期血流动力学、凝血状况、肝肾功能、内环境的改变及液体治疗等方面的异同。结果无肝期即刻A组平均动脉压(68±6)mm Hg显著高于B组(64±5)mm Hg(t=2.561,P=0.014),A组中心静脉压(5.4±3.3)mm Hg高于B组(3.5±2.3)mm Hg(t=2.362,P=0.022),A组心脏指数(3.7±0.8)L.min-1.m-2显著高于B组(3.2±0.6)L.min-1.m-2(t=2.500,P=0.016)。新肝期即刻A组平均动脉压(66±6)mm Hg明显高于B组(62±5)mm Hg(t=2.561,P=0.014),A组中心静脉压(8.4±4.0)mm Hg与B组(10.6±4.2)mm Hg无统计学差异(t=-1.897,P=0.064)。再灌注综合征的发生率A组(2/25,8.0%)低于B组(8...     

经典式原位肝移植术弃用静脉转流的经验总结

目的：观察经典式原位肝移植术不作静脉转流的效果,分析不转流对术后胃肠道及肾脏功能的影响。方法：总结自１９９９年来我所４５例经典式原位肝移植术弃用静脉转流的经验。结果：４５例术中无肝期时间平均为５４．５ｍｉｎ,术后与不转流相关的胃肠道和肾功能明显损害的并发症有４例：３例术后近期发生急性肾功能衰竭,２例经血透后恢复,１例死亡;另１例于术后１．５月发生急性坏死性胰腺炎。结论：若无肝期控制在１ｈ内,经典式原位肝移植不作转流,并不显著增加胃肠道和肾脏功能损害等并发症,且有缩短手术时间和节省费用等优点。     

不作转流的经典式原位肝移植术（附15例报道）

目的：观察不转流的经典工原位肝移植的效果,分析不转流对胃肠道及肾脏功能的影响。方法：1999年以来我所共为15例终末期肝病患施行了不转流的经典式原位肝移植术,术中门静阻断时间平均为40．5min,下年以来我所共为15例终末期肝病患施了不转流的经典式原位肝移植术,术中门静脉阻断时间平均为40.5min,下腔静脉阻断时间58.7min;无肝期血压维持在78-96/52-64mmHg.开放门静后从肝下下腔静放血150-20ml结果:15例一月内除1例术后7天死于DIC外,余14例无一例发生与不转流相关的胃肠道和肾功能明显损害的并发症.结论:不转流经典式原位肝移植若无肝期小于1h和血压在80/50mmHg以上,并不增加胃肠道和肾脏功能损害等产发症,有手术时间短和节省费用等优点.