Ciancio Gaetano, Burke George W, Suzart Kiliana, Roth David, Kupin Warren, Rosen Anne, Olson Les, Esquenazi Violet, Miller Joshua
Department of Surgery, Division of Transplantation, University of Miami School of Medicine, Miami, FL 33101, USA.
Transplantation. 2002 Apr 15;73(7):1100-6. doi: 10.1097/00007890-200204150-00015.
Recent reports have demonstrated the efficacy of interleukin-2-receptor blockers in lowering the incidence of early acute rejection in cyclosporine-treated kidney recipients when compared to patients not induced with an antibody product. The addition of daclizumab to a tacrolimus-mycophenolate mofetil-based immunosuppressive protocol was tested to evaluate whether there might be an additional reduction of the risk of rejection after renal transplantation.
Since March 1998, we studied the effect of daclizumab in a nonrandomized, prospective study of 233 sequential recipients of first renal transplant. They were retrospective compared with a control group of 225 renal transplant recipients receiving a 10-day course of OKT3 induction, and tacrolimus, mycophenolate mofetil, and methylprednisolone maintenance. The study group received the same immunosuppressive regimen with the addition of daclizumab at 1 mg/kg for five doses over 10 weeks in the place of OKT3 therapy. There was at least 1HLA DR antigen compatibility match present between all donors and recipients. Patients were followed for 1 year after renal transplantation for the incidence of biopsy-proven acute rejection, patient and graft survival, and adverse events.
At 12 months, patient and graft survival for the daclizumab was 98 and 96 vs. 96 and 94% for the OKT3 group, respectively, and were not statistically different. Acute rejection rates (<6 months) were lower in the daclizumab group as compared with the OKT3 group, i.e., 5 (2.1%) vs. 16 (7.1%) (P=0.011) respectively. The incidence of infection requiring hospitalization appeared to be lower with daclizumab (7.3 vs. 16%, P<0.0036) with a similar trend with cyclomegalovirus infection, i.e., 1.6 vs. 4%, respectively (P=0.14).
The combination of daclizumab, tacrolimus, mycophenolate mofetil, and steroids is safe and effective for kidney transplant recipients in lowering the incidence of early acute rejection and without any increase in morbidity when compared to our previous protocol, which may have an eventual impact in long-term graft survival.
最近的报告显示，与未使用抗体产品诱导治疗的患者相比，白细胞介素-2受体阻滞剂在降低接受环孢素治疗的肾移植受者早期急性排斥反应发生率方面具有疗效。在基于他克莫司-霉酚酸酯的免疫抑制方案中添加达利珠单抗，以评估肾移植后排斥反应风险是否可能进一步降低。
自1998年3月起，我们在一项对233例首次接受肾移植的连续受者进行的非随机前瞻性研究中，研究了达利珠单抗的作用。将他们与225例接受10天OKT3诱导治疗、并使用他克莫司、霉酚酸酯和甲泼尼龙维持治疗的肾移植受者对照组进行回顾性比较。研究组接受相同的免疫抑制方案，在10周内分5剂给予1mg/kg的达利珠单抗，以替代OKT3治疗。所有供者与受者之间至少有1个HLA DR抗原相容性匹配。肾移植后对患者随访1年，观察活检证实的急性排斥反应发生率、患者和移植物存活率以及不良事件。
12个月时，达利珠单抗组的患者和移植物存活率分别为98%和96%，OKT3组分别为96%和94%，差异无统计学意义。达利珠单抗组的急性排斥反应率（<6个月）低于OKT3组，分别为5例（2.1%）和16例（7.1%）（P=0.011）。达利珠单抗组需要住院治疗的感染发生率似乎较低（7.3%对16%，P<0.0036），巨细胞病毒感染也有类似趋势，分别为1.6%对4%（P=0.14）。
与我们之前的方案相比，达利珠单抗、他克莫司、霉酚酸酯和类固醇联合应用对肾移植受者安全有效，可降低早期急性排斥反应的发生率，且发病率无任何增加，这可能最终对长期移植物存活产生影响。
