Vo Ashley A, Lukovsky Marina, Toyoda Mieko, Wang Jennifer, Reinsmoen Nancy L, Lai Chih-Hung, Peng Alice, Villicana Rafael, Jordan Stanley C
Comprehensive Transplant Center, Transplant Immunology Laboratory, Cedars-Sinai Medical Center, Los Angeles 90048, USA.
N Engl J Med. 2008 Jul 17;359(3):242-51. doi: 10.1056/NEJMoa0707894.
Few options for transplantation currently exist for patients highly sensitized to HLA. This exploratory, open-label, phase 1-2, single-center study examined whether intravenous immune globulin plus rituximab could reduce anti-HLA antibody levels and improve transplantation rates.
Between September 2005 and May 2007, a total of 20 highly sensitized patients (with a mean [+/-SD] T-cell panel-reactive antibody level, determined by use of the complement-dependent cytotoxicity assay, of 77+/-19% or with donor-specific antibodies) were enrolled and received treatment with intravenous immune globulin and rituximab. We recorded rates of transplantation, panel-reactive antibody levels, cross-matching results at the time of transplantation, survival of patients and grafts, acute rejection episodes, serum creatinine values, adverse events and serious adverse events, and immunologic factors.
The mean panel-reactive antibody level was 44+/-30% after the second infusion of intravenous immune globulin (P<0.001 for the comparison with the pretreatment level). At study entry, the mean time on dialysis among recipients of a transplant from a deceased donor was 144+/-89 months (range, 60 to 324). However, the time to transplantation after desensitization was 5+/-6 months (range, 2 to 18). Sixteen of the 20 patients (80%) received a transplant. At 12 months, the mean serum creatinine level was 1.5+/-1.1 mg per deciliter (133+/-97 micromol per liter), and the mean survival rates of patients and grafts were 100% and 94%, respectively. There were no infusion-related adverse events or serious adverse events during the study. Long-term monitoring for infectious complications and neurologic problems revealed no unanticipated events.
These findings suggest that the combination of intravenous immune globulin and rituximab may prove effective as a desensitization regimen for patients awaiting a transplant from either a living donor or a deceased donor. Larger and longer trials are needed to evaluate the clinical efficacy and safety of this approach. (ClinicalTrials.gov number, NCT00642655.)
对于高度致敏于人类白细胞抗原（HLA）的患者，目前可供选择的移植方案很少。这项探索性、开放标签、1-2期、单中心研究考察了静脉注射免疫球蛋白联合利妥昔单抗是否能降低抗HLA抗体水平并提高移植率。
在2005年9月至2007年5月期间，共纳入20例高度致敏患者（通过补体依赖细胞毒性试验测定的平均[±标准差]T细胞群体反应性抗体水平为77±19%，或存在供体特异性抗体），并接受静脉注射免疫球蛋白和利妥昔单抗治疗。我们记录了移植率、群体反应性抗体水平、移植时的交叉配型结果、患者和移植物的存活率、急性排斥反应发作、血清肌酐值、不良事件和严重不良事件以及免疫因素。
第二次静脉注射免疫球蛋白后，平均群体反应性抗体水平为44±30%（与预处理水平相比，P<0.001）。在研究开始时，接受来自已故供体移植的受者中，平均透析时间为144±89个月（范围为60至324个月）。然而，脱敏后至移植的时间为5±6个月（范围为2至18个月）。20例患者中有16例（80%）接受了移植。在12个月时，平均血清肌酐水平为1.5±1.1mg/dL（133±97μmol/L），患者和移植物的平均存活率分别为100%和94%。研究期间未发生与输注相关的不良事件或严重不良事件。对感染并发症和神经问题的长期监测未发现意外事件。
这些发现表明，静脉注射免疫球蛋白和利妥昔单抗联合使用可能被证明是一种有效的脱敏方案，适用于等待来自活体供体或已故供体移植的患者。需要进行更大规模和更长时间的试验来评估这种方法的临床疗效和安全性。（ClinicalTrials.gov编号，NCT00642655。）
