Division of Pulmonary and Critical Care Medicine, Hospital of the University of Pennsylvania, Philadelphia, Pennsylvania.
Department of Medicine.
Ann Am Thorac Soc. 2019 Sep;16(9):1131-1137. doi: 10.1513/AnnalsATS.201812-869OC.
There is significant variation in approach to pre-lung transplant donor-specific antibodies (DSA), with some centers declining to cross any DSA. We implemented a protocol for transplantation for candidates with pretransplant DSA so long as a prospective complement-dependent cytotoxicity crossmatch was negative, regardless of number, specificity, class, or mean fluorescence intensity. To compare post-transplant outcomes including overall survival, chronic lung allograft dysfunction-free survival, antibody-mediated rejection, and acute cellular rejection in lung transplant recipients where pretransplant DSA was and was not present. This was a single-center retrospective cohort study. For recipients with pretransplant DSA, if the prospective complement-dependent cytotoxicity crossmatch was negative, the donor offer was accepted and plasmapheresis was performed within 24 hours of transplantation and continued until retrospective crossmatch results returned. Immunosuppression and post-transplant management were not otherwise modified. Of the 203 included recipients, 18 (8.9%) had pretransplant DSA. The median DSA mean fluorescence intensity was 4,000 (interquartile range, 2,975-5,625; total range, 2,100-17,000). The median number of DSA present per patient was one (interquartile range, 1-2). The presence of pretransplant DSA was not associated with increased mortality (hazard ratio, 1.2; 95% confidence interval [CI], 0.4-3.4) or decreased chronic lung allograft dysfunction-free survival (hazard ratio, 1.1; 95% CI, 0.6-2.1). Recipients with pretransplant DSA were more likely to require prolonged mechanical ventilation (adjusted odds ratio, 7.0; 95% CI, 2.3-21.6) and to have antibody-mediated rejection requiring treatment (adjusted odds ratio, 7.5; 95% CI, 1.0-55.8). A protocol of accepting donor offers for lung transplant candidates with preformed, complement-dependent cytotoxicity crossmatch-negative DSA is associated with increased need for prolonged mechanical ventilation and antibody-mediated rejection without affecting short-term overall or chronic lung allograft dysfunction-free survival.
在肺移植前供体特异性抗体(DSA)的处理方法上存在显著差异,有些中心拒绝交叉任何 DSA。我们为有移植前 DSA 的候选者制定了一个移植方案,只要前瞻性补体依赖性细胞毒性交叉配型为阴性,无论 DSA 的数量、特异性、类别或平均荧光强度如何,都可以进行移植。比较肺移植受者中存在和不存在移植前 DSA 的情况下,包括总体存活率、慢性肺移植物功能障碍无失败存活率、抗体介导的排斥反应和急性细胞排斥反应的移植后结果。这是一项单中心回顾性队列研究。对于有移植前 DSA 的受者,如果前瞻性补体依赖性细胞毒性交叉配型为阴性,则接受供体,并在移植后 24 小时内进行血浆置换,直到回顾性交叉配型结果返回。否则,免疫抑制和移植后管理没有改变。在 203 名纳入的受者中,有 18 名(8.9%)有移植前 DSA。DSA 的平均荧光强度中位数为 4000(四分位距,2975-5625;总范围,2100-17000)。每位患者存在的 DSA 中位数为一个(四分位距,1-2)。移植前 DSA 的存在与死亡率增加无关(危险比,1.2;95%置信区间[CI],0.4-3.4)或慢性肺移植物功能障碍无失败存活率降低(危险比,1.1;95%CI,0.6-2.1)。移植前 DSA 的受者更有可能需要长时间的机械通气(调整后的优势比,7.0;95%CI,2.3-21.6)和需要治疗的抗体介导排斥反应(调整后的优势比,7.5;95%CI,1.0-55.8)。对于有预形成、补体依赖性细胞毒性交叉配型阴性 DSA 的肺移植候选者,接受供体的方案与需要长时间机械通气和抗体介导排斥反应的风险增加有关,而不影响短期总体或慢性肺移植物功能障碍无失败存活率。