Abstract：
BACKGROUND: The lack of evidence regarding optimal desensitization strategies for lung transplant candidates with preformed donor specific anti-human leukocyte antigen antibodies (DSAs) has led to varying approaches among centers towards this patient group. Our institution\'s desensitization protocol for recipients with preformed DSAs and negative flow cytometry crossmatch (FCXM) consists of intravenous immunoglobulin (IVIG) as the sole therapy. The study aimed to determine outcomes using this approach.
METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models.
RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups.
CONCLUSIONS: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.
METHODS: This retrospective study included adults who underwent lung-only transplantation for the first time between January 2015 and March 2022 at a single center. We excluded patients with positive or missing FCXM results. Transplant recipients with any DSA ≥ 1000 MFI on latest testing within three months of transplant were considered DSA-positive, while recipients with DSAs <1000 MFI and those without DSAs were assigned to the low-level/negative group. Graft survival (time to death/retransplantation) and chronic lung allograft dysfunction (CLAD)-free times were compared between groups using Cox proportional hazards models.
RESULTS: Thirty-six out of 167 eligible patients (22%) were DSA-positive. At least 50% of preformed DSAs had documented clearance (decrease to <1000 MFI) within the first 6 months of transplant. Multivariable Cox regression analyses did not detect a significantly increased risk of graft failure (aHR 1.04 95%CI 0.55-1.97) or chronic lung allograft dysfunction (aHR 0.71 95%CI 0.34-1.52) in DSA-positive patients compared to patients with low-level/negative DSAs. Incidences of antibody-mediated rejection (p = 1.00) and serious thromboembolic events (p = 0.63) did not differ between study groups.
CONCLUSIONS: We describe a single-center experience of administering IVIG alone to lung transplant recipients with preformed DSAs and negative FCXM. Further studies are required to confirm the efficacy of this strategy against other protocols.
摘要：
背景：缺乏关于使用预先形成的供体特异性抗人白细胞抗原抗体（DSA）的肺移植候选者的最佳脱敏策略的证据，已导致中心之间针对该患者组的不同方法。我们机构针对预先形成的DSA和阴性流式细胞术交叉匹配（FCXM）的受体的脱敏方案包括静脉内免疫球蛋白（IVIG）作为唯一的治疗。该研究旨在使用这种方法确定结果。
方法：这项回顾性研究包括2015年1月至2022年3月首次在单个中心接受仅肺移植的成年人。我们排除了FCXM结果阳性或缺失的患者。移植后三个月内最新检测的任何DSA≥1000MFI的移植受者被认为是DSA阳性。而DSA<1000MFI的接受者和没有DSA的接受者被分配到低水平/阴性组。使用Cox比例风险模型比较两组之间的移植物存活（死亡/再移植时间）和无慢性同种异体肺移植功能障碍（CLAD）时间。
结果：167名符合条件的患者中有36名（22%）为DSA阳性。在移植的前6个月内，至少有50％的预制DSA已记录清除（降低至<1000MFI）。与低水平/阴性DSA患者相比，多变量Cox回归分析未发现DSA阳性患者移植失败（aHR1.0495CI0.55-1.97）或慢性肺移植功能障碍（aHR0.7195CI0.34-1.52）的风险显着增加。抗体介导的排斥反应（p=1.00）和严重血栓栓塞事件（p=0.63）的发生率在研究组之间没有差异。
结论：我们描述了对预先形成的DSA和FCXM阴性的肺移植受者单独施用IVIG的单中心经验。需要进一步的研究来确认该策略相对于其他方案的有效性。
方法：这项回顾性研究包括2015年1月至2022年3月首次在单个中心接受仅肺移植的成年人。我们排除了FCXM结果阳性或缺失的患者。移植后三个月内最新检测的任何DSA≥1000MFI的移植受者被认为是DSA阳性。而DSA<1000MFI的接受者和没有DSA的接受者被分配到低水平/阴性组。使用Cox比例风险模型比较两组之间的移植物存活（死亡/再移植时间）和无慢性同种异体肺移植功能障碍（CLAD）时间。
结果：167名符合条件的患者中有36名（22%）为DSA阳性。在移植的前6个月内，至少有50％的预制DSA已记录清除（降低至<1000MFI）。与低水平/阴性DSA患者相比，多变量Cox回归分析未发现DSA阳性患者移植失败（aHR1.0495CI0.55-1.97）或慢性肺移植功能障碍（aHR0.7195CI0.34-1.52）的风险显着增加。抗体介导的排斥反应（p=1.00）和严重血栓栓塞事件（p=0.63）的发生率在研究组之间没有差异。
结论：我们描述了对预先形成的DSA和FCXM阴性的肺移植受者单独施用IVIG的单中心经验。需要进一步的研究来确认该策略相对于其他方案的有效性。
