Department of Cardiovascular Surgery, Mayo Clinic, Rochester, Minnesota, USA.
Department of Cardiovascular Medicine, Mayo Clinic, Rochester, Minnesota, USA; William J von Liebig Center for Transplantation and Clinical Regeneration, Mayo Clinic, Rochester, Minnesota, USA.
J Am Coll Cardiol. 2021 Mar 16;77(10):1331-1340. doi: 10.1016/j.jacc.2021.01.013.
In patients undergoing heart transplantation, significant allosensitization limits access to organs, resulting in longer wait times and high waitlist mortality. Current desensitization strategies are limited in enabling successful transplantation.
The purpose of this study was to describe the cumulative experience of combined heart-liver transplantation using a novel heart-after-liver transplant (HALT) protocol resulting in profound immunologic protection.
Reported are the results of a clinical protocol that was instituted to transplant highly sensitized patients requiring combined heart and liver transplantation at a single institution. Patients were dual-organ listed with perceived elevated risk of rejection or markedly prolonged waitlist time due to high levels of allo-antibodies. Detailed immunological data and long-term patient and graft outcomes were obtained.
A total of 7 patients (age 43 ± 7 years, 86% women) with high allosensitization (median calculated panel reactive antibody = 77%) underwent HALT. All had significant, unacceptable donor specific antibodies (DSA) (>4,000 mean fluorescence antibody). Prospective pre-operative flow cytometric T-cell crossmatch was positive in all, and B-cell crossmatch was positive in 5 of 7. After HALT, retrospective crossmatch (B- and T-cell) became negative in all. DSA fell dramatically; at last follow-up, all pre-formed or de novo DSA levels were insignificant at <2,000 mean fluorescence antibody. No patients experienced >1R rejection over a median follow-up of 48 months (interquartile range: 25 to 68 months). There was 1 death due to metastatic cancer and no significant graft dysfunction.
A heart-after-liver transplantation protocol enables successful transplantation via near-elimination of DSA and is effective in preventing adverse immunological outcomes in highly sensitized patients listed for combined heart-liver transplantation.
在接受心脏移植的患者中，显著的同种异体致敏限制了器官的可获得性，导致等待时间延长和高等待名单死亡率。目前的脱敏策略在实现成功移植方面受到限制。
本研究旨在描述一种新的心脏-肝移植后（HALT）方案在实现深度免疫保护方面的累积经验，该方案导致显著的免疫保护。
报告了一项临床方案的结果，该方案旨在在一家机构为需要联合心脏和肝脏移植的高度致敏患者进行移植。患者被双重器官列入名单，由于高水平的同种异体抗体，预计排斥反应风险高或等待名单时间明显延长。获得了详细的免疫数据和长期的患者和移植物结果。
共有 7 名（年龄 43 ± 7 岁，86%为女性）高度致敏（中位计算的 panel reactive antibody = 77%）的患者接受了 HALT。所有人都有明显的、不可接受的供体特异性抗体（DSA）（>4000 平均荧光抗体）。所有患者的术前前瞻性流式细胞术 T 细胞交叉匹配均为阳性，7 例中有 5 例 B 细胞交叉匹配阳性。在 HALT 后，所有患者的回顾性交叉匹配（B 和 T 细胞）均变为阴性。DSA 显著下降；在最后一次随访时，所有预先形成或新形成的 DSA 水平均显著低于<2000 平均荧光抗体。中位随访 48 个月（四分位距：25 至 68 个月）内无患者发生>1R 排斥反应。有 1 例因转移性癌症死亡，无明显移植物功能障碍。
心脏-肝移植后方案通过几乎消除 DSA 实现了成功移植，并在预防高度致敏患者接受联合心脏-肝移植时发生不良免疫结果方面是有效的。
