背景:延长心脏移植(HT)后的移植物存活对于儿童受者实现成年后的存活至关重要。急性排斥反应是一个重要的不良事件,与抗体介导的排斥反应(AMR)相比,活检仍然是诊断急性细胞排斥反应(ACR)的最特异性手段。
方法:纳入儿科心脏移植协会(PHTS)注册中心的所有儿童,他们在2015年1月6日至2022年6月期间接受了HT,并且有≥1次治疗排斥反应。比较AMR患者和仅ACR患者排斥后的生存率。感染的次要结果,恶性肿瘤,和心脏移植血管病变(CAV)进行评估。使用Cox比例风险模型确定AMR后移植物丢失的危险因素。
结果:在2022年12月12日随访期间接受排斥治疗的906名儿童中,包括697名(77%)具有完整活检信息的儿童。261例(37%)患者的活检中存在AMR;436例(63%)患者仅存在ACR。AMR患者治疗排斥反应的时间较早,从HT到拒绝的中位时间为0.11年对0.29年,p=0.0006。当拒绝在第一年内发生时,AMR后的生存率低于仅ACR后的生存率。AMR后移植物丢失的预测因素在HT时年龄较小,先天性心脏病的诊断,和排斥与血液动力学妥协。CAV在时间上没有区别,感染,或恶性肿瘤后,治疗组之间的排斥反应。
结论:对接受排斥治疗的儿童HT受者进行最大的分析,通过活检数据确定AMR,强调了AMR对生存的持续重要性。与ACR相比,当发生在HT后的第一年时,AMR与较高的移植物损失有关。AMR后移植物丢失的预测因素确定可能从增加监测中受益的患者,更积极的排斥治疗,或增强的维持免疫抑制。
BACKGROUND: Extending graft survival after heart transplant (HT) is of paramount importance to achieve survival well into adulthood for childhood recipients. Acute rejection is a significant adverse event, and biopsy remains the most specific means for diagnosing acute cellular rejection (ACR) versus antibody-mediated rejection (AMR).
METHODS: All children in the Pediatric Heart Transplant Society (PHTS) Registry who underwent HT between 1/2015 and 6/2022 and had ≥1 episode of treated rejection were included. Survival after rejection was compared between those with AMR and those with ACR-only. Secondary outcomes of infection, malignancy, and cardiac allograft vasculopathy (CAV) were assessed. Risk factors for graft loss after AMR were identified using Cox proportional hazard modeling.
RESULTS: Among 906 children treated for rejection during follow-up through 12/2022, 697 (77%) with complete biopsy information were included. AMR was present on biopsy in 261 (37%) patients; ACR-only was present in 436 (63%) patients. Time to treated rejection was earlier in those with AMR, median time from HT to rejection 0.11 versus 0.29 years, p=0.0006. When rejection occurred within the 1st year, survival after AMR was lower than survival after ACR-only. Predictors of graft loss after AMR were younger age at HT, diagnosis of congenital heart disease, and rejection with hemodynamic compromise. There was no difference in time to CAV, infection, or malignancy after treated rejection between groups.
CONCLUSIONS: The largest analysis of pediatric HT recipients treated for rejection with biopsy data to identify AMR underscores the continued importance of AMR on survival. AMR is associated with higher graft loss versus ACR when occurring in the first-year post HT. Predictors of graft loss after AMR identify patients who may benefit from increased surveillance, more aggressive rejection treatment, or augmented maintenance immunosuppression.