Background

ABO-incompatible heart transplantation increases donor availability in young children and is evolving into standard of care in children younger than 2 years. Previous smaller studies suggest similar outcomes to ABO-compatible heart transplantation, but persisting alterations of the immune system in ABO-incompatible recipients might increase the risk of some infections or benefit the graft owing to reduced HLA reactivity. We aimed to assess long-term outcomes in young children after they received ABO-incompatible or ABO-compatible heart transplantation.

Methods

In this multicentre, prospective cohort study, we analysed data from the Pediatric Heart Transplant Society registry to compare children who received ABO-incompatible or ABO-compatible heart transplantation before age 2 years between Jan 1, 1999, and June 30, 2018. Given significantly different clinical demographics between the two groups, we also matched each ABO-incompatible recipient to two ABO-compatible recipients using propensity score matching. We assessed patient and graft survival, coronary allograft vasculopathy, malignancy, acute rejection (any episode resulting in augmentation of immunosuppression), and infections (requiring intravenous antibiotic or antiviral therapy or life-threatening infections treated with oral therapy).

Findings

We included 2206 children who received a heart transplant before age 2 years, with 11 332·6 patient-years of cumulative observation time. Children who received an ABO-incompatible transplant (n=364) were younger and a larger proportion had congenital heart disease and ventilator and mechanical circulatory support than the ABO-compatible recipients (n=1842). After matching, only differences in blood group (more O in ABO-incompatible and more AB in ABO-compatible groups) and use of polyclonal induction therapy with anti-thymocyte globulins persisted. The two matched groups had similar post-transplantation graft survival (p=0·74), freedom from coronary allograft vasculopathy (p=0·75), and malignancy (p=0·51). ABO-incompatible recipients showed longer freedom from rejection (p=0·0021) in the overall cohort, but not after matching (p=0·48). Severe infections (p=0·0007), bacterial infections (p=0·0005), and infections with polysaccharide encapsulated bacteria (p=0·0005) that share immunological properties with blood group antigens occurred less frequently after ABO-incompatible heart transplantation.

Interpretation

ABO-incompatible heart transplantation for children younger than 2 years is a clinically safe approach, with similar survival and incidences of rejection, coronary allograft vasculopathy, and malignancy to ABO-compatible recipients, despite higher-risk pre-transplant profiles. ABO-incompatible transplantation was associated with less bacterial infection, particularly encapsulated bacteria, suggesting that the acquired immunological changes accompanying ABO tolerance might benefit rather than jeopardise transplanted children.

Funding

Pediatric Heart Transplant Society.

中文翻译：

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多中心队列研究：接受ABO不相容与接受ABO相容的儿童的临床结局

背景

不兼容ABO的心脏移植可增加年幼儿童的供体可用性，并正在发展为2岁以下儿童的标准治疗。先前的较小研究表明，与ABO相容性心脏移植的结果相似，但与ABO不相容的受体中免疫系统的持续变化可能会由于HLA反应性降低而增加某些感染的风险或使移植物受益。我们旨在评估年幼儿童接受ABO不相容或ABO相容性心脏移植后的长期结局。

方法

在这项多中心，前瞻性队列研究中，我们分析了儿科心脏移植协会注册表中的数据，以比较1999年1月1日至2018年6月30日之间2岁之前接受ABO不兼容或ABO兼容心脏移植的儿童。两组之间的临床人口统计学特征不同，我们还使用倾向评分匹配将每个ABO不兼容的接受者与两个ABO兼容的接受者进行了匹配。我们评估了患者和移植物的存活率，同种异体冠状动脉血管病，恶性肿瘤，急性排斥反应（任何导致免疫抑制增强的发作）和感染（需要静脉使用抗生素或抗病毒治疗或通过口服疗法治疗的威胁生命的感染）。

发现

我们纳入了2206名2岁之前接受心脏移植的儿童，其累积观察时间为11 332·6患者年。与ABO不兼容的接受者（n = 1842）接受ABO不兼容的接受移植的儿童（n = 364）年龄较小，并且具有先天性心脏病，呼吸机和机械循环支持的比例更大。匹配后，仅存在血型差异（与ABO不相容的组中O含量更高，与ABO相容性组中AB含量更高）以及使用抗胸腺细胞球蛋白的多克隆诱导疗法的差异仍然存在。两组配对患者的移植后存活率相似（p = 0·74），不受冠状动脉同种异体血管病变的影响（p = 0·75）和恶性程度（p = 0·51）。与ABO不相容的接受者在整个队列中显示出更长的拒绝排斥时间（p = 0·0021），但在匹配后却没有（p = 0·48）。

解释

对于2岁以下的儿童，ABO不相容的心脏移植是一种临床安全的方法，尽管移植前的风险较高，但与ABO相容的接受者的生存率和排斥反应，冠状动脉同种异体血管病变和恶性肿瘤的发生率相似。与ABO不相容的移植与较少的细菌感染（尤其是包膜细菌）相关，这表明伴随ABO耐受的获得性免疫学改变可能有益而不是危害被移植的儿童。

资金

小儿心脏移植协会。