Department of Pediatric Cardiology, Washington University in St. Louis, St. Louis, Missouri, USA.
Department of Cardiovascular Surgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.
J Heart Lung Transplant. 2018 Apr;37(4):458-466. doi: 10.1016/j.healun.2017.05.010. Epub 2017 May 11.
Induction therapy is increasingly being used in pediatric heart transplantation. General versus risk-adapted use remains controversial. We aimed to determine the impact of induction therapy on outcomes after stratifying patients by diagnosis and risk.
The Pediatric Heart Transplant Study (PHTS) database was used to identify patients (age ≤18 years) who underwent transplantation between January 1, 2001 and December 31, 2014. Patients were excluded if they survived <48 hours or received multiple induction agents. Patients were stratified using a multivariable model to predict 1-year mortality. Patients within the top 25% risk of predicted mortality were defined as high risk (HR) and the bottom 75% as low risk (LR).
Of the 2,860 patients studied, 1,370 received anti-lymphocyte antibody (ALA), 707 received an interleukin-2 receptor antagonist (IL-2RA) and 783 received no induction (NI) therapy. Overall, patients with NI had lower survival (p < 0.01); however, multivariable analysis did not demonstrate an association with graft loss. Freedom from rejection was greater among LR congenital heart disease (CHD) and all cardiomyopathy (CMP) patients who received induction therapy (p < 0.01, for both), as confirmed in a multivariable analysis for CMP patients. Frequency of graft vasculopathy was higher in LR CMP patients who received NI. Freedom from infection was lower with IL-2RA in the LR groups.
Pediatric heart transplant survival has improved in the recent era, in concert with increased use of induction therapy. Although induction therapy is associated with decreased rejection, it was not found to directly influence survival on multivariable analysis. Lower risk patients may benefit the most from induction therapy, particularly IL-2RA, which may be correlated with decreased infection and rejection in this cohort.
诱导治疗在儿科心脏移植中越来越多地被使用。一般而言，适应性使用仍然存在争议。我们旨在通过分层患者的诊断和风险来确定诱导治疗对结果的影响。
使用儿科心脏移植研究（PHTS）数据库确定 2001 年 1 月 1 日至 2014 年 12 月 31 日期间接受移植的患者（年龄≤18 岁）。如果患者存活时间<48 小时或接受了多种诱导剂，则将其排除在外。使用多变量模型对患者进行分层，以预测 1 年死亡率。预测死亡率最高的 25%的患者被定义为高风险（HR），而最低的 75%为低风险（LR）。
在研究的 2860 名患者中，1370 名接受了抗淋巴细胞抗体（ALA），707 名接受了白细胞介素-2 受体拮抗剂（IL-2RA），783 名未接受诱导（NI）治疗。总体而言，NI 组患者的生存率较低（p<0.01）；然而，多变量分析并未显示与移植物丢失有关。LR 先天性心脏病（CHD）和所有心肌病（CMP）患者接受诱导治疗后，排斥反应的发生率较低（p<0.01，均如此），这在 CMP 患者的多变量分析中得到了证实。LR CMP 患者接受 NI 后，移植物血管病的发生率较高。LR 组中 IL-2RA 的感染发生率较低。
儿科心脏移植的存活率在最近的时代有所提高，这与诱导治疗的使用增加有关。尽管诱导治疗与降低排斥反应有关，但在多变量分析中并未发现其直接影响生存率。低危患者可能从诱导治疗中获益最多，尤其是 IL-2RA，这可能与该队列中的感染和排斥反应减少有关。
