Department of Congenital Heart Disease and Pediatric Cardiology, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.
Department of Cardiovascular Surgery, Faculty of Medicine, University Heart Center Freiburg - Bad Krozingen, Medical Center - University of Freiburg, University of Freiburg, Freiburg, Germany.
Pediatr Transplant. 2024 Mar;28(2):e14698. doi: 10.1111/petr.14698.
Immunosuppression after heart transplantation (HTX) with mammalian target of rapamycin (mTOR) inhibitors serves as a prophylaxis against rejection and to treat coronary vascular injury. However, there is little data on the early, preventive use of everolimus after pediatric HTX.
Retrospective study of 61 pediatric HTX patients (48 cardiomyopathy and 13 congenital heart disease), 28 females, median age 10.1 (range 0.1-17.9) years transplanted between 2008 and 2020. We analyzed survival, rejection, renal function, occurrence of lymphoproliferative disorder, and allograft vasculopathy together with adverse effects of early everolimus therapy combined with low-dose calcineurin inhibitors.
Everolimus therapy was started at a median 3.9 (1-14) days after HTX. Median follow-up was 4.3 (range 0.5-11.8) years, cumulative 184 patient years. The estimated 1- and 5-year survival probability was 89% (CI 82%:98%) and 87% (CI 78%:97%). Four patients developed rejection (6.6%) (maximum 2R ISHLT criteria). No patient suffered from chronic renal failure. Three patients (4.9%) developed post-transplant lymphoproliferative disorder. Five patients suffered relevant wound-healing disorders after transplantation, four of them carrying relevant risk factors before HTX (mechanical circulatory support (n = 3), delayed chest closure after HTX (n = 3)). No recipient developed cardiac allograft vasculopathy.
Initiating everolimus within the first 14 days after HTX seems to be well tolerated, enabling a low incidence of rejection, post-transplant lymphoproliferative disorders, renal failure, and reveals no evidence of cardiac allograft vasculopathy as well as good overall survival in pediatric heart transplant recipients.
心脏移植(HTX)后使用哺乳动物雷帕霉素靶蛋白(mTOR)抑制剂进行免疫抑制可预防排斥反应并治疗冠状动脉损伤。然而,关于儿科 HTX 后早期预防性使用依维莫司的数据很少。
回顾性分析 2008 年至 2020 年间接受 HTX 的 61 例儿科 HTX 患者(48 例心肌病和 13 例先天性心脏病),其中女性 28 例,中位年龄 10.1(范围 0.1-17.9)岁。我们分析了生存、排斥反应、肾功能、淋巴增殖障碍的发生以及同种异体移植物血管病,同时分析了早期依维莫司联合低剂量钙调神经磷酸酶抑制剂治疗的不良反应。
依维莫司治疗于 HTX 后中位 3.9(1-14)天开始。中位随访时间为 4.3(范围 0.5-11.8)年,累积 184 患者年。估计 1 年和 5 年生存率分别为 89%(CI 82%:98%)和 87%(CI 78%:97%)。4 例患者发生排斥反应(6.6%)(最大 2R ISHLT 标准)。无患者发生慢性肾衰竭。3 例患者(4.9%)发生移植后淋巴增殖障碍。5 例患者移植后发生相关伤口愈合障碍,其中 4 例患者在 HTX 前有相关危险因素(机械循环支持(n=3),HTX 后胸部闭合延迟(n=3))。无受者发生心脏移植物血管病。
在 HTX 后 14 天内开始使用依维莫司似乎耐受性良好,排斥反应、移植后淋巴增殖障碍、肾衰竭的发生率较低,并且在儿科心脏移植受者中未发现心脏移植物血管病的证据以及良好的总体生存率。