MedicalPark Goztepe Hospital, Pediatric Bone Marrow Transplantation Unit, Istanbul, Turkey.
MedicalPark Antalya Hospital, Pediatric Bone Marrow Transplantation Unit, Antalya, Turkey.
Clin Transplant. 2021 Jul;35(7):e14328. doi: 10.1111/ctr.14328. Epub 2021 May 3.
The selection of graft-vs. -host disease (GvHD) prophylaxis is vital for the success of hematopoetic stem cell transplantation (HSCT), and calcineurin inhibitors (CNI) have been used for decades as the backbone of GvHD prophylaxis. The aim of this study is to analyze the results of switching cyclosporine (CSA) to tacrolimus because of acute GvHD, engraftment syndrome (ES), persistent low level of CSA, or various CSA-associated adverse events in the first 100 days of pediatric HSCT.
This is a retrospective analysis of 192 patients who underwent allogeneic hematopoietic stem cell transplantation at Medicalpark Göztepe and Antalya Hospitals between April 2014 and May 2019 had therapy switched from CSA to tacrolimus-based immunosuppression within 100 days of transplant.
The reasons for conversion to tacrolimus were low level of CSA (n = 70), aGvHD (n = 63), CSA-associated neurotoxicity (n = 15), CSA-associated nephrotoxicity (n = 10), hypertension (n = 10), allergic reactions (n = 9), ES (n = 7), CSA-associated hepatotoxicity (n = 5), and vomiting (n = 3). The median day after transplant for conversion to tacrolimus for all patients was day 20 (range 0-100 days). Response rates to conversion were 38% for GvHD, 86% for neurotoxicity, 50% for nephrotoxicity, 60% for hepatotoxicity, 80% for hypertension, 66% for vomiting, and 57% for ES. Twenty-nine patients (15%) experienced tacrolimus-associated toxicities after therapy conversion to tacrolimus. Neurotoxicity emerged as posterior reversible encephalopathy syndrome (PRES), which was the most common toxicity observed after conversion (18/29 patients).
Our data support the quick conversion to tacrolimus in the condition of persistent low CSA levels with acceptable efficacy and safety. Although both drugs are CNI and share a very similar mechanism of action, the conversion could be preferred especially in specific organ toxicities with special attention for neurotoxicity after conversion.
移植物抗宿主病（GVHD）预防方案的选择对造血干细胞移植（HSCT）的成功至关重要，数十年来钙调神经磷酸酶抑制剂（CNI）一直被用作 GVHD 预防的基础。本研究旨在分析在 HSCT 后 100 天内，因急性 GVHD、植入综合征（ES）、持续低水平 CSA 或各种 CSA 相关不良事件而将环孢素（CSA）转换为他克莫司治疗的结果。
这是对 2014 年 4 月至 2019 年 5 月期间在 Medicalpark Göztepe 和 Antalya 医院接受同种异体造血干细胞移植的 192 名患者进行的回顾性分析，这些患者在移植后 100 天内将 CSA 转换为基于他克莫司的免疫抑制治疗。
转换为他克莫司的原因包括 CSA 水平低（n=70）、aGVHD（n=63）、CSA 相关神经毒性（n=15）、CSA 相关肾毒性（n=10）、高血压（n=10）、过敏反应（n=9）、ES（n=7）、CSA 相关肝毒性（n=5）和呕吐（n=3）。所有患者转换为他克莫司的中位时间为移植后第 20 天（范围 0-100 天）。GVHD 转换的反应率为 38%，神经毒性为 86%，肾毒性为 50%，肝毒性为 60%，高血压为 80%，呕吐为 66%，ES 为 57%。29 名患者（15%）在转换为他克莫司后出现他克莫司相关毒性。神经毒性表现为可逆性后部脑病综合征（PRES），这是转换后最常见的毒性（29 名患者中的 18 名）。
我们的数据支持在持续低 CSA 水平的情况下快速转换为他克莫司，具有可接受的疗效和安全性。虽然这两种药物都是 CNI，具有非常相似的作用机制，但转换可能是首选，特别是在特定器官毒性方面，转换后应特别注意神经毒性。
