Kawano Noriaki, Matsumoto Kana, Takami Akiyoshi, Tochigi Taro, Yoshida Shuro, Kuriyama Takuro, Nakaike Takashi, Shimokawa Tomonori, Yamashita Kiyoshi, Mashiba Koichi, Kikuchi Ikuo, Nakao Shinji
Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan.
Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Women's College of Liberal Arts, Kyotanabe, Japan.
Blood Cell Ther. 2020 Dec 28;4(1):15-19. doi: 10.31547/bct-2020-012. eCollection 2021 Feb 25.
Anti-thymocyte globulin (ATG) is an important component of preparative regimens for allogeneic bone marrow transplantation (BMT) for aplastic anemia (AA). However, the pharmacokinetics (PK) of ATG are unclear. A 38-year-old woman with severe AA underwent BMT using a fludarabine (Flu)-based and reduced-dose cyclophosphamide (CPA)-conditioning regimen comprising rabbit ATG (2.5 mg/kg, days -7 and -6), Flu (30 mg/sqm, days -5 to -2), CPA (25 mg/kg, days -5 to -2), and total body irradiation (2 Gy, day -1), following a human leukocyte antigen-match with an unrelated donor. Notably, ATG was administered earlier than that recommended by conventional schedules. The engraftment was achieved on day 15 without reactivation of the Epstein-Barr virus and residual recipient cells. Absolute lymphocyte recovery (>0.5×10/L) was achieved on day 22. The ATG concentration on day 0 and the area under the concentration-time curve (AUC) for ATG after allogeneic BMT were 21.8 μg/mL and 464 μg・day/mL, respectively. The patient remained disease-free for 6 years after BMT without acute or chronic graft-versus-host disease. Moreover, based on serum PK monitoring of ATG, including ATG concentration on day 0 and the AUC for ATG after BMT, the patient safely underwent the less-toxic, Flu-based, reduced-dose CPA regimen containing a low dose of ATG. In conclusion, we present the first report that analyzed the PK of ATG in a patient with AA treated with BMT from a matched unrelated donor. These findings might be helpful to determine ATG dosages for such patients receiving similar transplantations.
抗胸腺细胞球蛋白（ATG）是再生障碍性贫血（AA）异基因骨髓移植（BMT）预处理方案的重要组成部分。然而，ATG的药代动力学（PK）尚不清楚。一名38岁的重症AA女性患者接受了BMT，采用基于氟达拉滨（Flu）和低剂量环磷酰胺（CPA）的预处理方案，包括兔ATG（2.5mg/kg，第-7天和-6天）、Flu（30mg/sqm，第-5天至-2天）、CPA（25mg/kg，第-5天至-2天）以及全身照射（2Gy，第-1天），供者为人类白细胞抗原匹配的无关供者。值得注意的是，ATG的给药时间早于传统方案推荐的时间。第15天实现植入，未出现爱泼斯坦-巴尔病毒再激活和残留受者细胞。第22天实现绝对淋巴细胞恢复（>0.5×10⁹/L）。异基因BMT后第0天的ATG浓度和ATG浓度-时间曲线下面积（AUC）分别为21.8μg/mL和464μg·天/mL。该患者在BMT后6年无病生存，未发生急性或慢性移植物抗宿主病。此外，基于对ATG的血清PK监测，包括第0天的ATG浓度和BMT后ATG的AUC，该患者安全地接受了毒性较小的基于Flu、低剂量CPA且含低剂量ATG的方案。总之，我们首次报告了对一名接受匹配无关供者BMT治疗的AA患者的ATG PK进行分析的情况。这些发现可能有助于确定接受类似移植的此类患者的ATG剂量。
