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Case Report
Pharmacokinetics of anti-thymocyte globulin in a patient with severe aplastic anemia treated with allogeneic bone marrow transplantation from a matched unrelated donor
Noriaki Kawano1, Kana Matsumoto2, Akiyoshi Takami3, Taro Tochigi1, Shuro Yoshida1, Takuro Kuriyama1, Takashi Nakaike1, Tomonori Shimokawa1, Kiyoshi Yamashita1, Koichi Mashiba1, Ikuo Kikuchi1, Shinji Nakao4

1Department of Internal Medicine, Miyazaki Prefectural Miyazaki Hospital, Miyazaki, Japan,

2Department of Clinical Pharmaceutics, Faculty of Pharmaceutical Sciences, Doshisha Womenʼs College of Liberal Arts, Kyotanabe, Japan,

3Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Yazakokarimata, Nagakute, Japan,

4Department of Hematology, Faculty of Medicine, Institute of Medical Pharmaceutical and Health Sciences, Kanazawa University, Kanazawa, Japan

Keywords
aplastic anemia, pharmacokinetics, anti-thymocyte globulin, reduced conditioning, total body irradiation
Submitted:August 4, 2020
Accepted:October 26, 2020
Published online:December 28, 2020

Abstract

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 (>0.5×109/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 21.8μg/mL and 464μg・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.

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Online ISSN:2432-7026