Pharmacokinetics of anti-thymocyte globulin in a patient with severe aplastic anemia treated with allogeneic bone marrow transplantation from a matched unrelated donor

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 21.8 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.