Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation

  • Kanako Wakahashi
  • Motohiro Yamamori
  • Kentaro Minagawa
  • Shinichi Ishii
  • Shinichirou Nishikawa
  • Manabu Shimoyama
  • Hiroki Kawano
  • Yuko Kawano
  • Yuriko Kawamori
  • Akiko Sada
  • Toshimitsu Matsui
  • Yoshio Katayama
Original Article

Abstract

Mycophenolate mofetil (MMF) has been widely used for prophylaxis against graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-SCT). However, no clear advantage over methotrexate has been reported, other than reduced incidence of mucositis. We speculated that the wide inter-individual variation of plasma mycophenolic acid (MPA) levels veiled the benefits of MMF. Data from 36 unrelated allogeneic bone marrow (allo-BMT) and cord blood transplantation (CBT) were analyzed retrospectively based on MPA area under the curve (AUC0–24h). In allo-BMT, high AUC0–24h (>30 μg h/ml) resulted in no incidence of grade II–IV acute/extensive chronic GVHD and tended to show higher overall and disease-free survival, lower relapse rates, and non-relapse mortality. In CBT, AUC0–24h less than 30 μg h/ml was sufficient for low incidence of acute/chronic GVHD and high survival. Strong correlation between AUC0–24h and C2h, plasma MPA concentration at 2 h after administration was observed. Single point assessment of C2h was shown to provide a useful surrogate of AUC0–24h to predict GVHD incidence. The results of this study suggest that individualized MMF dosing in a donor source-dependent fashion may be important for maximizing the benefit of MMF in allo-SCT.

Keywords

MMF GVHD prophylaxis Drug monitoring Unrelated donor 

Copyright information

© The Japanese Society of Hematology 2011

Authors and Affiliations

  • Kanako Wakahashi
    • 1
  • Motohiro Yamamori
    • 2
  • Kentaro Minagawa
    • 1
  • Shinichi Ishii
    • 1
  • Shinichirou Nishikawa
    • 1
  • Manabu Shimoyama
    • 1
  • Hiroki Kawano
    • 1
  • Yuko Kawano
    • 1
  • Yuriko Kawamori
    • 1
  • Akiko Sada
    • 1
  • Toshimitsu Matsui
    • 1
  • Yoshio Katayama
    • 1
  1. 1.Division of Hematology, Department of MedicineKobe University Graduate School of MedicineKobeJapan
  2. 2.Department of Clinical Pharmacy, School of Pharmacy and Pharmaceutical SciencesMukogawa Women’s UniversityNishinomiyaJapan

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