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

Research output: Contribution to journalArticlepeer-review

22 Scopus citations

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 (AUC 0-24h). In allo-BMT, high AUC 0-24h (>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, AUC 0-24h less than 30 μg h/ml was sufficient for low incidence of acute/chronic GVHD and high survival. Strong correlation between AUC 0-24h and C 2h, plasma MPA concentration at 2 h after administration was observed. Single point assessment of C 2h was shown to provide a useful surrogate of AUC 0-24h 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.

Original languageEnglish (US)
Pages (from-to)193-202
Number of pages10
JournalInternational journal of hematology
Volume94
Issue number2
DOIs
StatePublished - Aug 2011

All Science Journal Classification (ASJC) codes

  • Hematology

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