TY - JOUR
T1 - Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation
AU - Wakahashi, Kanako
AU - Yamamori, Motohiro
AU - Minagawa, Kentaro
AU - Ishii, Shinichi
AU - Nishikawa, Shinichirou
AU - Shimoyama, Manabu
AU - Kawano, Hiroki
AU - Kawano, Yuko
AU - Kawamori, Yuriko
AU - Sada, Akiko
AU - Matsui, Toshimitsu
AU - Katayama, Yoshio
N1 - Funding Information:
Acknowledgments This work was supported, in part, by the Grants-in-Aid for Scientific Research from the Ministry of Health, Welfare, and Labor in Japan.
PY - 2011/8
Y1 - 2011/8
N2 - 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.
AB - 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.
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U2 - 10.1007/s12185-011-0888-6
DO - 10.1007/s12185-011-0888-6
M3 - Article
C2 - 21751082
AN - SCOPUS:80052369329
SN - 0925-5710
VL - 94
SP - 193
EP - 202
JO - International journal of hematology
JF - International journal of hematology
IS - 2
ER -