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 journalArticle

18 Citations (Scopus)

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 1 2011

Fingerprint

Mycophenolic Acid
Cell Transplantation
Area Under Curve
Pharmacokinetics
Graft vs Host Disease
Hematopoietic Stem Cell Transplantation
Incidence
Fetal Blood
Transplantation
Mucositis
Methotrexate
Disease-Free Survival
Bone Marrow
Recurrence
Mortality

All Science Journal Classification (ASJC) codes

  • Hematology

Cite this

Wakahashi, Kanako ; Yamamori, Motohiro ; Minagawa, Kentaro ; Ishii, Shinichi ; Nishikawa, Shinichirou ; Shimoyama, Manabu ; Kawano, Hiroki ; Kawano, Yuko ; Kawamori, Yuriko ; Sada, Akiko ; Matsui, Toshimitsu ; Katayama, Yoshio. / Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation. In: International journal of hematology. 2011 ; Vol. 94, No. 2. pp. 193-202.
@article{06e747a1a9e14e70af717d6d3497e2ed,
title = "Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation",
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.",
author = "Kanako Wakahashi and Motohiro Yamamori and Kentaro Minagawa and Shinichi Ishii and Shinichirou Nishikawa and Manabu Shimoyama and Hiroki Kawano and Yuko Kawano and Yuriko Kawamori and Akiko Sada and Toshimitsu Matsui and Yoshio Katayama",
year = "2011",
month = "8",
day = "1",
doi = "10.1007/s12185-011-0888-6",
language = "English (US)",
volume = "94",
pages = "193--202",
journal = "International Journal of Hematology",
issn = "0925-5710",
publisher = "Springer Japan",
number = "2",

}

Wakahashi, K, Yamamori, M, Minagawa, K, Ishii, S, Nishikawa, S, Shimoyama, M, Kawano, H, Kawano, Y, Kawamori, Y, Sada, A, Matsui, T & Katayama, Y 2011, 'Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation', International journal of hematology, vol. 94, no. 2, pp. 193-202. https://doi.org/10.1007/s12185-011-0888-6

Pharmacokinetics-based optimal dose prediction of donor source-dependent response to mycophenolate mofetil in unrelated hematopoietic cell transplantation. / Wakahashi, Kanako; Yamamori, Motohiro; Minagawa, Kentaro; Ishii, Shinichi; Nishikawa, Shinichirou; Shimoyama, Manabu; Kawano, Hiroki; Kawano, Yuko; Kawamori, Yuriko; Sada, Akiko; Matsui, Toshimitsu; Katayama, Yoshio.

In: International journal of hematology, Vol. 94, No. 2, 01.08.2011, p. 193-202.

Research output: Contribution to journalArticle

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

PY - 2011/8/1

Y1 - 2011/8/1

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.

UR - http://www.scopus.com/inward/record.url?scp=80052369329&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052369329&partnerID=8YFLogxK

U2 - 10.1007/s12185-011-0888-6

DO - 10.1007/s12185-011-0888-6

M3 - Article

C2 - 21751082

AN - SCOPUS:80052369329

VL - 94

SP - 193

EP - 202

JO - International Journal of Hematology

JF - International Journal of Hematology

SN - 0925-5710

IS - 2

ER -