期刊
INTERNATIONAL JOURNAL OF HEMATOLOGY
卷 94, 期 2, 页码 193-202出版社
SPRINGER JAPAN KK
DOI: 10.1007/s12185-011-0888-6
关键词
MMF; GVHD prophylaxis; Drug monitoring; Unrelated donor
类别
资金
- Ministry of Health, Welfare, and Labor in Japan
- Grants-in-Aid for Scientific Research [22591037] Funding Source: KAKEN
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 mu g 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 mu g 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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