title: Use of mycophenolate mofetil and a calcineurin inhibitor in allogeneic hematopoietic stem-cell transplantation from HLA-matched siblings or unrelated volunteer donors: Japanese multicenter phase II trials.
abstract: To test the feasibility of mycophenolate mofetil (MMF) for graft-versus-host disease (GVHD) prophylaxis in Japanese patients, we conducted two multicenter prospective phase II trials of allogeneic hematopoietic stem-cell transplantation (HSCT) from HLA-matched related donors (MRD group) with MMF and cyclosporine or HLA 7-8/8 allele-matched unrelated bone-marrow donors (URD group) with MMF and tacrolimus. The cumulative incidences of grade II-IV acute GVHD on day 100, which was the primary endpoint in these trials, were 45.0% (90% CI 25.8-62.5) and 25.8% (90% CI 13.9-39.5) in the MRD (n = 20) and URD (n = 31) groups, respectively. The rates of 3-year overall survival and non-relapse mortality were 80.0 and 15.0% in the MRD group and 74.2 and 6.5% in the URD group, respectively. GVHD prophylaxis with MMF may lead to a lower incidence of severe mucositis and faster neutrophil engraftment compared to that with methotrexate. A pharmacokinetics study of mycophenolic acid (MPA) showed that a relatively higher plasma concentration of MPA was associated with a lower incidence of acute GVHD. In conclusion, the results of these studies suggest that GVHD prophylaxis with MMF may be useful as an alternative in Japanese patients who may benefit from faster engraftment or less severe mucositis after allogeneic HSCT.
authors.affiliation: Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Takahiko
authors.initials: T
authors.lastname: Nakane
authors.affiliation: Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Hirohisa
authors.initials: H
authors.lastname: Nakamae
authors.affiliation: Division of Biostatistics, Tohoku University Graduate School of Medicine, Miyagi, Japan.
authors.forename: Takuhiro
authors.initials: T
authors.lastname: Yamaguchi
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Saiko
authors.initials: S
authors.lastname: Kurosawa
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan.
authors.forename: Atsuo
authors.initials: A
authors.lastname: Okamura
authors.affiliation: Department of Hematology, National Hospital Organization, Kumamoto Medical Center, Kumamoto, Japan.
authors.forename: Michihiro
authors.initials: M
authors.lastname: Hidaka
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan.
authors.forename: Shigeo
authors.initials: S
authors.lastname: Fuji
authors.affiliation: Department of Hematology and Oncology, JA Aichi Konan Kosei Hospital, Konan, Japan.
authors.forename: Akio
authors.initials: A
authors.lastname: Kohno
authors.affiliation: Division of Clinical Oncology and Hematology, Department of Internal Medicine, Jikei University School of Medicine, Tokyo, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Saito
authors.affiliation: Department of Hematology, Seichokai Fuchu Hospital, Izumi, Japan.
authors.forename: Yasutaka
authors.initials: Y
authors.lastname: Aoyama
authors.affiliation: Department of Hematology/Oncology, Wakayama Medical University Hospital, Wakayama, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Hatanaka
authors.affiliation: Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Katayama
authors.affiliation: Department of Medical Oncology and Hematology, Kobe University Hospital, Kobe, Japan.
authors.forename: Kimikazu
authors.initials: K
authors.lastname: Yakushijin
authors.affiliation: Hematology, Department of Medicine, Kobe University Graduate School of Medicine, Kobe, Japan.
authors.forename: Toshimitsu
authors.initials: T
authors.lastname: Matsui
authors.affiliation: Department of Clinical Pharmacy, School of Pharmacy and Pharmaceutical Sciences, Mukogawa Women's University, Hyogo, Japan.
authors.forename: Motohiro
authors.initials: M
authors.lastname: Yamamori
authors.affiliation: Division of Hematology, Department of Internal Medicine, Aichi Medical University School of Medicine, Nagakute, Japan.
authors.forename: Akiyoshi
authors.initials: A
authors.lastname: Takami
authors.affiliation: Hematology, Graduate School of Medicine, Osaka City University, Osaka, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Hino
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, 5-1-1 Tsukiji, Chuo-ku, Tokyo, 104-0045, Japan. tafukuda@ncc.go.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
mesh_terms: D000328:Adult; D000368:Aged; D065095:Calcineurin Inhibitors / Q000008:administration & dosage*; D005260:Female; D006085:Graft Survival / Q000187:drug effects; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control; D006680:HLA Antigens / Q000276:immunology; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006648:Histocompatibility; D006801:Humans; D007564:Japan; D008297:Male; D008875:Middle Aged; D052016:Mucositis / Q000517:prevention & control; D009173:Mycophenolic Acid / Q000008:administration & dosage*; D035781:Siblings; D014184:Transplantation, Homologous; D061349:Unrelated Donors; D014838:Volunteers
chemical_list: D065095:Calcineurin Inhibitors; D006680:HLA Antigens; D009173:Mycophenolic Acid
keywords: Allogeneic hematopoietic stem-cell transplantation; Graft-versus-host disease prophylaxis; Mycophenolate mofetil