title: Phase II study of tacrolimus and methotrexate for prophylaxis of acute graft-versus-host disease after HLA-A, B, and DRB1 genotypically mismatched unrelated bone marrow transplantation among Japanese patients.
abstract: Bone marrow transplantation from unrelated donors (UR-BMT) has been considered to be effective for patients with hematological malignancies who have no suitable related donor. However, disparities of HLA between a recipient and a donor increase the risk of severe acute graft-versus-host disease (GVHD). We evaluated GVHD prophylaxis using tacrolimus and methotrexate for HLA-A, B, or DRB1 genotypically mismatched UR-BMT. Fifty-five patients were enrolled in this study. The incidence of grade III to IV acute GVHD was 23.6% for all patients. No significant difference in the incidence of grade III to IV acute GVHD was observed between HLA-A or B 1 locus mismatch transplantation (18.8%) and HLA-DRB1 1 locus mismatch transplantation (16.7%) (P = 0.96). The incidence of chronic GVHD was 71.7%. Disease-free survival at 5 years was 53.2% for patients with standard risk disease and 24.5% for patients with high-risk disease. Patients with chronic GVHD exhibited better disease-free survival than those without chronic GVHD (53.2 vs. 30.9%, P = 0.011). Twenty patients (36.4%) had a relapse of leukemia and 14 of them died of recurrent leukemia. This study indicates tacrolimus and methotrexate can lower the risk of severe acute GVHD after HLA-A, B, or DRB1 genotypically 1 locus mismatched UR-BMT.
authors.affiliation: Department of Internal Medicine, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan. tnishida@med.nagoya-u.ac.jp.|Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, 65 Tsurumai-cho, Showa-ku, Nagoya, Aichi, 466-8550, Japan. tnishida@med.nagoya-u.ac.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Nishida
authors.affiliation: Department of Hematology, Hyogo Cancer Center, Akashi, Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Murayama
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Tokyo, Japan.
authors.forename: Hisamaru
authors.initials: H
authors.lastname: Hirai
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Okamoto
authors.affiliation: Department of Hematology, Meitetsu Hospital, Nagoya, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sao
authors.affiliation: Division of Hematology, Ehime Prefectural Central Hospital, Matsuyama, Japan.
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hara
authors.affiliation: Department of Internal Medicine and Clinical Immunology, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
authors.forename: Heiwa
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Department of Preventive Medicine/Biostatistics and Medical Decision Making, Nagoya University Graduate School of Medicine, Nagoya, Japan.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center, Nagoya, Japan.
authors.forename: Keitaro
authors.initials: K
authors.lastname: Matsuo
authors.affiliation: Department of Hematology and Cell Therapy, Aichi Cancer Center Hospital, Nagoya, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Department of Internal Medicine, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan.
authors.forename: Yoshihisa
authors.initials: Y
authors.lastname: Kodera
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D044466:Asian People; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods* / Q000401:mortality; D002423:Cause of Death; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006680:HLA Antigens / Q000235:genetics*; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D006650:Histocompatibility Testing; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D016559:Tacrolimus / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D006680:HLA Antigens; D015234:HLA-A Antigens; D015235:HLA-B Antigens; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D016559:Tacrolimus; D008727:Methotrexate