title: A comparison of tacrolimus and cyclosporine combined with methotrexate for graft-versus-host disease prophylaxis, stratified by stem cell source: a retrospective nationwide survey.
abstract: This nationwide, retrospective study compared the efficacy of cyclosporine and tacrolimus with methotrexate (CsA/MTX and TAC/MTX) for acute graft-versus-host disease (aGVHD) prevention and transplant-related outcomes. Data were obtained from the Transplant Registry Unified Management Program of the Japan Society for Hematopoietic Cell Transplantation for ≥ 16-year-old leukemia patients who received CsA/MTX or TAC/MTX after bone marrow transplantation and peripheral blood stem cell transplantation from serological HLA-matched related donors (MRD), HLA 8/8 allele-matched, or one allele-mismatched unrelated bone marrow (UBM), or 0-2 antigen-mismatched unrelated cord blood (UCB) transplantation between January 2005 and December 2009. Separate analyses were performed for each cohort. Adjusted multivariate analyses indicated that in the MRD (n = 1524) and the UBM (n = 1466) cohorts, TAC/MTX significantly reduced grade II-IV aGVHD risk (HR 0.58, P = 0.006 and HR 0.77, P = 0.015, respectively) without affecting the other transplant-related outcomes. In the UCB cohort (n = 925), TAC/MTX significantly reduced the risk of non-relapse mortality (HR 0.63, P = 0.027) and chronic GVHD (HR 0.60, P = 0.02) without significant effects on grade II-IV aGVHD (HR 0.83, P = 0.21). Our results may provide the most up-to-date data regarding GVHD prevention in Japan.
authors.affiliation: Department of Medical Oncology, Kanagawa Cancer Center, 2-3-2 Nakao, Asahi-ku, Yokohama, 241-0815, Japan. sakair@kcch.jp.
authors.forename: Rika
authors.initials: R
authors.lastname: Sakai
authors.affiliation: Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. taguri@yokohama-cu.ac.jp.
authors.forename: Masataka
authors.initials: M
authors.lastname: Taguri
authors.affiliation: Division of Hematology and Oncology, St. Luke International Hospital, Tokyo, Japan. kumioshi@hiroshima-u.ac.jp.
authors.forename: Kumi
authors.initials: K
authors.lastname: Oshima
authors.affiliation: Division of Hematology, Department of Internal Medicine, Keio University School of Medicine, Tokyo, Japan. tmori@sc.itc.keio.ac.jp.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Mori
authors.affiliation: Division of Hematology and Oncology, Shimane Prefectural Central Hospital, Matsue, Japan. ago@spch.izumo.shimane.jp.
authors.forename: Hiroatsu
authors.initials: H
authors.lastname: Ago
authors.affiliation: Human Health Sciences, Graduate School of Medicine, Kyoto University, Kyoto, Japan. adachiso@kuhp.kyoto-u.ac.jp.
authors.forename: Souichi
authors.initials: S
authors.lastname: Adachi
authors.affiliation: Department of Biostatistics and Epidemiology, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. smorita@urahp.yokohama-cu.ac.jp.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Morita
authors.affiliation: Department of Hematology, Toranomon Hospital, Tokyo, Japan. taniguchi-s@toranomon.gr.jp.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Taniguchi
authors.affiliation: Division of Hematopoietic Stem Cell Transplantation, National Cancer Center Hospital, Tokyo, Japan. tafukuda@ncc.go.jp.
authors.forename: Takahiro
authors.initials: T
authors.lastname: Fukuda
authors.affiliation: Division of Hematology, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan. k.ohashi@cick.jp.
authors.forename: Kazuteru
authors.initials: K
authors.lastname: Ohashi
authors.affiliation: Department of Hematology, Hamanomachi Hospital, Fukuoka, Japan. eto-t@hamanomachi.jp.
authors.forename: Tetsuya
authors.initials: T
authors.lastname: Eto
authors.affiliation: Department of Hematology, Japanese Red Cross Nagoya First Hospital, Nagoya, Japan. miyamu@nagoya-1st.jrc.or.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Miyamura
authors.affiliation: Department of Hematology, Hiroshima Red Cross Hospital and Atomic-bomb Survivors Hospital, Hiroshima, Japan. iwatok@hiroshima-med.jrc.or.jp.
authors.forename: Koji
authors.initials: K
authors.lastname: Iwato
authors.affiliation: Department of Hematology, Sapporo Hokuyu Hospital, Sapporo, Japan. naokoba@mopera.net.
authors.forename: Naoki
authors.initials: N
authors.lastname: Kobayashi
authors.affiliation: Department of Hematology, Kanagawa Cancer Center, Yokohama, Japan. kanamori@kcch.jp.
authors.forename: Heiwa
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Division of Epidemiology and Prevention, Aichi Cancer Center Research Institute, Nagoya, Japan. ymorisim@aichi-cc.jp.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Morishima
authors.affiliation: Division of Hematology, Tokyo Metropolitan Cancer and Infectious Disease Center, Komagome Hospital, Tokyo, Japan. tokikoni@ims.u-tokyo.ac.jp.
authors.forename: Tokiko
authors.initials: T
authors.lastname: Nagamura-Inoue
authors.affiliation: Department of Cell Processing and Transfusion, Research Hospital, The Institute of Medical Science, The University of Tokyo, Tokyo, Japan. sakamaki-h@cick.jp.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Sakamaki
authors.affiliation: Department of Hematopoietic Stem Cell Transplantation Data Management and Biostatistics, Nagoya University Graduate School of Medicine, Nagoya, Japan. y-atsuta@med.nagoya-u.ac.jp.
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Atsuta
authors.affiliation: Department of Hematology and Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan. mmurata@med.nagoya-u.ac.jp.
authors.forename: Makoto
authors.initials: M
authors.lastname: Murata
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D016572:Cyclosporine / Q000008:administration & dosage*; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage*; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage*; D008875:Middle Aged; D012189:Retrospective Studies; D016559:Tacrolimus / Q000008:administration & dosage*; D055815:Young Adult
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D016559:Tacrolimus; D008727:Methotrexate
keywords: Cyclosporine; Graft-versus-host disease; Methotrexate; Tacrolimus