title: A randomized controlled trial of cyclosporine and tacrolimus with strict control of blood concentrations after unrelated bone marrow transplantation.
abstract: Previous studies have suggested that tacrolimus (TAC) is more potent than cyclosporine (CSA) for prophylaxis against acute GVHD after allogeneic hematopoietic stem cell transplantation (HSCT). However, the target blood concentrations of these drugs in these studies were not consistent with the current recommendations. Therefore, we performed a randomized controlled trial to compare CSA and TAC with target blood concentrations of 500 and 15 ng/ml, respectively, to prevent acute GVHD after unrelated HSCT. A total of 107 patients were randomized into a CSA group (n=53) or a TAC group (n=54). During the first 4 weeks after HSCT, more than 90% of the patients achieved a mean blood concentration of between 80 and 120% of the target concentration. The incidences of grade II-IV and grade III-IV acute GVHD were 39.6 and 7.5% for the CSA group and 33.3 and 9.4% for the TAC group, respectively (P=0.41 and P=0.76). Other clinical outcomes, including overall survival, disease-free survival and the incidences of relapse, non-relapse mortality, and organ toxicities, were also equivalent. We concluded that the combinations of CSA and TAC with strict dose adjustment showed similar efficacies and toxicities as prophylaxis against acute GVHD after unrelated HSCT.
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Kanda
authors.affiliation: Division of Haematology, Tokyo Metropolitan Cancer and Infectious Diseases Centre Komagome Hospital, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kobayashi
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Mori
authors.affiliation: Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Hematology, Chiba University Hospital, Chiba, Japan.
authors.forename: C
authors.initials: C
authors.lastname: Nakaseko
authors.affiliation: Department of Hematology, Chiba Aoba Municipal Hospital, Chiba, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Yokota
authors.affiliation: Department of Hematology, Saitama Medical Center, Saitama Medical University, Saitama, Japan.
authors.forename: R
authors.initials: R
authors.lastname: Watanabe
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kako
authors.affiliation: Division of Haematology, Tokyo Metropolitan Cancer and Infectious Diseases Centre Komagome Hospital, Tokyo, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Kakihana
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: J
authors.initials: J
authors.lastname: Kato
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: A
authors.initials: A
authors.lastname: Tanihara
authors.affiliation: Division of Haematology, Tokyo Metropolitan Cancer and Infectious Diseases Centre Komagome Hospital, Tokyo, Japan.
authors.forename: N
authors.initials: N
authors.lastname: Doki
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Ashizawa
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: S-I
authors.initials: SI
authors.lastname: Kimura
authors.affiliation: Division of Hematology, Saitama Medical Center, Jichi Medical University, Saitama, Japan.
authors.forename: M
authors.initials: M
authors.lastname: Kikuchi
authors.affiliation: Department of Hematology, Kanagawa Cancer Center, Kanagawa, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kanamori
authors.affiliation: Division of Hematology, Department of Medicine, Keio University School of Medicine, Tokyo, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Okamoto
mesh_terms: D000208:Acute Disease; D000328:Adult; D064591:Allografts; D016026:Bone Marrow Transplantation; D016572:Cyclosporine / Q000008:administration & dosage / Q000493:pharmacokinetics; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000097:blood / Q000401:mortality / Q000517:prevention & control; D019337:Hematologic Neoplasms / Q000097:blood / Q000401:mortality / Q000628:therapy; D006801:Humans; D008297:Male; D008875:Middle Aged; D015996:Survival Rate; D016559:Tacrolimus / Q000008:administration & dosage / Q000493:pharmacokinetics; D061349:Unrelated Donors
chemical_list: D016572:Cyclosporine; D016559:Tacrolimus