title: Decreased incidence of acute graft-versus-host disease by continuous infusion of cyclosporine with a higher target blood level.
abstract: Cyclosporine A (CsA) is the mainstay of pharmacologic prevention of acute graft-versus-host disease (GVHD). We previously reported that continuous infusion of CsA with a target blood level between 250 and 400 ng/ml significantly increased the incidence of acute GVHD compared to twice-daily infusion with a target trough level between 150 and 300 ng/ml. Thus, we raised the target level of CsA continuous infusion to 450-550 ng/ml. We treated 33 patients with the higher target level (CsA500) and compared the efficacy and toxicity with those in the 33 historical control patients (CsA300 group). Other transplantation procedures were not changed. The patients' characteristics were equivalent. The average CsA concentration was adjusted around 500 ng/ml and the actual daily dose was maintained at the initial dose (CsA 3mg/kg/day). Toxicities were equivalently observed among the two groups. The incidence of grades II-IV acute GVHD was significantly lower in the CsA500 group (27 vs. 52%, P = 0.033). The target level of CsA was identified as an independent significant risk factor for grades II-IV acute GVHD (P = 0.039), adjusted for the presence of HLA mismatch. The incidence of chronic GVHD was also decreased in the CsA500 group (47 vs. 73%, P = 0.016). We conclude that the toxicity of the continuous CsA infusion with a target level of 450-550 ng/ml is acceptable and the efficacy to prevent acute GVHD is significant. A larger comparative study is warranted to confirm these findings.
authors.affiliation: Department of Hematology and Oncology, Graduate School of Medicine, University of Tokyo, Bunkyo-ku, Tokyo, Japan.
authors.forename: Kumi
authors.initials: K
authors.lastname: Oshima
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Kanda
authors.forename: Hideki
authors.initials: H
authors.lastname: Nakasone
authors.forename: Shunya
authors.initials: S
authors.lastname: Arai
authors.forename: Nahoko
authors.initials: N
authors.lastname: Nishimoto
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sato
authors.forename: Takuro
authors.initials: T
authors.lastname: Watanabe
authors.forename: Noriko
authors.initials: N
authors.lastname: Hosoya
authors.forename: Koji
authors.initials: K
authors.lastname: Izutsu
authors.forename: Takashi
authors.initials: T
authors.lastname: Asai
authors.forename: Akira
authors.initials: A
authors.lastname: Hangaishi
authors.forename: Toru
authors.initials: T
authors.lastname: Motokura
authors.forename: Shigeru
authors.initials: S
authors.lastname: Chiba
authors.forename: Mineo
authors.initials: M
authors.lastname: Kurokawa
mesh_terms: D000208:Acute Disease; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage / Q000097:blood* / Q000627:therapeutic use*; D005260:Female; D006086:Graft vs Host Disease / Q000453:epidemiology / Q000517:prevention & control*; D018380:Hematopoietic Stem Cell Transplantation / Q000379:methods*; D006650:Histocompatibility Testing; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use; D015994:Incidence; D007262:Infusions, Intravenous; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000097:blood / Q000188:drug therapy / Q000628:therapy; D019520:Living Donors; D008297:Male; D008727:Methotrexate / Q000627:therapeutic use; D008875:Middle Aged; D014184:Transplantation, Homologous; D014916:Whole-Body Irradiation
chemical_list: D000970:Antineoplastic Agents; D007166:Immunosuppressive Agents; D016572:Cyclosporine; D008727:Methotrexate