title: Single-dose daily infusion of cyclosporine for prevention of Graft-versus-host disease after allogeneic bone marrow transplantation from HLA allele-matched, unrelated donors.
abstract: Peak blood concentration of cyclosporine (CsA) in renal transplantation patients was recently reported to be associated with clinical efficacy. We therefore evaluated the toxicity and efficacy of a regimen of once-daily infusion of CsA plus a short course of methotrexate as prophylaxis of graft-versus-host disease (GVHD) after allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor. Nineteen patients with hematologic malignancies received CsA, 3 mg/kg per day, as a 4-hour intravenous (IV) infusion from day -1. After engraftment, patients received CsA orally at twice the IV dose. The CsA dose was adjusted to maintain the blood trough level between 150 and 200 ng/mL. Methotrexate was administered IV at doses of 10 mg/m(2) on day 1 and 7 mg/m(2) on days 3, 6, and 11. Bone marrow engraftment occurred in all patients. Grade 1 and grade 2 GVHD occurred in 6 (31.6%) and 7 (36.8%) of the 19 patients, respectively. No patient had grade 3 or 4 GVHD. Acute nephrotoxicity developed in 1 (5.3%) of the 19 patients, and hypertension developed in 3 (15.8%) of the 19 patients. We evaluated the pharmacokinetics of 4-hour CsA infusion in 10 patients. The mean trough concentration, mean peak concentration, mean time to peak concentration, and area under the curve (24 hours) were 161 +/- 43 ng/mL, 1498 +/- 387 ng/mL, 3.2 +/- 1.0 hours, and 10,848 +/- 1,991 ng +/- h/mL, respectively. This regimen was well tolerated and did not enhance the risk of severe GVHD in patients undergoing allogeneic bone marrow transplantation from an HLA allele-matched, unrelated donor.
authors.affiliation: Division of Hematology, Ehime Prefectural Central Hospital, Japan. c-ynawa@eph.pref.ehime.jp
authors.forename: Yuichiro
authors.initials: Y
authors.lastname: Nawa
authors.forename: Masamichi
authors.initials: M
authors.lastname: Hara
authors.forename: Kazushi
authors.initials: K
authors.lastname: Tanimoto
authors.forename: Koichi
authors.initials: K
authors.lastname: Nakase
authors.forename: Teruhiko
authors.initials: T
authors.lastname: Kozuka
authors.forename: Yoshinobu
authors.initials: Y
authors.lastname: Maeda
mesh_terms: D000293:Adolescent; D000328:Adult; D000483:Alleles; D016026:Bone Marrow Transplantation / Q000276:immunology / Q000379:methods*; D016572:Cyclosporine / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000633:toxicity; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000517:prevention & control*; D006680:HLA Antigens; D019337:Hematologic Neoplasms / Q000150:complications / Q000628:therapy; D006801:Humans; D006973:Hypertension / Q000139:chemically induced; D007674:Kidney Diseases / Q000139:chemically induced; D008297:Male; D008875:Middle Aged; D010599:Pharmacokinetics; D014019:Tissue Donors; D014184:Transplantation, Homologous; D016896:Treatment Outcome
chemical_list: D006680:HLA Antigens; D016572:Cyclosporine