title: A pilot study of low-dose cyclosporin for graft-versus-host prophylaxis in marrow transplantation.
abstract: Nineteen patients with leukaemia, preleukaemia, and aplastic anaemia were treated by marrow transplantation from HLA-identical siblings. All were given postgrafting immunosuppression with a combination of methotrexate (days 1, 3, 6 and 11) and cyclosporin (days--1 to 180). In an attempt at reducing cyclosporin-associated toxicity, we explored whether the cyclosporin dose during the first 2 weeks could be decreased by 50% (from 3.0 to 1.5 mg/kg/d intravenously) without adversely affecting the incidence, onset, and severity of acute graft-versus-host disease (GVHD) and overall survival. Results from this pilot study were compared to those of a matched cohort of 38 patients given a standard dose of 3.0 mg cyclosporin/kg/d starting on day--1. The cumulative incidence of grade II and III acute GVHD in the 'low dose' cyclosporin group was 42% compared to 51% in the 'standard dose' group (P = 0.60). Three-year survival was 63% and 54% respectively (P = 0.59). Patients receiving the reduced cyclosporin dose during the first 14 d appeared to have less hepatotoxicity, and the methotrexate and cyclosporin doses administered were closer to the doses intended per protocol. We suggest that 'low dose' cyclosporin from day--1 to day 15 postgrafting might be as effective as 'standard dose' cyclosporin during that time period for the prevention of acute GVHD.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, Washington.
authors.forename: M
authors.initials: M
authors.lastname: Stockschlaeder
authors.forename: R
authors.initials: R
authors.lastname: Storb
authors.forename: M
authors.initials: M
authors.lastname: Pepe
authors.forename: G
authors.initials: G
authors.lastname: Longton
authors.forename: G
authors.initials: G
authors.lastname: McDonald
authors.forename: C
authors.initials: C
authors.lastname: Anasetti
authors.forename: F
authors.initials: F
authors.lastname: Appelbaum
authors.forename: K
authors.initials: K
authors.lastname: Doney
authors.forename: P
authors.initials: P
authors.lastname: Martin
authors.forename: K
authors.initials: K
authors.lastname: Sullivan
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D001663:Bilirubin / Q000097:blood; D016026:Bone Marrow Transplantation / Q000276:immunology*; D002648:Child; D002675:Child, Preschool; D003524:Cyclosporins / Q000008:administration & dosage* / Q000009:adverse effects / Q000627:therapeutic use; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D008297:Male; D008727:Methotrexate / Q000008:administration & dosage / Q000627:therapeutic use; D008875:Middle Aged; D010865:Pilot Projects; D013997:Time Factors
chemical_list: D003524:Cyclosporins; D001663:Bilirubin; D008727:Methotrexate