title: Therapy for chronic graft-versus-host disease: a randomized trial comparing cyclosporine plus prednisone versus prednisone alone.
abstract: Results of previous studies have suggested that transplantation-related mortality among patients with chronic graft-versus-host disease (GVHD) may be reduced by combined treatment with cyclosporine (CSP) and prednisone rather than by prednisone alone. In a randomized trial, we assessed the efficacy of cyclosporine plus prednisone versus prednisone alone as initial therapy for chronic GHVD among patients whose platelet counts were higher than 100,000/microL. Prednisone was administered initially at a dose of 1.0 mg/kg per day orally, followed by a prolonged taper, and cyclosporine was administered at 6 mg/kg orally twice daily every other day. The cumulative incidence of transplantation-related mortality at 5 years from enrollment was 17% (95% CI, 0.11-0.23) in the CSP plus prednisone arm and 13% (95% CI, 0.08-0.19) in the prednisone arm. The hazards of transplantation-related mortality, overall mortality, recurrent malignancy, secondary therapy, and discontinuation of all immunosuppressive therapy were not significantly different between the 2 arms, but survival without recurrent malignancy was lower in the 2-drug arm (P =.03). Avascular necrosis developed in 18 (13%) of the 142 patients in the CSP plus prednisone arm and in 32 (22%) of the 145 patients in the prednisone arm (P =.04). Treatment with CSP plus prednisone may reduce the risk for steroid-related toxicity, but results of the current study do not substantiate the hypothesis that the administration of CSP reduces transplantation-related mortality among patients with chronic GVHD.
authors.affiliation: Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA.
authors.forename: Sibel
authors.initials: S
authors.lastname: Koc
authors.forename: Wendy
authors.initials: W
authors.lastname: Leisenring
authors.forename: Mary E D
authors.initials: ME
authors.lastname: Flowers
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: H Joachim
authors.initials: HJ
authors.lastname: Deeg
authors.forename: Richard A
authors.initials: RA
authors.lastname: Nash
authors.forename: Jean E
authors.initials: JE
authors.lastname: Sanders
authors.forename: Robert P
authors.initials: RP
authors.lastname: Witherspoon
authors.forename: Rainer
authors.initials: R
authors.lastname: Storb
authors.forename: Frederick R
authors.initials: FR
authors.lastname: Appelbaum
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Martin
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002908:Chronic Disease; D016572:Cyclosporine / Q000008:administration & dosage* / Q000633:toxicity; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006086:Graft vs Host Disease / Q000188:drug therapy* / Q000401:mortality; D006402:Hematologic Diseases / Q000628:therapy; D018380:Hematopoietic Stem Cell Transplantation / Q000009:adverse effects / Q000401:mortality; D006801:Humans; D007166:Immunosuppressive Agents / Q000008:administration & dosage* / Q000633:toxicity; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage* / Q000633:toxicity; D016019:Survival Analysis; D013921:Thrombocytopenia / Q000401:mortality; D014184:Transplantation, Homologous / Q000276:immunology / Q000401:mortality
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D011241:Prednisone