title: Effectiveness and safety of lower dose prednisone for initial treatment of acute graft-versus-host disease: a randomized controlled trial.
abstract: We conducted a phase III study to test the hypothesis that initial therapy with "lower dose" prednisone is effective and safe for patients with newly diagnosed acute graft-versus-host disease. We hypothesized that a 50% decrease in the initial dose of prednisone for treatment of acute graft-versus-host disease would suffice to control graft-versus-host disease without increasing the incidence of secondary treatment. Patients with grade IIa manifestations (upper gastrointestinal symptoms, stool volumes <1.0 L/day, rash involving <50% of the body surface, no hepatic dysfunction; n=102) were randomized to start treatment with prednisone at 1 mg/kg/day or 0.5 mg/kg/day. Those with grade IIb or higher manifestations (rash involving ≥50% of the body surface, stool volumes ≥1.0 L/day or hepatic involvement; n=62) were randomized to start treatment with prednisone at 2 mg/kg/day or 1 mg/kg/day. The primary study end point (a ≥33% relative reduction of the mean cumulative prednisone dose by day 42 after initial treatment with lower dose prednisone) was not reached. With a median follow up of 36 months (range 7-53), initial treatment with lower dose prednisone appeared to be effective for patients presenting with grade IIa manifestations since it did not increase the likelihood of requiring secondary immunosuppressive therapy. Further exploratory analyses suggested that for patients presenting with skin-predominant grade IIb or higher manifestations, initial treatment with lower dose prednisone was associated with an increased risk of requiring secondary immunosuppressive therapy (41% vs. 7%; P=0.001). In summary, initial treatment of newly diagnosed acute graft-versus-host disease with lower dose prednisone is effective. Within the statistical limitations of the study, results showed no suggestion that initial use of lower dose prednisone adversely affected survival.
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA mmielcar@fhcrc.org.
authors: Marco
authors: M
authors: Mielcarek
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Terrence
authors: T
authors: Furlong
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA.
authors: Barry E
authors: BE
authors: Storer
authors: University of Washington, Seattle, WA, USA Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Margaret L
authors: ML
authors: Green
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA.
authors: George B
authors: GB
authors: McDonald
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA.
authors: Paul A
authors: PA
authors: Carpenter
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA.
authors: Mary E D
authors: ME
authors: Flowers
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA.
authors: Rainer
authors: R
authors: Storb
authors: University of Washington, Seattle, WA, USA Vaccines and Infectious Disease Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
authors: Michael
authors: M
authors: Boeckh
authors: Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA University of Washington, Seattle, WA, USA.
authors: Paul J
authors: PJ
authors: Martin
mesh_terms: D000208:Acute Disease; D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D005076:Exanthema / Q000139:chemically induced; D005260:Female; D005500:Follow-Up Studies; D006086:Graft vs Host Disease / Q000175:diagnosis* / Q000188:drug therapy* / Q000401:mortality; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011241:Prednisone / Q000008:administration & dosage* / Q000009:adverse effects*; D015996:Survival Rate / Q000639:trends; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D011241:Prednisone