title: The best endpoint for acute GVHD treatment trials.
abstract: The optimal primary endpoint for acute graft-versus-host disease (GVHD) therapeutic trials has not been established. In a retrospective analysis, we examined the response of 864 patients who received prednisone 60 mg/m(2)/d for 14 days, followed by an 8-week taper, as initial therapy for acute GVHD from 1990-2007 at the University of Minnesota. Patients received grafts of human leukocyte antigen-matched sibling bone marrow (BM) or peripheral blood (PB; n = 315), partially matched sibling BM or PB (n = 24), unrelated donor BM or PB (n = 313), single (n = 89) or double (n = 123) umbilical cord blood. Day 28 responses were similar to day 56 responses and better than day 14 responses in predicting transplantation-related mortality (TRM). In multiple regression analysis, patients with no response at day 28 were 2.78 times (95% CI, 2.17-3.56 times; P < .001) more likely to experience TRM before 2 years than patients with a response. Other factors associated with significantly worse 2-year TRM include older age, high-risk disease, severe GVHD, and partially matched related BM/PB. No other differences in response by donor source were observed. These data suggest that day 28 is the best early endpoint for acute GVHD therapeutic trials in predicting 2-year TRM.
authors.affiliation: Blood and Marrow Transplant Program, University of Minnesota Medical School, 420 Delaware Street SE, Minneapolis, MN 55455, USA. macmi002@umn.edu
authors.forename: Margaret L
authors.initials: ML
authors.lastname: MacMillan
authors.forename: Todd E
authors.initials: TE
authors.lastname: DeFor
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: Weisdorf
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D002986:Clinical Trials as Topic; D005260:Female; D005938:Glucocorticoids / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy*; D006801:Humans; D008297:Male; D011241:Prednisone / Q000627:therapeutic use*; D012189:Retrospective Studies; D014184:Transplantation, Homologous; D055815:Young Adult
chemical_list: D005938:Glucocorticoids; D011241:Prednisone