title: The global severity of chronic graft-versus-host disease, determined by National Institutes of Health consensus criteria, is associated with overall survival and non-relapse mortality.
abstract: BACKGROUND
  The 2005 National Institutes of Health Consensus Development Conference on chronic graft-versus-host disease proposed major changes in the classification and grading of severity of chronic graft-versus-host disease.
  
  
  METHODS
  We aimed to study the association of the proposed chronic graft-versus-host disease classification and global severity with transplantation outcomes among a consecutive series of patients who received pharmacokinetically-targeted doses of intravenous busulfan and fludarabine conditioning followed by transplantation of allogeneic peripheral blood stem cells.
  
  
  RESULTS
  From a total cohort (n = 242) of patients surviving more than 100 days after hematopoietic stem cell transplantation, 181 (75% of those at risk) had some manifestations of graft-versus-host disease after day 100. Of these, at onset 13 (7%) had late acute graft-versus-host disease, 62 (34%) had classic chronic graft-versus-host disease, and 106 (59%) had the overlap subtype of chronic graft-versus-host disease. The global severity of the chronic graft-versus-host disease was mild in 25% of cases, moderate in 46%, and severe in 29%. Multivariable modeling demonstrated the independent association of global severity of chronic graft-versus-host disease with overall survival (moderate/severe versus mild; HR 2.9, 95% CI 1.8-4.7, P < 0.0001) and non-relapse mortality (moderate versus mild; HR 3.86, 95% CI 1.17-12.73, P = 0.03, and severe versus mild (HR 10.06, 95% CI 3.07-32.97, P < 0.001). The type of onset of progressive chronic graft-versus-host disease and the platelet count at the time of diagnosis of the disease were significantly associated with overall survival. The occurrence and severity of chronic graft-versus-host disease was also significantly associated with primary disease relapse.
  
  
  CONCLUSIONS
  Patients with moderate to severe chronic graft-versus-host disease, as determined by National Institutes of Health Consensus criteria, have an inferior overall survival and worse non-relapse mortality. Clinical and research advances are needed to improve the outcomes of affected patients.
authors.affiliation: Department of Blood and Marrow Transplantation, Moffitt Cancer Center, Tampa, Fl 33612 USA. joseph.pidala@moffitt.org
authors.forename: Joseph
authors.initials: J
authors.lastname: Pidala
authors.forename: Jongphil
authors.initials: J
authors.lastname: Kim
authors.forename: Claudio
authors.initials: C
authors.lastname: Anasetti
authors.forename: Taiga
authors.initials: T
authors.lastname: Nishihori
authors.forename: Brian
authors.initials: B
authors.lastname: Betts
authors.forename: Teresa
authors.initials: T
authors.lastname: Field
authors.forename: Janelle
authors.initials: J
authors.lastname: Perkins
mesh_terms: D000208:Acute Disease; D000328:Adult; D000368:Aged; D015331:Cohort Studies; D015975:Consensus Development Conferences, NIH as Topic; D018572:Disease-Free Survival; D005260:Female; D006086:Graft vs Host Disease / Q000209:etiology / Q000401:mortality*; D019337:Hematologic Neoplasms / Q000401:mortality* / Q000628:therapy*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009316:National Institutes of Health (U.S.); D036102:Peripheral Blood Stem Cell Transplantation; D012720:Severity of Illness Index; D015996:Survival Rate; D014184:Transplantation, Homologous; D014481:United States