title: Overlap subtype of chronic graft-versus-host disease is associated with an adverse prognosis, functional impairment, and inferior patient-reported outcomes: a Chronic Graft-versus-Host Disease Consortium study.
abstract: BACKGROUND
  The National Institutes of Health Consensus Conference proposed the term "overlap" graft-versus-host disease to describe the situation when both acute and chronic graft-versus-host disease are present.
  
  
  METHODS
  We examined whether the overlap subtype of graft-versus-host disease was associated with a different prognosis, functional limitations, or patient-reported outcomes compared to "classic" chronic graft-versus-host disease without any acute features.
  
  
  RESULTS
  Prospective data were collected from 427 patients from nine centers. Patients were classified as having overlap (n=352) or classic chronic (n=75) graft-versus-host disease based on reported organ involvement. Overlap cases had a significantly shorter median time from transplantation to cohort enrollment (P=0.01), were more likely to be incident cases (P<0.001), and had a lower platelet count at onset of the graft-versus-host disease (P<0.001). Patients with overlap graft-versus-host disease had significantly greater functional impairment measured by a 2-minute walk test, higher symptom burden and lower Human Activity Profile scores. Quality of life was similar, except patients with overlap graft-versus-host disease had worse social functioning, assessed by the Short Form-36. Multivariable analysis utilizing time-varying covariates demonstrated that the overlap subtype of graft-versus-host disease was associated with worse overall survival (HR 2.1, 95% CI 1.1-4.7; P=0.03) and higher non-relapse mortality (HR 2.8, 95% CI 1.2-8.3; P=0.02) than classic chronic graft-versus-host disease.
  
  
  CONCLUSIONS
  These findings suggest that the presence of acute features in patients with chronic graft-versus-host disease is a marker of adverse prognosis, greater functional impairment, and higher symptom burden.
authors: Moffitt Cancer Center, Tampa, FL, USA. joseph.pidala@moffitt.org
authors: Joseph
authors: J
authors: Pidala
authors: Georgia
authors: G
authors: Vogelsang
authors: Paul
authors: P
authors: Martin
authors: Xiaoyu
authors: X
authors: Chai
authors: Barry
authors: B
authors: Storer
authors: Steven
authors: S
authors: Pavletic
authors: Daniel J
authors: DJ
authors: Weisdorf
authors: Madan
authors: M
authors: Jagasia
authors: Corey
authors: C
authors: Cutler
authors: Jeanne
authors: J
authors: Palmer
authors: David
authors: D
authors: Jacobsohn
authors: Sally
authors: S
authors: Arai
authors: Stephanie J
authors: SJ
authors: Lee
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D006086:Graft vs Host Disease / Q000145:classification / Q000175:diagnosis* / Q000453:epidemiology; D006801:Humans; D008875:Middle Aged; D009017:Morbidity; D011379:Prognosis; D016019:Survival Analysis; D014481:United States / Q000453:epidemiology; D055815:Young Adult