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

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. Design and 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.