Clinical and Immunologic Characteristics of Patients with Chronic Graft-Versus-Host Disease Persisting Seven or More Years after Diagnosis

Background Chronic graft-versus-host disease (cGVHD) is a leading cause of morbidity and mortality after allogeneic hematopoietic stem cell transplant (SCT). Median duration of systemic immunosuppression (IS) for cGVHD is approximately 2 years; however, 15% of patients still require IS 7 years after SCT. Previous studies identified factors that were associated with longer duration of IS or cGVHD. Our aim was to identify clinical and immunologic factors associated with cGVHD that is persistent ≥7 years after cGVHD diagnosis. Methods Patients were drawn from a prospective cross-sectional study of the natural history of cGVHD at the National Institutes of Health (NCT00092235). A cohort of patients who enrolled on the study ≥7 years from the time of cGVHD diagnosis, and thus had persistent cGVHD (pcGVHD), was compared to those who enrolled Results There were 38 patients with pcGVHD and 83 control patients Conclusions Although cGVHD is often self-limited, late forms requiring long duration of IS exist, and the predictive factors or underlying pathogenesis are unknown. Our analysis of cGVHD patients who enrolled on a clinical trial ≥7 years after diagnosis showed more lung and sclerotic skin involvement, less inflammatory signs, and higher B cells, immunoglobulins, and autoantibodies. These new findings suggest that pcGVHD may reflect irreversible damage rather than an active immune process; however, standardly accepted measures of disease severity were not associated with pcGVHD, suggesting that further tools are needed to differentiate accumulated damage from active disease. Distance from transplant center, which may contribute to access to care, was not associated, although increasing IS was recommended more frequently for pcGVHD patients. Factors that were previously identified as associated with longer duration of IS were not different or conflicted with our findings, suggesting that further study is needed. To further elucidate potential immune dysfunction in patients with pcGVHD, our ongoing studies are measuring BAFF, cytokine, and chemokine levels. Our results contribute to further hypotheses in the pathogenesis and contributing factors in patients who have pcGVHD. Table 1. Univariate analysis - factors significantly associated with pcGVHD ≥7 years from diagnosis (N=38) Disclosures No relevant conflicts of interest to declare.