Longitudinal Study of Late Acute and Chronic Graft-Versus-Host Disease after Allogeneic Hematopoietic Cell Transplantation: A Long-Term Follow-up Study from the Chronic Graft-Versus-Host Disease Consortium

Late acute and chronic graft-versus-host disease (GVHD) contribute to morbidity and death after allogeneic hematopoietic cell transplantation (HCT). A prior national Chronic GVHD Consortium longitudinal study enrolled patients pre- or early post-HCT and identified the incidence of late acute GVHD, chronic GVHD, and chronic GVHD subtypes of bronchiolitis obliterans syndrome (BOS) and cutaneous sclerosis. We now report 10-yr follow-up from that study in a long-term follow-up analysis (N = 911 subjects). Late acute GVHD occurred in 11% at a median of 5.5 mo. Chronic GVHD in total occurred in 54% with median onset of 7.4 mo. BOS (4% of subjects, median onset 12.6 mo) and cutaneous sclerosis (10% of subjects, median onset of 17.2 mo) were less frequent and had later-onset. The long-term analysis demonstrated additional GVHD events occurring beyond 1 to 2 yr post-HCT. Inter-conversion between GVHD types was common, and notably included new development of BOS and cutaneous sclerosis after initial chronic GVHD presentation without these manifestations. GVHD-free, relapse-free survival (GVHD-DFS, survival without relapse or development of late acute or chronic GVHD) was 22% at 2 yr, 18% at 5 yr, and 15% at 10 yr post-HCT. Non-relapse mortality continued to increase beyond 2 yr, with 10-yr estimates up to 35% (late acute), 31% (chronic GVHD), 62% (BOS), and 36% (cutaneous sclerosis). Durable complete discontinuation of immune suppression was uncommon for all GVHD types. These data suggest that extended surveillance for late acute and chronic GVHD is needed post-HCT due to late occurrences, and that associated mortality is high through 10 yr post-GVHD onset.