Graft-Versus-Host Disease: Acute and Chronic Staging

Graft-versus-host disease (GVHD) occurs when immunocompetent donor T lymphocytes recognize host tissues as foreign after allogeneic hematopoietic stem cell transplantation (allo-HSCT). The pathophysiology follows three phases: (1) Conditioning phase — pretransplant chemotherapy/radiation damages host tissues, releasing danger-associated molecular patterns (DAMPs) and pro-inflammatory cytokines (TNF-α, IL-1, IL-6) that activate host antigen-presenting cells (APCs); (2) Donor T-cell activation — donor T cells recognize host HLA-displayed antigens on activated APCs, undergo clonal expansion, and differentiate into effector cells (Th1, Th17, cytotoxic CD8+ T cells); (3) Effector phase — activated donor lymphocytes and inflammatory mediators attack target organs. Acute GVHD (classically < 100 days post-transplant) primarily affects skin (maculopapular rash), liver (cholestatic jaundice), and GI tract (profuse secretory diarrhea, abdominal pain). Chronic GVHD (> 100 days) resembles autoimmune diseases with fibrotic/sclerotic changes affecting skin (scleroderma-like), oral mucosa (lichenoid), eyes (keratoconjunctivitis sicca), lungs (bronchiolitis obliterans), and liver. Staging uses the Glucksberg system (acute) and NIH consensus criteria (chronic) to guide treatment intensity.