Graft-versus-host disease (GVHD) is a multisystem immune-mediated complication of allogeneic hematopoietic stem cell transplantation (allo-HSCT) caused by mature donor T-cells in the graft recognizing recipient tissue antigens as foreign and mounting immune responses against host tissues. GVHD remains a major cause of morbidity and non-relapse mortality after allo-HSCT despite prophylactic immunosuppression, occurring in 30-60% of patients with overall mortality 15-20% from severe disease. Risk factors include HLA mismatch (haploidentical and unrelated donors > matched siblings), older recipient age, female donor to male recipient (especially multiparous donors with anti-male H-Y antigens), donor-recipient sex mismatch, peripheral blood vs bone marrow grafts (higher chronic GVHD), reduced-intensity conditioning, prior acute GVHD, and CMV serostatus mismatch.
Acute GVHD (aGVHD) traditionally occurred within 100 days post-transplant, but distinction is now based on clinical features rather than timing. Classical acute GVHD affects skin (maculopapular rash starting on palms/soles spreading to trunk, can progress to bullous lesions and toxic epidermal necrolysis), gastrointestinal tract (diarrhea, abdominal pain, nausea, vomiting; can be hemorrhagic), and liver (cholestatic jaundice with elevated bilirubin and alkaline phosphatase). Severity grading uses Glucksberg or MAGIC (Mount Sinai Acute GVHD International Consortium) criteria with stage 0-IV for each organ and overall grade I-IV based on combined organ stages and performance status. MAGIC biomarker algorithm using ST2 and REG3-alpha at day +7 predicts treatment response.
Chronic GVHD (cGVHD) is a complex autoimmune-like multisystem disease typically occurring after day +100 with features overlapping several connective tissue diseases (scleroderma, Sjogren syndrome, autoimmune cholangitis, inflammatory bowel disease, primary biliary cholangitis, lichen planus). NIH 2014 consensus criteria define diagnostic and distinctive features for skin (scleroderma, lichen planus, papulosquamous), nails (dystrophy, ridging), scalp/body hair (alopecia, premature graying), mouth (lichen-type changes, ulcers, restricted mouth opening), eyes (dry eyes, keratoconjunctivitis), genitalia (lichen planus, vaginal scarring), gastrointestinal (esophageal stricture, dysphagia), liver (cholestasis), lungs (bronchiolitis obliterans), musculoskeletal (fasciitis, joint stiffness), and hematopoietic (cytopenias) systems. Severity scored as mild, moderate, or severe based on number of organs involved and functional impairment. Treatment of acute GVHD: first-line systemic corticosteroids (methylprednisolone 1-2 mg/kg/day) achieve response in 30-50%; steroid-refractory acute GVHD treated with ruxolitinib (REACH-2 trial), extracorporeal photopheresis (ECP), anti-IL-2 receptor (basiliximab), MMF, sirolimus, vedolizumab (alpha4-beta7 integrin for GI involvement), or alpha-1 antitrypsin. Treatment of chronic GVHD: first-line corticosteroids +/- calcineurin inhibitors; second-line/steroid-refractory options include ruxolitinib (REACH-3), ibrutinib (BTK inhibitor with anti-fibrotic effects), belumosudil (ROCK2 inhibitor specifically approved for cGVHD 2021), ECP, rituximab, MMF, low-dose IL-2, and abatacept. Supportive care: nutrition, ophthalmologic care for dry eyes, skin care, dental care, vaginal estrogen, pulmonary rehabilitation, infection prophylaxis.