Graft Versus Host Disease (GVHD) is the condition that occurs when immune cells transplanted from the graft recognize the host as foreign and initiates an immune reaction that causes disease in the transplant recipient. GVHD is divided into acute and chronic GVHD (cGVHD) based on the time of onset using a cutoff of 100 days. However, signs of acute and chronic GVHD may occur outside of these periods.

The choice of initial treatment for acute GVHD depends on the organs involved, the severity of symptoms, the prophylactic regimen used. The severity of acute GVHD is determined by an assessment of the degree of involvement of the skin, liver, and gastrointestinal tract. Grade I GVHD defines cutaneous GVHD over ≤50 percent body surface area without liver or gastrointestinal tract involvement. Grade I GVHD is managed with topical treatments such as topical steroids. Patients with Grade II or higher GVHD are treated with systemic glucocorticoids and nonabsorbable oral steroids are added for patients with gastrointestinal involvement. The most commonly used glucocorticoid is methylprednisolone with a dosage of 2 mg/kg per day. Patients whose GVHD progress by day 5 or who do not respond by day 7 are considered as corticosteroid resistant. For patients with glucocorticoid-resistant acute GVHD, participation in a clinical trial is recommended. If no trial is available, ruxolitinib, mycophenolate mofetil, etanercept, extracorporeal photopheresis, anti-thymocyte globulin, alpha-1 antitrypsin, mesenchymal stromal cells, everolimus, or sirolimus can be used.

Clinical manifestations of cGVHD may be restricted to a single organ or widespread. The primary manifestations are skin involvement resembling lichen planus or cutaneous scleroderma, dry oral mucosa, ulcerations and sclerosis of the gastrointestinal tract, elevated serum bilirubin, and bronchiolitis obliterans. First-line treatment of cGVHD consists of steroids. For patients with mild cGVHD, localized/topical treatment can be preferred rather than systemic therapy. For initial treatment of moderate or severe cGVHD,  systemic treatment with prednisone or methylprednisone at an initial dose of 1 mg/kg body weight/day should be used. The addition of azathioprine,  mycophenolate mofetil, cyclosporine, thalidomide, or hydroxychloroquine to prednisone did not improve the response rate or other end-points in randomized trials. If symptoms progress during the first 4 weeks of first-line therapy or there is no improvement in symptoms within 8–12 weeks, second-line therapy should be initiated. For steroid refractory cGVHD patients ruxolitinib can be added to prednisone. Non-pharmacologic therapies such as extracorporeal phopheresis (ECP) has the advantage of being non-immunesuppressive. An immunosuppressive drug can be added to prednisone such as a calcineurin inhibitor or mycophenolate mofetil, but none shown to be effective. İbrutinib which is an inhibitor of Bruton's tyrosine kinase (BTK) has activity against cGVHD.