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Therapy of acute graft-versus-host diseaseKeywords: acute graft-versus-host disease , refractory , salvage therapy , toxicity , tolerance Abstract: Primary therapy of acute GvHD grade II–IV is still based on the systemic application of corticosteroids at doses of 1–2 mg/kg (e.g. prednisolone). Typically, investigators combine this approach with therapeutic doses of calcineurin inhibitors, which are used as prophylactic regimens. Patients not responding to steroids within 5–7 days or those with progressive disease within 72 hours represent a high-risk population that requires further immunosuppressive escalation. Pharmacological second-line therapy is mainly based on centre policies and individual decisions since no strategy has been associated with an improvement in survival within a controlled prospective trial. Compounds with efficacy in phase II trials are mycophenolate mofetil, methotrexate, pentostatin, mTOR inhibitors, antibodies targeting TNFalpha or IL-2 pathways, and monoclonal or polyclonal anti-T cell antibodies. Non-pharmacological options include extracorporeal photopheresis and the infusion of allogeneic mesenchymal stromal cells. For most interventions, earlier treatment (e.g., within two weeks) is associated with a better outcome. However, the overall efficacy and toxicity of most approaches are unsatisfactory. Future developments include the use of regulatory T cells and more targeted approaches using small molecules interacting with specific signalling pathways of antigen-presenting and effector cells.
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