Systemic treatment of chronic GVHD

Severe chronic graft versus host disease (GVHD) is the main factor for late morbidity and mortality in long-term survivors after allogeneic hematopoietic cell transplantation. The only established treatment of chronic graft versus host disease is the use of high dose corticosteroids. However, multiple different treatment approaches have been evaluated mostly in small phase 2 studies. These included calcineurin inhibitors for blocking T-cell activation, classical cytotoxic drugs, like methotrexate or azathioprine, as well as immunomodulatory substances like cytokine inhibitors or thalidomide. More recently novel treatment approaches have been evaluated. These include the use of B-cell antibodies and the tyrosine kinase inhibitor imatinib. Furthermore treatment options beyond mere immunosuppression that aim to induce tolerance are currently under investigation. These include extra-corporal photopheresis and treatment with inhibitors of the mammalian target of rapamycin. This review will discuss these different treatment approaches.