Hematopoietic stem cell transplantation has evolved as a central treatment modality for the management of various hematologic malignancies. Despite adequate posttransplantation immunosuppressive therapy, acute GVHD remains a major cause of morbidity and mortality, even for the patients who have received HLA identical sibling grafts. Once established, acute GVHD is difficult to treat, and the best primary treatments such as corticosteroid have shown responses of approximately 50%. Once GVHD becomes steroid-refractory, the chances of survival are slim at best, and the possibility of long-term complications from chronic GVHD is almost always the rule. Many agents are currently being evaluated to treat this malady, including ATG, monoclonal antibodies, pentostatin, denileukin diftitox, etc. We reported here on a case of steroid refractory acute GVHD that was treated with IL-2 and TNF-alpha blocker in myelodysplastic syndrome patient who underwent unrelated allogeneic stem cell transplantation.