Furthermore, favorable results of recent pilot studies, case series or case studies have suggested that tocilizumab may have broad application for other diseases. These diseases include systemic autoimmune diseases such as systemic lupus erythematosus [ 74 - 76 ], systemic sclerosis [ 77 ], polymyositis [ 78 ], vasculitis syndrome including giant cell arteritis [ 79 - 84 ], Takayasu arteritis [ 79 , 82 , 85 - 87 ], cryoglobulinemia [ 88 ], myeloperoxidase-antineutrophil cytoplasmic antibody-associated crescentic glomerulonephritis [ 89 ] and rheumatoid vasculitis [ 90 ]. The application of tocilizumab may also extend to organ-specific autoimmune diseases including Crohn's disease [ 91 ], relapsing polychondritis [ 92 , 93 ], acquired hemophilia A [ 94 ], autoimmune hemolytic anemia [ 95 , 96 ], as well as to chronic inflammatory diseases such as adult-onset Still's disease [ 97 - 113 ], amyloid A amyloidosis [ 114 - 120 ], polymyalgia rheumatica [ 79 , 84 , 121 ], remitting seronegative symmetrical synovitis with pitting edema [ 122 ], Behcet's disease [ 123 , 124 ], uveitis [ 125 ], graft-versus-host diseases [ 126 , 127 ], and tumor necrosis factor receptor-associated periodic syndrome [ 128 ] ( Table 1 ). Some studies have reported that tocilizumab is efficacious for spondyloarthritis [ 129 - 135 ], although others observed only minor effects [ 136 - 138 ]. In addition, tocilizumab is reportedly effective for pulmonary arterial hypertension [ 139 - 141 ], atopic dermatitis [ 142 ], and sciatica [ 143 ]. Finally, it was observed that during tocilizumab treatment of patients with rheumatoid arthritis, HbA1c levels and insulin resistance indices such as the homeostasis model assessment of insulin resistance (HOMA-IR) and the leptin-to-adiponectin ratio improved [ 144 , 145 ], while serum levels of reactive oxygen metabolites decreased [ 146 ]. It can thus be expected that long-term tocilizumab treatment may offer protection against the progression of atherosclerosis leading to cardiovascular events [ 147 ]. Indeed, large-scale genetic analyses demonstrated a causal association between IL-6R-related pathways and coronary heart disease [ 148 , 149 ], and a randomized, open-label, parallel-group, multicenter study to evaluate the rate of cardiovascular events of tocilizumab in comparison to a TNF inhibitor, etanercept in patients with rheumatoid arthritis (, Identifier: NCT01331837) is now in progress. To establish broad clinical indications for tocilizumab for various diseases, however, further clinical studies will be needed to verify its efficacy and safety. The current clinical trials are listed in Table 2 .
Intravenously administered glucocorticoids , such as prednisone , are the standard of care in acute GvHD  and chronic GVHD.  The use of these glucocorticoids is designed to suppress the T-cell-mediated immune onslaught on the host tissues; however, in high doses, this immune-suppression raises the risk of infections and cancer relapse. Therefore, it is desirable to taper off the post-transplant high-level steroid doses to lower levels, at which point the appearance of mild GVHD may be welcome, especially in HLA mis-matched patients, as it is typically associated with a graft-versus-tumor effect. [ citation needed ] . Cyclosporine and tacrolimus are inhibitors of calcineurin. Both substances are structurally different but have the same mechanism of action. Cyclosporin binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase A (known as cyclophilin), while tacrolimus binds to the cytosolic protein Peptidyl-prolyl cis-trans isomerase FKBP12. These complexes inhibit calcineurin, block dephosphorylation of the transcription factor NFAT of activated T-cells and its translocation into the nucleus.  Standard prophylaxis involves the use of cyclosporine for six months with methotrexate. Cyclosporin levels should be maintained above 200 ng/ml.  Other substances that have been studied for GvHD prophylaxis include, for example: sirolimus, pentostatin and alemtuzamab.