Tocilizumab, in search for a role in acute GVHD

Acute graft versus host disease (aGVHD) was first described by Barnes et al. in 1962, who reported a 'secondary disease' in mice after irradiation and infusion of allogeneic spleen cells. The disease manifested as fatal diarrhea and skin abnormalities. They postulated that aGVHD resulted from introducing immunologically competent cells into an immunocompetent host. Treatments were developed to address this problem, and most centers use calcineurin inhibitors (tacrolimus or cyclosporine) combined with mycophenolate mofetil or methotrexate to prevents aGVHD. This classic GVHD prophylaxis is associated with an incidence of acute GVHD of approximately sixty percent. Other methods of GVHD prevention, including T-cell depletion and more recently post-trasnplant cyclophosphamid, have been tested, but all have their own limitations. The most effective methods tend to be more immunosuppressive and are not clearly superior in regards to long-term survival. Acute GVHD then remains a major problem in hematopoietic stem cell allogeneic transplantation (HCT). Its initial treatment consists of high-dose glucocorticosteroids (1-2 mg/kg daily). However, only one-third of patients are cured, leaving the majority of patients requiring more therapy. Patients with glucocorticosteroid refractory acute GVHD (SR aGVHD) have a very high mortality and to date, there is no effective treatment.