Sandmaier BM, et al. - In this trial run at nine haemopoietic stem cell transplantation (HSCT) centres based in the USA, Denmark, and Germany, researchers investigated whether acute graft-versus-host-disease (GVHD) can be effectively prevented by adding sirolimus to the standard cyclosporine and mycophenolate mofetil prophylaxis therapy in patients following non-myeloablative human leucocyte antigen (HLA)-matched, unrelated donor, allogeneic HSCT. Either the standard GVHD prophylaxis regimen (cyclosporine and mycophenolate mofetil) or the triple-drug combination regimen (cyclosporine, mycophenolate mofetil, and sirolimus) was randomly administered to patients. The occurrence of acute GVHD was reported in a significantly lower proportion of patients in relation to treatment with sirolimus added to cyclosporine and mycophenolate mofetil vs treatment with cyclosporine and mycophenolate mofetil alone. At the Fred Hutchinson Cancer Research Center, the novel standard GVHD prophylaxis regimen for patients treated with non-myeloablative conditioning and HLA-matched unrelated HSCT is the combination of cyclosporine, mycophenolate mofetil, and sirolimus, based on these findings.