High-dose cyclophosphamide for graft-versus-host disease prevention

Administration of high-dose cyclophosphamide after transplantation inhibits both graft rejection and graft-versus-host disease (GvHD) in mouse models of allogeneic blood or marrow transplantation (alloBMT). This strategy has recently been adapted to human transplantation.

The safety and efficacy of high-dose posttransplantation cyclophosphamide, when given in combination with tacrolimus and mycophenolate mofetil, was first demonstrated after nonmyeloablative conditioning and allografting using human leukocyte antigen (HLA)-mismatched related donors. Further analysis shows that increasing HLA disparity does not worsen overall outcome. High-dose posttransplantation cyclophosphamide was also found to be effective as sole prophylaxis of acute and chronic GvHD after HLA-matched alloBMT.

Taking advantage of the differential susceptibility of proliferating, alloreactive T cells over nonproliferating, nonalloreactive T cells to high-dose cyclophosphamide, and owing to the drug's stem cell sparing effects, this novel strategy provides a unique opportunity to optimize GvHD prophylaxis after HLA-matched alloBMT and increase the use of HLA-mismatched related donors. Well tolerated and effective mismatched related alloBMT provides access to essentially everyone, such as patients with sickle cell anemia, in need of the procedure.