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


RESULTS
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.


CONCLUSIONS
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.
Luznik
Leo
L
Sidney Kimmel Comprehensive Cancer Center and Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, Maryland 21231, USA. luznile@jhmi.edu
Jones
Richard J
RJ
Fuchs
Ephraim J
EJ
D000818:Animals; D016026:Bone Marrow Transplantation / Q000276:immunology; D003520:Cyclophosphamide / Q000627:therapeutic use*; D004195:Disease Models, Animal; D006084:Graft Rejection / Q000276:immunology; D006086:Graft vs Host Disease / Q000517:prevention & control*; D006801:Humans; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D051379:Mice
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide
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