Suppressive effect of cyclophosphamide on the progression of lethal graft-versus-host disease in mice--a therapeutic model of fatal post-transfusion GVHD.
In this paper, we examine in a murine system whether cyclophosphamide (CY) could prevent the development of fatal GVHD and furthermore whether it could be used to treat on-going GVHD. (C57BL/6xDBA/2)F1 (BDF1) mice were injected with spleen cells from B6 donors and their thoraces were opened to mimic cardiac operation. These mice lost body weight gradually and most of them died during 2-4 weeks post-transfusion. They showed splenomegaly, thymic atrophy and marked bone-marrow aplasia. When CY was administered at 100 mg kg-1 on days 0, 2, 7 and 9, all mice were relieved of GVHD and their organs were almost free of signs of GVHD. CY (100 mg kg-1) administered on days 7 and 9 also save mice from lethal GVHD. Moreover, CY administered at a dose of 20 mg kg-1 on days 9 and 11 when GVHD became apparent was also effective. These data suggest that CY might be used as a therapeutic agent for lethal post-transfusion GVHD.
Uchida
S
S
Japanese Red Cross Blood Center, Tokyo.
Suzuki
K
K
Akiyama
S
S
Miyamoto
M
M
Juji
T
T
Fujiwara
M
M
D000818:Animals; D001803:Blood Transfusion; D003520:Cyclophosphamide / Q000627:therapeutic use*; D006086:Graft vs Host Disease / Q000188:drug therapy / Q000473:pathology / Q000517:prevention & control*; D007166:Immunosuppressive Agents; D008221:Lymphoid Tissue / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D016019:Survival Analysis
D007166:Immunosuppressive Agents; D003520:Cyclophosphamide