A short course of high-dose cyclophosphamide induces long-term survival of intestinal allografts in mice.
Several transplant programs have recently added cyclophosphamide (CyP) to their immune suppression protocols in an attempt to reduce intestinal graft rejection rates. The present study was undertaken to confirm the benefits of this drug in a murine small bowel transplant model. A short course of monotherapy with CyP 20 mg/kg per dose resulted in a mean survival time (MST) of 17.5 +/- 3.6 days, compared with a MST of 7.5 +/- 0.7 days in the untreated controls (P < 0.01). Cyclosporin A (CsA) 30 mg/kg per day produced comparable survival rates when used as monotherapy (MST: 14.2 +/- 1.3 days) or in combination with CyP 20 mg/kg per dose (MST: 21.3 +/- 5.1 days). Treatment with high dose CyP (40 mg/kg per dose) completely prevented graft loss in 8 of 10 animals (MST: 72.5 +/- 5.3 days, P < 0.01). However, adding CsA abrogated the induction of long-term survival achieved by CyP alone (MST: 23 +/- 0.4 days). These data have important implications for the use of CyP in clinical transplantation.
Kellersmann
R
R
J.P. Robarts Research Institute and the Department of Surgery, London Health Sciences Centre, 339 Windermere Rd., London, Ontario, Canada, N6A 5A5.
Zhong
R
R
Garcia
B
B
Gao
Z H
ZH
Kellersmann
A
A
Kiyochi
H
H
Grant
D R
DR
D000818:Animals; D003520:Cyclophosphamide / Q000627:therapeutic use*; D016572:Cyclosporine / Q000627:therapeutic use; D006084:Graft Rejection; D006085:Graft Survival / Q000187:drug effects*; D006086:Graft vs Host Disease / Q000517:prevention & control; D007166:Immunosuppressive Agents / Q000627:therapeutic use*; D007421:Intestine, Small / Q000637:transplantation*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D014184:Transplantation, Homologous
D007166:Immunosuppressive Agents; D016572:Cyclosporine; D003520:Cyclophosphamide