A short course of high-dose cyclophosphamide induces long-term survival of intestinal allografts in mice.

Abstract

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.