Abstract
Pretransplant total lymphoid irradiation (TLI) plus donor bone marrow can result in donor-specific tolerance, but graft-versus-host disease is not consistently avoided. TLI may have greater applicability as an adjuct to generalized immunosuppressive treatment. In a clinical trial, preoperative TLI posed problems for patients with a high percentage of cytotoxic antibodies who sometimes had a long wait for a transplant after completion of TLI. It would be logistically advantageous if TLI could be given in the perioperative period. We investigated the feasibility of this approach in an ACI (RT-1 a) to Lewis (RT-1 l) rat heart allograft model. Untreated recipients rejected the grafts at a mean of 6.1 days. TLI 400 or 600 rads administered as one dose 1 day preoperative did not prolong graft survival (rejected a mean of 5.6 and 6.3 days). A dose fraction schedule previously found to be effective when given preoperatively, 200 rads × 5 consecutive days, did not prolong graft survival when administered beginning the first day postoperatively (mean rejection at 6.3 days). Higher dose fractions were effective: 300 rads × 3, 300 rads × 5, 400 rads × 3, and 400 rads × 4 gave mean rejection times of 11.8, 16.8, 11.5, and 13.6 days, respectively. Combining 600 rads preoperative with 200 rads × 5 days postoperative did not prolong graft survival. Six hundred rads preoperative plus 300 rads × 3 days postoperative prolonged graft survival, but was no more effective than 300 rads × 3 days postoperative alone. The most effective schedule for postoperative TLI was 300 rads × 3, 0 rads × 2, and 200 rads × 5 days; this treatment delayed rejection to 25 days. In conclusion, one dose preoperative TLI has no effect on heart allograft survival, but postoperative TLI in dose fractions of 300 rads is effective in delaying rejection. Postoperative TLI may be an alternative treatment for patients who must wait for suitable crossmatch negative cadaver kidneys.
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