Comparing high and low total body irradiation dose rates for minimum-intensity conditioning of dogs for dog leukocyte antigen-identical bone marrow grafts

Abstract

We tested the hypothesis that total body irradiation (TBI) given at a high dose rate would be more immunosuppressive and lead to a higher incidence of stable hematopoietic cell engraftment after suboptimal levels of conditioning irradiation compared with TBI at a low dose rate. We assessed the engraftment success of dog leukocyte antigen-identical bone marrow transplantation in recipients of 100, 150, and 200 cGy TBI administered at a rate of 7 or 70 cGy/min. Dogs received donor marrow on the same day as TBI and were subsequently treated with postgraft immunosuppression consisting of mycophenolate mofetil (for 28 days) and cyclosporine (for 37 days). Donor chimerism was monitored until the end of study and was characterized by either graft rejection or stable engraftment. Increasing the radiation dose rate from the traditional 7 cGy/min to 70 cGy/min did not lead to increased engraftment success at any of the irradiation doses tested. The dose rate of 70 cGy/minute was no more hematotoxic than the rate of 7 cGy/minute. TBI delivered at a high dose rate was well tolerated but was not associated with a better rate of allogeneic hematopoietic cell engraftment compared with TBI delivered at a lower dose rate.

Keywords: Dog; Dose rate; Hematopoietic cell transplantation; Mixed chimerism; Nonmyeloablative conditioning regimen.