Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, Washington; Department of Medicine, University of Washington, Seattle, Washington.
Biol Blood Marrow Transplant. 2013 Nov;19(11):1650-4. doi: 10.1016/j.bbmt.2013.08.007. Epub 2013 Aug 28.
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.
我们测试了这样一个假设,即与低剂量率全身照射(TBI)相比,高剂量率全身照射(TBI)会产生更强的免疫抑制作用,并导致在条件照射剂量不足的情况下,稳定的造血细胞植入的发生率更高。我们评估了在 7 或 70 cGy/min 的速率下给予 100、150 和 200 cGy TBI 后,犬白细胞抗原相同的骨髓移植受者的植入成功。狗在接受 TBI 的同一天接受供体骨髓,并随后接受包括吗替麦考酚酯(28 天)和环孢素(37 天)在内的移植后免疫抑制治疗。监测供体嵌合体直到研究结束,并通过移植物排斥或稳定植入来描述。将辐射剂量率从传统的 7 cGy/min 增加到 70 cGy/min,在任何测试的照射剂量下都不会导致植入成功率的提高。70 cGy/min 的剂量率与 7 cGy/min 的剂量率一样不会引起更多的血液毒性。高剂量率 TBI 耐受性良好,但与低剂量率 TBI 相比,并不与更高的同种异体造血细胞植入率相关。