Storb R, Raff R F, Appelbaum F R, Schuening F W, Sandmaier B M, Graham T C, Thomas E D
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1988 Oct;72(4):1300-4.
In view of reported attempts at marrow grafting after nuclear accidents with a broad range of radiation exposures, the present study explored the total-body irradiation (TBI) conditions needed for engraftment in a canine model by using marrow from DLA-identical littermates. Previous studies have shown that such grafts are consistently successful when recipients are exposed to 920 cGy of TBI delivered at a rate of 7 cGy/min from opposing dual cobalt sources. The present TBI doses were all in the lethal range. Five dogs were administered 450 cGy; seven dogs, 600 cGy; five dogs, 700 cGy; and five dogs, 800 cGy of TBI administered at 7 cGy/min. They received a median of 3.3 x 10(8) marrow cells/kg intravenously after completion of radiation. Results showed transient allogeneic marrow engraftment in all dogs administered the lowest dose of TBI studied (450 cGy). Importantly, transient grafts permitted four of five dogs to live long enough for autologous marrow recovery to occur. At increasing radiation doses, 600, 700, and 800 cGy, the risk of graft failure lessened, with 3 of 7, 2 of 5, and 1 of 5 dogs, respectively, showing graft rejection. Fewer dogs survived with autologous marrow recovery, and more showed sustained allogeneic engraftment (4 of 7, 3 of 5, and 4 of 5 dogs, respectively). We conclude that DLA-identical littermate marrow grafts are beneficial in the setting of otherwise lethal radiation exposures, with most dogs either experiencing sustained allogeneic engraftment or surviving with autologous marrow recovery due to the extended support provided by a transient allogeneic graft.
鉴于有报道称在核事故后进行了一系列不同辐射暴露剂量下的骨髓移植尝试，本研究通过使用来自DLA相同的同窝仔犬的骨髓，探索了犬类模型中实现骨髓植入所需的全身照射（TBI）条件。先前的研究表明，当接受者从相对的双钴源以7 cGy/分钟的速率接受920 cGy的TBI照射时，此类移植始终是成功的。目前的TBI剂量均在致死范围内。五只犬接受了450 cGy的TBI照射；七只犬接受了600 cGy；五只犬接受了700 cGy；五只犬接受了800 cGy的TBI照射，照射速率为7 cGy/分钟。在完成辐射后，它们静脉内接受了中位数为3.3×10⁸个骨髓细胞/千克的移植。结果显示，在接受研究中最低TBI剂量（450 cGy）的所有犬中均出现了短暂的同种异体骨髓植入。重要的是，短暂的移植使得五只犬中有四只存活时间足够长，从而实现了自体骨髓恢复。随着辐射剂量增加到600、700和800 cGy，移植失败的风险降低，分别有7只犬中的3只、5只犬中的2只和5只犬中的1只出现了移植排斥反应。存活并实现自体骨髓恢复的犬数量减少，更多的犬出现了持续的同种异体植入（分别为7只犬中的4只、5只犬中的3只和5只犬中的4只）。我们得出结论，在其他情况下致死性辐射暴露的情况下，DLA相同的同窝仔犬骨髓移植是有益的，由于短暂的同种异体移植提供的延长支持，大多数犬要么经历持续的同种异体植入，要么存活并实现自体骨髓恢复。
