Storb R, Raff R F, Appelbaum F R, Graham T C, Schuening F G, Sale G, Pepe M
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1989 Aug 15;74(3):1139-43.
We explored the ability of fractionated total body irradiation (TBI) given at a rate of 7 cGy/min from opposing dual 60Co sources at otherwise lethal doses of 450, 600, 700, 800, and 920 cGy to condition dogs for marrow grafts from DLA-identical littermates. Results were compared with those of a previously reported study using single-dose TBI administered under otherwise identical conditions. Fractionated TBI was less immunosuppressive than single-dose TBI, as evidenced by a significantly higher rate of graft rejection (P = .001). Specifically, sustained allogeneic engraftment was observed in only two of 18 (11%) dogs that received 600 to 800 cGy fractionated TBI as compared with 11 of 17 (65%) dogs that received comparable doses of single-dose TBI. Only at 450 cGy (none of the ten dogs studied had sustained engraftment) and at 920 cGy (four of five dogs that received fractionated and 20 of 21 dogs that received single-dose TBI engrafted) were we unable to find differences between the two modes of radiation. Most dogs that rejected their graft survived with autologous recovery (13 of 22 that received fractionated and eight of 12 that received single-dose TBI; P = .49), presumably the result of extended support provided by the transient allogeneic grafts. We conclude that at equivalent doses fractionated TBI is significantly less effective than single-dose TBI to condition DLA-identical littermate dogs for marrow transplantation. These findings have implications for the design of conditioning programs in clinical transplantation, especially when T-cell-depleted marrow grafts are used.
我们研究了以7 cGy/分钟的速率从相对的双60Co源给予分次全身照射（TBI），剂量分别为450、600、700、800和920 cGy（这些剂量在其他情况下是致死性的），对犬进行预处理以接受来自DLA相同同窝幼仔的骨髓移植的能力。将结果与先前报道的在其他相同条件下使用单剂量TBI的研究结果进行比较。分次TBI的免疫抑制作用比单剂量TBI弱，这表现为移植物排斥率显著更高（P = 0.001）。具体而言，在接受600至800 cGy分次TBI的18只犬中，只有2只（11%）实现了持续的同种异体植入，而接受相同剂量单剂量TBI的17只犬中有11只（65%）实现了植入。仅在450 cGy（所研究的10只犬中没有一只实现持续植入）和920 cGy（接受分次照射的5只犬中有4只植入，接受单剂量TBI的21只犬中有20只植入）时，我们未发现两种照射方式之间存在差异。大多数排斥移植物的犬通过自体恢复存活（接受分次照射的22只中有13只，接受单剂量TBI的12只中有8只；P = 0.49），这可能是短暂同种异体移植物提供的延长支持的结果。我们得出结论，在等效剂量下，分次TBI在对DLA相同同窝幼仔犬进行骨髓移植预处理方面明显不如单剂量TBI有效。这些发现对临床移植预处理方案的设计具有启示意义，尤其是在使用T细胞去除的骨髓移植物时。
