Storb R, Raff R F, Appelbaum F R, Deeg H J, Graham T C, Schuening F G, Shulman H, Yu C, Bryant E, Burnett R
Fred Hutchinson Cancer Research Center, Seattle, WA.
Blood. 1994 Nov 15;84(10):3558-66.
Previous studies found that bone marrow (BM) allografts from DLA-identical littermates resulted in survival of two thirds of recipient dogs after otherwise lethal doses of 450 to 600 cGy of total body irradiation (TBI) because of successful allografts or autologous recovery after rejection of the allografts. The current study asked whether survival could be further improved by treating allograft recipients with recombinant canine granulocyte colony-stimulating factor (G-CSF), stem cell factor (SCF), or G-CSF/SCF. Of 21 dogs, 14 (67%) receiving allografts but no growth factors survived, 10 with successful allografts (including 5 mixed chimeras) and 4 with autologous recovery; whereas 7 animals died, 5 from infections during BM aplasia and 2 from acute graft-versus-host disease. By comparison, 30 of 34 dogs (88%) receiving hematopoietic growth factors in addition to the BM graft survived, 17 with successful allografts (including 10 mixed chimeras) and 13 with autologous recovery; whereas 4 died, all with infection related to BM aplasia after rejection of the allograft. Survival was similar for recipients of G-CSF, SCF, or the combination of G-CSF and SCF. Logistic regression analyses, which accounted for possible effects of TBI dose, showed a trend for improved survival in dogs receiving growth factors (P = .09), no change in allogeneic engraftment (P = .74), and a slight increase in autologous recovery (P = .22). In agreement with previous data, we found that grafts of BM from DLA-identical littermates improved survival of recipient dogs exposed to low but otherwise lethal doses of TBI. A further improvement in survival could be achieved by additional treatment with G-CSF, SCF, or G-CSF/SCF. Results suggest that treatment by hematopoietic growth factors along with BM grafts should be considered for victims of radiation accidents.
先前的研究发现，来自DLA相同同窝仔犬的骨髓（BM）异体移植，在给予450至600 cGy全身照射（TBI）的致死剂量后，三分之二的受体犬存活，这是由于异体移植成功或异体移植排斥后自体恢复。当前研究探讨了用重组犬粒细胞集落刺激因子（G-CSF）、干细胞因子（SCF）或G-CSF/SCF治疗异体移植受体是否能进一步提高存活率。21只犬中，14只（67%）接受异体移植但未接受生长因子的犬存活，10只异体移植成功（包括5只混合嵌合体），4只自体恢复；而7只动物死亡，5只因骨髓再生障碍期间感染死亡，2只因急性移植物抗宿主病死亡。相比之下，34只犬中30只（88%）在接受骨髓移植的同时还接受造血生长因子治疗后存活，17只异体移植成功（包括10只混合嵌合体），13只自体恢复；而4只死亡，均在异体移植排斥后因与骨髓再生障碍相关的感染死亡。接受G-CSF、SCF或G-CSF与SCF联合治疗的受体犬存活率相似。逻辑回归分析考虑了TBI剂量的可能影响，结果显示接受生长因子治疗的犬存活率有提高趋势（P = 0.09），同种异体植入无变化（P = 0.74），自体恢复略有增加（P = 0.22）。与先前数据一致，我们发现来自DLA相同同窝仔犬的骨髓移植提高了暴露于低但致死剂量TBI的受体犬的存活率。通过额外给予G-CSF、SCF或G-CSF/SCF治疗可进一步提高存活率。结果表明，对于辐射事故受害者，应考虑造血生长因子联合骨髓移植治疗。
