Schuening F G, Storb R, Goehle S, Graham T C, Hackman R, Mori M, Souza L M, Appelbaum F R
Division of Clinical Research, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1990 Aug 1;76(3):636-40.
We studied whether treatment of dogs with recombinant human granulocyte colony-stimulating factor (rhG-CSF), after 920 cGy total body irradiation (TBI) and transplantation of 3.3 +/- 1.0 x 10(8) bone marrow cells per kilogram from a DLA-identical littermate, accelerated hematopoietic recovery and influenced the incidence of subsequent marrow graft failure or graft-versus-host disease (GVHD). Ten animals were treated with 100 micrograms rhG-CSF/kg/d from days 1 through 10 after TBI. Results were compared with those of historical control of 14 dogs not administered rhG-CSF. Neither group of dogs received GVHD prophylaxis. The median time to recovery of 1,000 neutrophils/mm3 was 8 days for dogs administered rhG-CSF compared with 14 days in controls (logrank test: P less than .03). The median time to reach 100 monocytes/mm3 was 17 days in G-CSF-treated dogs compared with 49 days in controls (P less than .002). The median time to attain 500 lymphocytes/mm3 was 15 days versus 31 days, respectively (P less than .01). The median time to reach 20,000 platelets/mm3 was 26 versus 20 days (P = .68). Graft failure occurred in 1 of 10 G-CSF-treated dogs versus 2 of 14 controls (two-tailed Fisher's exact test: P = 1.00). GVHD was seen in 4 of 9 rhG-CSF-treated dogs compared with 1 of 12 controls (P = .12). Two G-CSF-treated dogs died of GVHD versus none of the controls (P = .17). No unusual toxicities were seen in dogs receiving rhG-CSF. In summary, rhG-CSF significantly accelerated recovery of neutrophils, monocytes, and lymphocytes after DLA-identical littermate marrow transplantation without altering platelet recovery. Graft failure was not seen more often than in controls, but there was a trend toward an increased incidence of GVHD.
我们研究了在给予犬920 cGy全身照射（TBI）并移植每千克3.3±1.0×10⁸个来自DLA相同同窝幼仔的骨髓细胞后，用重组人粒细胞集落刺激因子（rhG-CSF）治疗犬是否能加速造血恢复并影响随后骨髓移植失败或移植物抗宿主病（GVHD）的发生率。10只动物在TBI后第1天至第10天接受100微克rhG-CSF/千克/天的治疗。将结果与14只未给予rhG-CSF的历史对照犬的结果进行比较。两组犬均未接受GVHD预防。接受rhG-CSF治疗的犬恢复到1000个中性粒细胞/立方毫米的中位时间为8天，而对照组为14天（对数秩检验：P＜0.03）。接受G-CSF治疗的犬达到100个单核细胞/立方毫米的中位时间为17天，而对照组为49天（P＜0.002）。达到500个淋巴细胞/立方毫米的中位时间分别为15天和31天（P＜0.01）。达到20000个血小板/立方毫米的中位时间为26天和20天（P = 0.68）。10只接受G-CSF治疗的犬中有1只发生移植失败，而14只对照组中有2只（双侧Fisher精确检验：P = 1.00）。9只接受rhG-CSF治疗的犬中有4只出现GVHD，而12只对照组中有1只（P = 0.12）。2只接受G-CSF治疗的犬死于GVHD，而对照组无死亡（P = 0.17）。接受rhG-CSF的犬未观察到异常毒性。总之，rhG-CSF在DLA相同同窝幼仔骨髓移植后显著加速了中性粒细胞、单核细胞和淋巴细胞的恢复，而不改变血小板的恢复。移植失败的发生率并不高于对照组，但GVHD的发生率有增加的趋势。
