Schuening F G, Appelbaum F R, Deeg H J, Sullivan-Pepe M, Graham T C, Hackman R, Zsebo K M, Storb R
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA 98104.
Blood. 1993 Jan 1;81(1):20-6.
The effects of recombinant canine stem cell factor (rcSCF) on hematopoiesis were studied in normal dogs and in dogs given otherwise lethal total body irradiation (TBI) without marrow transplant. Results were compared with previous and concurrent data with recombinant granulocyte colony-stimulating factor (rG-CSF). Four normal dogs received 200 micrograms rcSCF per kilogram body weight daily either by continuous intravenous infusion for 28 days (n = 2) or by subcutaneous (SC) injection in two divided doses for 20 days (n = 2). All dogs showed at least a twofold increase in peripheral blood neutrophil counts starting approximately 7 days after the initiation of treatment. Hematocrit level and monocyte, lymphocyte, eosinophil, reticulocyte, and platelet counts were not elevated. Marrow sections after rcSCF treatment showed panhyperplasia. The only toxicity was facial edema during the first few days of rcSCF administration, presumably caused by mast cell stimulation. Ten dogs were given 400 cGy TBI at 10 cGy/min from two opposing 60Co sources. They were given no marrow infusion and received 200 micrograms/kg/d rcSCF SC in two divided doses for 21 days starting within 2 hours of TBI. Five of the 10 dogs showed complete and sustained hematopoietic recovery and survived as compared with 1 of 28 control dogs not receiving growth factor (P < .005). RcSCF treatment allowed for hematopoietic recovery in two of seven dogs administered 500 cGy of TBI but in none of five dogs given 600 cGy of TBI. Results with rcSCF are similar to those obtained with rG-CSF. The rate of neutrophil recovery in rcSCF-treated dogs after 400 cGy TBI was not different from that of rG-CSF-treated dogs (P = .65), but the rate of platelet recovery was faster (P = .06) in the rcSCF-treated animals. Combined treatment with rcSCF and rcG-CSF after 500 cGy TBI did not result in strongly improved survival as compared with results obtained with either factor alone.
在正常犬以及接受致死剂量全身照射（TBI）但未进行骨髓移植的犬中，研究了重组犬干细胞因子（rcSCF）对造血功能的影响。将结果与先前及同期使用重组粒细胞集落刺激因子（rG-CSF）的数据进行了比较。4只正常犬每天按每千克体重200微克的剂量接受rcSCF，其中2只犬通过连续静脉输注28天，另外2只犬通过皮下（SC）注射，分两次给药，共20天。所有犬在治疗开始约7天后外周血中性粒细胞计数至少增加两倍。血细胞比容水平以及单核细胞、淋巴细胞、嗜酸性粒细胞、网织红细胞和血小板计数均未升高。rcSCF治疗后的骨髓切片显示全血细胞增生。唯一的毒性反应是在rcSCF给药的最初几天出现面部水肿，推测是由肥大细胞刺激引起的。10只犬以10 cGy/分钟的剂量从两个相对的60Co源接受400 cGy的TBI。它们未接受骨髓输注，并在TBI后2小时内开始，以分两次给药的方式，每天按每千克体重200微克的剂量接受rcSCF皮下注射，共21天。10只犬中有5只显示出完全且持续的造血恢复并存活，而28只未接受生长因子的对照犬中只有1只存活（P <.005）。在接受500 cGy TBI的7只犬中，rcSCF治疗使其中2只犬实现了造血恢复，但在接受60 cGy TBI的5只犬中无一例实现造血恢复。rcSCF的结果与rG-CSF相似。400 cGy TBI后，rcSCF治疗的犬中性粒细胞恢复率与rG-CSF治疗的犬无差异（P =.65），但rcSCF治疗的动物血小板恢复率更快（P =.06）。与单独使用任一因子的结果相比，500 cGy TBI后联合使用rcSCF和rcG-CSF并未显著提高生存率。
