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重组犬干细胞因子(一种c-kit配体)对犬DLA同基因同窝骨髓移植后造血恢复的影响。

Effect of recombinant canine stem cell factor, a c-kit ligand, on hematopoietic recovery after DLA-identical littermate marrow transplants in dogs.

作者信息

Schuening F G, von Kalle C, Kiem H P, Appelbaum F R, Deeg H J, Pepe M, Gooley T, Graham T C, Hackman R C, Storb R

机构信息

The University of Wisconsin, Madison, USA.

出版信息

Exp Hematol. 1997 Nov;25(12):1240-5.

PMID:9357967
Abstract

We studied the effect of recombinant canine stem cell factor (rcSCF) on hematopoietic recovery, incidence of graft failure, graft-vs.-host disease (GVHD), and survival after marrow transplantation from dog leukocyte antigen (DLA)-identical canine littermates. Ten animals received 100 microg rcSCF/kg/day b.i.d. by subcutaneous injection on days 1 through 10 after 920 cGy total body irradiation and transplantation of a mean of 3.7x10(8) marrow cells/kg body weight. None of the dogs received GVHD prophylaxis. All animals showed hematopoietic engraftment. The median number of days to achieve 1000 neutrophils/mm3 was 9; 100 monocytes/mm3 were reached after 15 days, 500 lymphocytes/mm3 after 21 days, and 20,000 platelets/mm3 after 16 days. One animal developed GVHD involving skin, gut, and liver and died of bacterial pneumonia 21 days after transplantation. The remaining nine dogs were observed for a median of 37 days (range 29-84 days) posttransplantation until they were killed. Facial edema was seen in three dogs during the first 2-3 days of rcSCF administration. These results show that within the limits of this study it appears to be safe to administer SCF after DLA-identical littermate marrow transplants in dogs. Comparison with previously published data in the same model showed that neutrophil and monocyte recovery was significantly faster in dogs receiving SCF treatment compared with dogs without growth factor treatment (recovery to achieve 1000 neutrophils/mm3: median 9 days vs. 13 days, p = 0.002; recovery to 100 monocytes/mm3: median 15 days vs. 105 days, p = 0.0002). Otherwise, no significant differences were seen. Results obtained with SCF treatment were similar to those previously obtained in the same model with recombinant human granulocyte colony-stimulating factor (rhG-CSF) treatment except that recovery of lymphocytes to 500/mm3 appeared to be more rapid in G-CSF-treated dogs (median 15 days vs. 21 days, p = 0.03).

摘要

我们研究了重组犬干细胞因子(rcSCF)对同基因犬白细胞抗原(DLA)的同窝犬骨髓移植后造血恢复、移植物失败发生率、移植物抗宿主病(GVHD)及生存情况的影响。10只动物在接受920 cGy全身照射并移植平均3.7×10⁸个骨髓细胞/kg体重后,于第1至10天每天皮下注射100 μg rcSCF/kg,分两次给药。所有犬均未接受GVHD预防措施。所有动物均出现造血植入。达到1000个中性粒细胞/mm³的中位天数为9天;15天后达到100个单核细胞/mm³,21天后达到500个淋巴细胞/mm³,16天后达到20000个血小板/mm³。1只动物发生了累及皮肤、肠道和肝脏的GVHD,并在移植后21天死于细菌性肺炎。其余9只犬在移植后中位观察37天(范围29 - 84天)直至处死。在给予rcSCF的前2 - 3天,3只犬出现面部水肿。这些结果表明,在本研究范围内,同基因同窝犬骨髓移植后给予SCF似乎是安全的。与同一模型中先前发表的数据相比,接受SCF治疗的犬中性粒细胞和单核细胞恢复明显快于未接受生长因子治疗的犬(恢复至1000个中性粒细胞/mm³:中位9天对13天,p = 0.002;恢复至100个单核细胞/mm³:中位15天对105天,p = 0.0002)。否则,未观察到显著差异。SCF治疗获得的结果与先前在同一模型中重组人粒细胞集落刺激因子(rhG - CSF)治疗获得的结果相似,只是G - CSF治疗的犬淋巴细胞恢复至500/mm³似乎更快(中位15天对21天,p = 0.03)。

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