Watts K L, Beard B C, Wood B L, Kiem H P
Clinical Research Division, Fred Hutchinson Cancer Research Center, Seattle, WA, USA.
J Med Primatol. 2009 Dec;38(6):425-32. doi: 10.1111/j.1600-0684.2009.00368.x. Epub 2009 Jul 22.
We used total body irradiation (TBI) as conditioning for cord blood transplantation studies in pigtailed macaques. In these studies, different doses of TBI were explored to obtain optimal myelosuppression with acceptable radiation-related side effects.
Four macaques received TBI ranging from 800 to 1320 cGy, followed by standard post-transplant care. Hematopoietic recovery was monitored by CBC and donor contribution by variable number of tandem repeats analysis.
Animals receiving 800 or 1020 cGy TBI tolerated the irradiation well with autologous recovery of neutrophils within 24 days. At a dose of 1200 cGy, neither autologous recovery nor extramedullary toxicity was observed. A fourth animal received 1320 cGy of TBI and suffered significant toxicity necessitating termination of the study.
We conclude that previously considered myeloablative doses of TBI allowed for autologous recovery in the pigtailed macaque, and that a dose of 1200 cGy may be most appropriate, providing both myeloablation and acceptable non-hematopoietic toxicities.
我们使用全身照射(TBI)作为猪尾猕猴脐血移植研究的预处理方案。在这些研究中,探索了不同剂量的TBI,以获得最佳的骨髓抑制效果,并使辐射相关副作用在可接受范围内。
4只猕猴接受了800至1320厘戈瑞(cGy)的TBI,随后接受标准的移植后护理。通过全血细胞计数(CBC)监测造血恢复情况,并通过可变数目串联重复序列分析监测供体贡献。
接受800或1020 cGy TBI的动物对照射耐受性良好,中性粒细胞在24天内实现自体恢复。在1200 cGy的剂量下,既未观察到自体恢复,也未观察到髓外毒性。第四只动物接受了1320 cGy的TBI,并出现严重毒性,因此必须终止研究。
我们得出结论,先前认为的清髓剂量的TBI可使猪尾猕猴实现自体恢复,1200 cGy的剂量可能最为合适,既能实现清髓,又能使非造血毒性在可接受范围内。