白血病负荷与胸苷激酶/丙氧鸟苷分离急性GVHD和GVL效应的关系

Relationship between leukemia burden and function of TK/GCV separatingacute GVHD and GVL effect.

目的研究白血病负荷与胸苷激酶（TK）／丙氧鸟苷（GCV）分离急性移植物抗宿主病（aGVHD）和移植物抗白血病效应（GVL）的关系。方法选择雄性C57BIJ6小鼠为供鼠，雌性F1小鼠为受鼠，进行H-2半相合CD三细胞和TK^＋T细胞移植。将48只受鼠随机分为3个接种组，接种EL9611红白血病细胞（H-2^d）分别为10^5、10^6、10^7个。每组受鼠经。Co9．0Gy照射后，输入cD三细胞和TK^＋T细胞分别为10^5、10^7；再随机分为对照组和GCV组。GCV组腹腔注射GCV50mg／（kg．d），连用7d，根据病理结果确定死因。结果第1、2接种组中的对照组均死于急性GVHD；GCV组30％～40％死于白血病，其余长期生存。GCV组生存时间较对照明组显延长（P〈0．05）。第3接种组均死于白血病，其对照组和GCV组生存时间无统计学差异。结论TK^＋T细胞数量不变时，白血病负荷是影响TK／GCV分离急性GVHD和GVL效应的重要因素。

[ Objective] To explore the relationship between leukemia burden and function of thymidine kinase/gancielovir （TK/GCV） separating acute graft versus host disease （GVHD） and graft versus leukemia （GVL） effect. [ Methods ] Male C57BIJ6 mice acted as donors and female F1 mice acted as recipients. H-2 haplotyped matched CD34^＋ cells and TK^＋ T lymphocytes transplant was performed. 48 recipient mice were divided into three vaccination groups. 10^5, 10^6 and 10^7 EL9611 leukemic cells（ H-2^d） were vaccinated . Recipient mice in cohorts 1-3 were inoculated 10^5, 10^6 and 10^7 EL9611 erythroblastic leukemia cells respectively. Every recipient mouse was irradiated by ^60Co at 9. 0 Gy ,infused 105 CD34^＋ cells and 107 TK^＋ T lymphocytes ,then divided into control group and GCV group in which GCV peritoneal injected was performed at 50 mg/（ kg. d） for 7 d. Death cause was identified by pathological examinations. [ Results] Mice of control groups in the first ,second vaccination group were died of acute GVHD;30%-40% mice of GCV group were died of leukemia ,the rest had long term survival, live time in GCV group was obviously prolonged than control group（ P 〈 0.05 ）. The mice in the third vaccination group all died of leukemia ,there was no statistically difference of survivals between control group and GCV group（P 〉 0.05）. [ Conclusion] At a fixed TK^＋T lymphocyte number, the leukemia cell burden of transplanted mice is an important factor to influence the effect of TK/GCV separating acute GVHD and GVL.