【作者】 刘红；

【导师】 吴德沛； 李彩霞；

【作者基本信息】 苏州大学 ， 血液病学， 2009， 硕士

【摘要】 目的:(1)研究根据预后危险度分组,对成人急性淋巴细胞白血病进行个体化分组治疗的疗效及安全性,并探讨微小残留病与复发和长期生存的关系,建立以危险度为基础的个体化治疗体系。(2)研究CD4+CD25+CD127low/-调节性T细胞在成人急性淋巴细胞白血病中的动态变化,探讨CD4+CD25+CD127low/-调节性T细胞与微小残留病灶的关系。方法:(1)将2006年1月至2009年2月在我科治疗的55例初诊成人急性淋巴细胞白血病患者根据白细胞数,染色体核型及对治疗的反应等因素分为标危组和高危组,两组患者均予CDOLP诱导化疗,标危组患者按方案化疗,高危组患者在巩固治疗过程中积极寻找供体行造血干细胞移植。所有患者在治疗的不同时间点进行微小残留病(MRD)检测,采用Kaplan-Meier曲线评估患者的无事件生存(EFS)率和总生存(OS)率。(2)采集35例成人急性淋巴细胞白血病患者初诊时及化疗不同时期(首次完全缓解时、完全缓解后2月、完全缓解后4月、完全缓解后6月)的外周血,应用流式细胞技术动态监测外周血中CD4+CD25+CD127low/- T细胞占CD4+T细胞的比例(CD4+CD25+CD127low/-/CD4+)的变化并结合实时定量PCR方法检测外周血单个核细胞中FOXP3基因的表达量,研究CD4+CD25+CD127low/-调节性T细胞在成人急性淋巴细胞白血病的动态变化情况及其与微小残留病灶的关系。结果:(1)55例成人急性淋巴细胞白血病中52例获得完全缓解(CR),CR率为94.5%。39例患者行化疗,16例患者行HSCT。中位随访时间359(19～1097)天。1年及3年OS率分别为(79.0±6.3)%、(59.3±10.1)%,1年及3年EFS率分别为(60.5±7.7)%、(57.3±7.9)%。标危组患者EFS率高于高危组患者(P=0.012)。诱导治疗结束后(+1月)微小残留病(MRD)值>10-2,巩固治疗后(+4月)MRD>10-3的患者易复发(P值分别为0.000和0.020)。(2)初诊成人急性淋巴细胞白血病外周血中CD4+CD25+CD127low/-/CD4+的比例高于正常对照组;CD4+CD25+CD127low/-调节性T细胞表达在初诊组和MRD10-2组高于MRD10-3和MRD10-4组,且与复发有一定的相关性。结论(1)在危险度分组的基础上对成人急性淋巴细胞白血病进行个体化分组治疗,诱导完全缓解率高,毒副作用可耐受。(2)治疗过程中定期监测微小残留病可预测复发。(3)成人急性淋巴细胞白血病外周血中CD4+CD25+CD127low/-调节性T细胞表达增加,可能参与了急性淋巴细胞白血病的免疫耐受机制。(4)CD4+CD25+CD127low/-调节性T细胞与微小残留病有相关性,在一定程度上可以预测成人急性淋巴细胞白血病的预后。更多还原

【Abstract】 Objective:(1)To evaluate the efficacy and security of risk-adjusted therapy of adult acute lymphoblastic leukemia(ALL),to explore the relationship between minimal residual disease and relapse, and to establish a individualized treatment system. (2)To explore the dynamic changes of CD4+CD25+CD127low/- regulatory T cells in adult acute lymphoblastic leukemia, to evaluate the relationship between CD4+CD25+CD127low/- regulatory T cells and minimal residual disease. Methods (1)55 adult ALL patients hospitalized in our institute between January 2006 and Feburary 2009 were divided into standard-risk group and high-risk group.The standard-risk group received standard chemotherapy,and the high-risk group patients who had matched donor received hematopoietic stem cell transplantation. Minimal residual disease were detected at different time points during the treatment process. Event free survival(EFS)and overall survial(OS) were estimated by Kaplan-Meier method. (2)Thirty-five patients aged from 15 to 50 years were enrolled in this study. Collect peripheral blood of adult acute lymphoblastic leukemia at different time during the process of chemotherapy (at diagnosis, at the first complete remission, 2 month, 4 month, 6 month after first complete remission ,respectively). The CD4+CD25+CD127low/- subpopulations ratios in CD4+T lymphocytes (CD4+CD25+CD127low/-/CD4+) were detected with flow cytometry, and the expression of FOXP3 gene were analyzed with the real-time PCR assays to study the changes of CD4+CD25+CD127low/- regulatory T cell in adult ALL during the chemotherapy and the the correlations of minimal residual disease with CD4+CD25+CD127low/- regulatory T cell. Results (1)The complete remission rate was 94.5%. The 1 year and 3 year OS rate were (79.0±6.3)% and (59.3±10.1)%, respectively. The 1 year and 3 year EFS rate were (60.5±7.7)% and(57.3±7.9)%, respectively (P=0.012). Patients with MRD>10-2 after induction therapy(after 1 month)and patients with MRD>10-3 after consolidation therapy(after 4 month)were prone to relapse(P=0.000 and 0.020,respectively)(.2)The CD4+CD25+CD127low/-/CD4+ ratio were higher in newly diagnosed acute lymphoblastic leukemia than that in normal control. The CD4+CD25+CD127low/-regulatory T cells in the newly diagnosed group and MRD10-2 group were higher than that in MRD10-3 and MRD10-4 group, and were associated with relapse. Conclusion (1)Risk-adjusted therapy regimen improve CR rate, and have good tolerance.(2)MRD results could predict the risk of relapse. (3)The expression of CD4+CD25+CD127low/- regulatory T cells in newly diagnosed adult ALL, which may contribute to the immunological tolerance of ALL. ( 4 ) The expression of CD4+CD25+CD127low/- regulatory T cells could be used to assess the prognosis.更多还原