《地西他滨联合cag治疗老年aml疗效观察(3)》由会员分享，可在线阅读，更多相关《地西他滨联合cag治疗老年aml疗效观察(3)（23页珍藏版）》请在金锄头文库上搜索。
1、地西他滨联合地西他滨联合 CAGCAG 治疗老年治疗老年 AMLAML 的疗效观察的疗效观察摘要：目的 AML（老年畸形髓系白血病）在所有白血病患者当中占比例达到55%，而且 AML 化疗相关的死亡率较高，患者生存周期较短，迫切的需要有一种毒性较低而且相对安全的化疗方案来进行治疗。为此我们进行了一项具有前瞻性的临床试验采用 DAC（地西他宾）联合 GAC（阿糖胞苷、阿克拉霉素以及 G-CSF）采用半相合外周的血淋巴细胞回输方式来进行老年 AML 患者的治疗，在方案执行的过程当中我们对于该方案进行了安全性以及有效性的相关评价，并且对于 DAC（地西他宾）联合 GAC（阿糖胞苷、阿克拉霉素以及 G
2、-CSF）对于髓系白血病细胞株的影响进行了探析。方法 从 2013 年 2 月 1 日到 2015 年 4 月 1 日间在我院进行治疗的 20 例AML 患者为研究对象，对于患者进行 DAC（地西他宾）联合 GAC（阿糖胞苷、阿克拉霉素以及 G-CSF），采用半相合外周的血淋巴细胞回输方式来进行老年 AML患者的治疗并且对于患者的治疗反应、基本临床特征、GVHD（移植抗宿主病）以及治疗过程当中的相关不良事件来进行分析。对于 SKNO-1、Kasumi-1、U937以及 THP-1 四种白血病细胞株分别进行 G-CSF 单药、不给药、DAC（地西他宾）联合 GAC（阿糖胞苷、阿克拉霉素以及 G-
3、CSF）处理以及地西他宾单药处理，干预两天之后，采用流式细胞检测仪来进行细胞的分化以及掉网的检测，并且同时采用 CCK-8 来进行细胞增殖的检测，对于 SKNO-1、Kasumi-1 进行克隆形成的试验，克隆形成实验，并用定量 PCR 检测地西他滨处理后的 G-CS F 受体 CSF3R基因的表达变化，硫化测序观察其 5 UTR 的甲基化状态的变化，利用流式细胞仪检测 CSF3R 的蛋白变化。结果 所有患者平均年龄为 65 岁(57-77 岁)，共有 17 例(85 %)患者至少有 1 种不良预后因素。第一周期治疗后，14 例(7000)患者获得完全缓解(CR)，5 例(25%)获得部分缓解(
4、PR)，总反应率为 95 % (19/20 )；两周期治疗后，共17 例患者获得完全缓解，CR 率为 85 %。最常见的不良事件是 3 级或 4 级的骨髓抑制，第一周期治疗后，中性粒细胞和血小板的中位恢复时间分别是 11 天和巧天。所有患者均不需要转至重症监护病房，均未发生治疗相关死亡。第一周期患者回输的单个核细胞和 CD3+T 细胞的中位值分别为 1.230x108/kg 和 0.949x 108/kg，所有患者均未观察到任何急性或慢性 GVHD 临床表现。地西他滨能明显抑制髓系白血病细胞株细胞的增殖能力、克隆形成能力，能诱导细胞的分化，不会引起细胞的明显调亡；G-CSF 不影响地西他滨抑制
5、细胞增殖、克隆形成的能力，但能明显促进地西他滨的诱导分化的能力；地西他滨能上调 G-CSF 的受体 CSF3R 的 mRNA 水平的表达，但不能上调其蛋白质水平的表达，CSF3R 的 5 UTR 为低甲基化状态。结论:DAC 联合改良 CAG 及半相合外周血淋巴细胞回输方案作为老年 AML 患者的诱导治疗能获得较高的完全缓解率，能明显缩短血细胞减少的持续时间，同时不会发生 GVHD，是治疗老年 AML 患者的一种安全的、有效的诱导治疗方法。G-CSF 促进了地西他滨诱导髓系白血病细胞株分化的能力，可能是临床方案疗效好的原因之一。关键词：DAC；地西他宾；阿糖胞苷；阿克拉霉素；髓系白血病；Abs
6、tract: objective the AML (old deformity of myeloid leukemia) in all leukemia patients accounted for 55% and AML chemotherapy was associated with a higher mortality rate, the shorter the survival period, urgent need to have a less toxic and relatively safe chemotherapy to treat. For this purpose, we
7、carried out a prospective clinical trial with the DAC (to the West He Bin) combined with GAC (ARA, clarithromycin and G-CSF) with haploidentical peripheral blood lymphocytes to form of transport for the treatment of elderly patients with acute myeloid leukemia (AML), in the process of implementation
8、 of the program we for the program were safety and effectiveness evaluation, and DAC (to the West for his guest) combined with GAC (cytarabine, O clarithromycin and G-CSF) effects on myeloid leukemia cell lines of.Methods from 2 January 2013 to 2015, April 1 day in our hospital for treatment of pati
9、ents with 20AML as the object of study, for patients of DAC (to the West He Bin) combined GAC (cytarabine, clarithromycin and G-CSF) by haploidentical peripheral blood lymphocyte reinfusion method in the treatment of elderly AML patients and for the patients response to treatment, basic clinical cha
10、racteristics, GVHD (graft versus host disease (GVHD) and treatment related adverse events were analyzed. For skno-1, Kasumi-1, U937 and THP-1 four white blood Disease cell lines were G-CSF single drug and no drug, DAC (to the West He Bin) combined with GAC (cytarabine, aclarubicin and G-CSF) and dec
11、itabine single drug treatment, intervention for two days after using flow cytometry to cell differentiation and out of network detection, and at the same time by CCK-8 detection of cell proliferation, for skno-1, Kasumi-1 clonogenic test, clone formation assay, and by quantitative PCR detection of d
12、ecitabine treatment after g-cs F receptor CSF3R gene expression changes and curing sequencing to observe the 5 The changes of methylation status of UTR, the protein of CSF3R was measured by flow cytometry.Results all patients with an average age is 65 years old (age.), a total of 17 cases (85 %) in
13、patients with at least one adverse prognostic factors. After the first cycle of treatment, 14 cases (70) patients achieved complete remission (CR), 5 cases (25%) achieved partial remission (PR), the total response rate was 95% (19 / 20)； after two cycles of treatment, a total of 17 patients obtained
14、 complete remission. The CR rate was 85%. The most common adverse events is bone marrow suppression of grade 3 or 4, after the first cycle of treatment, neutrophil and platelet median recovery time are 11 days and 15 days . all patients were not transferred to the intensive care unit, there were no
15、treatment related death. Lose mononuclear cells and CD3 + T cells in the bit values respectively 1.230x108/kg and 0.949x this first cycle patients return, all patients were not observed in the clinical manifestation of any acute or chronic GVHD. To the West with capecitabine can significantly inhibi
16、t the proliferation of myeloid leukemia cell lines were cultured in vitro and the colony forming ability and can induce cell differentiation, does not cause cell obvious apoptosis； G-CSF did not influence decitabine inhibited cell proliferation, colony forming ability, but can obviously promote the decitabine The ability to induce differentiation； decitabine can upregulate the expression of G-CSF receptor CSF3R expression level of mRNA, but can not in
