化疗联合CIK细胞序贯疗法治疗老年急性髓系白血病患者临床意义初探

发布时间：2018-05-20 08:22

本文选题：细胞因子诱导的杀伤细胞 + 急性髓系白血病　；参考：《安徽医科大学》2017年硕士论文

【摘要】：背景急性髓系白血病(Acute Myeloid Leukemia,AML)是一种起源于造血干细胞的恶性克隆性疾病,发病时骨髓中异常的原始细胞及幼稚细胞大量增殖并抑制正常造血引起血细胞减少,出现贫血、出血、感染和肝、脾、淋巴结肿大等临床表现。AML是成人最常见的一类白血病,世界平均年发病率约为2.25/10万,随着年龄的增长老年患者所占的比例日渐升高。急性髓系白血病治疗主要为化疗诱导缓解,近年来即使化疗方案的不断个体化调整,老年患者临床疗效仍无明显改善,主要与老年患者身体基础疾病较多、脏器功能不佳、个体一般情况较差、对高强度化疗不耐受、各类毒副反应发生有关,同时存在严重感染、血栓、出血等风险会影响存活情况;因此保证理想的缓解率及缓解时间,降低治疗过程中的并发症,延长生存期及改善生活质量为老年AML患者化疗后维持治疗的关键。近年来随着免疫学技术的不断进步与发展,细胞免疫治疗成为一个最有应用前景的新的血液肿瘤治疗方法。细胞因子诱导的杀伤细胞(cytokine-induced killer cells CIK细胞)在1991年由斯坦福大学Schmidt-Wolf首次报道,是过继性细胞免疫治疗中较为重要的一类。CIK细胞是将人体单个核细胞在体外经IL-2、抗CD3抗体、IFN-γ等细胞因子共培养后获得的一群兼具T淋巴细胞及NK细胞的生物学特点的免疫细胞。CIK细胞杀伤肿瘤细胞可直接与靶细胞结合杀灭肿瘤,同时还可以通过分泌多种细胞因子,激活Fas途径等方式诱导细胞凋亡。CIK细胞杀瘤作用强大,同时对正常骨髓造血干细胞无明显抑制作用。长期的临床研究表明CIK细胞在血液恶性肿瘤治疗中清除微小残留(micro resist disease,MRD)、维持缓解状态、改善生活质量及延长生存期方面显示出较好的疗效。因此本研究以不能耐受化疗的老年AML患者为研究对象,采取化疗联合CIK细胞辅助治疗的方法,对其疗效和临床价值进行初步探索和评价。目的初步观察及评价化疗联合CIK细胞序贯疗法治疗老年急性髓细胞白血病患者的临床疗效,为老年AML患者建立新的副作用较小的维持治疗方法。方法选择多疗程化疗后疾病达缓解或部分缓解后因各种合并症,无法继续耐受化疗的老年AML患者为研究对象,辅以自体CIK细胞序贯治疗。观察分析5例患者CIK细胞输注后一般症状及不良反应,细胞免疫功能状态、MRD水平、Karnofsky功能状态评分(KPS评分)及生存期。结果1、5例患者共接受35次CIK细胞回输过程中均未出现发热、过敏等不良反应,回输后患者精神、食欲、体力等一般情况较前改善。2、CIK细胞输注前及输注后1周分别检测体内免疫状态,结果示CIK细胞回输后1周CD3+、CD3+CD8+、CD3+CD56+效应细胞的比例较回输前明显升高。回输后1月检测效应细胞仍可维持在较高的水平,CD3+细胞比例(73.3±2.56)%较回输前(68.6±2.9)%(P0.05);CD3+CD8+细胞比例(33.8±7.7)%较回输前(22.1±5.6)%(P0.05);CD3+CD56+细胞比例(7.74±4.6)%较回输前(5.17±2.9)%(P0.05)。调节性T细胞与效应T细胞比例(2.70±1.59)较CIK细胞输注前(5.35±5.50)明显降低(P0.05)。3、CIK细胞治疗前及治疗后2周分别检测患者外周血MRD水平,结果示CIK细胞输注后患者外周血MRD(0.16±0.30)%较CIK细胞治疗前(0.86±0.84)%明显降低(P0.05)。4、CIK细胞治疗前及治疗后根据KPS评分评估患者体能状态,结果示CIK细胞输注后患者KPS评分(88.8±6.03)较输注前(75.45±10.35)改善(P0.05),生活质量提高。5、5例患者中2例总生存期超过40个月,5例患者平均总生存期29.8个月。结论本研究初步显示化疗联合自体CIK细胞序贯疗法对老年AML患者安全有效。
[Abstract]:Background acute myeloid leukemia (Acute Myeloid Leukemia, AML) is a malignant clonogenic disease originating from hematopoietic stem cells. The abnormal primitive cells and immature cells in the bone marrow proliferate and inhibit normal hematopoiesis caused by hematopoiesis, anemia, bleeding, infection and liver, spleen, lymph node enlargement and other clinical manifestations.AML. The most common type of leukemia, the average annual incidence of the world is about 2.25/10 million, with the increase of age, the proportion of elderly patients is increasing. The treatment of acute myeloid leukemia is mainly chemotherapy induced remission. In recent years, the clinical efficacy of the elderly patients is still not obviously improved even if the chemotherapy regimen is constantly adjusted. The patient has more body base diseases, poor organ function, poor individual condition, high intensity chemotherapy intolerance, all kinds of toxic and side effects, serious infection, thrombus, bleeding and other risks affecting survival; therefore, to ensure the ideal remission rate and slow solution time, reduce the complications in the treatment process and prolong the survival period. And improving the quality of life is the key to the maintenance of AML patients after chemotherapy. In recent years, with the continuous progress and development of immunology, cellular immunotherapy has become the most promising new method for the treatment of blood cancer. Cytokine induced killer cells (cytokine-induced killer cells CIK cells) are in 1991 Schmidt-Wolf, first reported in Tanfu University, is an important class of.CIK cells in adoptive cell immunotherapy, which is a group of human mononuclear cells acquired by co culture of IL-2, anti CD3, IFN- gamma and other cytokines, which have the biological characteristics of T lymphocytes and NK cells to kill tumor cells. It can directly combine with target cells to kill the tumor, and can also induce apoptosis of.CIK cells by secreting a variety of cytokines, activating Fas pathway and so on. At the same time, there is no obvious inhibitory effect on normal bone marrow hematopoietic stem cells. Long term clinical study shows that CIK cells remove tiny residues in the treatment of malignant tumor of blood. (micro resist disease, MRD), to maintain the state of remission, improve the quality of life and prolong the survival time shows a better effect. Therefore, this study took the elderly patients with intolerance of chemotherapy as the research object, taking the method of chemotherapy combined with CIK cell adjuvant therapy to explore and evaluate its therapeutic effect and clinical value preliminarily. To observe and evaluate the clinical efficacy of chemotherapy combined with CIK cell sequential therapy in the treatment of elderly patients with acute myelocytic leukemia, and to establish a new maintenance therapy for older AML patients with less side effects. Methods the elderly AML patients who were unable to continue to tolerate chemotherapy after multiple courses of chemotherapy were remission or partial remission due to various complications. The general symptoms and adverse reactions, cellular immune function status, MRD level, Karnofsky function state score (KPS score) and survival period were observed and analyzed in 5 patients with CIK cells after infusion. Results there were no fever, allergy and other adverse reactions in the 35 1,5 patients undergoing CIK fine cell transfusion. The patients' mental, appetite, physical strength and other general conditions were improved.2, CIK cells before infusion and 1 weeks after infusion respectively to detect the immune state. The results showed that the proportion of CD3+, CD3+CD8+, CD3+CD56+ effect cells increased significantly at 1 weeks after CIK cells retransfused, and the detection effect cells in January can still maintain a higher level, CD3 The proportion of + cells (73.3 + 2.56)% (68.6 + 2.9)% (P0.05), CD3+CD8+ cell ratio (33.8 + 7.7)% (22.1 + 5.6)% (22.1)% (P0.05), CD3+CD56+ cell ratio (7.74 + 4.6)% (7.74 + 4.6)% (5.17 + 2.9)% (P0.05)). The proportion of regulatory T cells and effect T cells (2.70 + 1.59) was significantly lower than CIK cells (P0.05).3, CIK thin The MRD level of peripheral blood was measured before and 2 weeks after the treatment. The results showed that the peripheral blood MRD (0.16 + 0.30)% of the patients after the CIK cell infusion was significantly lower than that of the CIK cells (0.86 + 0.84)% (P0.05).4. The CIK cells before and after the treatment were evaluated according to the KPS score. The results showed the KPS score of the patients after the CIK cell infusion (88.8 + 6). .03) improved (75.45 + 10.35) before infusion (P0.05), the quality of life increased in 2 cases of.5,5 patients for more than 40 months, and the average total survival time of 5 patients was 29.8 months. Conclusion this study showed that chemotherapy combined with autologous CIK cell sequential therapy was safe and effective for the elderly patients with AML.
【学位授予单位】：安徽医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R733.71

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