本文選題：細(xì)胞因子誘導(dǎo)的殺傷細(xì)胞 + 急性髓系白血病��； 參考：《安徽醫(yī)科大學(xué)》2017年碩士論文

【摘要】：背景急性髓系白血病(Acute Myeloid Leukemia,AML)是一種起源于造血干細(xì)胞的惡性克隆性疾病,發(fā)病時骨髓中異常的原始細(xì)胞及幼稚細(xì)胞大量增殖并抑制正常造血引起血細(xì)胞減少,出現(xiàn)貧血、出血、感染和肝、脾、淋巴結(jié)腫大等臨床表現(xiàn)。AML是成人最常見的一類白血病,世界平均年發(fā)病率約為2.25/10萬,隨著年齡的增長老年患者所占的比例日漸升高。急性髓系白血病治療主要為化療誘導(dǎo)緩解,近年來即使化療方案的不斷個體化調(diào)整,老年患者臨床療效仍無明顯改善,主要與老年患者身體基礎(chǔ)疾病較多、臟器功能不佳、個體一般情況較差、對高強度化療不耐受、各類毒副反應(yīng)發(fā)生有關(guān),同時存在嚴(yán)重感染、血栓、出血等風(fēng)險會影響存活情況;因此保證理想的緩解率及緩解時間,降低治療過程中的并發(fā)癥,延長生存期及改善生活質(zhì)量為老年AML患者化療后維持治療的關(guān)鍵。近年來隨著免疫學(xué)技術(shù)的不斷進步與發(fā)展,細(xì)胞免疫治療成為一個最有應(yīng)用前景的新的血液腫瘤治療方法。細(xì)胞因子誘導(dǎo)的殺傷細(xì)胞(cytokine-induced killer cells CIK細(xì)胞)在1991年由斯坦福大學(xué)Schmidt-Wolf首次報道,是過繼性細(xì)胞免疫治療中較為重要的一類。CIK細(xì)胞是將人體單個核細(xì)胞在體外經(jīng)IL-2、抗CD3抗體、IFN-γ等細(xì)胞因子共培養(yǎng)后獲得的一群兼具T淋巴細(xì)胞及NK細(xì)胞的生物學(xué)特點的免疫細(xì)胞。CIK細(xì)胞殺傷腫瘤細(xì)胞可直接與靶細(xì)胞結(jié)合殺滅腫瘤,同時還可以通過分泌多種細(xì)胞因子,激活Fas途徑等方式誘導(dǎo)細(xì)胞凋亡。CIK細(xì)胞殺瘤作用強大,同時對正常骨髓造血干細(xì)胞無明顯抑制作用。長期的臨床研究表明CIK細(xì)胞在血液惡性腫瘤治療中清除微小殘留(micro resist disease,MRD)、維持緩解狀態(tài)、改善生活質(zhì)量及延長生存期方面顯示出較好的療效。因此本研究以不能耐受化療的老年AML患者為研究對象,采取化療聯(lián)合CIK細(xì)胞輔助治療的方法,對其療效和臨床價值進行初步探索和評價。目的初步觀察及評價化療聯(lián)合CIK細(xì)胞序貫療法治療老年急性髓細(xì)胞白血病患者的臨床療效,為老年AML患者建立新的副作用較小的維持治療方法。方法選擇多療程化療后疾病達緩解或部分緩解后因各種合并癥,無法繼續(xù)耐受化療的老年AML患者為研究對象,輔以自體CIK細(xì)胞序貫治療。觀察分析5例患者CIK細(xì)胞輸注后一般癥狀及不良反應(yīng),細(xì)胞免疫功能狀態(tài)、MRD水平、Karnofsky功能狀態(tài)評分(KPS評分)及生存期。結(jié)果1、5例患者共接受35次CIK細(xì)胞回輸過程中均未出現(xiàn)發(fā)熱、過敏等不良反應(yīng),回輸后患者精神、食欲、體力等一般情況較前改善。2、CIK細(xì)胞輸注前及輸注后1周分別檢測體內(nèi)免疫狀態(tài),結(jié)果示CIK細(xì)胞回輸后1周CD3+、CD3+CD8+、CD3+CD56+效應(yīng)細(xì)胞的比例較回輸前明顯升高。回輸后1月檢測效應(yīng)細(xì)胞仍可維持在較高的水平,CD3+細(xì)胞比例(73.3±2.56)%較回輸前(68.6±2.9)%(P0.05);CD3+CD8+細(xì)胞比例(33.8±7.7)%較回輸前(22.1±5.6)%(P0.05);CD3+CD56+細(xì)胞比例(7.74±4.6)%較回輸前(5.17±2.9)%(P0.05)。調(diào)節(jié)性T細(xì)胞與效應(yīng)T細(xì)胞比例(2.70±1.59)較CIK細(xì)胞輸注前(5.35±5.50)明顯降低(P0.05)。3、CIK細(xì)胞治療前及治療后2周分別檢測患者外周血MRD水平,結(jié)果示CIK細(xì)胞輸注后患者外周血MRD(0.16±0.30)%較CIK細(xì)胞治療前(0.86±0.84)%明顯降低(P0.05)。4、CIK細(xì)胞治療前及治療后根據(jù)KPS評分評估患者體能狀態(tài),結(jié)果示CIK細(xì)胞輸注后患者KPS評分(88.8±6.03)較輸注前(75.45±10.35)改善(P0.05),生活質(zhì)量提高。5、5例患者中2例總生存期超過40個月,5例患者平均總生存期29.8個月。結(jié)論本研究初步顯示化療聯(lián)合自體CIK細(xì)胞序貫療法對老年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.
【學(xué)位授予單位】：安徽醫(yī)科大學(xué)
【學(xué)位級別】：碩士
【學(xué)位授予年份】：2017
【分類號】：R733.71

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