本文關(guān)鍵詞：硼替佐米聯(lián)合方案治療多發(fā)性骨髓瘤的療效分析　出處：《第三軍醫(yī)大學》2015年碩士論文　論文類型：學位論文

  更多相關(guān)文章： 硼替佐米 多發(fā)性骨髓瘤 免疫球蛋白 療效 不良反應(yīng)

【摘要】：背景和目的:多發(fā)性骨髓瘤(multiple myeloma,MM)是免疫系統(tǒng)最常見的惡性腫瘤之一,骨髓瘤細胞來源于產(chǎn)生抗體的B淋巴細胞,惡性克隆性增殖的瘤細胞在骨髓中蓄積,侵犯骨髓,并產(chǎn)生大量異常的單克隆性免疫球蛋白,導致免疫功能進行性損害,發(fā)生反復感染、骨痛、貧血,若免疫球蛋白阻塞腎小管,即可引發(fā)腎功能衰竭。MM的表現(xiàn)具有多樣性,目前仍是一種不可治愈的疾病,大劑量化療聯(lián)合自體造血干細胞移植(autologous stem cell transplantation,auto-SCT)能夠提高患者的完全緩解(complete remission,CR)率,但容易復發(fā)。異基因造血干細胞移植(allogeneic stem cell transplantation,allo-SCT)理論上能夠治愈MM,但由于MM發(fā)病年齡晚,常常合并多臟器功能不全,且移植物抗宿主病發(fā)生率高,限制了allo-SCT在臨床的應(yīng)用。因此,化療仍是治療MM最主要的方法,但傳統(tǒng)的化療方案CR率低,緩解持續(xù)時間短。近年,隨著新的靶向藥物的研發(fā),MM的治療取得了顯著的進步。硼替佐米(bortezomib),第一代的蛋白酶體抑制劑,是一種經(jīng)過人工合成的丙氨酸基硼酸的衍生物質(zhì),它可以通過蛋白酶體泛素化信號通路發(fā)揮作用,能夠可逆性地抑制26S蛋白酶體的活性,阻斷蛋白酶體的泛素化通路,使體內(nèi)多種調(diào)節(jié)蛋白蓄積在細胞內(nèi),誘導惡性腫瘤細胞凋亡。自上市以來,顯示出了較好的療效及廣泛的應(yīng)用前景,給MM患者的治療帶來了新的曙光。多項研究表明,以硼替佐米為基礎(chǔ)的化療方案在初診和復發(fā)難治性MM都獲得了較高的完全緩解率,本研究回顧性分析了我院以硼替佐米為基礎(chǔ)的聯(lián)合化療方案治療新診斷MM患者的療效及安全性,為臨床選擇治療MM的方案提供理論依據(jù)。方法:回顧性分析2010年1月至2014年12月在第三軍醫(yī)大學附屬西南醫(yī)院35例新診斷的多發(fā)性骨髓瘤,依據(jù)張之南主編的《血液病診斷與療效標準》明確診斷,按照國際分期標準(ISS)分期,按照免疫球蛋白和輕鏈水平分型,依據(jù)EBMT標準評估療效反應(yīng),毒性分級按NCI-CTCAE(第3版)標準判斷。所有患者均給予硼替佐米為基礎(chǔ)的聯(lián)合方案化療3.3(2~7)個療程,中位隨訪時間為12.7(3~49)個月,治療前后完善骨髓穿刺及血清學指標的檢測,骨髓漿細胞的比例和血清免疫球蛋白水平的比較采用t檢驗,組間緩解的比較采用X 2檢驗。結(jié)果:35例患者總反應(yīng)率為82.9%,治療后患者骨髓漿細胞比例明顯減少(3.53%比42.19%;P0.01,與治療前相比);IgG型與IgA型MM患者血清中的免疫球蛋白水平較治療前明顯下降,分別由(67.23±34.04)g/L、(52.23±25.01)g/L降至(21.95±15.82)g/L、(11.49±15.79)g/L,差異有統(tǒng)計學意義(P0.01)。Ⅰ期的MM患者經(jīng)硼替佐米為基礎(chǔ)的聯(lián)合方案治療后77.8%至少達到了VGPR,其ORR達到了100.0%,明顯高于Ⅱ/Ⅱ期患者的ORR(76.9%)。5例腎功能不全患者經(jīng)治療后明顯好轉(zhuǎn),VGPR率與ORR均為80%。較常見的不良反應(yīng)是血液學毒性(46%)、乏力(46%)、周圍神經(jīng)病變(40%)以及感染(29%)。結(jié)論:以硼替佐米為基礎(chǔ)的聯(lián)合方案治療初診的MM患者,可明顯降低骨髓漿細胞的比例,使異常免疫球蛋白明顯下降,其療效好,完全緩解率高;不良反應(yīng)輕微,耐受性可,可推薦用于長期鞏固及維持治療。
[Abstract]:Background and objective: multiple myeloma (multiple myeloma MM) is one of the most common malignant tumor of the immune system, myeloma cells derived from antibody producing B lymphocytes, malignant clonal proliferation of tumor cells accumulation, bone marrow involvement in the bone marrow, and produce a large number of monoclonal immunoglobulin often leads to. The immune function of the lesion, repeated infection, bone pain, anemia, if immunoglobulin tubular obstruction can lead to renal failure, the performance of.MM with diversity, is still an incurable disease, high dose chemotherapy combined with autologous hematopoietic stem cell transplantation (autologous stem cell transplantation, auto-SCT) can improve the complete patients (complete remission, CR), but it is easy to relapse. Allogeneic hematopoietic stem cell transplantation (allogeneic stem cell transplantation, allo-SCT) theory can cure MM, but because M M late age of onset, often accompanied with multiple organ dysfunction, and graft-versus-host disease incidence rate is high, limiting the application of allo-SCT in clinical. Therefore, chemotherapy is still the main method for the treatment of MM, but the CR of traditional chemotherapy remission rate is low, short duration. In recent years, with the development of targeted drugs the treatment of MM has made significant progress. Boron for Zomi (bortezomib), the first generation of proteasome inhibitor, is a kind of derivative material after alanine boronic acid synthetic, it can be through the proteasome ubiquitin signaling pathways play a role, can reversibly inhibit the activity of the 26S proteasome. The ubiquitin proteasome pathway blocking, make the body a variety of regulatory protein accumulation in cells, induce apoptosis of malignant tumor cells. Since the market has shown good curative effect and wide application prospect, for the treatment of MM patients has brought new Dawn. A number of studies have shown that chemotherapy bortezomib based refractory MM in newly diagnosed and recurrence have gained complete remission rate, this study retrospectively analyzed the efficacy of our hospital with bortezomib combination regimens based therapy for patients with newly diagnosed MM and safety, provide the theoretical basis for clinical treatment of MM. Methods: a retrospective analysis from January 2010 to December 2014 in Southwest Hospital affiliated to the Third Military Medical University in 35 patients with newly diagnosed multiple myeloma, according to the standard of diagnosis and therapeutic effect of blood disease > Zhang Zhinan editor of < diagnosis, according to the international standard (ISS) staging, staging according to the immunoglobulin and light chain the level of classification, according to the EBMT standard to evaluate the efficacy, toxicity was graded by NCI-CTCAE (Third Edition) standard. All patients were treated with bortezomib based combination chemotherapy in 3.3 (2~7) in a course. The follow-up time was 12.7 months (3~49) before and after treatment, improve the detection of bone marrow puncture and serum indexes, compared with bone marrow plasma cell ratio and serum immunoglobulin level t test group remission compared with X 2 test. Results: 35 cases of patients with the total response rate was 82.9%, the percentage of plasma cells in bone marrow decreased significantly after treatment (3.53% vs. 42.19%; P0.01, compared with before treatment); serum immunoglobulin levels in patients with type IgG and type IgA in MM decreased significantly compared with before treatment, respectively (67.23 + 34.04) g/L, (52.23 + 25.01) g/L to (21.95 + 15.82) g/L, (11.49 + 15.79 g/L), the difference was statistically significant (P0.01). Combined of stage MM patients after bortezomib based treatment of at least 77.8% of the VGPR, the ORR reached 100%, significantly higher than II / II patients with ORR (76.9%).5 cases of renal insufficiency patients after treatment significantly improved the rate of VGPR and ORR All the adverse reaction of 80%. is relatively common hematological toxicity (46%), fatigue (46%), peripheral neuropathy (40%) and infection (29%). Conclusion: combined with bortezomib based therapy for newly diagnosed MM patients, can significantly reduce the proportion of bone marrow plasma cells, the abnormal immune globulin protein significantly decreased, the curative effect is good, high rate of complete remission; mild adverse reactions, can be tolerated, can be recommended for long-term consolidation and maintenance therapy.

【學位授予單位】：第三軍醫(yī)大學
【學位級別】：碩士
【學位授予年份】：2015
【分類號】：R733.3

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相關(guān)期刊論文 前1條

1 孫薏;匡紅;張小玉;張聰;呼永河;陳健;李碩;鐘國成;;DC-CIK過繼免疫聯(lián)合沙利度胺治療復發(fā)難治性多發(fā)性骨髓瘤的回顧性研究[J];免疫學雜志;2012年04期

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本文編號：1357340