硼替佐米联合方案治疗多发性骨髓瘤的疗效分析

发布时间：2017-12-31 00:52

本文关键词：硼替佐米联合方案治疗多发性骨髓瘤的疗效分析　出处：《第三军医大学》2015年硕士论文　论文类型：学位论文

【摘要】：背景和目的:多发性骨髓瘤(multiple myeloma,MM)是免疫系统最常见的恶性肿瘤之一,骨髓瘤细胞来源于产生抗体的B淋巴细胞,恶性克隆性增殖的瘤细胞在骨髓中蓄积,侵犯骨髓,并产生大量异常的单克隆性免疫球蛋白,导致免疫功能进行性损害,发生反复感染、骨痛、贫血,若免疫球蛋白阻塞肾小管,即可引发肾功能衰竭。MM的表现具有多样性,目前仍是一种不可治愈的疾病,大剂量化疗联合自体造血干细胞移植(autologous stem cell transplantation,auto-SCT)能够提高患者的完全缓解(complete remission,CR)率,但容易复发。异基因造血干细胞移植(allogeneic stem cell transplantation,allo-SCT)理论上能够治愈MM,但由于MM发病年龄晚,常常合并多脏器功能不全,且移植物抗宿主病发生率高,限制了allo-SCT在临床的应用。因此,化疗仍是治疗MM最主要的方法,但传统的化疗方案CR率低,缓解持续时间短。近年,随着新的靶向药物的研发,MM的治疗取得了显著的进步。硼替佐米(bortezomib),第一代的蛋白酶体抑制剂,是一种经过人工合成的丙氨酸基硼酸的衍生物质,它可以通过蛋白酶体泛素化信号通路发挥作用,能够可逆性地抑制26S蛋白酶体的活性,阻断蛋白酶体的泛素化通路,使体内多种调节蛋白蓄积在细胞内,诱导恶性肿瘤细胞凋亡。自上市以来,显示出了较好的疗效及广泛的应用前景,给MM患者的治疗带来了新的曙光。多项研究表明,以硼替佐米为基础的化疗方案在初诊和复发难治性MM都获得了较高的完全缓解率,本研究回顾性分析了我院以硼替佐米为基础的联合化疗方案治疗新诊断MM患者的疗效及安全性,为临床选择治疗MM的方案提供理论依据。方法:回顾性分析2010年1月至2014年12月在第三军医大学附属西南医院35例新诊断的多发性骨髓瘤,依据张之南主编的《血液病诊断与疗效标准》明确诊断,按照国际分期标准(ISS)分期,按照免疫球蛋白和轻链水平分型,依据EBMT标准评估疗效反应,毒性分级按NCI-CTCAE(第3版)标准判断。所有患者均给予硼替佐米为基础的联合方案化疗3.3(2~7)个疗程,中位随访时间为12.7(3~49)个月,治疗前后完善骨髓穿刺及血清学指标的检测,骨髓浆细胞的比例和血清免疫球蛋白水平的比较采用t检验,组间缓解的比较采用X 2检验。结果:35例患者总反应率为82.9%,治疗后患者骨髓浆细胞比例明显减少(3.53%比42.19%;P0.01,与治疗前相比);IgG型与IgA型MM患者血清中的免疫球蛋白水平较治疗前明显下降,分别由(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,差异有统计学意义(P0.01)。Ⅰ期的MM患者经硼替佐米为基础的联合方案治疗后77.8%至少达到了VGPR,其ORR达到了100.0%,明显高于Ⅱ/Ⅱ期患者的ORR(76.9%)。5例肾功能不全患者经治疗后明显好转,VGPR率与ORR均为80%。较常见的不良反应是血液学毒性(46%)、乏力(46%)、周围神经病变(40%)以及感染(29%)。结论:以硼替佐米为基础的联合方案治疗初诊的MM患者,可明显降低骨髓浆细胞的比例,使异常免疫球蛋白明显下降,其疗效好,完全缓解率高;不良反应轻微,耐受性可,可推荐用于长期巩固及维持治疗。
[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.

【学位授予单位】：第三军医大学
【学位级别】：硕士
【学位授予年份】：2015
【分类号】：R733.3

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