Fms样酪氨酸激酶3表达对评估急性髓系白血病预后的意义

目的 探讨Fms样酪氨酸激酶3(FLT3)表达对评估急性髓系白血病(AML)预后的意义.方法 选取AML患者50例,其中核型正常的AML患者20例,核型异常的AML患者30例.分别于化疗前抽取骨髓3 ml,用PCR方法检测白血病细胞FLT3的表达情况.结果 核型正常的AMLFLT3的表达率为5.0％,核型异常的AMLFLT3的表达率为26.7％.难治复发的AMLFLT3的表达率是33.3％,持续完全缓解的AMLFLT3的表达率是4.5％.FLT3的表达情况与骨髓中高白血病细胞所占比例和高外周血白细胞计数有关,与FAB亚型无关.有FLT3表达的AML患者无病生存(DFS)和总体生存(OS)时间短,无FLT3表达的AML患者DFS和OS时间长,二者差异有统计学意义(x2=4.17,P＜0.05).结论 FLT3是AML患者预后不好的因素,可以指导临床个体化治疗AML.     

治疗急性髓系白血病新药:FLT3抑制剂 gilteritinib

FMS样酪氨酸激酶3 (FLT3)的基因在造血干细胞增殖、分化及存活方面发挥重要作用。FLT3内部串联重复突变(FLT3-ITD)在急性髓系白血病(AML)中常见,且与迅速复发及生存率低密切相关。gilteritinib (Gil)为新型FLT3抑制剂,由Astellas制药公司生产,于2018年11月经美国食品和药物管理局批准用于FLT3突变型复发难治性AML的治疗。临床试验表明对其他FLT3抑制剂耐药的AML患者,采用Gil治疗仍可取得较好疗效,其最常见的不良反应包括肌肉痛、关节痛、转氨酶升高、疲劳、发热等。     

FLT3抑制剂治疗急性髓系白血病及耐药机制研究进展

近年来,多药联合强烈化疗、支持治疗加强和造血干细胞移植术发展等,使急性髓系白血病(AML)预后得到较大改善,但耐药、化疗耐受性差和不良反应等因素使目前的治疗效果还不尽理想。FMS样酪氨酸激酶3(FLT3)的突变大约发生在30%的AML患者中,与白血病的发病密切相关,可作为治疗的靶点。目前研发的小分子的FLT3酪氨酸激酶抑制剂(TKI)已经用于治疗FLT3突变的AML,这些药物目前处于临床试验阶段。本综述总结关于目前FLT3抑制剂的临床试验及治疗的耐药机制。1 AML中的FLT3突变     

酪氨酸激酶抑制剂治疗慢性粒细胞白血病的临床疗效分析

目的探讨慢性粒细胞白血病(CML)采用酪氨酸激酶抑制剂(TKI)治疗临床效果。方法 100例慢性粒细胞白血病患者,依据病程分为慢性期组(80例)、加速期组(10例)、急变期组(10例)。均采用TKI治疗。观察并比较三组疗效。结果全部患者完全血液学缓解(CHR)率为92.0%,细胞遗传学缓解(MCy R)率为76.0%,完全细胞遗传学缓解(CCy R)率为73.1%,分子学缓解(MMR)率为47.9%。慢性期组有效率为80.0%,加速期组有效率为60.0%,急变期组有效率为30.0%,三组比较差异有统计学意义(P<0.05)。慢性期组、加速期组、急变期组总生存率(OS)比较差异无统计学意义(P>0.05),但5年无事件生存(EFS)率慢性期组明显长于其他两组,差异有统计学意义(P<0.05)。结论针对慢性粒细胞白血病患者,采用酪氨酸激酶抑制剂治疗,可显著提高临床效果,延长患者生存时间。临床需重视病情的评估,对不同药物剂量进行选择,以最大程度改善预后。     

酪氨酸激酶抑制剂治疗慢性粒细胞白血病的不良反应及临床对策

酪氨酸激酶抑制剂(tyrosine kinase inhibitors,TKIs)抑制BCR-ABL融合基因,使慢性粒细胞白血病(chronic myelocytic leukemia,CML)患者能够较长期生存。患者使用TKIs早期出现不良反应都较轻,可自行恢复或者给予对症处理和选择其他TKIs。而TKIs长期的使用的安全性问题国内少有报道,本文通过查阅国内外文献,综述TKIs引起的骨髓、皮肤、胃肠、肝和胰、骨骼肌、肺、液体潴留、心血管方面的不良反应以及其临床对策。     

二代酪氨酸激酶抑制剂治疗慢性粒细胞性白血病继发T315I突变1例报道及分析

正慢性粒细胞白血病(chronic myeloid leukemia,CML)为血液系统恶性肿瘤性疾病。近年来,随着伊马替尼等酪氨酸激酶抑制剂(TKIs)的问世,CML的治疗取得极大进展,多数病人通过TKIs治疗已能获得长期生存,并取得较好生活质量。尽管如此,仍有少部分患者接受TKIs治疗疗效欠佳甚至治疗失败,疾病很快进展至加速急变期乃至死亡。     

酪氨酸激酶抑制剂治疗慢性粒细胞白血病的不良反应及处理的研究进展

酪氨酸激酶抑制剂(TKI)抑制BCR-ABL基因,改善慢性粒细胞白血病(CML)患者长期生存,与正常人寿命无差异.CML患者使用TKI早期出现不良反应较轻,可对症处理或自行恢复,较严重时可考虑更换TKI.国内报道TKI长期使用的安全性问题多表现在血液学不良反应,其他不良反应文献报道少见,本文通过查询国内外文献,对TKI...     

酪氨酸激酶抑制剂治疗慢性髓性白血病不良反应的处理

1前言慢性髓性白血病(CML)伴有特异性Ph染色体/BCR-ABL融合基因,酪氨酸激酶抑制剂(TKI)针对CML致病基因BCR-ABL的治疗方式开启了肿瘤靶向治疗的新时代。第一代TKI伊马替尼因其卓越的疗效和安全性,成为全球慢性髓性白血病患者的一线治疗首选。伊马替尼治疗CML患者的10年生存率达85%以上。尽管     

二代酪氨酸激酶抑制剂治疗老年慢性粒细胞性白血病的临床效果

目的 分析二代酪氨酸激酶抑制剂(TKI-Ⅱ)治疗老年慢性粒细胞性白血病(CML)的临床效果,为临床医师选择合理用药方案提供参考。方法 50例老年CML患者为研究对象,依据随机数字表法分为观察组和对照组,每组25例。对照组患者接受一代酪氨酸激酶抑制剂(TKI-Ⅰ)——伊马替尼治疗,观察组采用TKI-Ⅱ——尼洛替尼治疗。对比两组患者的免疫功能指标、临床疗效指标及不良反应发生率。结果 治疗后,观察组患者的CD3⁺、CD4⁺/CD8⁺、NK细胞水平分别为(68.10±2.66)%、(1.55±0.13)、(40.11±4.60)%,均高于对照组的(58.97±2.64)%、(1.23±0.15)、(35.45±4.66)%,差异具有统计学意义(P<0.05)。观察组患者的完全血液学缓解(CHR)、主要细胞遗传学缓解(MCyR)、完全细胞遗传学缓解(CCyR)、主要分子生物学缓解(MMR)率分别为92.0%、92.0%、88.0%、44.0%,均高于对照组的68.0%、48.0%、52.0%、16.0%,差异具有统计学意义(...     

New treatment for acute myelogenous leukemia

Introduction: Acute myelogenous leukemia (AML) is a genetically heterogeneous disease. Yet current therapy has changed little over the decades and includes the nucleoside analog cytarabine in combination with an anthracycline as primary therapy. With this approach, durable cures occur in the minority of patients. With the recent improved scientific understanding of the underlying genetic and epigenetic aberrations in AML, there is now the potential of individualized and targeted therapeutic approaches for the curative treatment of AML.

Areas covered: The focus of this article is to review the therapeutic potential of many of the novel agents currently under investigation in the treatment of acute myeloid leukemia. The results of pivotal Phase III studies, as well as ongoing Phase II and III studies and selected Phase I studies with impact on the field of AML therapy will be discussed.

Expert opinion: Advances in the scientific knowledge of the various genetic and epigenetic alterations in AML, in conjunction with more effective, rationally designed and/or novel targeted therapeutics, offers a real hope and expectation of improved AML outcomes in the future.     

Mitoxantrone in the treatment of relapsed and refractory acute leukemia

Summary Twenty-four patients with acute leukemia or blast crisis (BC) of chronic myelocytic leukemia (CML) in relapse or refractory to standard chemotherapy, were eligible for treatment with mitoxantrone. Mitoxantrone (Novantrone®; dihydroxyanthracenedione) was administered in a dose of 8–13 mg/m² on five consecutive days. Five of 20 evaluable patients were induced into complete remission, one patient achieved a partial remission. Side-effects included moderate to severe bone marrow suppression, moderate mucositis and hair loss. No cardiotoxicity was observed. We believe that mitoxantrone is an active agent in the treatment of acute leukemia and suggest further studies in combination chemotherapy.     

索拉非尼治疗急性髓系白血病的研究进展

作为一种新型多激酶抑制剂,索拉非尼(sorafenib)已被美国FDA批准用于治疗肾细胞癌、肝细胞癌和分化甲状腺癌。而近年来的研究显示通过抑制FMS样酪氨酸激酶-3的活性,该药可发挥一定的抗白血病作用,特别是FMS样酪氨酸激酶-3近膜区的内部串联重复序列(FMS-like tyrosine kinase-3-internal tandem duplication,FLT3-ITD)突变阳性的急性髓系白血病。笔者通过查阅国内外相关文献,对其在治疗急性髓系白血病的药理作用、药物代谢动力学、临床疗效和安全性等方面的研究进展作一综述。     

Bcr-Abl酪氨酸激酶抑制剂联合用药治疗慢性粒细胞白血病研究进展

以伊马替尼为代表的酪氨酸激酶抑制剂对慢性粒细胞白血病(CML)的治疗产生了重要影响,但其耐药性已成为CML治疗领域的关键问题。伊马替尼、尼洛替尼、达沙替尼以及普纳替尼等Bcr-Abl酪氨酸激酶抑制剂与其他药物联合使用,可以协同抑制Bcr-Abl及其磷酸化蛋白的表达,显著降低STAT5、CRKL、ERK5等信号通路的磷酸化水平,改善肿瘤微环境,降低肿瘤细胞多药耐药性,已在基础研究和临床Ⅰ期研究中取得阶段性成果,为治疗CML提供新策略。     

治疗急性骨髓性白血病新药恩西地平

急性骨髓性白血病是成人常见的白血病类型,发病率随年龄的增长而升高,病情进展迅速,严重威胁人类健康。恩西地平（Enasidenib,Idhifa^®）是第一个异柠檬酸脱氢酶2抑制剂,能有效治疗该酶变异导致的急性骨髓性白血病,也是美国食品药品管理局批准的唯一一个针对这一患者群体的肿瘤代谢疗法新药。对恩西地平的作用机制、药效学、药动学、药物相互作用、临床评价和安全性等进行综述,旨在为临床应用提供有益的参考。     

Investigational FMS-like tyrosine kinase 3 inhibitors in treatment of acute myeloid leukemia

Introduction: Outcomes for the majority of patients with acute myeloid leukemia (AML) remain poor. Over the past decade, significant progress has been made in the understanding of the cytogenetic and molecular determinants of AML pathogenesis. One such advance is the identification of recurring mutations in the FMS-like tyrosine kinase 3 gene (FLT3). Currently, this marker, which appears in approximately one-third of all AML patients, not only signifies a poorer prognosis but also identifies an important target for therapy. FLT3 inhibitors have now undergone clinical evaluation in Phase I, II and III clinical trials, as both single agents and in combination with chemotherapeutics. Unfortunately, to date, none of the FLT3 inhibitors have gained FDA approval for the treatment of patients with AML. Yet, several promising FLT3 inhibitors are being evaluated in all phases of drug development.

Areas covered: This review aims to highlight the agents furthest along in their development. It also focuses on those FLT3 inhibitors that are being evaluated in combination with other anti-leukemia agents.

Expert opinion: The authors believe that the field of research for FLT3 inhibitors remains promising, despite the historically poor prognosis of this subgroup of patients with AML. The most promising areas of research will likely be the elucidation of the mechanisms of resistance to FLT3 inhibitors, and development of potent FLT3 inhibitors alone or in combination with hypomethylating agents, cytotoxic chemotherapy or with other targeted agents.     

小剂量三尖杉酯碱和阿糖胞苷联合粒细胞集落刺激因子治疗老年急性髓细胞白血病疗效观察

目的探讨小剂量三尖杉酯碱（HT,H）和阿糖胞苷（Ara-c,A）联合粒细胞集落刺激因子（G-CSF）治疗老年人急性髓细胞白血病的疗效及不良反应。方法35例AML患者均给予HT1mg·m^-2·d^-1,静脉滴注,第1—14天;Ara—c 10mg·m^-2,静脉滴注,每12h注射1次,第1～14天;G-CSF100—200μg·m^-2·d^-1,皮下注射,在第1次注射Ara—c之前开始使用,至最后1次注射Ara-c之前停用。结果35例AML患者化疗后完全缓解16例（46％）、部分缓解14例（37％）,总有效率83％,未缓解（NR）5例（14％）;2例患者化疗期间死亡。主要不良反应为骨髓抑制。结论小剂量HA方案联合G—CSF治疗老年人急性髓细胞白血病安全、有效。     

Homoharringtonine for the treatment of chronic myelogenous leukemia

Background: The anticancer activity of the natural alkaloid homoharringtonine (HHT) was first recognized by Chinese investigators. HHT exerts its activity through inhibition of protein synthesis and promotion of apoptosis. Methods: The authors reviewed the most relevant preclinical and clinical studies involving patients with chronic myelogenous leukemia (CML) receiving therapy with either natural HHT or omacetaxine mepesuccinate (Ceflatonin, Myelostat, CGX-653), a semisynthetic subcutaneously bioavailable form of HHT presently under development for the treatment of CML. Results: Prior to the advent of the tyrosine kinase inhibitor (TKI) imatinib mesilate, controlled clinical studies established HHT as the most active therapy in CML after failure of IFN-a for patients who were not candidates for allogeneic stem cell transplantation. Preliminary results from Phase II studies suggest that omacetaxine mepesuccinate is active in patients with imatinib-resistant CML, including those carrying the T315I mutation, which renders imatinib and second-generation TKIs ineffective. Conclusion: These encouraging results have propelled the development of several Phase II/III trials both in Europe and in the US to further delineate the activity of omacetaxine mepesuccinate in patients with CML who are resistant to TKI therapy.