甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果分析

目的 探讨甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果.方法 选择我院2008年5月至2011年5月慢性粒细胞白血病患者共50例,以上患者随机分为观察组和对照组.两组患者均根据具体临床分期等情况给予不同化疗方案.观察组给予甲磺酸伊马替尼治疗.评定两组患者治疗效果,记录两组不良反应发生情况.结果 观察组缓解率为96.0%,对照组缓解率为76.0%,观察组缓解率与对照组比较,差异有统计学意义(P<0.05);观察组恶心呕吐发生率、下肢浮肿发生率、皮疹发生率、肝功能异常发生率分别与对照组比较,差异有统计学意义(P<0.05).结论 甲磺酸伊马替尼治疗慢性粒细胞白血病临床效果显著,治疗过程中不良反应发生率低,值得借鉴.     

甲磺酸伊马替尼治疗慢性粒细胞白血病进展期疗效观察

目的：观察甲磺酸伊马替尼治疗慢性粒细胞白血病（CML）进展期的临床疗效。方法将41例 CML进展期患者随机分为观察组21例和对照组20例。观察组给予甲磺酸伊马替尼,对照组给予常规化疗,比较2组临床疗效和不良反应发生情况。结果观察组总有效率为80.95%高于对照组的20.00%,差异有统计学意义（P ﹤0.05）。结论与传统的常规化疗相比,甲磺酸伊马替尼对 CML 进展期患者近期疗效明显,不良反应可耐受。     

甲磺酸伊马替尼治疗慢性粒细胞白血病66例

目的观察甲磺酸伊马替尼治疗慢性粒细胞白血病的临床疗效。方法选取医院收治的慢性粒细胞白血病患者96例,根据治疗方法不同分为观察组（66例）和对照组（30例）。对照组采用化学治疗方案进行治疗,观察组采用甲磺酸伊马替尼治疗。结果观察组治疗的缓解率（96．67％）高于对照组（80．00％,P〈0．01）;观察组下肢浮肿、恶心呕吐、肝功能异常、皮疹等不良反应发生率均低于对照组（P〈0．05）。结论甲磺酸伊马替尼治疗慢性粒细胞白血病的临床疗效确切,患者耐受性好,值得,陆床借鉴。     

甲磺酸伊马替尼治疗慢性粒细胞白血病疗效观察

目的观察甲磺酸伊马替尼（IM）治疗慢性粒细胞白血病（CML）慢性期（CP）及进展期的疗效。方法回顾性分析2009年1月～2013年12月我院采用IM治疗的60例CML患者临床资料,其中30例为进展期患者,30例为CP患者。结果进展期患者DA化疗后血液学完全缓解0例,部分缓解6例,未缓解24例,总有效率20%;行IM治疗后完全缓解13例,部分缓解6例,未缓解11例,总有效率63.3%,两者治疗有效率差异有统计学意义（χ^2=4.36,P〈0.05）。30例CP患者行IM治疗后完全缓解26例,部分缓解0例,未缓解4例,总有效率86.7%,进展期及CP组IM治疗有效率差异有统计学意义（χ^2=11.59,P〈0.05）;进展期患者中McyR及CmoR的患者分别为10例（33.3%）和6例（20%）;CP组分别为26例（86.7%）和24例（80%）;CP患者IM治疗后遗传学疗效较进展期好。结论 IM是各期CML的理想治疗方法,有效率高。血液学毒性是其主要副作用,其余反应较轻,患者耐受良好。     

甲磺酸伊马替尼治疗慢性粒细胞白血病的临床效果及其对免疫功能的影响

目的观察甲磺酸伊马替尼治疗慢性粒细胞血管病的临床效果及其对免疫功能的影响。方法选择本院2009年2月~2014年2月收治的50例慢性粒细胞白血病患者为研究对象,掷骰子将其分为对照组和观察组,对照组患者行常规化疗治疗,观察组患者行甲磺酸伊马替尼口服治疗。比较两组的疗效、不良反应及治疗前后T细胞免疫功能变化。结果观察组缓解率、不良反应发生率分别为96.0%、8.0%,与对照组的76.0%、32.0%比较,差异有统计学意义(P<0.05)。观察组和对照组治疗后的CD3+[(1435.7±300.3)个/μl vs(1102.5±287.6)个/μl]、CD4+[(786.5±156.2)个/μl vs(700.1±100.8)个/μl]、CD4+/CD8+[(1.60±0.46)vs(1.20±0.41)]比较,差异有统计学意义(P<0.05)。结论甲磺酸伊马替尼治疗慢性粒细胞血管病安全有效,能有效改善其免疫功能。     

三氧化二砷与甲磺酸伊马替尼对慢性粒细胞白血病原代细胞增殖与凋亡的协同作用研究

目的：探讨三氧化二砷（Arsenic trioxide,ATO）对甲磺酸伊马替尼（STI571）在慢性粒细胞白血病（CML）原代细胞中对细胞增殖及凋亡的影响。方法：采用四甲基偶氮唑蓝（MTT）法观察STI571单独使用与联用ATO对慢性粒细胞白血病原代细胞增殖抑制的变化情况。流式细胞仪检测细胞凋亡。结果：无毒剂量的ATO（0.15μmol·L-1）联用STI571（IC500.324±0.011μmol·L-1）较单独使用STI571（0.580±0.007μmol·L-1）时对细胞抑制率显著增大,IC50下降1.79倍（P〈0.05）。细胞经ATO（0.15μmol·L-1）、STI571（0.5μmol·L-1）联合处理24h、48h时,细胞凋亡率增大为15.6%、50.7%,协同作用为增强（＋＋）。结论：ATO能增强STI571对CML原代细胞敏感性,能促进细胞凋亡与STI571具有增强的协同作用。     

甲磺酸伊马替尼临床研究概况

甲磺酸伊马替尼是一种蛋白质酪氨酸激酶抑制剂,用于治疗Ph染色体阳性慢性粒细胞白血病和恶性胃肠道间质肿瘤。本文从耐药机制、不良反应、生活质量考察、药物经济学成本-效用分析等方面综述了其最新临床研究进展。     

甲磺酸伊马替尼治疗慢性髓系白血病慢性期疗效及不良反应分析

目的 探讨甲磺酸伊马替尼(格列卫)治疗慢性髓系白血病慢性期(CML-CP)的疗效,并对其不良反应进行了初步分析.方法 20例CML-CP患者口服伊马替尼300～800mg/d,监测血常规指标、染色体核型及bcr/abl P210转录本表达,用药期间观察其不良反应.结果 中位随访时间15个月(3～36个月),累积获得的完全血液学缓解(CHR)率为90.0%(18/20例),主要细胞遗传学缓解(MCyR)率80.0%(16/20例),分子生物学缓解(CMoR)率为42.9%(6/14例).不良事件:(1)非血液学毒性,如体表水肿(体液潴留)9/20例,肌肉骨骼疼痛7/20例,关节痛6/20例,头痛3/20例;3个月以后均未发现以上不良反应.(2)血液学不良事件:中性粒细胞减少症13/20例(3个月)、7/18例(6个月)、3/10例(12个月),血小板减少症9/20例(3个月)、5/18例(6个月)、3/10例(12个月),贫血2/20例(3个月)、2/18例(6个月)、0/10例(12个月),SGOT/SGPT升高0/20例,胆红素升高0/20例.结论 甲磺酸伊马替尼治疗可以使CML-CP患者获得极高的血液学缓解率和较高的细胞遗传学缓解率,其不良反应多发生于甲磺酸伊马替尼治疗的早期,与其清除恶性克隆有关.随正常造血的恢复,其治疗相关不良反应发生率明显减少.     

甲磺酸伊马替尼治疗慢性粒细胞白血病13例护理

甲磺酸伊马替尼（格列卫）是一种分子靶向药物,通过形成酪氨酸激酶的抑制复合物而用于慢性粒细胞白血病（CML）的治疗。我科2005年1月至2008年12月,应用甲磺酸伊马替尼治疗13例Ph染色体阳性CML患者。现将护理情况报告如下。     

甲磺酸伊马替尼致黄疸

患者女,51岁,既往无药物过敏史及其他疾病史。于2003年发现白细胞增高,2004年无明显诱因出现乏力,偶伴头晕,2006年症状加重。2006年8月4日来院,查WBC     

格列卫治疗15例慢性粒细胞性白血病的临床疗效观察

目的：观察格列卫治疗对干扰素耐药的慢性粒细胞白血病（CML）患者的疗效及不良反应。方法：15例慢性期CML给予格列卫400mg/d口服,30d为一疗程,同时以同期住院接受传统方法治疗的CML患者为对照,观察格列卫对CML患者的血液学及遗传学缓解率,并记录不良反应。结果：15例患者有4例（26.7%）获得CHR;3例（20%）获得PHR;3例（20%）缓解后复发;5例（33.3%）无缓解。15例患者中3例（20%）获得遗传学完全缓解;4例（26.7%）获主要遗传学缓解,其中1例（6.7%）在3个月后复发。15例CML患者随访中位数时间3个月的总生存率为98%,随访中位数时间12个月的总生存率45%。结论：研究结果提示格列卫对传统药物治疗失败的慢粒患者有较高的血液学及遗传学缓解率。     

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.     

小剂量伊马替尼治疗慢性髓细胞白血病急变期患者的临床疗效

目的　评价小剂量伊马替尼治疗慢性髓细胞白血病急变期 (CML -BC)的有效性和安全性。方法　 8例经α -干扰素、羟基脲联合治疗 (部分结合阿糖胞苷 )发生急变的CML患者 ,口服伊马替尼 2 0 0～ 30 0mg·d-1,维持治疗 18～ 94周。结果　血液学完全缓解 4例 ,部分缓解 2例。细胞遗传学主要缓解 2例 ,改善 2例。不良反应少且耐受好。结论　小剂量伊马替尼对α-干扰素、羟基脲等联合治疗失败的CML -BC具有较好的近期血液学和细胞遗传学效应 ,远期疗效有待进一步观察。     

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.     

Relationship between elevated levels of the alpha 1 acid glycoprotein in chronic myelogenous leukemia in blast crisis and pharmacological resistance to imatinib (Gleevec) in vitro and in vivo

The Abl tyrosine kinase inhibitor imatinb is becoming a standard for the treatment of chronic myelogenous leukemia (CML). However, Bcr-Abl gene mutations have been reported mainly in relapsing or resistant patients. In primary resistant patients, only few mutations have been documented so far, suggesting alternative mechanisms. We aimed to investigate if alpha 1 acid glycoprotein (AGP), an acute phase drug binding protein, could be a biological marker for pharmacological resistance to imatinib in nine patients in acute phase CML. All patients (3/3) with high AGP dosages (2.31+/-0.17 mg/mL; normal values, 0.5-1.3mg/mL) were primary resistant to imatinib whereas an early clinical response was observed for the six patients with normal AGP levels (1.13+/-0.2mg/mL). No mutation in the adenosine triphosphate domain of Abl were detected before the initiation of imatinib therapy. By using in vitro tests combining various imatinib concentrations (1-10 microM) with purified human AGP (1 and 3 mg/mL), we demonstrate that imatinib-induced apoptosis of K562 or fresh leukemic CML cells is abrogated or reduced. The same effect was observed using sera from donors with high AGP levels (1.9-3.28 mg/mL). In patients with CML in blastic phase, AGP levels could reflect pharmacological resistance to imatinib, suggesting that increased dosage of imatinib or the use of a competitor to drug binding should be recommended to optimize the therapeutic effect of the drug.     

Dasatinib for the treatment of Philadelphia chromosome-positive chronic myelogenous leukaemia after imatinib failure

Dasatinib, a potent, oral kinase inhibitor, is presently approved for Philadelphia-positive chronic myelogenous leukaemia (CML) following imatinib failure. In an in vitro study, dasatinib had 325-fold greater potency than imatinib for inhibiting unmutated BCR-ABL. Phase I and II data show that dasatinib 70 mg b.i.d. is effective after imatinib failure in various phases of CML. Comparative data of dasatinib versus high-dose imatinib in patients with resistance or intolerance to imatinib demonstrated that dasatinib was associated with improved response rates and progression-free survival. Side effects of dasatinib, including pleural effusions, are manageable with modification of dose or schedule. Phase III dose optimisation studies and future indications are also discussed.     

异甘草酸镁对慢性髓细胞性白血病K562细胞系增殖的抑制作用

目的：观察异甘草酸镁对慢性髓细胞白血病K562细胞系增殖的抑制作用。方法：将异甘草酸镁以1640培养液倍比稀释成10,1,10-1,10-2,10-3,10-4,10-5,10-6g·L-1共8个浓度组,分别处理增殖期K562细胞,镜下观察不同时间点各浓度组细胞生长情况,应用CCK-8法检测细胞增殖能力,绘制生长曲线,计算抑制率和半数抑制浓度（IC50）。结果：在给药第3天,浓度大于10-3g·L-1的异甘草酸镁对K562细胞增殖具有抑制作用（P〈0.05）,细胞倍增时间为48h,并且具有时间和浓度依赖性。其中,10g·L-1和1g·L-1异甘草酸镁的抑制作用最强（P〈0.01）,IC50约为1.6g·L-1。结论：异甘草酸镁对K562细胞的增殖具有抑制作用,为临床应用异甘草酸镁预防和治疗白血病化疗相关肝损伤提供实验依据。     

Butadiene cancer exposure-response modeling: based on workers in the styrene-butadiene-rubber industry: total leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, and chronic myelogenous leukemia

Cox regression is used to estimate exposure-response models (with cumulative 1,3-butadiene (BD) ppm-years as the exposure metric) based on the most recent data and validated exposure estimates from UAB's study of North American workers in the styrene-butadiene-rubber industry. These data are substantially updated from those in USEPA's 2002 risk assessment. The slope for cumulative BD ppm-years is not statistically significantly different than zero for CML, AML, or, when any one of eight exposure covariates is added to the model, for all leukemias combined (total leukemia). For total leukemia, the EC(1/100,000) is approximately 0.15 BD environmental ppm and the corresponding unit risk factor is approximately 0.00007 per BD environmental ppm. The excess risk for CML is approximately 15-fold less than for total leukemia. The maximum likelihood estimates suggest that there is no excess risk for AML from cumulative BD ppm-years. For CLL, the slope is statistically significantly different than zero. The excess risk for CLL is approximately 2.5-fold less than for total leukemia. For both total leukemia and CLL, the slope is not statistically significantly different than zero when the exposure-response modeling is based on the person-years with cumulative BD ppm-years less than or equal to 300 ppm-years.     

地西他滨联合预激方案治疗急性髓系白血病的临床研究

目的 研究地西他滨联合预激方案治疗急性髓系白血病的临床疗效.方法 选取本院2013年1月至2016年1月38例急性髓系白血病患者为研究对象,将纳入患者抽签随机分为观察组和对照组,每组19例.观察组采用地西他滨联合预激方案,对照组采用单纯预激方案,比较两组的临床疗效与不良反应情况.结果 观察组的治疗总有效率显著高于对照组(73.7％比42.1％,P＜0.05).观察组的恶心呕吐、腹泻、脱发、肝功能损伤、肺部感染、血尿、心功能不足发生率分别为26.3％、15.8％、36.8％、15.8％、31.6％、5.3％、10.5％,与对照组(15.8％、10.5％、26.3％、10.5％、10.5％、0.0％、5.3％)比较差异无统计学意义(P＞0.05).结论 地西他滨联合预激方案治疗急性髓系白血病具有较高的缓解率,同时不会增加过多不良反应,患者耐受性较好,是一种较理想的治疗方案.     

氟达拉滨联合环磷酰胺治疗慢性淋巴细胞白血病疗效观察

目的观察氟达拉滨联合环磷酰胺治疗慢性淋巴细胞白血病(CLL)的疗效和安全性。方法将CLL患者24例随机分为治疗组和对照组各12例。治疗组予以氟达拉滨联合环磷酰胺方案治疗,对照组予以CHOP方案化疗。比较2组总有效率及不良反应。结果治疗组总有效率为83.3%高于对照组的66.7%(P<0.05);2组合并感染率、中性粒细胞减少发生率、血小板减少发生率及持续时间比较差异均无统计学意义(P>0.05)。结论氟达拉滨联合环磷酰胺组治疗CLL具有完全缓解率及总有效率高、不良反应轻等优点,值得临床推广应用。