伊马替尼治疗慢性粒细胞白血病的远期疗效观察

目的:对于慢性粒细胞白血病病人采取伊马替尼进行治疗的具体方法以及远期治疗效果进行分析和总结。方法:将我们医院在以往一年之内所收治的慢性粒细胞白血病病人资料100例施行分析,所选100例慢性粒细胞白血病病人采取数字法加以分组,给予对照组慢性粒细胞白血病病人达沙替尼治疗,给予研究组慢性粒细胞白血病病人伊马替尼进行治疗,对比两组病人远期治疗效果。结果:两组慢性粒细胞白血病病人接受治疗之后的完全细胞遗传学缓解率持续时间以及完全细胞遗传学缓解率对比存在明显差异。结论:临床中针对慢性粒细胞白血病病人,为其提供伊马替尼治疗具有理想的远期治疗效果,应该给予大力的推广与应用。     

伊马替尼治疗慢性粒细胞性白血病患者的临床疗效

目的观察应用伊马替尼治疗慢性粒细胞性白血病患者的临床疗效。方法选取2010年6月至2015年6月来本院治疗的86例粒细胞性白血病患者实施分析,所有患者均针对其分期类型给予伊马替尼治疗,观察不同分期患者在经伊马替尼治疗后的疗效评估。结果患者在慢性期、加速期及急变期的完全细胞遗传学缓解(CCy R)率、主要分子学缓解(MMo R)的结果有显著差异(P<0.05),慢性期患者59均实现完全血液学缓解(CHR),4例未实现;慢性期患者中,低危组血液学反应、细胞遗传学反应及分子学反应缓解率上均明显优于中、高危组。三组存在显著差异(P<0.05),统计学有意义。结论对慢性粒细胞性白血病患者实施伊马替尼治疗具有临床价值。     

伊马替尼治疗慢性粒细胞白血病期间血药浓度与临床疗效相关性分析

目的 探讨伊马替尼治疗慢性粒细胞白血病期间血药浓度与临床疗效相关性.方法 108例慢性粒细胞白血病患者均行伊马替尼治疗,观察患者的遗传学疗效及分子生物学疗效,并检测治疗期间患者的伊马替尼血药浓度,分析其与疗效之间的相关性.结果 获得遗传学缓解组患者伊马替尼的血浆谷浓度为( 1659.64±129.67) μg/L,显著高于未获得组的(794.51±93.62) μg/L(t =9.38,P＜0.05);获得分子生物学缓解组患者伊马替尼的血浆谷浓度为(1618.46±141.32)μg/L,显著高于未获得组的(904.78±80.77) μg/L(t=11.25,P＜0.05).治疗期间患者的伊马替尼血药浓度与遗传学疗效、分子生物学疗效之间的相关系数分别为0.235(P ＜0.05)及0.266(P ＜0.05).结论 伊马替尼治疗慢性粒细胞白血病期间血药浓度与临床疗效有一定相关性,监测伊马替尼血药浓度对判断患者病情及治疗效果有指导意义.     

伊马替尼联合化疗治疗ph+成人急性淋巴细胞白血病18例治疗分析

目的：探讨ph+成人急性淋巴细胞白血病患者的治疗过程中应用伊马替尼联合化疗方法进行治疗的临床效果。方法18例ph+成人急性淋巴细胞白血病患者,均应用伊马替尼联合化疗方法进行治疗,观察其临床治疗效果。结果18例患者,完全缓解12例,占66.7%,部分缓解4例,占22.2%,未缓解2例,占11.1%,治疗总有效率为88.9%。结论 ph+成人急性淋巴细胞白血病患者的治疗过程中,应用伊马替尼联合化疗方法进行治疗,具有较好的效果,值得临床推广。     

伊马替尼与干扰素联合治疗慢性粒细胞白血病的疗效分析

目的:探讨伊马替尼与干扰素联合化疗治疗慢性粒细胞白血病(CM L)的疗效。方法:2004年6月—2009年7月新诊断的58例Ph染色体阳性CM L慢性期患者,随机分为伊马替尼组和干扰素联合化疗组,比较两组临床疗效。结果:两组总有效率差异无统计学意义(P>0.05);伊马替尼组完全血液学缓解率,完全细胞遗传学缓解率、完全分子学效应率、5年总生存率均明显高于干扰素联合化疗组(P<0.05)。结论:伊马替尼和干扰素联合化疗都可作为CM L慢性期的有效治疗方法,应依据不同情况实施个体化治疗。     

伊马替尼联合化疗治疗ph+成人急性淋巴细胞白血病20例治疗分析

目的探讨伊马替尼联合化疗治疗ph+成人急性淋巴细胞白血病20例的疗效。方法 2009年10月至2011年03月期间,我院诊治的ph+成人急性淋巴细胞白血病20例,应用伊马替尼联合VDCP(长春新碱、柔红霉素、环磷酰胺、强的松)或VDCLP(长春新碱、柔红霉素、环磷酰胺、左旋门冬酰胺酶、强的松)化疗方案进行治疗,等症状完全缓解后,还要伊马替尼与化疗交替进行,已达到巩固和强化治疗的效果。结果伊马替尼联合化疗治疗后,20例ph+成人急性淋巴细胞白血病患者,完全缓解(CR)14例;部分缓解(PR)4例;未缓解2例。20例ph+成人急性淋巴细胞白血病患者,经过伊马替尼联合化疗治疗过程中,其中3例出现骨髓抑制,4例不同程度地出现感染,对症治疗后,所有不良反应都可以缓解,并且没有出现严重性出血,更无死亡。结论伊马替尼联合化疗的治疗方法,对20例ph+成人急性淋巴细胞白血病患者进行治疗,完全缓解率明显提高,值得临床广泛推广。     

Bcr-Abl激酶抑制剂尼罗替尼的药理与临床评价

慢性粒细胞性白血病(CML)和费城染色体阳性急性淋巴细胞白血病(Ph ALL),是由Bcr-Abl癌基因引起的.伊马替尼能抑制Bcr-Abl蛋白酪氨酸激酶活性,是一种有效的治疗慢性期CML的药物,但由于其耐药点突变,使加速期或急变期CML和Ph ALL患者常常复发.尼罗替尼是第2代Bcr-Abl激酶抑制剂,效果比伊马替尼强20倍,对伊马替尼耐药和不能耐受的患者(T3151除外)有广泛的活性.Ⅰ/Ⅱ期临床试验表明,尼罗替尼对伊马替尼耐药或不能耐受的CML患者仍能获得血液学和细胞遗传学的缓解.现对尼罗替尼的药理作用、药动学、药物相互作用、安全性进行综述.     

伊马替尼治疗慢性粒细胞性白血病的临床应用意义探究

目的:探究伊马替尼治疗慢性粒细胞性白血病的临床应用价值.方法:选取我院2014年9月~2015年12月收治的30例慢性粒细胞性白血病患者,通过伊马替尼治疗.结果:治疗后,完全血液学缓解CHR、部分血液学缓解PHR、未缓解NR分别为90%、6.67%、3.33%;完全遗传学缓解CCR、部分遗传学缓解PCR、未缓解NR分别为83.33%、10%、6.67%.随访6个月,复发率3.33%(1/30).结论:慢性粒细胞性白血病,经伊马替尼治疗,临床疗效显著,但应结合病情变化、耐受情况,适当调整药物的剂量,以便充分发挥伊马替尼的药效,提高临床效果.     

弥漫性大B细胞性淋巴瘤继发慢性粒细胞性白血病1例

报道1例弥漫性大B细胞性淋巴瘤继发慢性粒细胞性白血病患者。55岁的女性患者于2009年6月确诊弥漫性大B细胞性淋巴瘤,接受6个疗程R-CHOP方案化疗和1年评估后出现白细胞计数98.96×109/L。骨髓细胞遗传学和分子生物学检测出可疑费城染色体和BCR-ABL基因阳性,结合骨髓细胞形态学诊断为慢性粒细胞性白血病。患者服用羟基脲治疗1周后,开始服用伊马替尼,并很快获得完全血液学缓解。     

伊马替尼治疗Ph阳性进展期慢性粒细胞白血病

目的:观察伊马替尼治疗Ph阳性进展期慢性粒细胞白血病(CML)的疗效和耐药情况,研究改善伊马替尼耐药的方法。方法:32例Ph阳性进展期CML病人,其中加速期12例,急变期20例,每日口服伊马替尼600或800mg,持续3～9mo。结果:CML加速期病人血液学完全缓解率和总有效率分别为42%和83%,主要细胞遗传学缓解率25%,持续完全血液学缓解病例占25%。CML急变期各类型病人血液学完全缓解率和总有效率分别为20%和55%,主要细胞遗传学缓解率15%,持续完全血液学缓解病例占10%。CML急变期原发耐药和继发耐药分别为45%和20%,联合化疗与暂停伊马替尼对继发耐药可暂时改善其耐药性,但药物有效时间明显缩短。结论:伊马替尼对初治或复治的CML加速期和急变期病人均有效,可作为非移植CML治疗的标准一线方案,伊马替尼治疗CML急变期的原发耐药和继发耐药率较高,联合化疗和暂停伊马替尼可暂时改善其耐药性。     

新型抗肿瘤药物依曼替尼布

依曼替尼布是一种新型的 2 苯胺基嘧啶类酪氨酸激酶抑制药 ,用于α 干扰素治疗失败后的慢性髓样白血病 (CML)慢性期病人、加速期病人、急变期病人的治疗。临床研究表明该药对病人血液学缓解及主要细胞分化缓解显著     

Imatinib activity in vitro in tumor cells from patients with chronic myeloid leukemia in chronic phase and blast crisis

The aims of this study were to evaluate the feasibility of using the non-clonogenic fluorometric microculture cytotoxicity assay in drug sensitivity testing of tumor cells from patients with chronic myeloid leukemia. In nine samples (six chronic phase, three blast crisis), the drug sensitivities in tumor cells from blood versus from bone marrow and fresh tumor cells versus cryopreserved were compared. In 26 samples obtained in chronic phase (pretreatment), in six samples from patients in blast crisis and in the K 562 cell line, the activity of imatinib alone and in combination with cytarabine, vincristine, daunorubicin, interferon, arsenic trioxide and homoharringtonine was evaluated. All chronic myeloid leukemia chronic phase samples were sensitive to imatinib, with a mean IC50 at 10.3 mumol/l. The chronic myeloid leukemia samples from blast crisis (n=6) were significantly more sensitive to imatinib than the samples from chronic phase (n=26) (P<0.05), with an IC50 mean at 0.4 mumol/l. In blast crisis samples, significant positive interaction effects were observed between imatinib and all other tested drugs except for interferon. In chronic phase samples, interferon, daunorubicin and arsenic trioxide were the drugs with the highest frequency of positive interactions with imatinib (P<0.05). We conclude that the fluorometric microculture cytotoxicity assay may be a useful method for drug sensitivity testing in chronic myeloid leukemia patient samples from both chronic phase and blast crisis, and that testing primary tumor cells may have advantages over cell line studies. Imatinib shows a higher in vitro activity and more positive drug interactions in cells from blast crisis than chronic phase chronic myeloid leukemia patients. Combinations between imatinib and interferon, daunorubicin and arsenic trioxide may be interesting for future clinical trials in patients with chronic myeloid leukemia chronic phase.     

伊马替尼治疗Ph染色体阳性慢性粒细胞白血病的临床观察

目的:评价酪氨酸激酶抑制剂伊马替尼治疗Ph染色体阳性慢性粒细胞白血病的有效性及安全性。方法:90例慢性粒细胞白血病患者,其中慢性期67例,非慢性期23例(加速期14例,急变期9例),每天应用剂量分别为400,600mg。每周复查血常规,每3个月进行骨髓象及细胞遗传学检查,根据血象和骨髓象调整剂量。结果:观察截止时,84例(93.3%)获得血液学完全缓解;68例可评价遗传学效应,35例(51.5%)发生主要遗传学效应(慢性期30例,加速期3例,急变期2例),其中31例(88.6%)为遗传学完全缓解(慢性期27例,加速期2例,急变期2例)。11例(12.2%)患者发生严重白细胞和/或血小板减少,但可通过调整剂量控制。严重非血液学不良反应发生较少。结论:伊马替尼治疗Ph染色体阳性慢性粒细胞白血病患者疗效较好,可获得较高的完全血液学缓解率和主要细胞遗传学缓解率,起效迅速,且不良反应较少,可耐受或自行消失。     

慢性粒细胞白血病骨髓磁共振成像表现及临床应用分析

目的探讨慢性粒细胞白血病(chronicmyeloid leukemia,CML)骨髓磁共振成像(MRI)表现及临床价值。方法收集成人CML50例,其中初诊慢性期患者16例,治疗后病情稳定于慢性期者18例,病情发展到加速期者7例,发生急性变者9例。所有患者均行骨盆及股骨中上段MRI检查。结果初诊慢性期及进展到加速和急变期的患者SE序列T1WI表现为髂骨及股骨骨髓弥漫性低信号或仅有在股骨头、大转子处残留斑片状高信号。治疗后维持在慢性期的患者SE序列T1WI表现为髂骨弥漫性低信号为主,夹杂点片状高信号,股骨主要表现为高低混杂信号。初诊慢性期组与治疗后组、治疗后组与加速急变组MRI表现差异有统计学意义(P<0.01);初诊慢性期组与加速急变期组差异无统计学意义(P>0.05)。结论CML患者骨髓MRI能反映其病程演变,与临床特点结合,有助于CML的诊断分期,对监测病情发展、提示加速和急变有重要价值。     

慢性髓细胞白血病急变期细胞遗传学及分子遗传学研究

目的 研究慢性髓细胞白血病急变期（CML-BC）细胞遗传学及分子遗传学改变。方法 随机选取25例CML-BC病例,进行常规细胞遗传学分析,并同时以双色双融合荧光原位杂交（FISH）技术检测其染色体标本。对于FISH技术检测到的间期细胞中只有单个融合信号的标本,则观察其中期细胞,以明确是否为衍生9号染色体[der（9）]缺失。结果 在随机选取的25例CML-BC病例中有5例以检测存在der（9）缺失,而R显带在25例中均未发现der（9）的缺失。der（9）缺失的病例未显示出细胞遗传学上的不稳定趋势。CML-BC中具有新遗传学异常的病例其CML-BC较短。CML-BC急淋变与急非淋变病例中der（9）缺失概率无差异。结论 FISH技术可有效检测der（9）缺失。der（9）缺失与CML-BC中细胞遗传学上不稳定性无相关性,同时不导致CML向某一特定类型转化。     

达沙替尼治疗伊马替尼耐药的 BCR／ABL阳性白血病

目的评价达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病的疗效和安全性。方法对9例伊马替尼耐药的慢性髓系白血病（CML）或Ph阳性急性淋巴细胞白血病（Ph＋ALL）患者,给予达沙替尼100～140 mg·d-1口服治疗,评估疗效和耐受情况。结果 9例伊马替尼耐药的BCR/ABL阳性白血病,2例CML-CP患者均获得CHR,1例达CCyR;5例CML-BC患者中4例获得CHR和PCyR,1例NR;2例Ph＋ALL患者中1例检测到E255V突变,采用达沙替尼治疗达CHR和PCyR,1例诱导缓解时,同时行VDP方案化疗,继发严重感染死亡。结论达沙替尼治疗伊马替尼耐药的BCR/ABL阳性白血病患者可获得血液学甚至细胞遗传学缓解,且耐受性好。     

髓系白血病患者骨髓单个核细胞β-连环蛋白mRNA的表达

目的观察急慢性髓系白血病患者骨髓单个核细胞β-连环蛋白的表达及其意义。方法 41例髓系白血病患者,其中25例急性髓系白血病（AML）,16例慢性髓系白血病（CML）。同时选择18例非恶性血液病患者作为对照。肝素抗凝骨髓2 ml,Ficoll液分离骨髓单个核细胞,荧光定量逆转录聚合酶链反应法检测β-连环蛋白的表达。结果β-连环蛋白在AML组表达量明显高于CML组及对照组（P〈0.01）;CML组表达量高于对照组表达量,差异有统计学意义（P〈0.05）;CML组4例急变患者的β-连环蛋白表达量也较高。β-连环蛋白表达量与患者年龄、性别无关;与骨髓原始细胞含量有关,含量≥30%的患者β-连环蛋白表达量较高。结论β-连环蛋白在AML和CML急变的患者骨髓单个核细胞中异常高表达,Wnt/β-连环蛋白通路在AML和CML急变病例中异常激活可能与白血病细胞的异常增殖有关。     

Nilotinib

Nilotinib is an orally administered BCR-ABL tyrosine kinase inhibitor that has shown good clinical efficacy in imatinib-resistant or -intolerant, Philadelphia chromosome-positive, chronic myeloid leukaemia (CML) in a phase I/II trial. The phase I component of the trial established the dosage regimen used in the phase II part of the trial, which included several arms. Three of these arms, or phase II trials, evaluated nilotinib in each of the three phases of CML (chronic, accelerated or blast crisis).I n the phase II trial in patients with chronic-phase CML, major cytogenetic response (primary endpoint) was achieved in 48% of the 280 patients who received nilotinib and had a follow-up period of > or = 6 months. Major cytogenetic response rates did not differ between imatinib-resistant and -intolerant patients, and nilotinib was effective in patients with BCR-ABL mutations (except T315I). Haematologic response rate (primary endpoint) was 47% in the phase II trial with nilotinib in patients with accelerated-phase CML (n = 119). Complete haematologic response was achieved in 26% of patients and 21% had no evidence of leukaemia or returned to chronic-phase CML. Major cytogenetic response, an important secondary endpoint in the trial, occurred in 29% of patients. Data from the phase II trial in patients with CML in blast crisis (n = 135) also showed promising results, with 39% of patients achieving haematologic response with nilotinib. Adverse events reported with nilotinib have generally been of mild to moderate severity. Grade 3 or 4 neutropenia and thrombocytopenia were reported in 29% of patients each.     

Imatinib: new preparation. For Chronic myeloid leukaemia: further assessment required

(1) Chronic myeloid leukaemia goes through three clinical phases: a chronic phase, an acceleration phase, and a terminal blast crisis. In the chronic phase, interferon alfa-2 is more effective than cytotoxic chemotherapies but it also has more adverse effects. (2) Imatinib inhibits tyrosine kinase, an enzyme encoded by the pathological gene BCR-ABL, which is created during a reverse translocation between chromosomes 9 and 22 (characteristic of chronic myeloid leukaemia). This translocation almost always creates the pathological chromosome Philadelphia in blood cell lines. (3) 1 027 patients were recruited to three non comparative trials of imatinib, each focusing on a different phase of chronic myeloid leukaemia. Efficacy was evaluated largely on the basis of blood cell count and clearance of cells harbouring the Philadelphia chromosome. (4) During the chronic phase, in patients in whom interferon alfa-2 had failed or been poorly tolerated, a major cytogenetic response, lasting at least one month, occurred in 35% of patients on imatinib, compared to 20% of patients on interferon alfa-2 + cytarabine (historical comparison). It is not known whether this translated into longer survival. (5) Preliminary results from a randomised but unblinded trial comparing imatinib with interferon + cytarabine seem to favour imatinib. Some patients developed relapses resistant to imatinib, owing to mutations in the BCR-ABL gene. (6) In patients going through the acceleration phase or blast crisis, imatinib did not improve survival compared with standard treatments. (7) The main adverse effects so far described with imatinib are gastrointestinal problems, oedema and fluid retention, and muscle and joint pain, which prompted patients to stop treatment in no more than 5% of cases. (8) Imatinib has a strong potential to interact with other drugs, including paracetamol, but few specific studies have been done. (9) In practice imatinib may be a useful option during the chronic phase, after interferon alfa-2 has failed or been stopped because of adverse effects, provided that its benefits, so far shown only in surrogate endpoints, translate into longer survival. During the acceleration phase and blast crisis imatinib may cause fewer side effects than existing treatments.