甲磺酸伊马替尼治疗慢性粒细胞白血病的疗效观察

目的：探讨甲磺酸伊马替尼(IM)治疗慢性粒细胞白血病(CML)的临床疗效。方法选择我院2009年1月~2013年12月收治入院的经病理学证实的CML患者100例,根据治疗方法不同分为两组,对照组给予联合化疗方法,观察组给予IM治疗,比较两组患者治疗后临床疗效。结果观察组患者完全缓解38例,部分缓解17例,未缓解45例,总有效率55.0%;对照组患者治疗后完全缓解8例,部分缓解18例,未缓解74例,总有效率26.0%,两者治疗有效率差异有统计学意义(χ2=8.028,P<0.05)。两组患者治疗过程中不良反应发生情况比较差异无统计学意义(P>0.05)。结论 IM是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。     

一种多激酶抑制剂对慢性髓细胞样白血病有效

法国La Miletrie大学中心医院的Francois Guilhot博士和一个国际研究组的研究者在5月15日的《血液》（Blood，2007；109：4143—4150.）杂志上报道，新的口服多靶标激醇抑制剂dasatinib（百时美-施贵宝公司）可诱导对伊马替尼抵抗或不耐受的慢性髓细胞样白血病（CML）患者显著的血液学和细胞遗传学反应。     

慢性粒细胞白血病对BCR-ABL酪氨酸激酶 靶向抑制剂的耐药机制

BCR-ABL酪氨酸激酶抑制剂靶向治疗慢性粒细胞白血病（chronic myeloid leukemia, CML)能够达到良好的临床效应,然而随着其临床广泛应用,对其产生耐药逐渐增多。CML细胞多药耐药是目前导致化疗失败,缓解率降低,疾病复发的主要原因。本文就CML对BCR-ABL酪氨酸激酶靶向抑制剂耐药的主要机制进行了阐述。     

伊马替尼对慢性粒细胞白血病患者T细胞免疫功能的影响

目的:探讨伊马替尼(STI571)对慢性粒细胞白血病(CML)患者T细胞免疫功能的影响。方法:以30例CML患者为观察组,32例缺铁性贫血患者为对照组,用流式细胞术(FCM)检测患者骨髓体外加用STI571后CD3+、CD3+CD8-、CD3+CD8+内T淋巴细胞内INF-γ表达水平。结果:STI571干预后,观察组CD3+、CD3+CD8-、CD3+CD8+T淋巴细胞内IFN-γ水平明显降低,与干预前和对照组比较有统计学差异(P0.05),而对照组干预前后CD3+、CD3+CD8-、CD3+CD8+T淋巴细胞内IFN-γ水平变化无统计学意义。结论:STI571能够降低初发CML患者T淋巴细胞内IFN-γ的表达,影响初发CML患者的细胞免疫功能,使免疫功能受到抑制。     

慢性粒细胞白血病的分子生物学特征与临床研究进展

Ｐｈ染色体是慢性粒细胞白血病（ＣＭＬ）的细胞遗传学标记，而ｂｃｒ／ａｂｌ基因重排则为ＣＭＬ的分子基础。ＢＣＲ、ｃ－ａｂｌ基因重排及ｂｃｒ／ａｂｌ嵌合基因的结构，转录和表达是ＣＭＬ寻病的关键环节。随着分子生物学技术的迅速发展，对ｂｃｒ／ａｂｌ重组基因的研究日益深入有可能最终阐明ＣＭＬ的发病机制，并在临床上对ＣＭＬ诊断、分型、鉴别、预后判断及治疗等均有极其重要的指导意义。目前已在尝试利用分子生物学技术     

慢性粒细胞性白血病生存期有关因素的分析

对17例慢性料细胞性白血病之最初临床血液学指标和治疗进行分析,探讨慢性粒细胞性白血病预后有关的因素.根据Sokal公式认为相对危险值<1.2,且对马利兰敏感的病人生存期效长;相对危险值>1.2,并且对马利兰不敏感的病人生存期较短.相对危险值与马利兰敏感性无明显相关关系.这表明有较好的最初临床血液学指标,且对马利兰治疗初期较敏感的病人生存期较长,反之则较短.     

荧光原位杂交检测慢性粒细胞白血病

目的 探讨对慢性粒细胞白血病进行荧光原位杂交(fluorescence in situ hybridization,FISH)检测的意义.方法 对158例慢性粒细胞白血病标本采用24 h短期培养法制备染色体,然后应用双色双融合BCR/ABL探针进行FISH检测,部分标本同时采用R显带技术进行染色体核型分析.结果 158例中共检出Ph阳性标本98例,其中69例(70.4%)为典型双色双融合BCR/ABL探针信号模式(1R1G2F),其余29例(29.6%)为3类12种非典型模式.各种非典型信号模式中出现频率较高的依次为:1R1G1F7例(7.1%)、2R1G1F 5例(5.1%)、1R1G2F&1R1G3F 4例(4.1%)、2R2G1F 3例(3.1%).对18例有核型资料的非典型信号的病例分析显示:其中3例特殊信号系由变异Ph易位引起;2例中出现的3个融合信号来源于附加的Ph染色体;4例核型与FISH结果不吻合,提示染色体分析存在错漏之处;3例染色体为典型Ph易位,而FISH结果为单个融合信号,系由der(9)号的部分缺失所致;3例核型中未发现Ph染色体.但FISH显示40%～64%的细胞中存在一个融合信号,从而明确慢性粒细胞白血病诊断;3例是移植或经格列卫治疗后的患者,染色体均为正常核型,而FISH检测到极小比例的阳性细胞.结论 FISH在慢性粒细胞白血病诊断、判断变异易位、隐匿Ph易位、衍生9号缺失、干扰素及格列卫的疗效观察以及移植后监测等诸多方面均具有重要价值.     

苏尼替尼治疗46例慢性粒细胞白血病的临床分析

目的比较和评价苏尼替尼治疗慢性粒细胞白血病(CML)的临床效果。方法回顾分析近7年来收治我院的46例CML患者的临床诊疗资料,统计其完全缓解(CR)率、生存期及影响因素。结果完全缓解35例,占总病例数的76.09%;部分缓解7例,占15.22%;未缓解4例,占8.69%。统计至2010年12月,五年存活26例,五年生存率56.52%。结论苏尼替尼是早期治疗CML的有效手段,能较为明显的缓解病情,减少并发症的发生率,提高患者的生存率,治疗过程中仍需要患者及其家属的密切配合。     

提高伊马替尼对慢粒白血病敏感性的方法

随着伊马替尼耐药机制的不断阐明,出现了许多应对耐药的策略.其中提高慢性粒细胞白血病(chronic myeloid leukemia,CML)对伊马替尼敏感性是研究较多的领域,主要方法有提高细胞内伊马替尼的药物浓度、调节信号通道、下调细胞凋亡抑制因子的表达等.     

伴CSF3RT618I突变的慢性粒单核细胞白血病1例并文献复习

目的：提高对伴CSF3RT618I突变的慢性粒单核细胞白血病(chronic myelomonocytic leukemia, CMML)的认识。方法：分析1例伴CSF3RT618I突变的CMML,结合文献复习讨论。结果：我们首次在CMML中报道CSF3RT618I突变。CSF3R突变的患者预后较差,酪氨酸激酶抑制剂能否改善其预后尚不清楚。结论：CSF3RT618I突变对CMML患者的预后影响还需要进一步临床研究来确定。     

Practice Patterns of Physician Treatment for Pediatric Chronic Myelogenous Leukemia

Chronic myelogenous leukemia (CML) is a rare disease in children for which pediatric evidence-based guidelines are lacking. We designed an anonymous survey for practicing pediatric oncologists and bone marrow transplantation (BMT) physicians to assess their willingness to recommend BMT for a patient with CML based on various clinical scenarios. A total of 274 physicians responded to the survey (13.4% response rate). Nearly all pediatric oncologists and BMT physicians recommended against BMT at time of diagnosis of CML in the chronic phase, with only 8.0% and 1.9% recommending BMT if a matched sibling donor (MSD) and a matched unrelated donor (MUD), respectively, was available. Similarly, after a first poor response to tyrosine kinase inhibitor (TKI) therapy or hematologic relapse, physicians continued to recommend against BMT (39.5% and 23.3% recommended BMT in patients with a matched sibling donor and matched unrelated donor, respectively). However, 81.7% and 69.8% of respondents would recommend BMT after 2 hematologic relapses on TKI therapy, if an MSD and an MUD, respectively, were available. In addition, there was great interest in developing a clinical trial evaluating the safety and efficacy of stopping TKIs in children with CML who achieve and maintain a deep molecular response, with 86.7% of respondents stating they would offer such a trial to their pediatric patients. This survey highlights the need for evidence-based, pediatric-specific guidelines for the management of children and adolescents with CML.     

Proposal of a morphologic bone marrow response score for imatinib mesylate treatment in chronic myelogenous leukemia

Cytogenetic and molecular analyses are essential disease-monitoring parameters in chronic myelogenous leukemia (CML) treated with imatinib. However, a bone marrow morphologic response has not been defined. We reviewed bone marrow histology and cytology of 39 imatinib-treated patients with CML over 49 weeks and introduced a morphologic response score. A significant positive correlation with a complete cytogenetic response was shown for absence of dry tap (P = .04) and abnormal megakaryocytes (P < 0.001), normalization of cellularity (P = .001) and reduction of fibrosis (P = .01), myelopoiesis:erythropoiesis index (P = .001), blast (P = .001) and basophil count (P < 0.001). The morphologic score integrating these parameters showed an early and late correlation with cytogenetic response. In conclusion, morphologic criteria for complete cytogenetic response in patients with CML treated with imatinib can be defined. Persistent high-level morphologic abnormalities herald early on a high likelihood to fail treatment and call for more intense or alternative therapy.     

酪氨酸激酶抑制剂治疗后慢性髓细胞白血病患者Ph阴性细胞中染色体异常的遗传学特征和转归

目的 观察酪氨酸激酶抑制剂治疗后慢性髓细胞白血病(chronic myelogenous leukemia,CML)Ph阴性细胞中染色体异常(chromosomal abnormalities in Ph negative cells,Ph- CAs)的遗传学特征和转归.方法 对15例接受酪氨酸激酶抑制剂治疗后出现Ph- CAs的CML患者进行遗传学和分子学动态观察.结果 出现Ph- CAs患者中,依马替尼治疗12例,达沙替尼治疗2例,伯舒替尼治疗1例,染色体异常以+8最为多见,占46.7％.Ph- CAs出现在ph+克隆减少或消失时,出现的平均时间为11.1个月(1～28个月);7例Ph- CAs已经消失,Ph- CAs持续的平均时间为10.9个月(3～24个月).Ph- CAs出现时,所有病例均未见骨髓病态造血或急性白血病;Ph- CAs出现后,除1例患者演变为ph+急性单核细胞白血病外,其余均获得骨髓缓解,11例获完全细胞遗传学反应,4例获完全分子学反应.结论 依马替尼、达沙替尼和伯舒替尼治疗CML患者均可能出现Ph- CAs;Ph- CAs多数为一过性,对酪氨酸激酶抑制剂治疗效果无影响.     

Extramedullary Relapse of Acute Leukemia after Allogeneic Hematopoietic Stem Cell Transplantation: Different Characteristics between Acute Myelogenous Leukemia and Acute Lymphoblastic Leukemia

Extramedullary relapse (EMR) of acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT) is a contributor to post-transplantation mortality and remains poorly understood, especially the different characteristics of EMR in patients with acute myelogenous leukemia (AML) and those with acute lymphoblastic leukemia (ALL). To investigate the incidence, risk factors, and clinical outcomes of EMR for AML and ALL, we performed a retrospective analysis of 362 patients with AL who underwent allo-HSCT at the First affiliated Hospital of Soochow University between January 2001 and March 2012. Compared with patients with AML, those with ALL had a higher incidence of EMR (12.9% versus 4.6%; P = .009). The most common site of EMR was the central nervous system, especially in the ALL group. Multivariate analyses identified the leading risk factors for EMR in the patients with AML as advanced disease status at HSCT, hyperleukocytosis at diagnosis, history of extramedullary leukemia before HSCT, and a total body irradiation–based conditioning regimen, and the top risk factors for EMR in the patients with ALL as hyperleukocytosis at diagnosis, adverse cytogenetics, and transfusion of peripheral blood stem cells. The prognosis for EMR of AL is poor, and treatment options are very limited; however, the estimated 3-year overall survival (OS) was significantly lower in patients with AML compared with those with ALL (0 versus 18.5%; P = .000). The characteristics of post–allo-HSCT EMR differed between the patients with AML and those with ALL, possibly suggesting different pathogenetic mechanisms for EMR of AML and EMR of ALL after allo-HSCT; further investigation is needed.     

Adoptive Immunotherapy with Cord Blood for the Treatment of Refractory Acute Myelogenous Leukemia: Feasibility,Safety, and Preliminary Outcomes

Adoptive immunotherapy has shown efficacy in patients with relapsed/refractory acute myelogenous leukemia (AML). We conducted a prospective evaluation of cord blood (CB)-based adoptive cell therapy following salvage chemotherapy in patients with AML or myelodysplastic syndrome (MDS) and describe the safety and early outcomes of this approach. To enhance the antileukemic effect, we selected CB units (CBUs) with a shared inherited paternal antigen (IPA) and/or noninherited maternal antigen (NIMA) match with the recipients. Furthermore, the CBUs had total nucleated cell (TNC) dose <2.5?×?10⁷/kg and were at least 4/6 HLA-matched with the patients; a higher allele-level match was preferred. Heavily pretreated adult patients with AML/MDS were enrolled. CBU searches were performed for 50 patients. CBUs with shared IPA targets were identified for all, and CBUs with NIMA matches were found for 80%. Twenty-one patients underwent treatment (AML, primary induction failure, n?=?8; refractory relapse, n?=?10, including 7 recipients of previous allogeneic HSCT; blast crisis chronic myelogenous leukemia, n?=?1; MDS, n?=?2). Most received combination chemotherapy; those not fit for intensive treatment received a hypomethylating agent. Response was defined as <10% residual blasts in hypocellular bone marrow at approximately 2 weeks after treatment. Ten of the 19 evaluable patients responded, including 5 of the 7 recipients of previous transplant. Response was seen in 4 of 4 patients with full CBU-derived chimerism, 2 of 2 of those with partial, low-level chimerism and 4 of 12 of the recipients with no detectable CBU chimerism. The most common adverse events were infections (bacterial, n?=?5; viral, n?=?2; fungal, n = 5). Grade IV acute graft-versus-host disease (GVHD) developed in 2 patients with full CBU chimerism; 2 other patients had grade 1 skin GVHD. A total of 11 patients died, 7 from disease recurrence and 4 from infections (1 early death; the other 3 in remission at the time of death). Overall, 12 patients proceeded to allogeneic HSCT; of those, 7 had responded to treatment, 3 had not (and had received additional therapy), and 2 had persistent minimal residual disease. In conclusion, the use of CB as adoptive immunotherapy in combination with salvage chemotherapy for patients with refractory AML/MDS is feasible, can induce disease control, can serve as a bridge to allogeneic HSCT, and has an acceptable incidence of adverse events. Alloreactivity was enhanced through the selection of CBUs targeting a shared IPA and/or NIMA match with the patients. CBUs with lower cell doses, already available in the CB bank and unlikely to be adequate grafts for adult transplants, can be used for cell therapy within a short time frame.     

急性髓系白血病患者治疗前后T淋巴细胞亚群测定的临床意义

为探讨急性髓系白血病患者治疗前后T淋巴细胞亚群变化的临床意义,选择初发确诊的急性髓系白血病患者30例(初治组); 经标准方案化疗,26例完全缓解(缓解组); 健康人30名(正常对照组).应用流式细胞术检测这三组人群T淋巴细胞亚群的变化情况.结果显示,初治组CD3+T 细胞、CD4+T细胞、CD8+T细胞百分率、CD4+...     

急性白血病起始的慢粒急变4例报道并文献复习

目的探讨急性白血病起病的慢性粒细胞白血病急变期患者的临床特点及治疗方法。方法对4例以急性白血病起始的慢性粒细胞白血病急变期患者的诊疗过程进行报道,结合相关文献分析以急性白血病起始的慢性粒细胞白血病急变期患者的临床特点和治疗方法。结果4例患者均符合以急性白血病起始的慢性粒细胞白血病急变期,其中2例患者采用化疗及靶向治疗将患者的病情转变为慢性期,再进行异基因外周血干细胞移植,2例患者至今存活,生存期至少4年;1例予以甲磺酸伊马替尼治疗后转为慢性期,未行异基因造血干细胞移植,再次急变后死亡,生存期约100天;另1例诊断后仅接受羟基脲治疗,生存期1年。结论急性白血病起始的慢性粒细胞白血病急变期患者临床上较为罕见,使用化疗或靶向药物治疗使骨髓象得到缓解后再进行异基因造血干细胞移植,有望延长此类患者的生存期。     

急性髓系白血病血管内皮生长因子表达与预后的研究

目的 :观察人白血病细胞系血管内皮生长因子 (VEGF)表达水平 ,研究急性髓系白血病 (AML)患者血清VEGF表达水平与预后的关系。方法 :采用酶联免疫吸附法 (ELISA)对 4 9例初治、10例复发AML患者血清及人白血病细胞系U937、K5 6 2、HL - 6 0、TF - 1和NB4培养上清液 (4 8小时 )VEGF表达水平进行检测。结果 :五种人白血病细胞系培养上清液中均测到VEGF高表达。 4 9例初治、10例复发AML患者的血清VEGF表达水平分别为 2 0 1 17± 110 93pg ml和 2 32 5 9± 118 6 2pg ml,均明显高于正常对照组 (12 5 6 2± 4 5 4 3pg ml;p <0 0 5 )。初治AML患者中VEGF高表达组 (>2 0 1 17pg ml)完全缓解 (CR)率为 4 8% ,低表达组 (<2 0 1 17pg ml)CR率为 77% ,两者比较差异显著 (p<0 0 5 )。结论 :血管内皮生长因子在刺激白血病细胞增殖、迁移中发挥重要作用。AML患者血清VEGF水平与预后具相关性     

急性髓系白血病患者治疗前后血清VEGF和SE-CAD检测的临床意义

目的：探讨了急性髓系白血病患者治疗前后血清VEGF和SE—CAD水平的变化。方法：应用酶联双抗体夹心法（ELISA）对35例急性髓系白血病患者进行了血清VEGF（血管内皮生长因子）和SE—CAD（可溶性上皮型钙黏蛋白）水平测定，并与30名正常人作比较。结果：急性髓系白血病患者在治疗前均非常显著地高于正常人组（P〈0．01），经6个月治疗后复发者血清VEGF和SE—CAD水平持续异常，未复发者血清VEGF和SE—CAD水平恢复正常。结论：血清VEGF和SE—CAD水平的变化与急性髓系白血病患者的病情和预后密切相关，有一定的临床实用价值。