血管内皮生长因子检测对伊马替尼治疗慢性粒细胞白血病的疗效判定价值

目的检测伊马替尼治疗前后的慢性粒细胞白血病(CML)患者VEGF质量浓度,研究血管内皮生长因子(VEGF)在CML中的表达及临床意义,探讨VEGF对伊马替尼治疗CML疗效判定的价值。方法2003-08～2005-02中国医科大学第一临床学院选择CML患者32例。伊马替尼治疗达血液学完全缓解12例。应用ELISA法检测血浆VEGF的表达质量浓度。结果32例患者血浆VEGF表达质量浓度为(296.16±18.19)ng/L,明显高于对照组(P<0.01)。伊马替尼治疗达血液学完全缓解的CML患者的VEGF质量浓度为(198.23±16.51)ng/L,明显低于治疗前(P<0.05)。结论CML患者血浆VEGF表达明显增高。血浆VEGF可能成为判定伊马替尼疗效的一个指标。     

接受伊马替尼治疗的患者出现骨和无机物代谢的改变

伊马替尼可以抑制与疾病相关的多种酪氨酸激酶,包括慢性髓性白血病(CML)的BCR-ABL、胃肠间质肿瘤的C-KIT及骨髓增生紊乱患者的血小板衍生生长因子(PDGF)受体α、β等。大部分患者对伊马替尼可以很好地耐受,在常规电解质分析中未见持续的代谢异常。然而我们发现一些初诊的CML患者开始用伊马替尼后出现低磷酸盐血症。因此本研究对16例接受伊马替尼治疗出现低磷酸血症的患者及8例血清磷酸盐水平正常的患者和14名健康志愿者进行了生化检测。方法16例低磷酸血症患者来自2002年4月至2003年7月接受伊马替尼治疗的患者,其中CML8例,胃肠道…     

慢性髓性白血病患者伊马替尼耐药相关因素分析

目的 分析慢性髓性白血病（CML）患者发生伊马替尼耐药的相关因素.方法 选择CML患者60例,均口服伊马替尼400 mg/d,于治疗第1年每3个月行血常规、Ph染色体、BCR-ABL基因及骨髓细胞学检查,以后每半年复查1次;治疗12个月时,评价治疗效果,判断患者是否获得主要分子生物学反应（MMR）、完全细胞遗传学反应（CCyR）.采用SPSS19.0统计软件对患者的临床资料进行伊马替尼耐药的单因素和多因素COX分析.结果 60例患者共11例（18.3％）发生耐药.单因素分析结果显示,HGB及获得MMR、CCyR与伊马替尼耐药有关（P均＜0.05）.多因素COX分析显示,获得CCyR是影响伊马替尼耐药的独立因素（P＜0.05）.结论 CML患者获得CCyR是发生伊马替尼耐药的危险因素.     

尼洛替尼治疗伊马替尼耐药的慢性髓系白血病的临床观察

目的:探讨尼洛替尼在伊马替尼耐药的慢性髓系白血病( CML)患者中的疗效及不良反应.方法:9例伊马替尼耐药的CML患者,其中慢性期6例,进展期3例,持续口服尼洛替尼400 mg 2次/d,观察其疗效及不良反应.结果:6例CML慢性期患者,5例获得完全血液学反应,2例获得主要细胞遗传学反应；3例CML进展期患者均获得血液...     

伊马替尼血浆谷质量浓度与慢性粒细胞白血病慢性期疗效相关性研究

目的评价伊马替尼血浆谷质量浓度对慢性粒细胞白血病(CML)慢性期(CP)患者疗效的影响。方法收集2009年6月至2010年2月北京大学人民医院55例经标准剂量伊马替尼治疗的CML-CP患者,于治疗后3、6或12个月后检测伊马替尼血浆谷质量浓度。对疗效欠佳或治疗失败患者予增加伊马替尼剂量后3～6个月再次检测伊马替尼血浆谷质量浓度。结果服用400 mg/d伊马替尼患者中,血浆伊马替尼谷质量浓度为981～4170μg/L,平均为(1685±637)μg/L。治疗后18个月获得主要分子学反应(MMR)患者平均伊马替尼谷质量浓度(1881±669)μg/L显著高于未获得MMR患者(1262±346)μg/L(P<0.05)。17例未获MMR患者中,7例伊马替尼加量至600 mg/d后,其谷质量浓度显著升高,中位9个月时,6例(86%)获得MMR,而10例未加量者继续治疗,3例(30%)获得MMR(P=0.05)。结论伊马替尼的血浆谷质量浓度与CML-CP患者良好的分子学疗效相关。疗效不佳患者增加伊马替尼的剂量,有助于提高伊马替尼谷质量浓度和分子学疗效。     

慢性髓性白血病慢性期的一线治疗策略:规范管理,序贯治疗,首选一代

<正>自第一个酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)甲磺酸伊马替尼上市后,其卓越的疗效使慢性髓性白血病(chronic myeloid leukemia,CML)的治疗取得了里程碑式的进展。2003年伊马替尼迅速取代干扰素、造血干细胞移植等治疗手段,成为一线治疗CML慢性期(CP)患者的首选~([1])。随后TKI药物不断更新换代,二代TKI尼洛替尼、达沙替尼和博舒替尼,甚至三代TKI普纳     

慢性髓性白血病慢性期的一线治疗策略:规范管理,序贯治疗,首选一代

<正>自第一个酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)甲磺酸伊马替尼上市后,其卓越的疗效使慢性髓性白血病(chronic myeloid leukemia,CML)的治疗取得了里程碑式的进展。2003年伊马替尼迅速取代干扰素、造血干细胞移植等治疗手段,成为一线治疗CML慢性期(CP)患者的首选~([1])。随后TKI药物不断更新换代,二代TKI尼洛替尼、达沙替尼和博舒替尼,甚至三代TKI普纳     

难治及复发性慢性粒细胞白血病的治疗进展

近年来,慢性粒细胞白血病(CML)的治疗取得重要进展,应用马力兰、羟基脲、联合化疗、干扰素以及中药靛玉红、异靛甲等常规治疗,使患者平均生存期维持在3～5a的年代已经过去,伊马替尼的应用开辟了治疗CML的新时代,也对造血干细胞移植(HSCT)作为治愈该病的惟一手段提出了挑战.当然仍有部分CML患者伊马替尼原发耐药或治疗有效后失效或HSCT后复发.本文就近年来CML(特别是难治及复发)患者的治疗进展作简要介绍.     

酪氨酸激酶抑制剂选择的困惑

<正>酪氨酸激酶抑制剂(tyrosine kinase inhibitor,TKI)使慢性粒细胞白血病(chronic myeloid leukemia,CML)疗效取得了划时代的改变,也成为国际国内CML治疗的一线选择。近年陆续有更多的TKI上市,目前国内上市的3种TKI包括一代药物伊马替尼和二代药物尼洛替尼及达沙替尼。中国CML诊治指南2016年版TKI一线选择包括伊马替尼和尼洛替尼~([1]),国际上3种TKI均已成为     

二代酪氨酸激酶抑制剂达沙替尼治疗慢性髓性白血病安全性研究进展

正慢性髓性白血病(CML)是一种起源于造血干细胞的恶性增殖性疾病。目前经酪氨酸激酶抑制剂(TKI)治疗的CML患者生存期接近一般人群,在其治疗过程中依从性和持续性尤为重要,在TKI中进行药物选择时,安全谱是必须考量的因素。二代TKI达沙替尼对导致伊马替尼耐药的100多种BCR-ABL突变有效~([1]),与伊马替尼相比能够达到     

Imatinib‐associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia

Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)‐positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib‐associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph‐positive or Ph‐negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib‐associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.     

Drug treatment is superior to allografting as first-line therapy in chronic myeloid leukemia

Early allogeneic hematopoietic stem cell transplantation (HSCT) has been proposed as primary treatment modality for patients with chronic myeloid leukemia (CML). This concept has been challenged by transplantation mortality and improved drug therapy. In a randomized study, primary HSCT and best available drug treatment (IFN based) were compared in newly diagnosed chronic phase CML patients. Assignment to treatment strategy was by genetic randomization according to availability of a matched related donor. Evaluation followed the intention-to-treat principle. Six hundred and twenty one patients with chronic phase CML were stratified for eligibility for HSCT. Three hundred and fifty four patients (62% male; median age, 40 years; range, 11-59 years) were eligible and randomized. One hundred and thirty five patients (38%) had a matched related donor, of whom 123 (91%) received a transplant within a median of 10 months (range, 2-106 months) from diagnosis. Two hundred and nineteen patients (62%) had no related donor and received best available drug treatment. With an observation time up to 11.2 years (median, 8.9 years), survival was superior for patients with drug treatment (P = .049), superiority being most pronounced in low-risk patients (P = .032). The general recommendation of HSCT as first-line treatment option in chronic phase CML can no longer be maintained. It should be replaced by a trial with modern drug treatment first.     

Imatinib-associated neutropenia may not be overcome by filgrastim treatment in patients with blastic phase of chronic myeloid leukaemia

Imatinib mesylate is a very effective treatment in patients with Philadelphia (Ph)-positive chronic myeloid leukaemia (CML). However, in patients with advanced phase CML, it is still unclear whether, in the presence of myelosuppression, therapy with imatinib should be continued. It has been reported that intermittent filgrastim treatment may overcome imatinib-associated neutropenia and allow improved delivery of imatinib. Such combined sequential treatment is theoretically attractive as it may lead to better disease response. Here, we report a patient with blastic phase CML who developed severe and prolonged myelosuppression during imatinib treatment. Despite cessation of imatinib and 2 months of filgrastim therapy neither recurrence of Ph-positive or Ph-negative cells occurred. We conclude that filgrastim treatment may not always reverse imatinib-associated neutropenia therefore the decision of continued imatinib therapy in patients with advanced CML should be taken with caution.     

Challenges for allogeneic hematopoietic stem cell transplantation in chronic myeloid leukemia in the era of tyrosine kinase inhibitors

Following the introduction of the tyrosine kinase inhibitor (TKI) imatinib in the treatment of chronic myeloid leukemia (CML) patients, the allogeneic hematopoietic stem cell transplantation (HSCT) scene in CML has changed dramatically. The number of patients receiving HSCT in first chronic phase (CP) has declined rapidly, as allogeneic HSCT in CP is now performed in these patients only in case of failure or intolerance of TKIs. Second, those CML patients who undergo allogeneic HSCT represent a selection of high-risk patients due to more advanced disease with high rates of accelerated or blast phase (being associated with an increased relapse risk), advanced age and relevant co-morbidities. Efforts at meeting these special challenges are being developed: treatment with TKIs aims to improve the pre-transplant remission status before HSCT. Dose-reduced conditioning protocols were introduced to decrease transplant-related mortality in patients with co-morbidities or older age. In the post-transplant period, TKIs may be administered for prophylaxis and for treatment of post-transplant relapse. Still, the outcome of patients in advanced CML phases remains guarded, and requires an improvement in current transplant strategies.     

Chronic myelocytic leukaemia presenting in blastic transformation. Two cases primarily diagnosed as acute myelocytic leukaemia.

The interval from diagnosis of chronic myelocytic leukaemia (CML) to onset of blastic transformation (BT) can vary from days to several years. This blastic phase of CML is indistinguishable from acute myelocytic leukaemia (AML), both clinically and morphologically. The Ph1 chromosome has occasionally been demonstrated in acute leukaemia and it has been suggested that these cases may represent CML presenting in BT. 2 such patients are reported, in 1 of whom the characteristics after treatment further confirmed the diagnosis of CML. Differentiation between CML presenting in BT and AML has both prognostic and therapeutic value. For this reason it is recommended that cytogenetic screening for the Ph1 chromosome should be included in the initial examination of patients with acute leukaemia.     

Hematopoietic cell transplantation for chronic myeloid leukemia in developing countries: perspectives from Latin America in the post-tyrosine kinase inhibitor era

Tyrosine kinase inhibitors (TKIs) are currently the first line treatment for chronic myelogenous leukemia (CML) in countries with high and intermediate-high gross national income. Hematopoietic cell transplantation (HCT) in these countries is considered salvage therapy for eligible patients who failed TKI or progress to advanced disease stages. In Latin America, treatment for CML also changed with availability of TKI in the region. However, many challenges remain, as the cost of this class of medication and recommended monitoring is high. CML treatment practices in Latin America demonstrate that the majority of patients are treated with TKI at some point after diagnosis, most commonly imatinib mesylate, but still TKI can only be used after interferon failure in some countries. Other treatment practices are different from established international guidelines, outlying the importance of continuing medical education. Allogeneic HCT is a treatment option for CML in this region and could be considered a cost-effective approach in a small subset of young patients with available donors, as the overall cost of long-term non-transplant treatment may surpass the cost of transplantation. However, there are many challenges with HCT in Latin America such as access to experienced transplant centers, donor availability, and cost of essential drugs used after transplant, which further impacts expansion of this treatment approach in patients in need. In conclusion, Latin American patients with CML have access to state of the art CML treatment. Yet, drug costs have a tremendous impact on developing health systems. Optimization of CML treatment in the region with appropriate monitoring, recognizing patients who would be transplant candidates, and expanding access to transplantation for eligible patients may curtail these costs and further improve patient care.     

Chronic Myelocytic Leukaemia Presenting in Blastic Transformation: Two Cases Primarily Diagnosed as Acute Myelocytic Leukaemia

The interval from diagnosis of chronic myelocytic leukaemia (CML) to onset of blastic transformation (BT) can vary from days to several years. This blastic phase of CML is indistinguishable from acute myelocytic leukaemia (AML), both clinically and morphologically. The Ph¹ chromosome has occasionally been demonstrated in acute leukaemia and it has been suggested that these cases may represent CML presenting in BT. 2 such patients are reported, in 1 of whom the characteristics after treatment further confirmed the diagnosis of CML. Differentiation between CML presenting in BT and AML has both prognostic and therapeutic value. For this reason it is recommended that cytogenetic screening for the Ph¹ chromosome should be included in the initial examination of patients with acute leukaemia.     

Chronic myeloid leukaemia

Chronic myeloid leukaemia (CML) was the first neoplastic disease for which knowledge of the genotype led to a rationally designed therapy. As a result of its well known pathophysiology, straightforward diagnosis, well established prognostic factors, and treatment for the cause of disease, CML has been studied to an extent that far exceeds that expected from its frequency, and serves as a model disease for other cancers. Imatinib, an inhibitor of BCR-ABL tyrosine kinase, has revolutionised treatment of this disease, and is now recommended as standard treatment for chronic-phase CML. Interferon alfa is an acceptable alternative treatment in the early chronic phase for patients who do not tolerate imatinib. If imatinib treatment fails, allogeneic stem-cell transplantation, a dose increase of imatinib, or new drugs are recommended. Up to 87% of patients achieve complete cytogenetic remission, therefore we provide guidance for monitoring disease status. Many trials of new drugs and combination therapies that include imatinib are underway.