非清髓性移植治疗慢性淋巴细胞性白血病合并慢性髓细胞性白血病1例

慢性淋巴细胞性白血病(CLL)合并慢性髓细胞性白血病(CML)极少见，我科曾发现1例，并成功地进行非清髓性异基因外周血造血干细胞移植术(nonmyeloablative stem cell transplantation．NAST)，特报道如下。     

慢性粒细胞白血病靶向治疗研究进展

酪氨酸激酶抑制剂（TKI）的应用革命性地改善了慢性粒细胞白血病（CML）患者的治疗结果和生存。当前治疗CML的新目标是如何获得持续的深度分子生物学反应,以减少耐药复发,甚至实现无治疗的缓解维持和治愈。国际上已有4种TKI获批用于一线治疗初诊的慢性期CML,并且不断有新的药物和治疗方案在研发和临床研究中。文章结合第62届美国血液学会年会相关报道介绍CML靶向治疗研究进展。     

慢性髓性白血病的现代治疗

 伊马替尼（IM）以及二代酪氨酸激酶抑制剂（TKI）的问世不仅彻底改革了慢性髓性白血病（CML）的治疗模式, 也成为其他肿瘤发病机制和治疗研究的范例。 IM可使90 %以上慢性期患者获得血液学缓解,80 %以上的患者获得遗传学完全缓解（CCyR）及主要分子学缓解（MMoR）。明显延长无病生存期,使CML自然病程大为改观。然而,也存在目前难以克服的缺点：TKI并非疾病基因清除剂,对CML干细胞不敏感,获得CCyR／MMoR者仍需长期持续服用,小部分患者发生抗药或不耐受。现阶段的TKI 仍是根治CML的起始。     

急性髓细胞性白血病靶向治疗的研究进展

急性髓细胞性白血病(AML)是一种危及生命的血液系统恶性疾病.近年来,随着治疗方案的改进,患者预后有所改善,但仍难以解决高危患者预后差的问题.针对AML特定基因或白血病细胞表面靶抗原的靶向治疗是克服耐药性并改善AML预后的新希望.近年来,用于治疗AML的新型靶向药物数量空前增长,包括B细胞淋巴瘤/白血病-2抑制剂、FM...     

慢性粒细胞白血病靶向治疗和靶向鸡尾酒疗法研究进展

酪氨酸激酶抑制剂（TKI）的应用显著改善了慢性粒细胞白血病（CML）患者的预后,但目前单用 TKI 仍难以根治 CML。除更有效 TKI 类药物的研发及现有药物的精确使用外,CML 其他分子靶点的开发、针对 CML 肿瘤干细胞的治疗研究和联合用药为改进治疗和治愈 CML 带来新的希望。文章就相关研究进展进行综述。     

STI571用于慢性髓细胞性白血病的疗效和安全性

ＳＴＩ5 71是人工合成的酪氨酸激酶抑制物 ,可以通过竞争性抑制酪氨酸激酶ＡＴＰ结合位点发挥作用 ,抑制酪氨酸磷酸化 ,使表达ｂｃｒ ａｂｌ的造血细胞停止生长或凋亡。临床前期试验已证明ＳＴＩ5 71的抗白血病活性 ,在此基础上 ,选择经α 干扰素治疗失败ＣＭＬ患者进行ＳＴＩ5 71的Ⅰ期试验。方法 :选择 83例慢性期慢性髓细胞性白血病(ＣＭＬ)患者 ,分为 14个剂量组 (2 5ｍｇ/ｄ～ 10 0 0ｍｇ/ｄ)口服ＳＴＩ5 71。 80 0ｍｇ/ｄ和 10 0 0ｍｇ/ｄ组每日口服 2次 ,每次分别为 4 0 0ｍｇ和 5 0 0ｍｇ ,余治疗组为每日口服 1次。在最初 4周内 ,…     

STI571治疗慢性粒细胞白血病相关策略

慢性髓细胞白血病 (CML)是一类造血干细胞克隆增殖紊乱性疾病 ,预后较差 ,蛋白酪氨酸激酶抑制剂STI5 71的出现使其治疗出现转机 ,其能阻断Bcr Abl蛋白激酶的活性 ,选择性抑制白血病细胞增殖。但随着临床应用的深入 ,常出现对STI5 71耐药及治疗后复发病例。因此针对耐药和复发的机制及相关治疗策略的研究也在不断深入 ,现综述STI5 71治疗策略的研究进展。     

STI571治疗慢性粒细胞白血病相关策略

慢性髓细胞白血病(CML)是一类造血干细胞克隆增殖紊乱性疾病,预后较差,蛋白酪氨酸激酶抑制剂STI571的出现使其治疗出现转机,其能阻断Bcr-Abl蛋白激酶的活性,选择性抑制白血病细胞增殖.但随着临床应用的深入,常出现对STI571耐药及治疗后复发病例.因此针对耐药和复发的机制及相关治疗策略的研究也在不断深入,现综述STI571治疗策略的研究进展.     

难治性和复发性急性髓性白血病的治疗策略

难治性和复发性急性髓性白血病的治疗策略上海医科大学附属华山医院血液学研究室（２０００４０）丁训杰难治性和复发性白血病包括对常规诱导缓解方案（第一线药物）治疗无效者；首次缓解病例６个月内早期复发者；初次缓解后６个月以上复发而用原诱导方案无效者和二次或多...     

Treatment of chronic myeloid leukemia with imatinib mesylate

Philadelphia (Ph) chromosome is the cytogenetic hallmark of chronic myeloid leukemia (CML). The translocation forms a chimeric gene, bcr-abl, which generates BCR-ABL. This fusion protein constitutively activate ABL tyrosine kinase and causes CML. Imatinib mesylate is a selective tyrosine kinase inhibitor on ABL, c-Kit and PGDF-receptor, and functions through competitive inhibition at the ATP-binding site of the enzyme, which leads to growth arrest or apoptosis in cells that express BCR-ABL. Imatinib has revolutionized the management of patients with CML, and at a dose of 400 mg daily has become the current standard therapy for newly diagnosed patients with CML even when they have HLA-matched family donors. Although imatinib therapy has only a 5-year history, it is hoped that CML will be cured with this drug and with forthcoming second-generation tyrosine kinase inhibitors as well as by allogeneic stem cell transplantation in patients who have become resistant to these drugs.     

Implications of BCR-ABL1 kinase domain-mediated resistance in chronic myeloid leukemia

Patients with chronic myeloid leukemia develop resistance to both first-generation and second-generation tyrosine kinase inhibitors (TKIs) as a result of mutations in the kinase domain (KD) of BCR-ABL1. A wide range of BCR-ABL1 KD mutations that confer resistance to TKIs have been identified, and the T315I mutant has proven particularly difficult to target. This review summarizes the prevalence, impact, and prognostic implications of BCR-ABL1 KD mutations in patients with chronic myeloid leukemia who are treated with current TKIs and provides an overview of recent treatment guidelines and future trends for the detection of mutations.     

Role of autophagy in acute myeloid leukemia therapy

Despite its dual role in determining cell fate in a wide array of solid cancer cell lines, autophagy has been robustly shown to suppress or kill acute myeloid leukemia cells via degradation of the oncogenic fusion protein that drives leukemogenesis. However, autophagy also induces the demise of acute leukemia cells that do not express the known fusion protein, though the molecular mechanism remains elusive. Nevertheless, since it can induce cooperation with apoptosis and differentiation in response to autophagic signals, autophagy can be manipulated for a better therapy on acute myeloid leukemia.     

影响慢性粒细胞白血病疗效的因素

慢性粒细胞白血病（CML）简称慢粒,是一种发生在多能造血干细胞的恶性骨髓增殖性肿瘤。慢粒现有的治疗方法包括羟基脲、干扰素、酪氨酸激酶抑制剂（TKI）、造血干细胞移植等。这些治疗方法均存在一些因素影响了慢粒的疗效,通过阅读相关文献总结发现:慢粒疗效的减弱可能与以下几个方面如信号传导、血红素加氧酶-1的作用、自噬、药物代谢与生物活性、个体差异、一氧化氮以及移植物抗宿主病等相关。本文对这些因素进行阐述,通过对这些因素的深入研究可以进一步改善慢粒的疗效以提升慢粒患者的生存质量。     

慢性粒细胞白血病疾病转化及停药的研究进展

自BCR-ABL融合基因的鉴定和针对性的酪氨酸激酶抑制剂(TKI)问世后,慢性粒细胞白血病(CML)患者已经在慢病化的道路上“行走”了约二十年。近年来,二代、三代TKI为CML患者的长期生存提供了进一步的保障。但TKI停药和少数TKI耐药或携带不良预后基因患者的预后情况仍是CML相关研究的热点问题。文章对2020年第62届美国血液学会年会上关于CML研究进展的报道作一介绍。     

How to treat chronic myeloid leukemia (CML) in older adults

Chronic myeloid leukemia (CML), a myeloproliferative neoplasm defined by the t(9;22)(q34;q11) chromosomal translocation, primarily affects older adults. Historically, effective treatment options were not available for older CML patients ineligible for curative allogeneic stem cell transplant, and the disease was therefore usually fatal within several years of diagnosis. The development of tyrosine kinase inhibitors (TKIs) that effectively target the constitutively active mutant tyrosine kinase in CML has dramatically improved outcomes for all patients with CML, including older patients. While older patients were underrepresented in prospective trials, TKI therapy can be successfully administered to older adults with CML with excellent efficacy and proven tolerability. TKI selection and monitoring for adverse events should be tailored based on co-morbidities. As with younger patients, life expectancy of older adults with CML now approaches that of age-matched controls. Here we review guidelines for management of older adults with CML.     

Patient preferences for stopping tyrosine kinase inhibitors in chronic myeloid leukemia

Background

We used an interview-assisted survey of patients with chronic myeloid leukemia (cml) at a single tertiary care centre to explore patient reactions to and preferences for, and the risk-acceptability of, stopping tyrosine kinase inhibitor (tki) treatment.

Methods

The study included patients with confirmed cml currently being treated with a tki. The survey was conducted by structured interview using a standard form. Patient preferences were explored in a case-based scenario using 0%–100% visual analog scales and 5-point Likert scales. Data were analyzed using proportions for dichotomous variables and medians and interquartile ranges for continuous variables.

Results

Of 63 patients approached, 56 completed the survey. Participant responses suggest that the idea of stopping tki use is appealing to many patients if there is a chance of long-term stable disease and a high probability of response upon restarting a tki. Participants were more likely to stop their tki as the risk of relapse decreased. Participants reported loss of disease control and failure of disease to respond to treatment as important concerns if they chose to stop their tki.

Conclusions

Given the current 60% estimated rate of relapse after discontinuation of tki therapy, most patients with cml chose to continue with tki. However, at the lower relapse rates reported with second-generation tkis, participants were more undecided, demonstrating a basic understanding of risk. Contrary to our hypothesis, neither compliance nor occurrence of side effects significantly affected patient willingness to stop their tki.