慢性淋巴细胞白血病治疗及影响因素分析

目的：分析慢性淋巴细胞白血病（ CLL ）患者的临床资料、治疗效果及预后影响因素。方法收集2000年1月至2013年12月首都医科大学附属北京友谊医院血液内科诊治的65例CLL患者临床资料。使用流式分析检测患者Zeta链相关蛋白-70（Zap70）表达,反转录-聚合酶链反应检测免疫球蛋白重链可变区基因（ IgHV）突变程度,荧光原位杂交技术（ FISH）检测细胞遗传学异常。按治疗方法分为含氟达拉滨组（32例）、利妥昔单抗联合含氟达拉滨组（20例）和其他治疗组（13例）。含氟达拉滨组患者主要采用FC或FCD方案,每28天为1个疗程,至少治疗4个疗程以上,F为氟达拉滨25 mg/（m^2· d）,共3 d,C为环磷酰胺200 mg/（ m^2· d）,共3 d,D为地塞米松9 mg/（ m^2· d）,共5 d。利妥昔单抗联合含氟达拉滨组患者采用利妥昔单抗联合氟达拉滨为基础的化疗,其中利妥昔单抗375 mg/m^2,化疗前1 d使用,共1 d, FCD方案同上。其他治疗组患者口服苯丁酸氮芥6 mg/（ m^2· d）,服用30 d,每周监测血常规以调整剂量。比较不同治疗方法的总有效率。结果①有52例患者行Zap70检测,结果显示阳性患者16例,阴性患者36例,阳性患者总有效率低于阴性患者,差异有统计学意义[43．8％（7/16）比86．1％（31/36）,P＜0．05];有34例患者检测IgHV基因突变程度,其中基因突变阳性患者21例,阴性患者13例,阳性患者总有效率高于阴性患者,差异有统计学意义[95．2％（20/21）比61．5％（8/13）,P＜0．05];有24例患者使用FISH技术检测染色体,其中正常核型7例（29．2％）,其余17例（70．8％）患者至少有1种遗传学异常。②含氟达拉滨组患者治疗后总有效率为71．9％（23/32）,利妥昔单抗联合含氟达拉滨组治疗后总有效率为95．0％（19/20）,其他治疗组治疗后总有效率为30．8％（4/13）。前2组与其?     

环孢素治疗难治性慢性淋巴细胞白血病

目的探讨环孢素对难治性慢性淋巴细胞白血病的治疗效果。方法应用环孢素口服[5mg/(kg d)]治疗2例既往经多次含氟达拉滨及利妥昔单抗方案化疗效果不佳的难治性CLL患者,通过观察其治疗前后临床表现、血常规指标、外周血片分类、骨髓涂片、肝肾功能、流式细胞仪检测外周血及骨髓中CD5与CD19共阳性细胞比例变化评估治疗效果。结果 2例患者自觉症状明显好转,外周血治疗前均三系严重减低,治疗后三系均恢复,淋巴细胞比例均有不同程度下降,外周血及骨髓中CD5和CD19共阳性细胞比例均下降。一例患者完全缓解,一例患者部分缓解。治疗不良反应轻微。结论环孢素对难治性慢性淋巴细胞白血病有较好的治疗效果及安全性。     

Rituximab可用于治疗慢性淋巴细胞白血病

罗氏(Roche)公司与生物基因艾迪克(Biogen Idec)公司联合开发的抗CD20药物Rituxan/MabThera(通用名:利妥昔单抗),近期已获美国FDA批准,与化疗联合用于初发或已经接受过治疗(复发性或顽固性)的慢性淋巴细胞白血病(chronic lymphocytic leukaemia,CLL)患者.     

40例慢性淋巴细胞白血病的治疗分析

目的探讨氟达拉滨联用环磷酰胺（CTX）对慢性淋巴细胞白血病（CLL）的疗效。方法对40例CLL均采用FC方案,氟达拉滨50mg／d,第1～3天或第1～5天;CTX0．2g／d,第1～3天,28—30d为1周期。结果本组完全缓解（CR）21例,部分缓解（PR）5例,总有效率65％。治疗前外周血淋巴细胞绝对值（63．18±88．35）×10^9／L,治疗后为（7．31±19．79）×10^9／L,两者差异具有显著性（P〈0．01）。治疗期间,5例出现感染并伴发热,1例出现皮肤淤点、牙龈出血,4例出现恶心、呕吐,经处理后均治愈或缓解。结论氟达拉滨联用环磷酰胺近期疗效好,不良反应轻,可作为成人cLL的一线化疗方案。     

慢性淋巴细胞白血病21例分析

慢性淋巴细胞白血病２１例分析何争春，杨绵本，杨弘，魏彩霞，李维佳，黎承平慢性淋巴细胞白血病（ＣＬＬ）是一种在我国少见的白血病类型，临床及治疗均有其特殊性。现将我科１９７６～１９９２年诊治的２１例报告分析如下。临床资料临床表现年龄２８～７３岁，平均５３...     

乳腺癌伴慢性淋巴细胞白血病1例

<正> 患者女,41岁。发现左乳包块3d入院。查体:体温正常,皮肤、粘膜无黄染和出血点,双侧锁骨上、左腋窝及左腹股沟可触及大小不等肿大淋巴结,胸骨无压痛。左乳外上象限触及5cm×4cm包块,质硬,无压痛,表面不光滑,活动度差。心     

慢性淋巴细胞白血病的治疗进展

慢性淋巴细胞白血病(CLL)是一种成人最常见的白血病。95％患者的该肿瘤来源于B淋巴细胞(B-CLL)，仅有一小部分是由T淋巴细胞(T-CLL)恶性转化而来。细胞凋亡的抑制和抗凋亡蛋白BCL-2的表达上调是B-CLL主要的病理生理机制。细胞凋亡和细胞周期的功能失调是临床应用传统的化学疗法不能治愈CLL的主要原因。近年来，在研究CLL病理改变的分子基础及探索新的治疗策略等方面取得了许多进展。嘌呤类似物如氟达拉滨可明显提高缓解率；大鼠或小鼠单克隆抗体与人类抗体的嵌合体如利妥昔单抗(rituximab)及阿来珠单抗(alemtuzumab)等由于无明显的骨髓毒性，似乎比传统的化疗药物更有吸引力；已开始研究应用骨髓清除化疗后自体或异基因干细胞移植，以期获得治愈CLL的效果。     

13例慢性淋巴细胞白血病细胞遗传学分析

慢性淋巴细胞白血病是造血组织原发恶性肿瘤 ,系单株免疫无能的长寿小淋巴细胞恶性增殖与积蓄性疾病。 95 %的 CL L 系 B细胞性 ,因此既往用 PHA所作的研究绝大多数报告核型正常 ,只有在多克隆 B细胞激活剂如美州商陆 ,脂多糖 (L PS)和 EB病毒 (EBV)等应用后才发现半数 CL L有克隆性染色体异常。与慢性粒细胞白血病 (CML )不同的是其畸变类型呈异质性 ,数目异常中以 12号三体 ( 12 )最为常见 ,结构畸变主要为 14 q 和 13q-。1　资料与方法1.1　一般资料　自 2 0 0 1年 7月～ 2 0 0 3年 8月共收集 13例CL L 病例 ,全部为男性 ,年…     

慢性淋巴细胞白血病初始治疗进展

目前对慢性淋巴细胞白血病（CLL）预后因素的认识还不是十分明确,使得CLL患者不能像急性白血病患者那样根据预后风险选择相应的治疗手段。对于CLL患者来说,即使是预后最差者其预期生存期也有数年,但目前除了造血干细胞移植外,尚无有效的治疗手段,且对什么时候开始治疗和疗和使用什么方法进行治疗尚未达成一致。决定何时开始治疗的因素有：疾病进展、临床症状、肿瘤负荷、年龄、并发症、不利预后因素和治疗对生存期的影响等。     

FC联合强的松治疗慢性淋巴细胞白血病的疗效观察

【】 目的 研究慢性淋巴细胞白血病患者采取FC结合强的松治疗的临床效果。方法 选择我院2015年5月-2016年9月纳入的100例慢性淋巴细胞白血病患者,按照入院顺序分为两组,其中50例患者采取FC方式作为对照组,另50例患者采取FC结合强的松作为研究组,比较两组患者临床效果。结果 经过观察两组患者临床效果看出,研究组患者发热、水肿、腹胀、发热、疼痛以及脾大等症状消失时间均比对照组时间少(P＜0.05);研究组患者总有效率90.00%,明显比对照组总有效率80.00%高;且不良反应发生率仅6.00%比对照组发生率16.00%低,差别均具有统计学意义(P＜0.05)。结论 慢性淋巴细胞白血病患者采取FC结合强的松治疗效果显著,明显缓解患者相关症状,提高其生存质量,安全性较高,具有推广及应用的价值。     

Lenalidomide in the treatment of chronic lymphocytic leukemia

Introduction: Lenalidomide is an immunomodulatory drug (IMiD) with a unique mode of action (MOA) that may vary across disease-type. It is currently approved in multiple myeloma (MM), myelodysplastic syndrome (MDS) and mantle cell lymphoma (MCL), yet is also clinically active in a host of lymphoproliferative diseases, including chronic lymphocytic leukemia (CLL). Due to its protean effects on the immune system, lenalidomide may be particularly appealing in CLL, which is distinct in its ability to evade immune recognition and cause immunosuppression.

Areas covered: This review recaps the biological mechanisms of lenalidomide specific for CLL, and summarizes the clinical data in previously untreated and relapsed/refractory (R/R) CLL patients, with emphasis on toxicity. Moreover, lenalidomide treatment is put into the context of the highly effective targeted agents that are drastically changing the therapeutic approach in CLL.

Expert opinion: Lenalidomide is a potent drug in CLL, both in first line and relapse. However, in comparison to other newly available agents, lenalidomide has slow onset of efficacy and notable toxicity profile that limits both its single agent use and combinations with chemotherapy. Future trials will hopefully direct our ability to harness lenalidomide MOA to best incorporate it in the rapidly evolving landscape of CLL treatment.     

On the front line: first choice pharmacotherapeutics for chronic lymphocytic leukemia

ABSTRACT

Introduction: Chronic lymphocytic leukemia (CLL) is a common hematologic malignancy with a highly variable clinical course. Frontline treatments include cytotoxic chemotherapies, immunotherapies, and small molecule inhibitors. Clinical and molecular factors guide treatment initiation and selection. Over the last decade, refinement of CLL risk stratification tools and growth of the arsenal of effective therapeutics have profoundly improved outcomes. These advances have concurrently increased the complexity of managing the early phases of treatment.

Areas covered: This review describes the factors considered in the determination of first-line treatment of CLL. Areas of emphasis include assessment of patient fitness, disease classification and risk stratification, and the mechanisms, efficacy, and toxicities associated with available pharmacotherapeutics.

Expert opinion: Multiple different treatments may be appropriate for a specific clinical scenario, and selection among them requires discussion of relative risks and benefits. Advances in frontline CLL treatment will continue to shift the treatment paradigm toward prioritizing quality of life alongside survival, limiting treatment and toxicity, and the development of biologically rational synergistic drug combinations and sequences.     

The safety profile of monoclonal antibodies for chronic lymphocytic leukemia

Introduction: Monoclonal antibodies (MoAbs), non-chemotherapeutic agents targeting the antigens present on chronic lymphocytic leukemia (CLL) lymphocytes, are being implemented increasingly more often as treatment options.

Areas covered: This article reviews the similarities and differences in the structure, mechanism of action, efficacy and safety profile of commercially-available MoAbs and prevents new agents potentially useful for CLL treatment. Publications in English before June 2016 were surveyed on the MEDLINE database for articles. Proceedings of the American Society of Hematology held during the last five years were also included.

Expert opinion: MoAbs, especially those targeting CD20, are highly effective biological options for first-line and salvage treatment of CLL, particularly in chemoimmunotherapy, and possibly also as maintenance therapy. Treatment with MoAbs is associated with reduced risk of such adverse events as cytopenias, infections and secondary neoplasias and is generally well tolerated. Depending on antibody type, the most common adverse events are usually transient and limited to grade 1 and 2 infusion-related reactions. In addition to commercially available MoAbs, several other antibodies exist which are targeted against different antigens studied in the clinical trials.     

Bendamustine therapy in chronic lymphocytic leukemia

Background: Bendamustine is now approved in the US for the treatment of chronic lymphocytic leukemia and low grade non-Hodgkin's lymphoma, and is currently being explored in the treatment of several solid tumor types. Objective: The bi-functionality of bendamustine was used to provide a therapeutic understanding of both its benefit as well as adverse effects. Methods: Pertinent biochemistry and molecular biology pathways are reviewed with regards to bendamustine activity. In view of these pathways bendamustine was reviewed in human clinical trials. Results/conclusion: Bendamustine combines alkylating properties with purine analogue properties making it an effective drug in chronic lymphocytic leukemia where agents that affect these pathways have proven useful. There is limited evidence of cross-reactivity with this agent and other pure purine analogues and alkylators.     

IL-27 impact on NK cells activity: Implication for a robust anti-tumor response in chronic lymphocytic leukemia

Interleukin 27 (IL-27) belongs to IL-12 cytokine family, has shown anti-tumor potential in several solid tumors, as well as hematologic malignancies. IL-27 can inhibit tumor growth and progression through direct and indirect mechanisms, such as inhibition of proliferation, angiogenesis, induction of apoptosis in tumor cells, and anti-tumor immune response. B-CLL is characterized by remarkable immune perturbation, which leads to disease complications and reduced effectiveness of the treatment. Natural killer cells (NK) are considered as an important arm for the elimination of transformed cells. However, NK cells have shown significant impairment in patients with CLL. Here we analyzed the activity of recombinant human (rh) IL-27-stimulated NK cells in bone marrow (BM) and peripheral blood (PB) of CLL patients using cell surface flow cytometry assessment, and cytotoxicity assay. We showed that rhIL-27 can increase CD69 on NK cells both in BM and PB. Interestingly, BM-NK cells treated with rhIL-27 exhibited a significant increase in degranulation and NK cell-mediated cytotoxicity as compared with untreated NK cells, whereas it did not improve NK cell activity of PB. These observations added further explanation to the anti-tumor activity of IL-27 and also could pave the way to adoption immunostimulatory adjuvant for therapies in CLL.     

表现异质的大颗粒淋巴细胞白血病6例临床分析

目的提高对大颗粒淋巴细胞白血病（LGLL）的认识及鉴别诊断。方法对6例临床表现显著异质的LGLL的临床特征及实验室检查并结合文献进行临床分析。结果2例惰性T—LGLL和1例慢性NK—LGLL,临床呈慢性病程,主要表现为贫血和脾肿大,对治疗反应好;1例侵袭性T—LGLL及2例侵袭性NK—LGLL,临床以全身症状明显并有肝、脾肿大,预后极差。4种LGLL分别有各自的免疫表型特点。结论LGLL的诊断需结合临床、细胞学检测、免疫分型综合分析并加与鉴别诊断。     

Magic pills: new oral drugs to treat chronic lymphocytic leukemia

Introduction: A deeper understanding of chronic lymphocytic leukemia (CLL) biology has led to the identification of new promising therapeutic targets. Different classes of molecules are currently under investigation and novel oral drugs have recently been approved or are in a late stage of clinical development.

Areas covered: We present biological data illustrating the heterogeneous mechanisms of action of new oral drugs in CLL. Moreover, we provide clinical data from phase I to III studies, and discuss efficacy and side effects profile of these new therapies. Data are derived from peer-reviewed articles indexed in PubMed and from abstracts presented at major international meetings.

Expert opinion: Novel oral drugs represent a valuable alternative to chemo-immunotherapy for patients with CLL, especially when high-risk disease features are present and when age or comorbidities preclude the use of standard treatments. Based on data from ongoing clinical trials, the indications of already approved agents will most likely be expanded and new options will soon be available. Moreover, treatment combinations will broaden the therapeutic armamentarium of physicians treating CLL. The availability of multiple choices is of benefit for patients with CLL, but also represents a challenge for the need of choosing the right drug for each patient.     

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.