慢性淋巴细胞白血病IgV（H）基因突变研究进展

慢性淋巴细胞白血病(CLL)免疫球蛋白重链易变区[IgV(H)]基因突变的研究已成为目前CLL异质性研究的热点。根据IgV(H)基因突变情况将CLL分为两型，本文从两型生物学特性、CD38表达、细胞遗传学改变、预后、性别、细胞形态和治疗等方面的异质性作一综述。     

慢性淋巴细胞白血病患者免疫球蛋白重链片段及其突变状态的研究

目的 探讨我国慢性淋巴细胞白血病(CLL)患者免疫球蛋白重链可变区基因(IgVH)突变状态、基因偏颇性及其预后价值.方法 应用多重PCR法检测CLL患者表达型IgVH片段使用情况及突变状态,并与患者生存和预后进行相关性分析.结果 ①共检测初诊CLL患者85例,80例(94.1%)成功测序.②IgVH片段的使用存在明显的偏颇性,其中常见的为VH3家族(32例,40.0%)、VH4家族(24例,30.O%),而VH5、VH6和VH7家族少见.VH4-39是最常见的VH基因片段.而J4和D3分别是JH家族和DH家族中使用频率最高的片段.③IgVH突变型56例(70.0%),非突变型24例(30.O%).其中VH3家族突变率为90.7%(29例),VH4家族突变率为62.5%(15例).④突变组与未突变组患者无进展生存时间(82个月和17个月,P=0.000)和总生存时间(90个月和41个月,P=0.009)差异均有统计学意义.⑤CLL患者IgVH CDR3区序列具重现性,2例VH片段为VH1-69的患者其CDR3序列与文献报道序列有很高的同源性.VH片段为VH1-18、VH3-7、VH3-23的患者中分别有2例CDR3序列完全相同.结论 不同地区间CLL患者IgVH基因家族使用情况和突变状态存在一定差异,IgVH CDR3区序列具重现性,推测相对有限的抗原参与了CLL的发病.     

慢性B淋巴细胞白血病患者免疫球蛋白Fab段基因克隆及其可变区序列分析

目的：分析慢性B淋巴细胞白血病患者外周血单个核细胞免疫球蛋白Fab段基因。方法：提取慢性B淋巴细胞白血病患者外周血单个核细胞RNA,选用与Ig FR1 5′和CH1Cμ3′或CL区（Cκ／Cλ）3′互补的多对引物,通过RT－PCR扩增Ig Fab段基因,进行克隆和序列测定,并通过DNAtools和计算机网络对其可变区基因同源性进行分析和基因家族归类。结果：7例患者中4例外周血单个核细胞扩增出轻链基因,3例扩增出重链基因。所扩增的4条轻链基因均属于κ轻链,3条重链均为μ链基因。利用DNAtools分析软件,对轻链和重链分别进行同源性比较,3条重 链可变区基因差异较大,轻链可变区基因具有一定的同源性。对所扩增的Ig基因进行归类,结果4例患者的轻链均属于VκⅠ亚组;3例患者的重链中2例属VH3家族,1例为VH5家族。结论：慢性Ｂ淋巴细胞白血病患者存在独特的决定簇和相似决定簇。     

慢性淋巴细胞白血病IgV（H）基因突变研究进展

慢性淋巴细胞白血病（CLL）免疫球蛋白重链易变区[IgV(H)]基因突变的研究已成为目前CLL异质性研究的热点。根据IgV(H)基因突变情况将CLL分为两型，本文从两型生物学特性，CD38表达，细胞遗传学改变。预后，性别，细胞形态和治疗等方面的异质性作一综述。     

慢性淋巴细胞白血病外周血免疫球蛋白异常研究

为了解慢性淋巴细胞白血病（CLL）患者外周血免疫球蛋白（Ig）异常与年龄、性别、疾病分期及预后的关系,运用免疫速率比浊法测定83例CLL患者血清中IgG、IgA和IgM水平,用多参数流式细胞术（FCM）检测患者外周血CD38、ZAP－70表达水平。结果表明：83例CLL患者中IgG减低12例（14．5％）;IgA减低26例（31．3％）,IgM减低34例（41．0％）。BinetC期组Ig减低发生率明显高于BinetA和B期组（P=0．011）,Rai分期高危组的Ig减低发生率明显高于低危组（P=0．011）。Ig减低组CD38和ZAP－70表达阳性率明显较Ig正常组高（P＝0．033和P=0．038）。CD38和ZAP－70在疾病晚期患者表达阳性率更高,其中BinetC期组ZAP－70表达阳性率明显高于BinetA和B期组（P=0．047）。而年龄和性别与Ig异常没有明显相关性（P〉0．05）。结论：CLL患者体液免疫功能与疾病分期密切相关,检测CLL患者外周血Ig水平的变化,对了解CLL患者免疫功能状态,从而判断病情及预后具有重要作用。     

慢性淋巴细胞白血病IgV(H)基因突变研究进展

慢性淋巴细胞白血病(CLL)免疫球蛋白重链易变区[IgV(H)]基因突变的研究已成为目前CLL异质性研究的热点。根据IgV(H)基因突变情况将CLL分为两型,本文从两型生物学特性、CD38表达、细胞遗传学改变、预后、性别、细胞形态和治疗等方面的异质性作一综述。     

慢性淋巴细胞白血病IgV(H)基因突变研究进展

慢性淋巴细胞白血病(CLL)免疫球蛋白重链易变区[IgV(H)]基因突变的研究已成为目前CLL异质性研究的热点。根据IgV(H)基因突变情况将CLL分为两型,本文从两型生物学特性、CD38表达、细胞遗传学改变、预后、性别、细胞形态和治疗等方面的异质性作一综述。     

儿童急性B淋巴细胞白血病免疫球蛋白重链可变区基因的分子特征

目的 探讨儿童急性B淋巴细胞白血病(B—ALL)的起源及其免疫球蛋白重链可变区(IgHV)上可被细胞毒性T淋巴细胞(cTL)识别的表位(epitope)。方法 PCR扩增108例儿童ALL的7个IgHV基因家族；PCR产物直接测序并翻译成氨基酸序列；利用生物信息资源分析B—ALL IgHV基因重排类型、胚系基因片段利用及体细胞突变情况，并预测CTL细胞识别的表位。结果 66％的ALL患儿检测到IgHV基因重排，其中单等位基因重排37例(52．1％)，双等位基因重排26例(36.6％)，寡克隆基因重排8例(11．3％)。40份B-ALL IgHV基因序列中，不含终止密码子的读码框内(in frame)重排8份(20．0％)。重排利用最多的VH家族为VH3、VH4和VH1，占75%；VH4—59和VH4—34是VH4家族中利用频率最高的片段。优先利用的D家族为D3(35．9％)和D2(28.2％),D7—27的利用率(15．4％)明显高于正常外周血淋巴细胞(P=0．02)。JH6是B-ALL利用最多的JH基因片段(47．5％)，JH4(27．5％)次之。20％的B—ALL在DJH连接区缺乏N核苷酸的插入，高于正常外周血淋巴细胞(P=0．02)。17．5％B—ALL IgHV基因发生替代突变，突变碱基散布于IgHV全长，互补决定区替代突变与静寂突变的比例≤1。26例B—ALL IgHV的HIA—I类分子结合肽80％以上位于框架区，同一IgHV家族的B-ALL有相同的1～2条九肽。结论 B—ALL起源于前B祖细胞或前B细胞，恶性转化往往发生于胚胎期，它们的IgHV基因具有胚系特征；生物信息分析B-ALL IgHV的T细胞表位主要位于框架1区和框架3区。     

应用多重PCR技术检测慢性淋巴细胞白血病IgVH基因突变

免疫球蛋白重链可变区（IgVH）基因突变是慢性淋巴细胞白血病（CLL）最重要的独立预后因素之一，为探讨CLL患者IgVH基因突变状态，应用多重PCR技术检测9例CLL患者的IgVH基因，纯化PCR扩增产物后直接测序，应用IMGT／V-QUEST工具分析，明确有无IgVH突变及突变位置。结果表明：9例CLL患者皆扩增出395-465bp区域（MIXⅠ）或290-360bp区域（MIXⅡ）单克隆条带，测序结果显示5例患者有突变，IgVH基因分别为IGHV3-11＊03、IGHV3-9＊01、IGHV3-23＊01、IGHV4-59＊01和IGHV4-34＊02；4例无突变．IgVH基因为IGHV3-53＊01、IGHV3-23＊03、IGHV3-33＊05和IGHV3-7＊01。结论：PCR检测IgVH基因突变，简化了繁琐的实验过程，缩短了实验时间，解决传统PCR对IgVH基因突变检测的桎梏，值得在临床和科研中推广使用。     

203例慢性淋巴细胞白血病患者预后相关因素分析

目的 探讨慢性淋巴细胞白血病(CLL)患者预后的主要影响因素.方法 回顾性分析2000年至2007年就诊于中国医学科学院血液病医院并获得有效随访的203例CLL患者临床资料,收集可能影响预后的因素,以Kaplan-Meier法绘制生存曲线,用Log-rank检验进行单因素分析,运用COX回归模型评估独立预后因素.结果 全组CLL患者中位随访时间为48.0(3.0～156.0)个月,5年总体生存(OS)率为(87.3±2.4)%,10年OS率为(77.4 ±3.3)%,死亡48例(23.6%).单因素分析显示临床分期为晚期、有B症状、结外器官受累、受累淋巴区≥3个、肝脏肿大、Hb<100 g/L、BPC<100 ×109/L、外周血淋巴细胞计数(ALC)>50 ×109/L、形态学表现为混合细胞型、病程中出现分期进展、对治疗无反应、并发感染、并发第二肿瘤或类型转化为不良预后因素.多因素分析显示受累淋巴区≥3个和彤态学表现为混合细胞型为独立的不良预后因素,根据这两项结果重新分组,低危、中危、高危组患者5年OS率分别为(89.8±3.5)%、(66.4±7.2)%、(15.0±13.8)%.各组间差异均具有统计学意义(P值均<0.05).结论 初诊时受累淋巴区数和CLL细胞形态学特征有助于评估CLL患者的预后.     

Caring for patients with chronic lymphocytic leukemia

Chronic lymphocytic leukemia (CLL) is the most commonly diagnosed form of leukemia in the Western world, accounting for approximately 20%-30% of all cases of leukemia. Despite recent medical and scientific advances, the literature on the subjective experience and nursing care of patients diagnosed with CLL remains scarce and sporadic. This article provides a brief overview on the pathophysiology, clinical characteristics, and treatment options of CLL with focus placed on implications for nursing care. Fatigue, the most common symptom reported by patients, and infection, the leading cause of disease-related deaths, also will be addressed. Emerging data examining quality of life and the incidence of anxiety and depression in this patient population will be reviewed, and strategies aimed at addressing the educational needs of patients and family members will be discussed.     

Complementary and alternative medicine in patients with chronic lymphocytic leukemia

Background  Despite the widespread use of complementary and alternative medicine (CAM) in the general population for the treatment of chronic diseases, only few data have been published for patients with leukemia. The aim of this survey was to study systematically the use of CAM in patients with chronic lymphocytic leukemia (CLL). Patients and methods  A structured questionnaire was sent to 247 CLL patients of all clinical stages and disease durations, treated and untreated. The questionnaire was returned anonymously by 87 patients (35%). Results  Thirty-nine patients (44%) had used alternative treatments. No correlation was seen with educational level, gender, or previous or current chemotherapy. The most common alternative or complementary treatment modality was vitamin supplementation (26%), followed by mineral (18%), homeopathic (14%), and mistletoe therapy (9.2%). Some 21% of patients considered their alternative treatment as being successful. Most patients reported that they decided to use CAM after conducting a personal investigation and based on the information they found, without outside recommendations (59%). The majority of the patients used patient brochures about CLL as an important source of information (54%), followed by specific lectures (34%) or the internet (32%). Conclusion  Our data show that patients with CLL use a wide range of CAM, among them potentially harmful methods. Rational, evidence-based medical information about the effects and risks of CAM use should be made available through patient brochures distributed by patient organizations, through information events with lectures, or via the internet.     

40例慢性淋巴细胞白血病临床分析

本研究旨在分析慢性淋巴细胞白血病(CLL)的临床和实验室特点及其对预后的影响。对2004年1月至2010年12月收住本院的40例CLL患者进行了回顾性分析。结果表明,本病主要发生于老年男性,中位年龄66岁(42-80岁);25例(62.5%)可见典型CLL免疫表型,所有病例均表达CD19和CD5,表达CD38和Zap70的分别有7例(17.5%)和14例(35%);8例检测出IgVH基因突变,其中有4例为VH3家族;FISH检测出P53基因缺失6例,RB1缺失3例,12三体1例,正常核型5例;31例患者接受了含氟达拉滨的化疗,中位无进展生存(PFS)时间为48个月(95%CI:39-57个月),其中有27例(87.1%)获完全缓解(CR)+部分缓解(PR),而接受其他治疗方法的患者有9例,PFS仅为14个月(95%CI:10-18个月,P<0.001),只有3例(33.3%)获CR+PR。诊断时β2微球蛋白水平正常者,36个月的总生存率为78%(95%CI:69%-87%),明显高于β2微球蛋白水平异常者的总生存率47%(95%CI:35%-59%,P=0.004)。Zap70表达阳性的患者中有7例(50%)治疗后获CR+PR,疗效差于表达阴性者,后者中有23例(88.5%,P=0.006)治疗后获CR+PR。IgVH基因突变者,治疗后都获CR,无IgVH基因突变者,治疗后只有4例(66.7%)获CR。结论:CLL具有独特的临床特征和分子遗传学标记,如Zap70、CD38和IgVH基因突变,并与预后相关。氟达拉滨治疗方案能明显提高CLL患者的长期生存率。     

Outcomes in critically ill chronic lymphocytic leukemia patients

Background

Although recent studies have demonstrated an improvement in the prognosis of critically ill cancer patients, little is known regarding the prognosis of patients with non-aggressive underlying malignancies. The aims of this study were to assess the prognosis of critically ill patients with chronic lymphocytic leukemia (CLL) and to evaluate risk factors for hospital mortality.

Methods

In retrospective mono-center cohort study, consecutive adult patients with CLL requiring ICU admission from 1997 to 2008 were included.

Results

Sixty-two patients of 67 years (62–75) were included. Median time interval between CLL diagnosis and ICU admission was 6.7 years (2.6–10.8). Nine patients (15 %) had stage C disease at the time of ICU admission, and seven patients (11 %) had Richter syndrome. Most ICU admissions were related to bacterial or fungal pulmonary infections (n?=?47; 76 %). ICU, in-hospital, and 90-day mortality were 35 % (n?=?22), 42 % (n?=?26), and 58 % (n?=?36), respectively. Only three factors were independently associated with in-hospital mortality: oxygen saturation lower than 95 % when breathing room air (odds ratio (OR) 5.80; 95 % confidence interval (CI) 1.23–27.33), need for vasopressors (OR 27.94; 95 % CI 5.37–145.4), and past history of infection (OR 6.62; 95 % CI 1.34–32.68). The final model did not change when disease-related variables (Binet classification, Richter syndrome, long-term steroids) or treatment-related variables (fludarabine, rituximab, or alemtuzumab) were included.

Conclusion

Acute pulmonary infections remain the leading cause of ICU admission in patients with CLL. The severity at ICU admission and past history of infection were the only factors associated with hospital mortality. Neither disease characteristics nor previous cancer treatments were associated with outcome.     

Nursing guidelines for managing infections in patients with chronic lymphocytic leukemia

Infections are a primary cause of death in patients with chronic lymphocytic leukemia (CLL). Such individuals are particularly susceptible to infectious complications stemming from immune deficits associated with the primary disease process and with immunosuppression secondary to treatment. Although the recent availability of new treatment modalities and more aggressive therapies are improving outcomes for patients with CLL, standardized approaches are needed so that nurses can monitor for and manage infections. The aim is overall reduction in morbidity and mortality, as well as improvement in quality of life. The current pharmacologic therapies for CLL are alkylating agents, purine nucleoside analogs, monoclonal antibodies, and combinations of those therapies, which may present their own unique risks for and different spectra of infectious events. This article provides an overview of the known risks for developing infections in CLL, as well as nursing guidelines for monitoring and managing patients with CLL.     

Rituximab in chronic lymphocytic leukemia

Rituximab (Rituxan®; iogen Idec, San Diego, CA, USA) is a human-mouse chimeric monoclonal antibody specific for CD20, a surface glycoprotein expressed on B lymphocytes. Administration of rituximab as a single agent to patients with chronic lymphocytic leukemia (CLL) has limited clinical activity, but generally does not eradicate leukemia from the marrow. However, when administered in combination with chemotherapy, rituximab can improve the survival of patients relative to those treated with chemotherapy alone. As a result of this, the US Food and Drug Administration approved the use of rituximab in previously untreated and previously treated CD20-positive CLL in combination with fludarabine monophosphate and cyclophosphamide. The results of clinical studies evaluating the activity of rituximab when used alone or in combination with other antileukemia agents for the treatment of this disease are reviewed here.     

38例慢性淋巴细胞白血病免疫表型分析

目的探讨慢性淋巴细胞白血病（CLL）的免疫表型特点与Moreau积分系统、临床分期的关系。方法应用三色流式细胞术对38例初诊CLL患者进行免疫表型分析，并与临床常用的CLL免疫表型积分系统及临床分期进行比较。结果38例CLL患者均表达CD19、HLA—DR，患者中CD5、CD20、CD22、CD23、FMC7、CD11C、K轻链、λ轻链阳性表达率分别为86．8％、97．3％、97．3％、97．3％、34．2％、26．3％、52．6％、26．3％。CD38阳性表达率为15．8％，无一例表达CD10。相关CD抗原表达与临床分期无明显相关性（P〉0．05）。按照Moreau积分系统分析显示38例患者中31例积分≤3分。结论流式免疫分析可为CLL的诊断提供有力依据，但与Moreau积分系统相比，本组患者呈现非典型的免疫表型。