慢性淋巴细胞白血病预后指标的研究概况

 慢性淋巴细胞白血病,特别在早期时,曾认为是一种进展缓慢的疾病,预后较好,不宜积极治疗,现已发现,本疾病至少可分为预后较好与较差的两大类,根据什么指标来尽早判断患者预后,是近年的研究热点,就此作一简要介绍。     

不同分期慢性淋巴细胞白血病患者淋巴细胞亚群特点及氟达拉滨对其的影响

 目的　探讨不同分期的慢性淋巴细胞白血病（CLL）患者的外周血淋巴细胞亚群特点以及应用以氟达拉滨为基础的化疗方案治疗前后淋巴细胞亚群的变化。方法　应用流式细胞术检测CLL患者以氟达拉滨为基础的化疗方案治疗前后外周血的T淋巴细胞亚群、NK细胞亚群并以健康人作对照。结果　CLL患者总T细胞、T辅助细胞（CD4）,CD4／CD8比值均低于健康人,Ⅲ～Ⅳ期患者尤为突出（P＜0.01）,0～Ⅱ期患者NK细胞略高于健康人（P＞0.05）,Ⅲ～Ⅳ期患者明显低于健康人（P＜0.05）。予以氟达拉滨为主的化疗方案治疗4个周期后,CLL患者总T细胞、T辅助细胞,CD4／CD8比值均较治疗前显著升高（P＜0.01）,NK细胞亦明显升高（P＜0.05）。结论　CLL患者存在细胞免疫调节异常,且机体免疫功能与疾病状态密切相关。观察CLL患者外周血T淋巴细胞亚群及NK细胞的比例有助于医生对病情的判断,还可作为CLL患者疗效判断的一项指标。氟达拉滨治疗有效的CLL患者细胞免疫功能明显改善,其在化疗后短时间内是否存在显著的免疫抑制还有待于进一步的临床观察。     

不同分期慢性淋巴细胞白血病患者淋巴细胞亚群特点及氟达拉滨对其的影响

Objective To study the feature of the subgroup of lyrnphocytes from patients with chronic lymphocytic leukemia(CLL)at different stages,and the changes in the treatment by the chemotherapy based on fludarabine.Methods The subgroup of T lyrnphocytes and NK cell were detected by flow cytometry during treatment which based on fludarabine from patients with CLL and normal people.Results The total of T.help T cells and ratio of CD4/CD8 of patients were significantly lower than that in normal people,especially in stage Ⅲ-Ⅳ(P＜0.01),and the NK cells in stage 0～Ⅱis higher than that in normal(P＞0.05),which is lower in stage Ⅲ-Ⅳ(P＜0.05).Four weeks after the chemotherapy mainly based on fludarabine,the total T,help T cell and ratio of CD4/CD8 of patients with CLL was significantly raised(P＜0.01),and meanwhile the NK cell was clearly raised (P＜0.05).Conclusion The cell mediated immunological regulation abnormal exists in patients with CLL,and the immune function correlated closely with the morbid state.Observation on the changes of T lymphocyte subsets and its ratio of NK cells,which were is helpful for the assement of the patient's condition,and also can evaluate the therapeutic effect.The cellular immune function was obviously improved in patients who are effective to fludarabine.whether there exists noticeable immune suppression shortly after chemotherapy should be studied in further clinical observation.     

慢性淋巴细胞白血病12例临床分析

慢性淋巴细胞白血病(CLL)在欧美国家常见,而在亚洲人中少见。近8年来我院诊治12例患者,现报告如下。 1 临床资料 1.1 一般资料 本组资料男性10例,女性2例,年龄42～70岁,平均年龄59.1岁。大于60岁7例。诊断标准参照张之南主编《血液病诊断及疗效标准》一书。 1.2 临床表现 多数患者有轻度乏力(8/12),往往     

慢性淋巴细胞白血病203例相关并发症研究

 目的　探讨慢性淋巴细胞白血病（CLL）患者并发症的临床特点。方法　回顾性分析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患者并发症的临床表现及其预后价值。结果　40例（19.7 ％）患者发生部位明确的感染,最常见感染部位为肺部（75.6 ％）。15例（7.4 ％）患者发生自身免疫性疾病（AID）,最常见的AID为自身免疫性溶血性贫血（AIHA）（31.3 ％）。8例（3.94 ％）患者并发第二肿瘤,包括肺癌等多种肿瘤。3例（1.48 ％）患者发生类型转化,其中,2例向幼淋巴细胞白血病（PLL）转化,1例向弥漫大B细胞淋巴瘤（DLBCL）转化（Richter综合征）。预后分析显示并发感染、第二肿瘤或转化与不良预后有关,并发AID与预后无明显相关。结论　CLL患者常见并发症包括感染、AID、第二肿瘤或转化,其中,以肺部感染及AIHA最为常见,未见明显高发的第二肿瘤类型。并发感染、并发第二肿瘤或转化为不良预后因素。     

慢性淋巴细胞白血病/小淋巴细胞淋巴瘤的治疗进展

慢性淋巴细胞白血病（CLL）/小淋巴细胞淋巴瘤（SLL）是一种慢性B淋巴细胞增殖性疾病。随着人们对CLL/SLL在临床和分子水平上的深入了解,CLL/SLL的新型治疗方案也不断涌现,包括靶向治疗、嵌合抗原受体T细胞免疫疗法和异基因造血干细胞移植。其中靶向治疗包括：布鲁顿氏酪氨酸激酶抑制剂、磷脂酰肌醇3激酶抑制剂、B细胞淋巴瘤因子2抑制剂和蛋白激酶Cβ抑制剂。除新型药物的不断涌现,各疗法之间的联合治疗和对固定疗程的探索在CLL/SLL的治疗中也备受关注。文章结合相关文献对CLL/SLL的最新治疗进展进行总结。     

慢性淋巴细胞白血病患者骨髓幼稚淋巴细胞与疾病预后的关系

目的:探讨慢性淋巴细胞白血病患者骨髓中幼稚淋巴细胞比例与疾病预后的关系。方法:收集西安交通大学医学院第一附属医院血液内科2012年6月至2015年5月收治的32例慢性淋巴细胞白血病患者的临床资料,其中骨髓涂片幼稚淋巴细胞≥5%的患者18例（A组）,骨髓涂片幼稚淋巴细胞<5%的患者14例（B组）,观察两组患者骨髓形态学、免疫分型、FISH检测结果及总生存率的差异。结果:A组患者CD38及FMC-7表达者较B组患者多见,FISH检测结果提示p53、ATM及+12预后不良指标在A组患者中更易见。A组慢性淋巴细胞白血病患者1年、3年及5年总生存率分别为93.3%、83.3%和59.3%,B组慢性淋巴细胞白血病患者均存活超过5年。结论:慢性淋巴细胞白血病患者骨髓涂片中幼稚淋巴细胞≥5%的患者预后较幼稚淋巴细胞<5%的患者差,骨髓幼稚淋巴细胞比例有可能作为初步预测预后的指标之一。     

伴幼淋巴细胞增多的慢性淋巴细胞白血病三例并文献复习

 【摘要】　目的　探讨伴幼淋巴细胞增多的慢性淋巴细胞白血病（CLL／PL）的临床特征与预后,为临床诊治提供依据。方法　回顾性分析3例CLL／PL患者的临床资料并复习相关文献,讨论其临床特征及预后。结果　CLL／PL在临床表现、免疫表型、细胞遗传学、分子生物学等方面具有特殊性。结论　CLL伴幼淋巴细胞增多与其临床特征密切相关,提示预后不良。     

慢性淋巴细胞白血病患者长期随访四例

 目的 对4例慢性淋巴细胞白血病（CLL）患者进行长期观察。方法 对患者起病时情况、随访中的临床表现、治疗情况以及外周血象、骨髓象改变进行观察、分析。结果 4例患者有2例病情进展，1例并发纯红细胞再生障碍性贫血，1例稳定。结论 CLL患者生存时间较长，尤其是起病时分期较早者；病程中需要恰当干预。     

同胞兄弟患慢性淋巴细胞白血病二例报告

家族白血病国内已有多篇报道，大部分为急性白血病，慢性白血病少见，同为慢性淋巴细胞白血病者罕见。本文同胞兄弟二人先后发生慢性淋巴细胞白血病，现报道如下：     

Prognostic significance of serum immunoglobulin paraprotein in patients with chronic lymphocytic leukemia

The aim of this study was to explore the clinical and other associated laboratory features of chronic lymphocytic leukemia (CLL) patients with immunoglobulin (Ig) paraproteinemia. Serum protein electrophoresis (SPE) and immunofixation electrophoresis (IFE) were performed to measure serum Ig paraprotein. The correlations between serum Ig paraprotein and other prognostic factors were analyzed. Univariate and multivariate Cox regression analyses were used to assess associations between survival time and potential risk factors. In 133 Chinese CLL patients, 27 (20.3%) patients occurred Ig paraproteinemia at diagnosis. According to the correlation analysis, advanced Binet stage (r = 0.314, P < 0.001), direct antiglobulin test (DAT)-positive (r = 0.366, P < 0.001), high level of serum β2-microglobulin (β2-MG) (r = 0.296, P = 0.001) and thymidine kinase (TK) 1 (r = 0.227, P = 0.037), unmutated immunoglobulin heavy chain variable gene (IGHV) status (r = 0.284, P = 0.002), ZAP-70-positive (r = 0.305, P = 0.001), CD38-positive (r = 0.284, P = 0.002), and cytogenetic abnormalities of del(17p13) or del(11q22.3) (r = 0.208, P = 0.032) emerged as factors significantly related to the occurrence of Ig paraproteinemia. Survival analysis showed that the patients with Ig paraproteinemia had significantly shorter survival times than the patients without serum Ig paraprotein (P = 0.013). Binet stage (P = 0.028), high levels of lactate dehydrogenase (LDH) (P = 0.004), IgG paraproteinemia (P = 0.048), IgM paraproteinemia (P = 0.001), ZAP-70-positive (P = 0.003), DAT-positive (P = 0.013), unmutated IGHV status (P = 0.009), and del(17p13) (P = 0.001) were the adverse factors in determining overall survival (OS). Del(17p13) (P = 0.006), ZAP-70 (P = 0.030), and IgM paraproteinemia (P = 0.040) were the variables strongly associated with OS by multivariate Cox regression analysis. It was showed that serum Ig paraprotein might be applied for the assessment of prognosis in patients with CLL.     

含氟达拉滨的联合化疗方案治疗慢性淋巴细胞白血病／小淋巴细胞性淋巴瘤

目的：评价以氟达拉滨为主的化疗方案治疗慢性淋巴细胞白血病／小淋巴细胞淋巴瘤（CLI／SLL）的疗效和不良反应。方法：采用氟达拉滨为主的化疗方案，FC方案：氟达拉滨＋环磷酰胺；FMD方案：氟达拉滨＋米托蒽醌＋地塞米松；FMC方案：氟达拉滨＋米托蒽醌＋环磷酰胺，共治疗18例CLL／SLL患者，其中初发9例，复发、难治9例。结果：18例患者平均完成4．2个周期，完全缓解（CR）率61．1％，部分缓解（PR）率22．2％，总的有效（OR）率83．3％。初发组CR率66．7％。PR率33．3％，OR率100％；复发、难治组CR率55．6％，PR率11．1％，OR率66．7％，两组CR、OR率无显著性差异（P〉0．05）。FC方案和FMD方案治疗组CR、OR率无显著性差异（P〉0．05）。主要不良反应为骨髓抑制和免疫功能抑制，27．8％的患者出现Ⅲ～Ⅳ级粒细胞减少，22．2％的患者出现Ⅲ～Ⅳ级血小板减少。5例患者出现感染、发热，其中1例死亡。其它毒性包括恶心、呕吐，轻度肝肾功能损害，自身免疫性溶血性贫血。中位随访时间24月（1～40月），2年生存率88．9％，2年PFS率81．8％。初发组2年生存率100％，2年PFS率100％；难治组2年生存率83．3％，2年PFS率66．7％，两组无显著性差异（P〉0．05）。结论：氟达拉滨为主的联合化疗方案对CIL／SLL疗效好，同时患者对其耐受性亦较佳。     

Extramedullary chronic lymphocytic leukemia: Systematic analysis of cases reported between 1975 and 2012

The prognostic significance of extra-medullary chronic lymphocytic leukemia (EM-CLL) is unknown. We conducted a Medline database systematic search analyzing English language articles published between 1975 and 2012 identifying 192 cases. Patients with EM-CLL were more commonly treated than not (p < .001). Skin and central nervous system (CNS) were the most commonly reported sites of organ involvement. Survival after diagnosis of EM-CLL appeared to depend on the site of EM involvement. Prospective evaluation and further studies of EM-CLL are warranted.     

Recent advances in chronic lymphocytic leukemia

Chronic lymphocytic leukemia is a low-grade B-lineage lymphoid malignancy. Based on recent findings, the disease appears to be more heterogeneous than previously thought. Many cases may require no treatment at all unless patients become symptomatic or develop signs of rapid progression. Even in this setting, treatment is noncurative and is directed at reducing the symptoms. Recently described molecular risk features may help delineate at initial diagnosis which patients will have a more aggressive course. Newer treatment regimens incorporating purine nucleoside analogs and monoclonal antibodies have increased the rate of molecular complete remissions, which may lead to increased survival. Reduced intensity conditioning regimens have made the potentially curative modality of allogeneic transplantation more widely available. All of these recent treatments have significant risks of infectious complications, which must be carefully weighed against the risks posed by the underlying disease, and many low-risk asymptomatic patients do not require any treatment. A proposed risk-based treatment algorithm will be discussed.     

Gene mutations in chronic lymphocytic leukemia

The recent discovery of genes mutated in chronic lymphocytic leukemia (CLL) has stimulated new research into the role of these genes in CLL pathogenesis. CLL cases carry approximately 5–20 mutated genes per exome, a lower number than detected in many human tumors. Of the recurrently mutated genes in CLL, all are mutated in 10% or less of patients when assayed in unselected CLL cohorts at diagnosis. Mutations in TP53 are of major clinical relevance, are often associated with del17p and gain in frequency over time. TP53 mutated and associated del17p states substantially lower response rates, remission duration, and survival in CLL. Mutations in NOTCH1 and SF3B1 are recurrent, often associated with progressive CLL that is also IgV_H unmutated and ZAP70-positive and are under investigation as targets for novel therapies and as factors influencing CLL outcome. There are an estimated 20–50 additional mutated genes with frequencies of 1%–5% in CLL; more work is needed to identify these and to study their significance. Finally, of the major biological aberration categories influencing CLL as a disease, gene mutations will need to be placed into context with regard to their ultimate role and importance. Such calibrated appreciation necessitates studies incorporating multiple CLL driver aberrations into biological and clinical analyses.     

急性髓系白血病合并慢性淋巴细胞白血病一例报道及文献复习

 目的 探讨急性髓系白血病（AML）合并慢性淋巴细胞白血病（CLL）的临床特点、病因、诊断、治疗及预后。方法 临床诊断1例AML合并CLL,并就相关文献进行复习。结果 患者经MA方案（米托蒽醌10 mg／d第1 ~ 3天,阿糖胞苷150 mg／d第1,3,5,7天,200 mg第2,4,6天）化疗后取得完全缓解,但CD19阳性的淋巴细胞（表达CD20,CD23,SIgM,部分表达CD5,CD22,CD25）仍然存在,于9个月后AML复发未能再次缓解而死亡。结论 AML合并CLL为一种具有特殊生物学特征的罕见疾病,免疫分型和细胞遗传学技术在疾病的诊断和认识中发挥重要作用,治疗应以AML为主。     

Initial therapy of chronic lymphocytic leukemia

Only chronic lymphocytic leukemia (CLL) patients with active or symptomatic disease or with advanced Binet or Rai stages require therapy. Prognostic risk factor profile and comorbidity burden are most relevant for the choice of treatment. For physically fit patients, chemoimmunotherapy with fludarabine, cyclophosphamide, and rituximab remains the current standard therapy. For unfit patients, treatment with an anti-CD20 antibody (obinutuzumab or rituximab or ofatumumab) plus milder chemotherapy (chlorambucil) may be applied. Patients with a del(17p) or TP53 mutation should be treated with the kinase inhibitors ibrutinib or a combination of idelalisib and rituximab. Clinical trials over the next several years will determine, whether kinase inhibitors, other small molecules, immunotherapeutics, or combinations thereof will further improve outcomes for patients with CLL.     

Treatment of early chronic lymphocytic leukemia: intermittent chlorambucil versus observation

The effect of early therapy on the course of chronic lymphocytic leukemia (CLL) has not been established. Fifty-nine patients with indolent Rai stage I and II CLL were randomized to receive intermittent chlorambucil once a month or to receive no treatment. The two groups were comparable in entry characteristics. At 5 years from randomization there was no significant difference in survival between the two groups although the proportion of patients exhibiting active disease 5 years after randomization is 70 per cent in the untreated group and 55 per cent in the treated group. In this study, early treatment of CLL with intermittent chlorambucil did not result in a survival advantage for patients with indolent stage I and II CLL.