成人急性淋巴细胞白血病免疫表型特点分析

目的研究成人急性淋巴细胞白血病(ALL)患者中不同亚型的各种白血病细胞免疫表型分布特点。方法采用当前国际通用的四色流式细胞术图像分析系统检测并综合分析76例ALL患者的免疫表型及其发生规律与特点。结果①76例ALL免疫表型系列来源可分为三种不同亚型,其中T-ALL亚型5例(占6.57%)、B-ALL亚型68例(89.48%)、T和B细胞混合型(T/B-ALL)亚型3例(3.95%)②ALL早期抗原表达特点:在B-ALL亚型中CD38、CD34、HLA-DR呈高表达;在T-ALL亚型中,CD38和CD34呈高表达,但HLA-DR不表达;在T/B-ALL亚型中,HLA-DR表达,CD34和CD38不表达。③按免疫分型相关抗原的敏感性和特异性分析:在B-ALL中,特异性抗原cCD79a占91.18%,敏感性抗原CD19表达占97.06%;在T-ALL中,特异性抗原cCD3和敏感性抗原CD7均表达为100%;在T/B混合型ALL中,cCD3、cCD79a、CD19均表达,CD7表达2例;④伴髓系抗原交叉表达分析:在B-ALL中,伴髓系抗原表达占21例(30.88%);在T-ALL中,伴髓系抗原表达1例(20%);T/...     

132例初发儿童急性淋巴细胞白血病免疫表型及细胞遗传学特征分析

目的：探讨儿童急性淋巴细胞白血病（ALL）的免疫表型及细胞遗传学特征,为其诊断及治疗提供依据。方法：采用多参数流式细胞术（FCM）对132例初发儿童 ALL 患者进行免疫表型分析,并应用荧光原位杂交（FISH）技术检测其细胞遗传学特点。结果：132例 ALL 患者中,12.9%（17/132）为 T 淋巴细胞急性淋巴细胞白血病（T - ALL）,87.1%（115/132）为 B 淋巴细胞急性淋巴细胞白血病（B - ALL）。46.2%（56/132）的ALL 患者表达髓系抗原,CD13是 ALL 中最常见的髓系抗原,其阳性率为28.0%。T - ALL 髓系相关抗原表达阳性率为47.1%,与 B - ALL 的46.1%比较,差异无统计学意义（χ2=0.006,P =0.940）。可供核型分析的96例 ALL 中,核型异常者50例（52.1%）,其中染色体数目异常26例,染色体结构异常24例。96例 ALL 患者中,TEL/ AML1融合基因阳性21例（21.8%）,BCR/ ABL 融合基因阳性14例（14.6%）,TCF3/ PBX1融合基因阳性5例（5.2%）,MLL 重排3例（3.1%）。对不同免疫分型患者细胞遗传学异常检出率进行比较,差异均无统计学意义（P >0.05）。结论：儿童 ALL 免疫表型和细胞遗传学具有一定的特点,两者联合检测对 ALL 的诊断及分型具有重要的价值。     

急性白血病首次复发后免疫表型及细胞遗传学改变

目的：分析成人急性白血病首次复发前后免疫表型和细胞遗传学改变。方法：采用间接荧光法分析急性白血病患者的免疫表型，用Ｇ分带技术研究患者的染色体核型。结果：５例中４例急性淋巴细胞白血病（ＡＬＬ）复发后的患者发生免疫表型变化，均涉及ＣＤ３４抗原表达；ＣＤ３４抗原的表达与再诱导治疗结果呈负相关。１０／１２例急性髓细胞白血病（ＡＭＬ）复发光患者免疫表型发生改变，涉及ＣＤ１４、ＣＤ１５、ＣＤ１３、ＣＤ３３、Ｃ     

成人急性髓细胞性白血病免疫表型与细胞遗传学及临床特征的关系

背景与目的:新的WHO分类已迅速应用于白血病的诊断。依据多个系相关抗原的表达,多参数高分辨流式细胞术可准确地识别白血病细胞的系列来源和分化阶段,而且某些抗原表达与细胞遗传学改变和预后密切相关。本研究旨在探讨初治成人急性髓细胞性白血病(acutemyeloidleukemia,AML)的免疫表型特征,并对其与FAB分类、细胞遗传学和临床表现的关系进行分析。方法:采用多参数高分辨流式细胞术对96例成人AML患者骨髓进行免疫表型分析,染色体G显带技术对其中的73例进行核型分析。结果:AML患者中,某些免疫表型特征与FAB分类具有相关性,包括M3中缺乏表达HLA鄄DR、CD34和CD56,但CD2的表达增加;M2中CD19、M5中CD14和CD56的表达增加,而M0中未见MPO的表达。本组AML核型异常率为54.8%,其中CD22、CD56和TdT的表达与核型异常有显著性相关。10例t(8;21)改变仅见于M2中,并高表达CD15、CD19、CD34和CD56,但未见CD2和CD7表达。7例伴t(15;17)的M3患者中未见淋系抗原的表达。此外,CD4和TdT抗原的表达与患者年龄、CD7和CD14的表达与外周血白细胞计数、CD4、CD14和CD56的表达与血小板计数等均有显著性正相关。结论:AML患者免疫表型与细胞遗传学的相关性提示AML抗原的异常表达可能与基因的异常改变密切相关。白血病免疫表型的检测有助于     

儿童急性淋巴细胞白血病免疫表型测定

急性淋巴细胞白血病 (ＡＬＬ)是儿童高发的恶性肿瘤之一。免疫表型 (免疫学 )在诊断该病中起着其它方法所不能替代的重要作用 ,如Ｔ ＡＬＬ和兼备淋、髓同时表达及伴ＣＤ3 4阳性的ＡＬＬ ,必须依靠免疫表型来诊断。作者在近 5年用免疫酶标法和 19种单克隆抗体 (单抗 )对 6 0例儿童ＡＬＬ进行了免疫表型的测定与分析 ,现报道如下。材料与方法一、对象　 6 0例为 1994年 8月～ 1999年 11月就诊的初发未经治疗的儿童ＡＬＬ ,男 37例 ,女 2 3例 ,年龄 2 0 8～ 13 6 7岁 ,平均 7 99岁。骨髓按ＦＡＢ分类Ｌ12 9例 ,Ｌ2 2 6例 ,Ｌ3 5例。同时 ,作…     

急性粒-单核细胞白血病的免疫表型及细胞遗传学特征

背景与目的:白血病中某些抗原的表达与细胞遗传学的改变密切相关。本研究旨在探讨急性粒-单核细胞白血病(acutemyelomonocyticleukemia,M4)的免疫表型特征,并分析其与细胞遗传学的关系,为其诊断及治疗提供依据。方法:采用一组系列相关单克隆抗体和三色流式细胞术对81例M4患者进行免疫表型分析,并分析有核型资料的73例患者的核型异常;同时应用双色间期荧光原位杂交(fluorescenceinsituhybridization,FISH)技术对有染色体标本的35例患者进行inv(16)检测,并分析inv(16)阳性患者的免疫表型特征。结果:81例M4患者中48例(59.3%)表达干细胞标志CD34;髓系标志以CD33(84.0%)表达最高,其次为CD13(81.5%)和CD14(24.7%);分别有23例(28.4%)和10例(12.3%)患者表达T系和B系相关抗原。11例M4Eo患者中CD13均阳性,10例CD33阳性,7例CD34阳性,5例CD2阳性。FISH检测发现14例患者inv(16)阳性,其中CD13阳性13例,CD33阳性11例,CD34阳性8例,CD14阳性5例,CD7阳性3例,CD2阳性3例。73例M4患者中,异常染色体检出率为41.1%(30/73),共检出11种主要异常核型。CD2和CD34在染色体异常患者中表达明显增高,而CD14表达减低。CD2在M4Eo中表达增高,但其表达与inv(16)无显著性相关。结论:急性粒-单核细胞白血病以髓系抗原表达为主,CD2和CD34在染色体异常患者中表达明显增高;CD2在M4Eo中表达增高。Inv(16)在M4中占40%,各抗原表达与inv(16)无显著相关性。     

急性髓系白血病M2型免疫表型及细胞遗传学研究

 目的　探讨急性髓系白血病M2型的免疫表型及细胞遗传学特征。方法　采用一组单克隆抗体和三色流式细胞术对112例M2患者进行免疫表型及核型分析。结果　112例M2患者中,70例（62.5 %）表达干细胞标志CD34。髓系标志中以CD13（87.5 %）M2患者表达最高,其次是CD33（83.9 %）和CD14（2.7 %）。分别有34例（30.4 %）及24例（21.4 %）患者表达T系及B系标志。112例M2患者中,73例（65.2 %）检出异常核型,共检出28种数目异常,25种结构异常。47例（42.0 %）患者检出t（8;21）。CD19及CD34单独或共同表达在核型异常及伴t（8;21）的M2患者中显著增高（P＜0.05）。结论　M2以髓系抗原表达为主,部分有淋系抗原表达,CD19及CD34表达与t（8;21）显著相关。     

急性白血病首次复发后免疫表型及细胞遗传学改变

目的 :分析成人急性白血病首次复发前后免疫表型和细胞遗传学改变。方法 :采用间接荧光法分析急性白血病患者的免疫表型 ,用 G分带技术研究患者的染色体核型。结果 :5例中 4例急性淋巴细胞白血病 ( ALL )复发后的患者发生免疫表型变化 ,均涉及 CD3 4 抗原表达 ;CD3 4 抗原的表达与再诱导治疗结果呈负相关。 10 /12例急性髓细胞白血病 ( AML )复发患者免疫表型发生改变 ,涉及 CD1 4 、CD1 5 、CD1 3 、CD3 3 、CD3 4 、CD7、HLA-DR等抗原 ;CD1 4 、CD3 3 、CD3 4 发生改变的患者再诱导治疗效果差 ;CD1 5 由阴性转为阳性的患者再诱导效果较好。 7例患者复发前后均进行了染色体核型分析 ,4例出现主要的染色体核型改变 ,其中 3例为异常核型转为正常核型 ;染色体核型发生改变的病例再诱导治疗效果均较差。结论 :成人急性白血病复发后免疫表型和细胞遗传学均可发生改变 ,这些改变与再诱导治疗的结果有关。     

急性髓系白血病M2型免疫表型及细胞遗传学研究

目的 探讨急性髓系白血病M2型的免疫表型及细胞遗传学特征.方法 采用一组单克隆抗体和三色流式细胞术对112例M3患者进行免疫表型及核型分析.结果 112例M3患者中,70例(62.5%)表达干细胞标志CD34.髓系标志中以CD13(87.5%)M2患者表达最高,其次是CD33(83.9%)和CD14(2.7%).分别有34例(30.4%)及24例(21.4%)患者表达T系及B系标志.112例M2患者中,73例(65.2%)检出异常核型,共检出28种数目异常,25种结构异常.47例(42.0%)患者检出t(8;21).CD19及CD34单独或共同表达在核型异常及伴t(8;21)的M2患者中显著增高(P＜0.05).结论 M3以髓系抗原表达为主,部分有淋系抗原表达,CD19及CD34表达与t(8;21)显著相关.     

成人急性双表型白血病的临床研究

目的 研究急性双表型白血病（BAL）的临床生物学特征和预后。方法 63例BAL患者骨髓标本分别进行细胞形态学及细胞化学染色,确定其FAB类型,运用一组系列相关单抗和流式细胞仪及直接免疫荧光标记技术 进行免疫分型,同时采用反转热变性姬姆萨（RHG）显带技术进行核型分析。运用针对急性髓性白血病（AML）,急性淋巴细胞白血病（ALL）或二者兼顾的方案治疗。结果 BAL患者的临床表现与AML和ALL患者差异无显著性。形态学上AML以M5、M1、M2亚型,ALL以L2、L1亚型居多,免疫分型显示,BAL患者中以髓系与B系抗原共表达为主,另外,CD34在BAL中高表达,提示BAL可能起源于较早期的造血干或（和）祖细胞,核型分析显示,BAL中Ph染色体较多见,占25.5%(13/51)。BAL患者对治疗反应差,生存期较短。结论 BAL具有独特的临床,生物学和预后特征。     

Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7Rα (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous, with the leukemic cell population differing from case to case. Through the comprehensive analysis of immunophenotypic patterns, the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis, therapeutic monitoring, and individualized therapies for common ALL.     

Blinatumomab治疗急性B淋巴细胞白血病的研究进展*

急性B淋巴细胞白血病（B-cell acute lymphoblastic leukemia,B-ALL）是一种恶性血液病。研究发现,以CD19作为治疗靶点的贝林妥欧单抗（blinatumomab）作为异基因造血干细胞移植（allogeneic hematopoietic stem cell transplantation,allo-HSCT）的桥梁显著改善了复发/难治性急性B淋巴细胞白血病（relapsed/refractory acute lymphoblastic leukemia,R/R B-ALL）患者的预后,其在新诊断急性淋巴细胞白血病（acute lymphoblastic leukemia,ALL）中与细胞毒性化疗药物或其他免疫治疗药物联用,在确保疗效的同时降低了方案的不良反应,在费城染色体阳性（Philadelphia chromosome-positive,Ph⁺）ALL患者中与二代/三代酪氨酸激酶抑制剂（tyrosine kinase inhibitors,TKIs）联合应用,有望使患者后期无需移植治疗。此外,治疗后微小残留病变（minimal residual disease,MRD）对患者的复发和长期生存（overall survival,OS）具有显著影响,blinatumomab可提高ALL患者的MRD转阴率,保障了患者的远期预后。本综述重点介绍blinatumomab在B-ALL不同患者群体中的临床研究及相关进展。     

Childhood acute lymphoblastic leukemia: Integrating genomics into therapy

Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer‐related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for the development of new therapeutic approaches in the era of precision medicine. In this review, the authors delineate the current genetic landscape of childhood ALL, emphasizing patient outcomes with contemporary treatment regimens as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. Cancer 2015;121:3577–3590 . © 2015 American Cancer Society.     

New insights into the pathophysiology and therapy of adult acute lymphoblastic leukemia

Significant advances have been made in the last decade toward a better understanding of the disease pathogenesis and the development of novel therapies that target specific subsets of adult acute lymphoblastic leukemia (ALL). Risk‐adapted strategies are transforming the disease treatment and prognosis. With current treatment regimens, long‐term survival is achieved by approximately 50% of patients with B‐cell ALL, 50% to 60% of patients with Philadelphia chromosome–positive ALL, and approximately 80% of patients with Burkitt's leukemia. Genomic profiling in ALL has identified new prognostic markers, new therapeutic targets, and novel ALL subtypes. These may be amenable to future targeted therapies that can further improve outcomes. The early recognition of early precursor T‐cell ALL, a distinct pathobiological entity with a poor prognosis, is essential for the development of an effective clinical management strategy. The role of monoclonal antibodies and cytotoxic T‐cell therapies continues to be defined. Many of the approaches are currently being evaluated for ALL salvage. Their incorporation into frontline adult ALL therapy, in concomitant or sequential strategies, may increase the cure rates to levels achieved in pediatric ALL and may reduce the need for prolonged intensive and maintenance chemotherapy. Cancer 2015;121:2517–2528 . © 2015 American Cancer Society.     

Proportion of long-term event-free survivors and lifetime of adult patients not cured after a standard acute lymphoblastic leukemia therapeutic program: adult acute lymphoblastic leukemia-94 trial

BACKGROUND: In adult acute lymphoblastic leukemia, treatment results generally are expressed in terms of overall survival or disease-free survival at 3 years. In this investigation, the authors attempted to express the results in terms of the proportion of long-term disease-free survivors and in terms of lifetime in patients who developed recurrent disease or died. METHODS: Univariate and multivariate analyses were used to assess the influence of different covariates on the 2 result criteria in 922 participants in the Adult Acute Lymphoblastic Leukemia-94 multicenter trial. RESULTS: The proportion of long-term survivors was 21.5% (95% confidence interval [95% CI], 18.1-25.4%) and was higher in women than in men. The proportion decreased with increasing age, white blood cell count, and lactate dehydrogenase level. The lowest proportion was observed in patients ages 44 years to 55 years (11.4%; 95% CI, 7-17.9%) and in patients with the t(9;22) BCR-ABL karyotype (13.4%; 95% CI, 8.8-19.8%), and the highest proportion was observed in patients with the t(4;11) MLL-AF4 karyotype (31.3%; 95% CI, 18.2-48.3%). The mean expected lifetime of patients who were not cured was 11.4 months (95% CI, 9.1-14.1 months). It was longer in men than in women and was shorter with increasing age, performance status, hemoglobin level, and white blood cell count. CONCLUSIONS: The results of this study highlighted and specified the importance of some classic prognostic factors in patients with acute lymphoblastic leukemia.     

CD10 antigen density in childhood common acute lymphoblastic leukaemia: Comparisons of race and sex

During the 25 month period from July 1989 until August 1991, 58 children with FAB defined acute lymphoblastic leukaemia (ALL) were referred for immunophenotypic analysis. Of these, 42 children with a common/pre-B phenotype (CD19/CD10-positive) were studied specifically to assess CD10 antigen density. A pattern of segregation was found between males and females and between black and white children. Black males, who are the worst prognostic group, had the lowest CD10 density, while white females, known to constitute the best prognostic group, had significantly higher CD10 antigen density than the other groups. Black females and white males occupied intermediate positions with respect to CD10 antigen density. A two way analysis of variance showed that although sex had contributed significantly to this variation (p = 0.0038), the contribution of race was marginal (p = 0.0530). It is hypothesized that low CD10 antigen density patterns in males and in Blacks could be causally related to poor prognosis.     

成人早期前体T急性淋巴细胞白血病（ETP-ALL）与非ETP-ALL的临床特点对比

目的:对比分析成人早期前体T急性淋巴细胞白血病（ETP-ALL）与非早期前体T急性淋巴细胞白血病（non-ETP-ALL）的临床特点。方法:回顾性分析于我科系统诊治的成人T细胞急性淋巴细胞白血病（T-ALL）患者19例,其中ETP-ALL 6例,non-ETP-ALL 13例,对比两组患者临床基本状况、血液及骨髓检测结果、免疫分型结果及诱导治疗后缓解情况。结果:ETP-ALL组患者白细胞水平显著低于non-ETP-ALL组患者,血小板水平显著高于non-ETP-AL组患者,主要见于pro-T-ALL,首次诱导治疗后完全缓解或接近完全缓解（CR/CRi）率显著低于后者。结论:ETP-ALL患者具有较独特的临床特点,对常规诱导治疗反应差,有必要积极探索新的治疗方法和药物。