Adult acute lymphoblastic leukemia

Much progress has been made in understanding the biology of and therapy for acute lymphoblastic leukemia (ALL). This progress has translated into the recognition of several subgroups of ALL and the institution of risk-adapted therapies. New therapies are emerging based on the definition of specific cytogenetic-molecular abnormalities. Changes in the pathologic classification of ALL have led to therapeutic consequences. Adaptation of successful treatment strategies in children with ALL has resulted in similar complete remission rates in adults. Prognosis has Improved especially in mature B-cell ALL and T-cell lineage ALL. However, regardless of ALL subgroup, long-term survival in adults is still inferior to that in children. Development of new drugs and agents tailored to subset-specific cytogenetic-molecular characteristics is vital to the therapeutic success in adult ALL.     

急性淋巴细胞白血病患者免疫表型分析

目的:探讨急性淋巴细胞白血病(acute lymphoblastic leukemia,ALL)的免疫表型特点.方法:运用流式细胞术及特异性单克隆抗体CD2,CD3,CD4,CD5,CD7,CD8,CD10,CD13,CD19,CD20,CD22,CD33,CD34,CD38,CD45,CD56,CD117,HLA-DR,sIgM,cyIg,cyCD79a,MPO和TdT对58例形态学诊断ALL患者进行免疫表型检测.结果:通过CD3、CD19、CD33和MPO的表达情况分出T-ALL 8例(13.79%),B-ALL 49例(84.48%),混合细胞白血病1例(1.72%).B-ALL进一步根据CD10,CD20,cyIg,sIgM的表达情况分为早前B型5例(8.62%),普通B型34例(58.62%),前B型9例(15.52%),成熟B型1例(1.72%).B-ALL异常细胞存在抗原跨系列表达、跨阶段表达、缺失表达.儿童ALL免疫分型及白血痛相关免疫表型与成人ALL差异无统计学意义.结论:ALL的异常骨髓细胞有明显本系列特征、原始细胞标记和跨系表达,在此基础上应用多参数流式细胞仪可有效检测微小残留病变.     

急性淋巴细胞白血病的治疗

联合化疗是目前急性淋巴细胞白血病(ALL)治疗的主要方法.ALL的化疗分为4个部分:诱导治疗、巩固治疗、维持治疗和中枢神经系统白血病的预防.现已证实儿童ALL方案在成人尤其是青少年ALL的疗效要优于成人方案,未来成人ALL的治疗将更多的引入儿童ALL的治疗经验.ALL治疗领域的进展主要在两方面:一是酪氨酸激酶抑制剂(TKI)在Ph阳性ALL的应用.TKI在Ph阳性ALL治疗中的作用已得到证实,但最佳用法还有待进一步研究.二是免疫治疗在ALL治疗中的应用,偶联毒素的免疫毒素治疗ALL的临床研究一直在进行中,而嵌合抗原受体T细胞(CAR-T)的临床研究近年获得了突破性进展,CAR-T很可能成为未来ALL治疗领域革命性的进展.     

儿童与成人急性淋巴细胞白血病临床特征的对比观察

目的 分析最近两年来儿童急性淋巴细胞白血病（ＡＬＬ）的临床预后并探讨其免疫学,细胞遗传学特征以及原发性多药耐药的发生率。方法 总结１５４例初治儿童ＡＬＬ的完全缓解（ＣＲ）率,同时动用免疫组织化学、细胞遗传学高等方法对白血病细胞的生物学特征进行研究。结果 儿童初治ＡＬＬ的平均ＣＲ率是９４．１％,显著高于成人（６７．８％）;免疫分型中,同时伴髓系表达者占１８．５％,Ｐｈ染色体的阳性率是４．８％,两组频     

Peg-asparaginase for acute lymphoblastic leukemia

Importance of the field: Asparaginase is a prominent component of pediatric and adolescent treatment for acute lymphoblastic leukemia. These treatment regimens are now being employed in adults. Knowledge of the efficacy and toxicity of asparaginase preparations is essential when using these treatments.

Areas covered by this review: The search terms used were asparaginase, leukemia, pegylated, oncaspar, adolescent and young adult. Literature was searched in Pubmed/Medline with no limitations on year of publication. Abstracts from the American Society of Hematology meetings and the American Society of Clinical Oncology were searched from 2004 – 2008 using the same terms.

What the reader will gain: The reader will gain knowledge of the tolerability and efficacy of pegylated asparaginase when treating acute lymphoblastic leukemia.

Take home message: Pegylated asparaginase is generally well tolerated in adult patients with efficacy that appears to be at least equivalent to native asparaginase preparations.     

伴t(1;19)(q23;p13)和E2A-PBX1成人急性T淋巴细胞白血病一例报告附文献复习

目的 总结1例伴有t(1;19)和E2A-PBX1融合基因阳性的成人T细胞急性淋巴细胞白血病(ALL)患者的诊疗体会.方法 对1例成人T细胞ALL患者进行染色体核型分析,流式细胞术检测免疫表型,同时进行融合基因多重RT-PCR扩增.结果 患者染色体核型为47,XY,9p+,15p+,17q-,der(19),t(1;19)(q23;p13)[5]/46,XY[15].E2A-PBX1融合基因阳性表达.给予hyperCVAD(环磷酰胺+长春新碱+阿霉素+地塞米松)方案治疗后患者获血液学完全缓解,染色体核型复查为46,XY[10],E2A-PBX1融合基因检测阴性.结论 E2A-PBX1+ t(1;19)也可以发生于T细胞ALL,E2a-PBX1白血病细胞在不同的癌基因协同信号或微环境下转化方向可变.     

伴t(1;19)(q23;p13)和E2A-PBX1成人急性T淋巴细胞白血病一例报告附文献复习

目的 总结1例伴有t(1;19)和E2A-PBX1融合基因阳性的成人T细胞急性淋巴细胞白血病(ALL)患者的诊疗体会.方法 对1例成人T细胞ALL患者进行染色体核型分析,流式细胞术检测免疫表型,同时进行融合基因多重RT-PCR扩增.结果 患者染色体核型为47,XY,9p+,15p+,17q-,der(19),t(1;19)(q23;p13)[5]/46,XY[15].E2A-PBX1融合基因阳性表达.给予hyperCVAD(环磷酰胺+长春新碱+阿霉素+地塞米松)方案治疗后患者获血液学完全缓解,染色体核型复查为46,XY[10],E2A-PBX1融合基因检测阴性.结论 E2A-PBX1+ t(1;19)也可以发生于T细胞ALL,E2a-PBX1白血病细胞在不同的癌基因协同信号或微环境下转化方向可变.     

E2A-PBX1融合基因阳性的儿童急性淋巴细胞白血病携带变异型融合转录本

为了研究儿童急性淋巴细胞白血病（ALL）中E2A-PBX1融合基因的表达,采用位于E2A基因不同位置的上游引物与下游PBX1引物,检测了410例儿童ALL,包括362例B细胞ALL和48例T细胞ALL.结果发现：17例患儿携带E2A-PBX1融合基因,检出率4.1%,且全部为B细胞ALL,而且所有阳性病例均表达一种变异型融合转录本,后者是由E2A基因的第13外显子（159 bp）被差异剪切形成的.经BLASTn比对分析,这种转录本保持了原来的开放阅读框,但导致53个氨基酸残基的丢失.这53个氨基酸残基位于活化区2,会导致融合蛋白中部分环-螺旋结构以及全部七聚体亮氨酸重复序列的丢失.结论：携带E2A-PBX1融合基因的儿童ALL表达典型和变异型2种融合转录本,后者是由E2A基因第13外显子被差异剪切而形成的,它将导致融合蛋白中53个氨基酸残基及其所构成的部分环-螺旋结构以及全部七聚体亮氨酸重复序列的丢失.     

Advances in acute lymphoblastic leukemia.

DATA SOURCES: Current literature. DATA SYNTHESIS: Acute lymphoblastic leukemia (ALL) is a stem cell disorder characterized by an overproduction of lymphoblasts in the bone marrow that eventually spill into circulation, producing lymphocytosis. As with the other acute leukemias, the most common symptoms experienced by patients include fatigue, bleeding, and recurrent infections resulting from the suppression of normal hematopoiesis in the bone marrow by the accumulating blasts. ALL primarily affects children and exhibits the best response to standard chemotherapy as compared to acute myeloblastic leukemias (AML). Further, remission rates are highest among ALL patients, many of whom are experiencing sustained remissions suggesting cure. In light of early treatment successes, researchers began to investigate modifications of standard treatment regimens to accommodate variability in weight, age, and response to therapy among children with ALL. Individualized treatment plans were implemented where some patients received a reduced intensity course of therapy to minimize drug toxicity while others received drug intensification to maximize response. More recently, research efforts have been directed at the elucidation of leukemogenic mechanisms implicated in ALL to identify specific protein mutants that can be used to design drugs tailored to interfere with the activity of these mutant protein targets. Identification of chimeric proteins produced from chromosomal translocations and gene expression profiles from microarray analyses are the primary techniques used to identify the potential therapeutic targets. CONCLUSION: Several reliable prognostic indicators have been identified and are being used to improve therapeutic planning and outcome prediction in ALL patients. Individualized treatment regimens have been developed based on the specific characteristics of each patient to minimize treatment related adverse events and maximize response. Through the use of cytogenetic, molecular, and microarray testing, ALL classification schemes have improved and potential therapeutic targets have been identified. It is anticipated that the next major advance in the treatment of ALL will involve the use of designer therapies developed to specifically interfere with particular molecular abnormalities producing the leukemogenic aberration to the normal signal transduction pathways.     

急性淋巴细胞性白血病免疫表型特点

目的　研究急性淋巴细胞性白血病 (ALL)中免疫表型的特点。方法　对 15 3例ALL应用流式细胞仪进行免疫表型分析。结果　① 15 3例ALL中T淋巴细胞性ALL(T ALL) 2 2 .9%、B淋巴细胞性ALL(B ALL) 6 6 .7% ;ALL 1型 (L1) 37.9% ,ALL 2型 (L2 ) 5 6 .9%和ALL 3型 (L3 ) 5 .2 %。②ALL中髓系白血病细胞抗原 (My)阳性率33.98% ,表达单一抗原的最多为 5 9.6 % ,CD13阳性率最多为 2 3.5 % ,CD33为 2 0 .9%和CD14为 3.9% ;B ALL中My阳性率 38.6 % ,明显高于T ALL的 14 .3% ,P <0 .0 1;L2 中My阳性率为 4 2 .5 % ,明显高于L1的 2 5 .7% ,P <0 .0 1。③CD34阳性率 :B ALL中为 5 8.3% ,明显高于T ALL中的 4 0 % ,P <0 .0 5 ;但My阳性ALL和My阴性ALL中阳性率分别是 6 5 .4 %和 4 9.5 % ,差异无统计学意义 (P >0 .0 5 )。结论　ALL中髓系抗原和CD34的表达与白血病形态学分型 (FAB亚型 )和免疫分型有关     

Molecular genetics of B-precursor acute lymphoblastic leukemia

B-precursor acute lymphoblastic leukemia (B-ALL) is the most common childhood tumor and the leading cause of cancer-related death in children and young adults. The majority of B-ALL cases are aneuploid or harbor recurring structural chromosomal rearrangements that are important initiating events in leukemogenesis but are insufficient to explain the biology and heterogeneity of disease. Recent studies have used microarrays and sequencing to comprehensively identify all somatic genetic alterations in acute lymphoblastic leukemia (ALL). These studies have identified cryptic or submicroscopic genetic alterations that define new ALL subtypes, cooperate with known chromosomal rearrangements, and influence prognosis. This article reviews these advances, discusses results from ongoing second-generation sequencing studies of ALL, and highlights challenges and opportunities for future genetic profiling approaches.     

Ph样急性淋巴细胞白血病的研究进展

Ph样急性淋巴细胞白血病(ALL)是一组前体B细胞急性淋巴细胞白血病(BCP-ALL)亚型,好发于儿童及成年人,并且一般预后差.该亚型与断裂点簇集区-Abelson白血病病毒(BCR-ABL) 1+ ALL有相似的基因表达谱,但是缺乏BCR-ABL1融合蛋白,基因异常主要涉及细胞因子信号通路、激酶信号通路,以及B细胞发育相关转录因子.激酶抑制剂联合化疗的治疗方案有望改善Ph样ALL的预后.通过对Ph样ALL的研究,有助于完善BCP-ALL的精确危险分层和靶向治疗.本文就Ph样ALL的流行病学特点、易感基因位点、常见基因异常、诊断、治疗及预后的研究进展进行综述.     

急性淋巴细胞白血病的规范治疗

急性淋巴细胞白血病(acute lymphoblastic leukemia, ALL)是一组高度异质性的来源于淋巴前体细胞的血液系统恶性克隆性肿瘤。近些年随着危险分层治疗体系的完善及酪氨酸激酶抑制剂、单克隆抗体、嵌合抗原受体T细胞、其它靶向药物等新药的出现,ALL的治疗效果得到了大幅度的提高,本文就ALL的诊疗规范及最新研究进展等有关内容进行简述。     

Ph样急性淋巴细胞白血病的研究进展

费城染色体样(Ph样)急性淋巴细胞白血病(ALL)是近年发现的B系ALL的高危亚型,其基因改变通常可引起酪氨酸激酶信号或细胞因子受体的激活并级联放大,从而导致下游ABL和JAK/STAT通路被激活。本文就目前Ph样ALL的研究进展做一概述。     

儿童急性淋巴细胞白血病细胞遗传学特征分析

目的 分析儿童急性淋巴细胞白血病(ALL)细胞遗传学变化的特点.方法 以2009年1月至2011年11月确诊的90例初发ALL患儿为研究对象,采用染色体核型分析及荧光原位杂交(FISH)技术检测患者骨髓白血病细胞的细胞遗传学和分子生物学变化.结果 ①染色体核型分析:有分裂象者66例,其中异常者35例(53.0%);无分裂象者24例.②FISH检测:对31例染色体核型正常和24例无分裂象的患者进行FISH检测,异常者分别为7例(占22.6%)和14例(58.3%),其中无分裂象患者异常检出率与有分裂象者核型分析异常检出率差异无统计学意义(P=0.655);55例患儿中TEL-AML1融合基因阳性16例(29.1%),MLL重排3例(5.5%),bcr-abl融合基因阳性2例(3.6%).③90例患儿通过两种检则方法 共检出细胞遗传学异常56例(占62.2%).结论 儿童ALL易出现细胞遗传学改变;对于有足够分裂象的患者,常规染色体核型分析仍是可靠的方法,对分裂象质量低或无分裂象的儿童ALL患者,FISH检测异常克隆能提高细胞遗传学异常检出率.     

Pneumatosis intestinalis in children with acute lymphoblastic leukemia and acute myeloid leukemia

Purpose  

To describe symptoms, diagnostic features, treatments, and outcomes of pneumatosis intestinalis (PI) in pediatric patients being treated for acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML).