儿童幼稚T细胞型急性淋巴细胞白血病1例

幼稚Ｔ细胞型急性淋巴细胞白血病（ＰｒｅｃｕｒｓｏｒＴｃｅｌｌａｃｕｔｅｌｙｍｐｈｏｂｌａｓｔｉｃｌｅｕｋｅｍｉａ,Ｐｒｅ－Ｔ－ＡＬＬ）是一种早期胸腺细胞恶性疾病,临床上少见。我院最近确诊１例,现将其临床和生物学特征报告如下：１　病例介绍患儿,男,１４岁,因进行性面色苍白、乏力、鼻出血１个月余,发热、皮肤出血点１周,于１９９８年３月１２日入院。既往身体健康。体检：体温３８．５℃,脉搏１２６次／ｍｉｎ,呼吸３６次／ｍｉｎ,血压１５／１１ｋＰａ（１ｍｍＨｇ＝０．１３３ｋＰａ）。中度贫血外貌,四肢及躯干…     

儿童急性淋巴细胞白血病患者T淋巴细胞免疫功能的研究

目的 :研究儿童急性淋巴细胞白血病 (ALL)患者初治时和完全缓解 (CR)后外周血T淋巴细胞亚群及其分泌细胞因子的能力。方法 :采集B淋巴细胞系ALL儿童初治时、CR后的外周血 ,分离出其中的单个核细胞 (MNC)。用单克隆抗体在流式细胞仪上测定CD3、CD4、CD8以及IL 2受体CD2 5的含量 ;通过T淋巴细胞内细胞因子IFN γ和TNF α的测定 ,在单个细胞水平上分析T淋巴细胞功能的变化。结果 :①初治时 ,患者的CD4 /CD8为 (1.10± 0 .79) ,较健康儿童 (2 .74± 1.2 1)明显降低 (P <0 .0 1) ,CD4、CD8产生细胞因子IFN γ和TNF α的能力均低于正常对照 (P <0 .0 5 )。②CR后 ,CD4 /CD8为 2 .5 4± 1.39,比初治时明显提高 (P <0 .0 5 ) ,CD4、CD8产生细胞因子的能力增强 ,但与正常对照组相比 ,各项数值仍低。③初治患者的CD4 + CD2 5 + T淋巴细胞为 (0 .76± 0 .5 6 ) ,明显低于CR组 (2 0 .4± 5 .1) (P <0 .0 1)和对照组 (16 .3± 6 .3) (P <0 .0 1)。这表明 ,免疫损害在白血病的发病过程中起重要作用的细胞因子的产生和CD2 5都趋于正常。结论 :T淋巴细胞的免疫功能与儿童白血病的预后关系密切 ,促进患者免疫功能的恢复对本病的治疗非常重要     

免疫双标记细胞的检测在中枢神经系统白血病诊断中的意义

目的：观察末端脱氧核苷酸转移酶（TdT）及淋巴细胞系列相关抗原双标记细胞在脑脊液中的检出对中枢神经系统白血病（CNS－L）的临床意义。方法：采用免疫荧光标记技术配合流式细胞术，检测初治或安全缓解期急性淋巴细胞白血病脑脊液中TdT及淋巴系列相关抗原双标记细胞及其治疗后的变化。结果：64例中8例脑脊液检出上述免疫双标记细胞，均为急性淋巴细胞白血病，其中1例无CNS－L临床迹象，免疫双标记细胞占3.38%，经治疗后免疫双标记细胞在脑脊液均明显减少或消失。结论：脑脊液中免疫双标记细胞的检出对CNS－L的诊断及治疗指导具有重要的临床意义。弥补了常规细胞形态学的不足。     

老年急性淋巴细胞白血病患者免疫表型差异

目的探讨老年急性淋巴细胞白血病患者的免疫表型。方法选择2011年1月至2013年11月来该院接受治疗的55例老年急性白血病患者,取患者肘静脉血标本,分离外周血单核细胞并用流式细胞术对B细胞和T细胞进行免疫分型,评价不同免疫分型特征。结果 55例老年急性白血病患者中有35例(63.64%)B型淋巴细胞白血病,9例(16.36%)T型淋巴细胞白血病,11例(20.00%)B/T混合型淋巴细胞白血病,其中B型比例高于T型。B型淋巴细胞分化抗原表达异常患者中有33例(71.74%)CD19阳性,18例(39.13%)CD79a阳性,2例(4.35%)CD20阳性和3例(6.52%)CD10阳性。T型淋巴细胞分化抗原表达异常患者中有5例(25.00%)Cy CD3阳性,19例(95.00%)CD2阳性,18例(90.00%)CD4阳性,2例(10.00%)CD7阳性,2例(10.00%)CD5阳性。结论老年急性白血病患者主要以B淋巴细胞类型为主,且主要以CD19和CD79a为主。     

急性淋巴细胞白血病免疫分型的特点及其临床意义

目的:为了探讨急性淋巴细胞白血病(ALL)各亚型免疫分型的特点及其临床意义。方法:采用CD45/SSC双参数散点图设门,应用三色流式细胞术,对81 例ALL的初诊患者骨髓标本进行免疫分型,并对其中45例进行核型分析。结果:①B细胞系列的ALL(B ALL)中CD19表达最常见(阳性率为100%),而T细胞系列的ALL(T ALL)中CD5和CD7表达阳性率最高,均为90%;B -ALL和T- ALL都存在抗原交叉表达的现象;两组患者的完全缓解(CR)率差异无统计学意义(P>0.05);②伴髓系抗原表达的急性淋巴细胞白血病(My+ALL)比较常见,本组达到39.5%,常累及B淋巴系统(占My+ ALL的84.4%);各髓系抗原中以CD13 表达阳性率最高;此类患者的CR率较高,儿童CR率为72.2%,成人为78.6%;③急性杂合性白血病(HAL)的发病率为19.8%,以髓系、B系共同表达者居多;并且CD34表达阳性率较高(81.3%),该类患者CR率较低(儿童和成人分别为50%和40%);④CD34在B ALL,My+ALL和HAL中表达阳性率较高,而T ALL中少见(P<0.05)。结论:免疫分型在诊断特殊类型的ALL(如HAL,My+ALL)中具有显著优势;CD19和CD5诊断B- ALL和T- ALL的灵敏度较好,但特异性不高,存在抗原交叉表达;CD34和髓系抗原的表达与CR率无相关性,但在HAL,CD34的表达与CR率成负相关。     

急性白血病的免疫标记诊断

急性白血病的免疫标记诊断同济医科大学附属协和医院血液病研究所邹萍近年来由于杂交瘤技术与分子生物学技术的发展，数目众多的单克隆抗体（ＭｃＡｂ）相继问世。为细胞表面抗原的研究、急性白血病、淋巴瘤等疾病的免疫标记诊断奠定了基础，免疫标记能够提供正常细胞在演...     

成人早期前体T细胞急性淋巴细胞白血病的临床特征分析

目的:总结分析成人早期前体T细胞急性淋巴细胞白血病(early T-cell precursor acute lymphoblastic leukemia, ETP-ALL)的临床特征、治疗效果及长期预后。方法:回顾性研究2020年4月至2023年12月诊治的15例ETP-ALL患者,分析基本临床特征、流式免疫分型、细胞遗传学及分子生物学异常、治疗方案与预后的关系。结果:成人急性T淋巴细胞白血病患者中ETP-ALL的发生率为21.8%,其中男性占73.3%,中位年龄43岁,中位骨髓原始细胞比例71.1%。髓系/干细胞抗原阳性表达CD34、CD117、HLA-DR、CD13、CD33等。22.2%的患者合并染色体异常,80.0%的患者合并分子生物学异常,常见的基因突变包括NOTCH1、PHF6、JAK3、ETV6、JAK1、WT1等。第1个疗程诱导缓解治疗后73.3%的患者达完全缓解,66.7%的患者达微小残留病阴性的完全缓解。中位随访时间15.4个月,1年及2年总生存率分别为90.9%和77.9%,1年及2年无复发生存率分别为86.2%和64.6%。结论:成人ETP-ALL同时具有淋系...     

成人和儿童急性淋巴细胞白血病免疫表型比较分析

回顾性分析651例急性淋巴细胞白血病(ALL)患者的免疫表型,以CD45/SSC双参数散点图设门方法进行三色流式细胞术测定.发现651例ALL患者中,39.47%伴有髓系相关抗原的表达,其中最常见为CD13.成人ALL患者CD13、CD33表达率均明显高于儿童ALL患者.成人T-ALL患者CD34表达率显著高于儿童T-ALL患者.提示成人和儿童ALL患者免疫表型存在一定的差异,这可能是它们长期预后不同的原因之一.     

急性淋巴细胞白血病患儿T淋巴细胞免疫功能的研究

目的　研究急性淋巴细胞白血病 ( AL L )患儿初治时和完全缓解 ( CR)后外周血 T淋巴细胞亚群数量及其功能 ,寻找更好的控制儿童白血病的方法。方法　采用单克隆抗体在流式细胞仪上测定了 18例 B淋巴细胞系 AL L 儿童初治时、CR后外周血单个核细胞 ( MNC) CD3、CD4、CD8以及 IL-2受体 ( CD2 5 )含量及其 T淋巴细胞内细胞因子 γ-干扰素 ( IFN-γ)和肿瘤坏死因子 -α( TNF-α)水平。结果　初治时患儿 CD4/ CD8为 ( 1.10± 0 .79) ,较健康儿童 [( 2 .74± 1.2 1) ]明显降低 ( P<0 .0 1) ;CD4、CD8产生细胞因子的能力 ( IFN-γ和 TNF-α水平 )均低于正常儿童 ( P<0 .0 5)。 CR后 ,CD4/ CD8为 ( 2 .54± 1.3 9) ,比初治时明显提高 ( P<0 .0 5) ,CD4、CD8产生细胞因子的能力增强 ,但与正常对照组比较 ,各项数值仍低。初治患儿 CD4T淋巴细胞中 CD2 5 细胞数量为 ( 0 .76± 0 .56) ,明显低于 CR患儿 [( 2 0 .4± 5.1) ]和对照组 [( 16.3± 6.3 ) ] ,P均 <0 .0 1。结论　免疫损害在白血病的发病过程中起重要作用 ;T淋巴细胞的免疫功能与儿童白血病的预后关系密切 ;促进患儿免疫功能的恢复对治疗有重要意义     

Clinical experience of CAR T cells for B cell acute lymphoblastic leukemia

Chimeric antigen receptor (CAR) T cell therapy has transformed the treatment for both pediatric and adult patients with relapsed or refractory (R/R) B cell acute lymphoblastic leukemia (B-ALL). Clinical trial results across multiple institutions with different CAR constructs report significant response rates in treated patients. One product (tisagenlecleucel) is currently FDA approved for the treatment of R/R B-ALL in patients <26 y/o. Successful application of this therapy is limited by high relapse rates, potential for significant toxicity, and logistical issues surrounding collection/production. Herein, we review published data on the use of CAR T cells for B-ALL, including results from early pivotal clinical trials, relapse data, incidence of toxicity, and mechanisms to optimize CAR T cell therapy.     

Hypergranular acute lymphoblastic leukemia (ALL)

Summary We report a case of adult acute lymphoblastic leukemia (ALL) with myeloid-like hypergranulation of blast cells. Like most of the granular ALLs described in the literature, the blast cells had L2 morphology and exhibited a common-ALL immunologic phenotype. The clinical findings at diagnosis were unremarkable. Cytogenetic analysis showed a 46XY karyotype. Molecular genetic analysis revealed T-cell receptor (TCR) and immunoglobulin heavy chain rearrangements; no rearrangement was found at the TCR gene locus. The polymerase chain reaction (PCR) for the BCR-ABL translocation was negative. The clinical course of the patient was uncomplicated. On standard ALL treatment protocol he achieved complete remission (CR) within 4 weeks, and he is currently disease free 8 months after diagnosis. The case contributes well-documented data to the characterization of adult granular ALL, with special regard to changes at the molecular genetic level.     

急性淋巴细胞白血病Ki-67抗原和Bcl-2的表达及临床意义

目的：通过增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测，观察其在急性淋巴细胞白血病（ALL）和慢性淋巴细胞白血病（CLL）中的表达，探讨其与ALL免疫学分型，临床疗效和预后的关系。方法：采用链霉菌抗生物素蛋白-碱性磷酸酶（SAP）免疫组织化学染色的方法，对120例白血病患者的骨髓或外周血进行Ki-67抗原和Bcl-2蛋白的检测。结果：（1）Ki-67抗原在成人ALL中的表达高于其在急性非淋巴细胞白血病（ANLL），CLL中的表达，Bcl-2蛋白在成人ALL中的表达明显低于ANLL，CLL中的表达。（2）在成人ALL各免疫表型中，T细胞，伴有髓系抗原标记的急性淋巴细胞白血病（My^ ALL)的Ki-67和Bcl-2阳性表达率较高。（3）完全缓解（CR）率在Ki-67和Bcl-2两项同时低表达组中最高，在仅一项低表达组中次之，在两项均高表达组中最低。（4）Ki-67高表达组的生存期比低表达组短，且差异有显著性意义。而Bcl-2的表达在两组之间无差异。结论：对成人ALL患者进行增殖相关抗原Ki-67和抗凋亡蛋白Bcl-2的检测，能反映患者肿瘤细胞的增殖活性和凋亡抑制情况，与白血病的类型，临床疗效和预后密切相关。     

No adverse prognostic influence of hepatitis B virus infection in acute childhood lymphoblastic leukemia

Summary In the years 1980–1985 72 children with acute lymphoblastic leukemia were diagnosed and treated by intensive combination chemotherapy (BFM protocols 79, 81, 83). Of these children 33 acquired a Hepatitis B-virus-carrier state with 1983 as the peak year of incidence. Both groups of patients, the infected and the uninfected ones, were comparable as to prognostic factors. All except 8 patients are off chemotherapy after a total duration of treatment of 1 1/2 or 2 years. Probability for event-free survival (life table analysis, maximum observation time 82 months, minimum 12 months) is equal (0.77 vs. 0.75) in both groups. With 3 exceptions, all HBV-infected patients still carry the HBs-antigen in the serum; 22 of the 30 living patients in the infected group developed anti-HBc.     

Phenotypic and clinical heterogeneity of CD56-positive acute nonlymphoblastic leukemia

Summary The precise phenotype and clinical course are described of a subgroup of acute nonlymphoblastic leukemias (ANLL) expressing the NK-cell differentiation antigen CD56. As previously reported, CD56+ leukemias occurred in a frequency of about 20% of ANLL cases showing clinical and immunophenotypical heterogeneity. Carrying various myelomonocytic markers, all cases were diagnosed to be of nonlymphoid origin. Positive or negative expression of CD34 allowed us to distinguish two major subtypes of CD56+ leukemias representing immature and more differentiated cells carrying further differentiation antigens (CD14 and/or CD15) of the myelomonocytic lineages. These phenotypes correlated with the M0, M2, M4, and M5 leukemias of the FAB classification.     

Detection of clonality by polymerase chain reaction in childhood B-lineage acute lymphoblastic leukemia

Summary DNA-based PCR with various sets of primers for TCR /, and Ig heavy chain (IgH) genes were used to study clonality in childhood B-lineage acute lymphoblastic leukemia. Amplification of the IgH CDR-III was observed in 75 of 120 analyzed cases (62.5%). From all analyzed groups, the IgH gene rearrangement was most often observed in pre-B ALL (85.7%) and was rather rare in null-ALL (34.5%). TCR delta gene rearrangement was the most common, and was observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as anincomplete V2 to D3, V2 to D2, or D3 to D3 to D2 recombination product. Rearrangements of TCR gamma gene we observed in 61 cases (50.8%). TCR gamma gene rearrangements were detected predominantly in null-ALL and early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. Of all eight V segments of VI group, the most frequent gene usage concerns regions V2, V4, and V7. We have confirmed that IgH gene amplification, together with TCR gamma and delta gene amplification, provides a rapid, sensitive approach to assessing clonality in ALL almost in 100% of cases.This work was financed by KBN grants 4.0551.91.01 and 6.6346.92.03     

Antibody based therapy in relapsed acute lymphoblastic leukemia

Outcomes for relapsed and refractory acute lymphoblastic leukemia (ALL) remain poor. With the advent of targeted monoclonal antibodies and antibody constructs, these outcomes have been significantly improved both in the frontline and salvage setting. These targets include a bispecific antibody that targets both CD3 and CD19, known as blinatumomab, as well as a conjugated antibody that targets CD22, known as inotuzumab ozogamicin. These agents have been thoroughly studied and successively approved for use as monotherapy, however, more recently they have been incorporated in combination or sequentially with cytotoxic chemotherapy. In this chapter, we will discuss the role that these monoclonal antibodies play as monotherapy and in combination in the treatment of ALL in the salvage setting, and how they continue to transform the treatment management of relapsed and refractory ALL.     

Granular acute lymphoblastic leukemia with hypereosinophilic syndrome

9 /l), features of hypereosinophilic syndrome, and acute lymphoblastic leukemia (ALL-L2), the latter characterized by the presence of granular blasts. Blasts were negative for myeloperoxidase, non-specific esterase, acid phosphatase, periodic-acid Schiff stain, and toluidine blue. They exhibited an early pre-B immunophenotype (TdT, CD19, CD10, CD20 and CD22 positive) and stained negative for T (CD7, CD2, CD5 and CD3) and myeloid markers (MPO, CD33 and CD13). Chromosomal analysis revealed a normal karyotype. To the best of our knowledge, this case represents the first report of the coexistence of granular ALL and hypereosinophilic syndrome. Received: 11 May 1999 / Accepted: 20 October 1999     

儿童急性淋巴细胞白血病分型及其不同治疗方案与预后的临床研究

目的：研究儿童急性淋巴细胞白血病(ALL)的细胞形态学、免疫表型分型及不同方案治疗与预后的相关性。方法：采用骨髓涂片染色进行细胞形态学检查，采用单克隆抗体(McAb)和流式细胞仪(FCM)进行免疫表型检测。结果：103例儿童ALL患者中，67例(65．05％)为L1型，33例(32．04％)为L2型，无L2型，3例(4．91％)为其他。行免疫分型的87例中，58例(66．67％)为B系表达，12例(13．79％)为T系表达，10例(11．49％)为B系、髓系混合表达，3例(3．45％)为T系、B系混合表达，1例(1．15％)为T系、髓系混合表达，1例(1．15％)为B系、T系、髓系混合表达，2例(2．30％)为髓系表达。采用XH-88方案治疗25例，缓解卒92％，复发率52．17％，死亡率43．48％；协作组方案治疗41例，缓解率92．68％，复发率36．84％，死亡率55．26％；SUM-99方案治疗29例，缓解率93．10％，复发率18．52％，死亡率14．81％。结论：结合免疫分型与细胞形态学分型，将儿童ALL患者分为标危(SR)、中危(IR)和高危(HR)三组，按型采用不同的治疗方案对提高儿童ALL缓解率和降低其复发率有重要意义。     

急性淋巴细胞白血病用甲氨喋啶治疗的动力学研究

目的 :根据不同年龄 ,采用两种不同大剂量甲氨喋啶 2 4h持续静滴下的稳态血药浓度及毒性反应。方法 :分别于甲氨喋啶静滴开始后 1、6、2 3、44、6 8h点采集静脉血 2 ml及 1、2 4h点脑脊液 2 m l,应用免疫偏振荧光法检测血清与脑脊液 MTX浓度。结果 :9例老年组采用 2 g· M- 2 剂量 ,在 1、6、2 3、44、6 8h点血清 MTX浓度分别为 5 6 .97± 4.7μmol/ L、40 .46± 7.0 6μmol/ L、17.31± 9.76μm ol/ L、0 .91± 1.34μm ol/ L、0 .2 5± 0 .2 2μmol/L ;在 1、2 4h点脑脊液 MTX浓度分别为 0 .38± 0 .2 4μm ol/ L、2 .0 7± 0 .76μmol/ L。 16例中青年组采用 3 g· M- 2剂量 ,各小时点血清 MTX浓度分别为 82 .15± 12 .13μmol/ L、6 2 .33± 10 .0 6μm ol/ L、14.75± 7.0 6μm ol/ L、1.71± 1.6 8μm ol/ L、0 .45± 0 .44 μmol/ L;脑脊液 MTX浓度分别为 0 .5 4± 0 .35 μmol/ L、1.96± 0 .5 2 μm ol/ L。结论 :此两种剂量能达到急性淋巴细胞白血病 (AL L)细胞聚谷氨酸盐 MTX饱和所需的剂量 ,毒性反应是可以接受的。