CD20阳性成人急性B淋巴细胞白血病患者临床特点及生存分析

本研究分析成人CD20阳性急性B淋巴细胞白血病(B-lineage acute lymphoblastic leukemia,B-ALL)患者的临床特点和生存情况。回顾性总结分析郑州大学第一附属医院血液科2004年5月至2008年12月收治的119例成人B-ALL患者的临床特点和生存情况。结果表明:119例成人B-ALL中CD20阳性40例(33.61%),CD20阴性者79例(66.39%),CD20阳性组和CD20阴性组男性患者比例分别为72.50%和50.63%(p0.05),CD20阳性组和CD20阴性组发病时外周血白细胞数分别为(27.35±30.29)×109/L和(50.11±81.72)×109/L(p0.05)。两组患者在年龄分布、肝脾、淋巴结和中枢神经系统浸润、发病时血红蛋白和血小板水平、髓系抗原表达、Ph染色体、超二倍体和正常核型比例、4周内完全缓解率、诱导死亡率和复发率方面的差异无统计学意义(p0.05);Kaplan-Meier曲线生存率分析显示,CD20阳性组和CD20阴性组成人B-Lin ALL的中位总体生存(OS)时间分别为11.0个月和12.0个月,3年总生存率分别为28%和20%,两组间差异无统计学意义(p=0.832)。结论:CD20在成人B-ALL中的表达与患者的性别分布、外周血白细胞数相关,与其它临床特点无显著相关性,对患者的预后无显著影响。     

CD20阳性成人急性B淋巴细胞白血病患者临床特点及预后相关分析

目的 分析CD20在成人急性B淋巴细胞白血病(B-ALL)患者中的表达及CD20阳性B-ALL患者的临床特点和预后.方法 回顾性分析郑州大学附属肿瘤医院血液科2007年5月至2011年7月收治的168例初治成人B-ALL患者,其中CD20阳性58例,阴性110例.对比分析两组患者的临床特点和生存情况.结果 CD20阳性与阴性组在性别、年龄分布及贫血、血小板减少、肝脾或淋巴结肿大、髓外浸润、Ph染色体阳性、髓系抗原表达、早期死亡、高危患者比例方面差异均无统计学意义(P值均＞ 0.05),CD20阳性组患者初诊时中位白细胞计数(19.2×109/L)和高白细胞计数患者比例(37.9％)明显高于CD20阴性组(6.93×109/L和20.9％),差异有统计学意义(P值均＜0.05);两组诱导缓解治疗4周完全缓解率分别为78.6％和76.9％,差异无统计学意义(P＞0.05),3年累积复发率分别为59.3％和42.5％,差异有统计学意义(P＜0.05).多因素分析显示CD20 阳性是影响患者总生存(P=0.004)和疾病无进展生存(P=0.001)的独立预后不良因素 结论 CD20阳性表达与成人B-ALL患者外周血白细胞计数相关,且CD20阳性者预后不良.     

儿童急性B淋巴细胞白血病微小残留病检测及其预后意义

摘要：目的：建立检测急性B淋巴细胞白血病（B-ALL）微小残留病（MRD）的流式细胞术,评估监测MRD对于判断B ALL预后的价值。 方法：用四色荧光抗体组合流式细胞术对33例确诊并接受SCMC-ALL-2005方案治疗的B-ALL患儿进行MRD检测,并随访5年,分析监测结果、复发率、5年无事件生存率。 结果：建立了正常骨髓细胞分布的分析模板;流式细胞术检测结果表明,18例MRD阳性患儿的白血病复发率为55. 6%(10/18)、15例MRD阴性患儿复发率为13.3%(2/15),差异有统计学意义（P＜0.05）。其5年无事件生存率分别为44%和93%,差异有统计学意义（χ²=6.37,P＜0.05）。 结论: 监测MRD对于B-ALL患儿预后评估有重要意义,并为治疗方案的选择提供依据。     

人源化靶向CD19 CAR-T细胞治疗复发/难治急性B淋巴细胞白血病的有效性及安全性北大核心CSCD

目的观察人源化靶向CD19嵌合抗原受体T细胞(CAR-T)治疗复发/难治急性B淋巴细胞白血病(R/R B-ALL)患者的有效性及安全性。方法分析2020年2月至2021年7月于浙江大学医学院附属第一医院接受人源化靶向CD19 CAR-T细胞治疗的41例R/R B-ALL患者的有效性和安全性。结果中位第15(9~47)天,41例患者的完全缓解率为95.1%(39/41),其中38例患者骨髓经流式细胞术检测微小残留病灶阴性。39例完全缓解的患者中17例未接受进一步治疗,70.6%(12/17)的患者在随访结束时仍处于缓解状态,输注最早的两例患者无进展生存期达12.6个月;另外17例患者缓解后行巩固性造血干细胞移植(10例)或CD22 CAR-T细胞序贯治疗(7例),76.5%(13/17)的患者在随访结束时仍处于缓解状态;其余5例患者未接受巩固性治疗,在CAR-T细胞治疗后中位第72(55~115)天复发。1年总生存率为73.6%(95%CI 55.2%~92.3%),1年无进展生存率为56.2%(95%CI 38.1%~75.2%)。所有患者均发生了细胞因子释放综合征,63.4%(26/41)为1~2级。3例患者发生免疫效应细胞相关神经毒性综合征。结论人源化靶向CD19 CAR-T细胞能有效诱导R/R B-ALL患者获得完全缓解,且不良反应可耐受。     

CD56在正常核型急性髓系白血病患者中的表达及临床意义

目的分析正常核型急性髓系白血病(cytogenetically normal acute myeloid leukemia,CN-AML)患者骨髓白血病细胞中CD56表达情况,探讨CD56对CN-AML患者预后的影响。方法76例初诊CN-AML患者,应用流式细胞术检测骨髓白血病细胞中CD33、CD13、CD123、CD38、人类白细胞抗原(human leukocyte antigen,HLA)-DR、CD19、CD56、CD64、CD7、CD4、CD11b、CD14、CD15阳性表达,并均在评估病情后给予蒽环类药物联合阿糖胞苷标准诱导方案化疗。依据CD56表达是否≥20%,将76例患者分为CD56阳性组32例和CD56阴性组44例,比较2组临床特征及骨髓白血病细胞免疫表型特征、完全缓解率,随访1年观察复发率、总生存率和无事件生存率。结果CD56阳性组年龄[(50.9±16.1)岁]大于CD56阴性组[(38.56±15.2)岁](P<0.05),急性髓系白血病-M5亚型比率(31.3%)高于CD56阴性组(4.5%)(P<0.05),CD4、CD11b、CD14阳性表达率(43.8%、34.4%、28.1%)高于CD56阴性组(15.9%、13.6%、2.3%)(P<0.05);CD56阳性组与CD56阴性组白细胞计数、血小板计数、血红蛋白、乳酸脱氢酶、骨髓原始细胞比率、外周血原始细胞比率及CD33、CD13、CD123、CD38、HLA-DR、CD19、CD56、CD64、CD7、CD15阳性表达率比较差异均无统计学意义(P>0.05)。CD56阳性组完全缓解率(65.6%)、部分缓解率(18.8%)、复发率(47.6%)与CD56阴性组(68.2%、18.2%、40.0%)比较差异均无统计学意义(P>0.05),CD56阳性组1年总生存率(53.1%)和无事件生存率(50.0%)均低于CD56阴性组(77.3%、79.5%)(P<0.05)。结论CD56阳性表达可能提示CN-AML患者预后不良。     

CD123在淋巴细胞白血病细胞中的表达及在微量残留病监测中的作用

目的 探讨CD123在淋巴细胞白血病中的表达特点及意义.方法 应用多参数流式细胞术检测139例淋巴细胞白血病患者CD123的表达.以10名正常人骨髓淋巴细胞作对照.对105例急性B淋巴细胞白血病(B-ALL)患者行细胞遗传学分析.对97例B-ALL患者进行白血病微量残留病(MRD)分析.结果 ①10名正常人骨髓中B淋巴干/祖细胞、成熟B淋巴细胞及T淋巴细胞均不表达CD123.139例淋巴细胞白血病患者中,5例T-ALL和23例慢性B淋巴细胞白血病(B-CLL)患者CD123均阴性.111例B-ALL患者中106例CD123阳性(阳性率95.49%),其中包括12例早期前B-ALL、57例普通B-ALL、37例前B-ALL;5例成熟B-ALL患者CD123阴性.②在B-ALL患者中,CD123表达水平与p-Akt表达水平呈正相关,超二倍体患者组CD123表达水平高于非超二倍体患者组.③MRD阳性与阴性组患者比较,12个月内复发率分别为63.04%和21.56%,差异有统计学意义(P<0.01).MRD阴性组无病生存率[(48.23±1.82)%]高于MRD阳性组[(36.06±2.62)%].CD123在复发B-ALL患者中表达稳定性高.结论 CD123在B-ALL患者中普遍中度至强度表达,复发时表达稳定性高,是MRD分析较好的标志之一.     

CD133两种亚型分子在儿童B系急性淋巴细胞白血病中的表达及其临床意义

本研究旨在探讨B系急性淋巴细胞白血病(B-ALL)患儿初诊和治疗33 d时CD133两种亚型分子CD133-1和CD133-2的表达及其与临床预后指标的关系。用流式细胞术检测B-ALL患儿上述两个时间点骨髓单个核细胞的CD133-1、CD133-2表达和治疗33 d时微量残留病(MRD)的变化。结果表明,B-ALL初诊组48例中CD133-1阳性表达18例(37.5%),CD133-2阳性表达30例(62.5%,P<0.05);治疗33 d组25例中CD133-1阳性表达2例(8.0%),CD133-2阳性表达23例(92.0%,P<0.05)。诱导化疗后CD133-1的表达显著减少,但高于正常对照组;而CD133-2的表达下降缓慢。结论:初诊B-ALL患者CD133表达与其性别、年龄、外周血白细胞计数、骨髓幼稚细胞比例、FAB亚型、细胞遗传学异常、融合基因表达、危险等级及完全缓解率等均无相关性。B-ALL患儿CD133-2阳性表达高于CD133-1,CD133表达与CD34表达无相关性。CD133-2的表达与MRD显著相关。     

MFC监测MRD在AML形态学缓解患者中的应用价值

目的探讨多参数流式细胞术(MFC)监测微小残留病灶(MRD)在急性髓系白血病(AML)形态学完全缓解(mCR)患者中的应用价值。方法选取2015年5月至2019年5月该院收治的经过1~2个疗程诱导化疗后达到mCR的138例AML患者(排除M3)为研究对象,于每次化疗后3周左右或下次化疗前抽取骨髓,使用MFC检测MRD,比较MRD阳性和阴性患者的复发及生存情况,分析MFC监测MRD在AML mCR患者预后评估中的价值。结果138例患者中,MRD阳性31例,占22.5%。在化疗第1疗程达到mCR的患者中,MRD阴性有89例(83.2%),MRD阳性有16例(51.6%),差异有统计学意义(P<0.05)。MRD阳性患者累计复发率为61.3%,高于MRD阴性患者的48.6%(χ²=4.407,P=0.036);MRD阳性患者总生存率为54.8%,低于MRD阴性患者的70.1%(χ²=4.332,P=0.037);MRD阳性患者的无复发生存率为38.7%,低于MRD阴性患者的49.5%(χ²=4.408,P=0.035)。MRD阳性患者中,巩固化疗患者总生存率为47.4%,低于异基因造血干细胞移植患者的66.7%(χ²=4.190,P=0.041)。结论mCR后的MRD阳性患者复发率高,采用MFC监测MRD对AML患者预后具有重要意义,可以早期发现易复发患者,为个性化地制订缓解后治疗方案提供依据。     

人源化抗CD19嵌合抗原受体T细胞治疗急性B淋巴细胞白血病的临床研究

目的:研究人源化CD19 CAR-T细胞治疗难治/复发性B-ALL患者的安全性和有效性。方法:入组的患者为15例既往未接受鼠源CD19 CAR-T细胞治疗的复发/难治的B-ALL儿童和成人患者。患者在氟达拉滨和环磷酰胺为基础的预处理化疗后,接受了1×10~6/kg的自体人源化CD19 CAR-T(hCART19)细胞的输注。在患者回输CAR-T细胞后观察其治疗的安全性及有效性。结果:15名患者中,13/14(92.9%)可评价的患者在hCART19输注后30 d获得了完全缓解(CR)或者CR伴血细胞不完全恢复(CRi)。180 d时总生存率及无病生存率分别达到73.3%和69.2%。累积复发率及非复发死亡率分别是24.5%和7.7%。15例患者中有12名患者(80%)发生了1-2级的细胞因子释放综合征(CRS),3名患者(20.0%)发生了3-5级的CRS,而只有1名患者(6.7%)发生了可逆性神经毒性。结论:hCART19s可有效治疗复发/难治的成人及儿童B-ALL患者,且治疗相关的CRS及神经毒性发生率较低。     

合并t(8;21)/RUNX1-RUNX1T1~+初治AML患儿预后影响因素分析

目的 :探讨合并t(8;21)/RUNX1-RUNX1T1+初治急性髓系白血病(AML)患儿预后影响因素。方法 :回顾性分析本院2009年1月-2017年1月收治合并t(8;21)/RUNX1-RUNX1T1+初治AML患儿41例临床资料,记录基线临床特征、累积复发、无事件生存及总生存情况,并通过χ2检验和Cox回归模型评价预后影响因素。结果 :41例患儿行诱导方案化疗后首个疗程和第2个疗程完全缓解率分别为82.93%(34/41)和97.56%(40/41);中位无事件生存时间和总生存时间分别为30和31个月。首个疗程达完全缓解患儿无事件生存率和总生存率显著高于未达完全缓解患儿(P0.05);男性患儿无事件生存率显著高于女性患儿(P0.05);发病年龄10岁患儿总生存率显著高于≥10岁患儿(P0.05)。第2次诱导缓解后RUNX1-RUNX1T1基因表达水平是患儿累积复发率、无事件生存率及总生存率影响因素(P0.05);Cox回归模型多因素分析显示,第2次诱导缓解后RUNX1-RUNX1T1基因表达下降3 log是影响患儿无事件生存率和总生存率独立危险因素(P0.05);同时RUNX1-RUNX1T1基因表达下降3 log水平后升高 1 log水平患儿累积复发率显著高于≤1 log水平患儿(P0.05)。结论 :合并t(8;21)/RUNX1-RUNX1T1+初治AML患儿行规范化疗后临床预后良好, RUNX1-RUNX1T1基因表达水平与AML患儿复发及远期生存密切相关。     

Determination of creatine kinase isoenzyme MB activity in serum using immunological inhibition of creatine kinase M subunit activity. Activity kinetics and diagnostic significance in myocardial infarction.

This is a new method for the determination of creatine kinase isoenzyme MB activity in serum. The method uses direct activity measurement of creatine kinase B subunit activity after blocking of CK-M subunit activity by inhibiting antibodies. The test takes no longer than 15 min. The method yields an intra-serial C.V. of 2.0-12.9%, and a C.V. from day to day of 5.5%. The detection limit is 3.4 U/l creatine kinase MB. In the 95 cases with proven myocardial infarction several types of creatine kinase MB activity kinetics could be determined. The percentage of creatine kinase MB of peak CK-total is 6-25%, with a mean of 11.1%. The amount of creatine kinase MB with respect to total CK activity after reinfarction is higher than the amount after initial infarction.     

Dissociable correlates of two classes of retrieval processing in prefrontal cortex

Although substantial evidence suggests that the prefrontal cortex (PFC) implements processes that are critical for accurate episodic memory judgments, the specific roles of different PFC subregions remain unclear. Here, we used event-related functional magnetic resonance imaging to distinguish between prefrontal activity related to operations that (1) influence processing of retrieval cues based on current task demands, or (2) are involved in monitoring the outputs of retrieval. Fourteen participants studied auditory words spoken by a male or female speaker and completed memory tests in which the stimuli were unstudied foil words and studied words spoken by either the same speaker at study, or the alternate speaker. On "general" test trials, participants were to determine whether each word was studied, regardless of the voice of the speaker, whereas on "specific" test trials, participants were to additionally distinguish between studied words that were spoken in the same voice or a different voice at study. Thus, on specific test trials, participants were explicitly required to attend to voice information in order to evaluate each test item. Anterior (right BA 10), dorsolateral prefrontal (right BA 46), and inferior frontal (bilateral BA 47/12) regions were more active during specific than during general trials. Activation in anterior and dorsolateral PFC was enhanced during specific test trials even in response to unstudied items, suggesting that activation in these regions was related to the differential processing of retrieval cues in the two tasks. In contrast, differences between specific and general test trials in inferior frontal regions (bilateral BA 47/12) were seen only for studied items, suggesting a role for these regions in post-retrieval monitoring processes. Results from this study are consistent with the idea that different PFC subregions implement distinct, but complementary processes that collectively support accurate episodic memory judgments.     

俯卧位通气对高海拔地区肺复张治疗无效急性呼吸窘迫综合征患者氧合的影响

目的 探讨俯卧位通气对高海拔地区肺复张术(RM)治疗无效急性呼吸窘迫综合征(ARDS)患者的治疗作用.方法 从海拔2260m的地区医院筛选RM治疗无效的41例ARDS患者[平均氧合指数( PaO2/FiO2)较RM前升高＜20％视为RM无效],依不同病因分为肺内源性ARDS组(ARDSp组)和肺外源性ARDS组(ARDSexp组),每组再按信封法随机分为俯卧位组和仰卧位组,即ARDSp俯卧位组(11例)、ARDSp仰卧位组(9例)、ARDSexp俯卧位组(10例)、ARDSexp仰卧位组(11例).在通气前及通气1、2、3、4h监测动脉血氧分压( PaO2)、PaO2/FiO2、静态顺应性(Cst)、气道阻力(Raw)的变化.结果 通气lh时,ARDSexp俯卧位组PaO2/FiO2( mm Hg,l mm Hg=0.133 kPa)即较通气前显著升高(157.4±40.6比129.3±48.7,P＜0.05),并随通气时间延长呈持续增高趋势,4h达峰值(219.1 ±41.1);且ARDSexp俯卧位组通气3h内PaO2/FiO2较其他3组显著增高,另3组间则差异无统计学意义.ARDSp俯卧位组、ARDSexp俯卧位组通气4h时PaO2/FiO2均较相应仰卧位组显著增高(208.8±39.7比127.4±47.1,219.1±41.1比124.9±50.8,均P＜0.05).4组通气前后Cst无显著改变,各组间差异也无统计学意义.ARDSp俯卧位组通气4h时Raw(cmH2O·L-1·s-1)较通气前显著降低(6.8±1.7比10.7±1.8,P＜0.05),且明显低于其他3组;其他3组各时间点Raw组内及组间比较差异均无统计学意义.结论 俯卧位通气作为ARDS机械通气重要策略之一,可以改善RM无效高原ARDS患者的氧合,为抢救患者赢得宝贵的时间.     

Digital imaging among medical facilities

The Department of Veterans Affairs (VA) in the USA operates a network of 172 medical centres which all utilize a hospital information system (HIS) which has been developed and is currently maintained by the VA. During the past several years, an image management and communication module has been developed, installed and clinically utilized at the Washington DC and Maryland VA Medical Centres. This image management and communication system, referred to as the decentralized hospital computer program (DHCP) imaging system, is fully integrated with a commercial picture archiving and communication system (PACS). The system is utilized to capture, archive, and display all images generated within the hospital including radiology, nuclear medicine, pathology, endoscopy, bronchoscopy, and dermatology, intraoperative photographs, ECG data, and a limited number of paper documents. The ultimate goal of the project is to have all patient text and image data available at any clinical workstation to any authorized user anywhere within the network of medical centres. Clinical requirements for an imaging workstation include ease of use, rapid and reliable access to the complete set of patient information, and images which are of acceptable quality to meet the requirements of the user and the subspecialty. Patient confidentiality and data security must be safeguarded at all times. Integration of the images with the remainder of the patient's database was found to be critical to the success of the project. The experience at the Washington and Maryland facilities suggests that an imaging system that is successfully integrated with a hospital information system can provide substantial clinical and economic benefits both within and among medical centres. Clinical acceptance and utilization of the system has been excellent, particularly in diagnostic radiology where DHCP Imaging has been interfaced to a commercial PAC system. Based upon this initial experience, the VA has begun to deploy the system throughout its large network of medical centres.     

Myocardial elastography at both high temporal and spatial resolution for the detection of infarcts

Myocardial elastography is a novel method for noninvasively assessing regional myocardial function, with the advantages of high spatial and temporal resolution and high signal-to-noise ratio (SNR). In this paper, in-vivo experiments were performed in anesthetized normal and infarcted mice (one day after left anterior descending coronary artery [LAD] ligation) using a high-resolution (30 MHz) ultrasound system (Vevo 770, VisualSonics Inc., Toronto, ON, Canada). Radiofrequency (RF) signals of the left ventricle (LV) in longitudinal (long-axis) view and the associated electrocardiogram (ECG) were simultaneously acquired. Using a retrospective ECG gating technique, 2-D full field-of-view RF frames were acquired at an extremely high frame rate (8 kHz) that resulted in high-quality incremental displacement and strain estimation of the myocardium. The incremental results were further accumulated to obtain the cumulative displacements and strains. Two-dimensional and M-mode displacement images and strain images (elastograms), as well as displacement and strain profiles as a function of time, were compared between normal and infarcted mice. Incremental results clearly depicted cardiac events including LV contraction, LV relaxation and isovolumetric phases in both normal and infarcted mice, and also evidently indicated reduced motion and deformation in the infarcted myocardium. The elastograms indicated that the infarcted regions underwent thinning during systole rather than thickening, as in the normal case. The cumulative elastograms were found to have higher elastographic SNR (SNR(e)) than the incremental elastograms (e.g., 10.6 vs. 4.7 in a normal myocardium, and 6.0 vs. 2.4 in an infarcted myocardium). Finally, preliminary statistical results from nine normal (m = 9) and seven infarcted (n = 7) mice indicated the capability of the cumulative strain in differentiating infracted from normal myocardia. In conclusion, myocardial elastography could provide regional strain information at simultaneously high temporal (>/=0.125 ms) and spatial ( approximately 55 microm) resolution as well as high precision ( approximately 0.05 microm displacement). This technique was thus capable of accurately characterizing normal myocardial function throughout an entire cardiac cycle, at the same high resolution, and detecting and localizing myocardial infarction in vivo.     

手转胎头术失败的原因与分娩结局临床分析

目的 探讨手转胎头术失败的原因与分娩结局.方法 选择2008年1月至2010年12月于我院住院分娩的持续性枕横位、枕后位产妇198例,根据行手转胎头术后结果分为成功组126例、失败组72例.比较两组分娩结局,对比分析失败原因.结果 失败组胎儿体质量≥3500 g的发生率[76.4％(55/72)]明显高于成功组[31.7％(40/126)],差异有统计学意义(x2=30.177,P=0.001)、失败组宫缩乏力发生率[58.3％(42/72)]高于成功组[38.1％ (48/126)],差异有统计学意义(x2=7.569,P=0.006)、失败组骨盆临界或轻度狭窄发生率[38.9％ (28/72)]高于成功组[23.8％(30/126)],差异有统计学意义(x2 =5.030,P=0.002)、失败组手转胎头时机不当(宫口开大＜6 cm、胎头位于坐骨棘上及宫口开大8～10 cm、胎头位于坐骨棘下≥2 cm)发生率[61.1％(44/72)]高于成功组[38.9％(49/126)],差异有统计学意义(x2=9.084,P=0.003).失败组母儿并发症(产后出血、产褥病率、胎儿窘迫、新生儿窒息)发生率高于成功组(x2 =9.586,P=0.002、x2=9.334,P=0.002、x2=5.910,P=0.015、x2=5.240,P=0.022)、失败组剖宫产发生率[72.2％(52/72)]明显高于成功组[34.1 ％(43/126),x2=26.641,P=0.001)].结论 手转胎头术能使难产变顺产,降低剖宫产率,减少母儿并发症,但须积极预防、处理导致手转胎头术失败的原因,对矫正失败后继续矫正及试产应慎重.