应用蛋白质芯片技术筛选急性淋巴细胞白血病患儿血清标志物的研究

目的探讨儿童急性淋巴细胞白血病(ALL)急性期、缓解期(CR)患儿血清蛋白质谱的变化,旨在筛选可用于ALL早期诊断、病情变化监测及预后判断的蛋白质标志物。方法应用蛋白质芯片CM10及表面增强激光解吸/离子化飞行时间质谱(SELDI-TOF-MS)技术获得ALL、正常健康儿童血清蛋白表达指纹图谱,并用Biomarker Wizard和Biomarker Patterns System5.0软件对数据进行分析,建立诊断模型。结果通过检测、分析发现,ALL组与正常对照组比较有显著差异(P<0.05)的蛋白质峰有14个,并获得质荷比(M/Z)为2770.43、7576.2和5288.68的蛋白质在ALL患儿血清蛋白质谱中波峰强度明显升高;进一步利用这3个蛋白质建成的诊断模型,可将ALL与正常儿童正确分组,其正确分组率分别为93%(25/27)和90%(19/21)。ALL完全缓解后血清蛋白质谱中,原高表达的蛋白质明显下调。结论SELDI-TOF-MS蛋白质芯片技术是一种快速、简单易行、用量少和高通量分析方法,能够直接检测出ALL患者血清中特异的蛋白标志物,其对于ALL的早期诊断具有一定的临床意义。     

急性淋巴细胞性白血病患儿血清唾液酸变化的探讨

唾液酸 ( sialic acid,SA)是 9碳糖神经氨酸衍生物的总称。它位于糖蛋白、糖脂结构的末端 ,是细胞膜的重要成分 ,参与细胞表面的多种生理功能。研究表明 ,细胞膜糖蛋白和糖脂的改变与肿瘤的侵入和破坏行为有关。唾液酸对于维护细胞表面的功能起着决定性的作用。对多种疾病的诊断、疗效观察及预后具有重要意义。为探讨急性淋巴细胞性白血病血清唾液酸的变化 ,本文做了如下一组报告并与正常对照组比较 ,现将结果报告如下。材料与方法1.研究对象　 ( 1)正常对照组 :随机选取正常健康儿童 2 6例 ,其中男 14例 ,女 12例 ,年龄 3～ 14岁。 ( 2 )…     

急性淋巴细胞性白血病患儿的护理

目的让护士增加急性淋巴细胞性白血病的知识，能敏锐观察到患儿的病情变化环节，及时救治，安全护理，预防差错，减轻患儿的痛苦，促进患儿的健康。方法描述患儿的病临床症状、体征，介绍一般护理与特殊治疗过程的护理，用一些关键性化验指标提示、提醒护理人员要注意观察患儿的病情变化及预防措施，强调个人卫生及心理护理和亲属的陪护，注意营养及无菌概念，预防院内感染。结果患儿在住院期间身心快乐，得到优质护理，减轻痛苦，减少并发症，缩短治疗时间，有效地配合医生治疗，促使疾病好转。结论护士通过有计划，系统地配合医生治疗，提供优质护理，保证了医疗护理的安全，促进了患儿早日康复，促进了医疗卫生事业的健康、有序的发展，维护了社会的稳定。     

急性淋巴细胞性白血病患儿脑脊液铁蛋白

研究目的发探讨白血病患儿脑脊液铁蛋白（CSF－Ft）含量的变化及其临床意义。研究方法经骨髓检查确诊的急性淋巴细胞性白血病患儿42例，分为3组，Ⅰ组（诱导治疗期不伴中枢神经系统白血病）14例，Ⅱ组（完全缓解期不伴中枢神经系统白血病）24例，Ⅲ组（合并中枢神经系统白血病）18例。病毒性脑炎（病脑）组17例，对照组15例均无中枢神经系统疾病。用放射免疫分析法检测CSF－Ft及血清铁蛋白。结果Ⅰ、Ⅱ、Ⅲ组、病脑组和对照组患者CSF－Ft含量分别为7．03±2．21μg／L，6．75±1．94μg／L，31．06±8．85μg／L，7．26±1．83μg／L和6．52±1．57μg／L。Ⅲ组患儿LCSF－Ft含量明显高于其它组（P均＜0．01）。10例中枢神经系统白血病患儿，随病情好转其CSF－Ft水平渐下降。结论CSF－Ft检测对中枢神经系统白血病诊断有重要价值，并可做为评价中枢神经系统白血病治疗效果的重要指标。     

急性淋巴细胞性白血病患儿巯嘌呤耐受性研究

目的 调查急性淋巴细胞性白血病(acute lymphoblastie leukemia,ALL)患儿,维持化疗期间巯嘌呤(6-mercaptopurine,6-MP)的耐受性,为进一步研究6-MP耐受性差异的原因提供依据.方法 选择规范应用北京儿童医院急性淋巴细胞性白血病2003年化疗方案(BCH-ALL-2003),随访至2008年9月30日的患儿.全部患儿处于骨髓缓解期,且维持化疗≥13个月.详细记录患儿6-MP服用情况,包括服用剂量以及恶心、呕吐、皮疹等用药反应,以调查6-MP的耐受性.所有患儿每周复查血常规,间隔4周复查肝功能,并根据检查结果进行6-MP毒性分级.记录6-MP停止时间和剂量减少程度.结果共133例,男81例,女52例,中位年龄67个月(18～188个月),中位缓解时间26个月(6～47个月).6-MP维持化疗(13.5±7.4)个月(3～25个月),其中6-MP标准剂量、全疗程者72例(54%),剂量46 ms/(m~2·d),白细胞(WBC)(3～4)×10~9/L,中性粒细胞(ANC)(1.5～2.0)×10~9/L,肝脏毒性小于Ⅱ级,4例(3%)患儿ANC持续在3×10~9/L以上,6-MP剂量增加为标准剂量125%.余61例患儿均为严重不耐受6-MP者,其中骨髓抑制48例(同时伴肝毒性9例),单纯肝脏功能异常12例,反复皮疹1例.平均毒性反应出现时间为2.5周.19例患儿平均停用6-MP 7 d,42例患儿平均6-MP实际剂量25～30 ms/(m~2·d).结论 ALL患儿个体间6-MP的耐受性差异很大,46%ALL患儿对6-MP的标准治疗剂量表现为明显的骨髓抑制和肝功能异常等不耐受反应,临床需要根据血常规不断调整6-MP的剂量,以避免较大的毒性反应的发生,而3%患儿给予标准剂量6-MP,表现为无轻度骨髓抑制等化疗反应,临床需要增加6-MP剂量以减少复发危险性.但如何更准确地进行6-MP剂量调整是临床研究的难题之一.选择6-MP严重不耐受患儿进行6-MP代谢酶活性和基因多态性研究,以明确ALL儿童6-MP耐受性差异的原因,为进一步进行个体化药物剂量的调整提供理论依据.     

急性淋巴细胞白血病患儿血清唾液酸变化的探讨

唾液酸（sialic acid,SA)是9碳糖神经氨酸衍生物的总称，它位于糖蛋白，糖脂结构的未端，是细胞膜的重要成分，参与细胞表面的多种生理功能，研究表明，细胞膜糖蛋白和糖脂的改与肿瘤的侵入和破坏行为有关。唾液酸对于维护细胞表面的功能起着决定性的作用，地多种疾病的诊断，疗效观察及预后具有重要意义，为探讨急性淋巴细胞性白血清唾液酸的变化，本文做了如下一组报告并与正常对照组比较，现将结果报告如下。     

急性淋巴细胞性白血病患儿中枢神经系统白血病预防的研究进展

采用联合化疗以来,儿童急性淋巴细胞性白血病（ALL）的预后大为改观。上世纪60年代的研究证实,约65％的白血病患儿在缓解期出现中枢神经系统（CNS）白血病,从而导致全身复发。所以,儿童ALL治疗成功与CNS的预防性治疗密切相关,进行CNS治疗的患儿有较高的无事件生存（EFS）及长期生存率。CNS预防性治疗最初使用的颅脑放射治疗,剂量是24Gy,同时加短期的鞘内注射。然而,生存者的长期随访发现,该治疗有严重的毒性反应,如：生长迟缓及内分泌紊乱、神经心理方面的问题等;继发性颅脑肿瘤的风险明显增加。由于颅脑放疗引起的晚期毒性反应逐渐被认识,随后发展为逐渐减少放疗剂量和（或）使用全身（或鞘内）化疗取代放疗。新的治疗包括延长鞘注的疗程、采用中～大剂量甲氨蝶呤（MTX）持续静脉输注以及在应用泼尼松的基础上使用地塞米松。任何形式的CNS治疗都可以引起急性的或晚期的毒性反应。后来对病情评估越来越详细,如：初诊时根据CNS情况、病情危险度分组等进行不同方法CNS预防治疗,这些临床研究的目的是为了减少治疗产生的毒性反应的风险,改善治疗效果。     

青少年急性淋巴细胞性白血病

近年来,由于采用精确的危险度分型策略、强烈的化疗方案以及支持治疗水平的提高,使得儿童急性淋巴细胞性白血病(ALL)的疗效得到显著提高,5年无事件生存率(event free survival,EPS)可达80%以上,而成人ALL的长期生存率仍较低,5年EFS仅在30%～40%左右,儿童与成人在这一类疾病的生物学特点、治疗方法和疗效上都存在巨大差异.     

急性淋巴细胞白血病患儿长期疗效分析

目的分析70例ALL患儿分型治疗的长期疗效和远期不良反应,以寻求提高患儿长期高质量无病生存的方法。方法随访并分析2000年1月-2009年12月在本院儿科血液/肿瘤病房诊断并坚持治疗的70例ALL患儿情况。临床分型:标危型、中危型、高危型和ALL-L3型患儿分别为42、12、7例和9例。采用Kaplan-Meier方法进行长期生存情况分析。结果 5 a无事件生存率在标危组、中危组和ALL-L3组分别为(93.87±4.22)%、(85.33±6.45)%和(88.89±7.48)%。高危型患儿目前无病存活率为42.86%(3/7例)。复发6例(8.57%),其中死亡4例,另有5例无复发死亡,总病死率12.86%。长期不良反应观察未发现二次肿瘤及蒽环类心肌病发生,4例(5.71%)患儿生长受限,1例患儿发生单侧股骨头无菌性坏死。结论分型治疗可提高ALL患儿长期生存率,改善ALL患儿生存的质量。     

Current management of childhood acute lymphocytic leukemia

Despite major advances in the treatment of childhood leukmia, there remain controversies in classification, prognostic importance of clinical and laboratory investigations, intensity of induction chemotherapy, presymptomatic CNS therapy, type and duration of maintenance chemotherapy and the role of bone marrow transplantation. In this review, some of these problems are highlighted and differences between long-term results of treatment from group studies, and those reported from Melbourne are discussed.     

儿童急性淋巴细胞白血病特殊的前期表现

<正> 报告5例小儿急性淋巴细胞白血病(ALL)特殊的前期表现,其发病及演变复杂,诊断困难,也是目前白血病研究中的难题。在此结合文献,总结分析如下。     

Prognostic factor analysis in acute lymphocytic leukemia of childhood

The analysis of clinical and hematological data for prognostic relevance in 200 children with acute lymphocytic leukemia (ALL), diagnosed between January 1964 and December 1980, showed that the importance of single risk factors has changed due to improvements in therapy. Morphology and cytochemistry lost their prognostic value they had in those patients treated before October 1971. In the children treated in the seventies, the WBC became the most important prognostic factor, followed by infiltrate size and age. (Age was less important than infiltrates for remission duration, but more for survival.) Immunological markers were evaluated in 56 children, since 1974. Because of the small number, no significance as risk factor was found. Those 25% with E+ blasts tended to have only a slightly worse course than "non-T-non-B"-ALL. Treatment became a highly significant risk factor, because of the improvement in results between those patients treated with CALGB protocol 6801 and those on protocol 7111. Two steps were responsible for this: better treatment strategies, and, most important, CNS-prophylaxis (or "sanctuary"-treatment) in all patients. Even in the sixties, where IT methotrexate alone was given sporadically, omitting the CNS-prophylaxis represented an important risk factor. Since 1971, most patients received cranial irradiation or intermediate dose methotrexate as second mode of CNS-prophylaxis. This resulted in a significant decrease in the incidence of CNS relapse. CNS-prophylaxis mode therefore represented a significant prognostic factor, although age, WBC and infiltrates had become more important. Evaluation of the clinical and hematological data gave the following limits for an increased or lesser risk: WBC over 30.G/l: high risk, under 10.G/l: favourable. Age: below 1 year and over 10 years: high risk, 1-2 years: probably moderately increased risk. Infiltrates: no palpable hepatosplenomegaly and no lymph nodes: favourable, all palpable infiltrates: "standard" or increased risk. Platelets (under 30.G/l) represented a minor good risk factor. The common ALL antigen (CALLA) was not yet examined in this series, calling it a favourable factor is based on recent experience from other centers. T-markers are probably not a risk factor by themselves, but other poor prognostic signs are usually associated and of primary importance. If treatment will be based on risk classification, it is important to keep in mind that treatment improvements might change the significance of any prognostic factor completely.     

Prognostic cytogenetic markers in childhood acute lymphoblastic leukemia

Objective To evaluate children with acute lymphoblastic leukemia (ALL) showing resistance to immediate induction chemotherapy in relation to conventional and advanced cytogenetic analysis. Methods This work was conducted on 63 ALL children (40 males and 23 females) with age range 4.5 months–16 years (mean = 7.76 years). They included 37 cases attained true remission and 26 complicated by failure of remission, early relapse or death. They were subjected to history, clinical examination and investigations including CBC, BM examination, karyotyping, FISH for translocations and flowcytometry for immunophenotyping and minimal residual disease diagnosis. Results Cases aged < 5 years; male sex with organomegaly had better remission although statistically insignificant. Initially low HB < 8 gm/dl, high WBCs and platelet counts > 50.000/mm³ also showed better but non-significant remission rates. Most of the present cases were L₂ with better remission compared to other immunophenotypes. Forty informative karyotypes were subdivided into 15 hypodiploid, 10 pseudodiploid, 8 normal diploid and 7 hyperdiploid cases; the best remission rates were noticed among the most frequent ploidy patterns. Chromosomes 9, 11 and 22 were the most frequently involved by structural aberrations followed by chromosomes 5, 12 and 17. Resistance was noted with aberrations not encountered among remission group; deletions involving chromosomes 2p, 3q, 10p and 12q; translocations involving chromosome 5; trisomies of chromosomes 16 and 21; monosomies of 5 and X and inversions of 5 and 11. Conclusion Some cytogenetic and molecular characterizations of childhood ALL could add prognostic criteria for proper therapy allocation.     

High dose methotrexate in acute lymphocytic leukemia in childhood.

Gonadal and other types of leukemic "sanctuaries" are probably the main causes of hematological relapse in the treatment of acute leukemia. The introduction of high-dose Methotrexate (HDM) in a consolidation phase is based on theoretical considerations and the use of HDM in malignant tumors. Three courses of Methotrexate, 500 mg/sq.m. at 3-weekly intervals, has been used as part of a consolidation therapy in Norway during the last two years to 59 children with ALL and one with AML. One child died following HDM. Postmortem examination showed that she was not in complete remission at the time. Among 154 courses of HDM in the 60 patients were eight severe reactions, including six cases of allergic-toxic skin reactions. Two patients developed a Stevens-Johnson's like syndrome. Stomatitis was common in those with toxic reactions. The risk of HDM in patients who are not in complete remission is stressed and the use of rescue therapy with two doses of Leukovorin instead of one is recommended. Forty of forty-two children in 1st complete remission have been in sustained primary remission for 4 to 28 months. Two of these 40 children died after about a year from infections. Only two patients so far have relapsed.