儿童急性淋巴细胞白血病的晚期复发

本文分析了进入英国医学研究委员会(MRC)ALL试验治疗的儿童急性淋巴细胞白血病(ALL)的长期随访资料,并估算了晚期复发的频率,以及导致这种复发的白血病类型及何种病人有这种危险。 材料和方法 病人来自1970～1984年在MRC ALL试验中治疗的儿童,随访时间均达10年以上,中数随访期18年。从骨髓片上取材抽提DNA,用聚合酶链反应(PCR)法扩增免疫球蛋     

婴儿急性淋巴细胞白血病:医学研究会儿童白血病工作组MRC UKALL试验治疗的经验报告

儿童急性淋巴细胞白血病(ALL)的治疗已有一定进展,但某些类型仍有高度复发的危险性。已知1岁以下婴儿白血病治疗多数失败,部分反映了其独特的临床生物学特性。不仅骨髓与中枢神经系统(CNS)的ALL有高度复发危险,年龄小也使其对治疗远期效应和神经心理毒性易感。本文报告了1岁     

尾型同源盒基因在成人急性淋巴细胞白血病中表达及临床意义

本研究旨在探讨同源盒基因CDX1,CDX2和CDX4在成人急性淋巴细胞白血病(ALL)中的表达及其临床意义.急性淋巴细胞白血病骨髓或外周血标本51份,采用逆转录聚合酶链反应(RT-PCR)检测CDX1,CDX2和CDX4在成人急性淋巴细胞白血病患者和14例正常对照组中的表达情况.结果表明,在14例健康成人中未见CDX1,CDX2和CDX4表达,15例缓解期急性淋巴细胞白血病患者中未见CDX1,CDX2和CDX4表达,在初治ALL患者中CDX2的表达率为60.8%,而在治疗缓解后其表达率明显下降(p<0.05);在复发组患者中CDX2表达率又升高(81.8%);CDX2表达与疾病危险分组相关,高危组CDX2阳性率为91.7%,高于标危组45.7%(p<0.05);CDX1和CDX4在初治及复发成人ALL中皆无表达.在初治和复发的成人ALL患者中CDX2表达阳性患者的完全缓解率(CR)低于表达阴性的患者(p<0.05);CDX2表达阳性患者的中位生存时间短于阴性表达的患者.结论:CDX2表达和成人ALL的发病、复发相关,CDX1和CDX4表达与成人ALL发病及复发无相关性;CDX2表达阳性的患者完全缓解率低,预后不良;CDX2可作为成人急性淋巴细胞白血病的发病、复发及预后判断的指标之一.     

糖皮质激素受体自我诱导在白血病细胞激素耐药中的作用

激素治疗反应好是儿童急性淋巴细胞白血病(ALL)预后佳的指标,而激素耐药是导致治疗失败和复发的主要原因.故研究激素耐药,对于进一步提高儿童ALL治疗效果有重要意义.     

急性淋巴细胞白血病的治疗

在美国,每年约有4 000例患者被诊断为急性淋巴细胞白血病(ALL),其中近2/3是儿童和青少年,这使得ALL成为该年龄组中最常见的恶性肿瘤。从20世纪50年代至80年代,通过不断完善合理使用抗白血病药物和在临床试验中应用按危险因素分组的化疗方案,使ALL治疗效果得以稳步改善。20世     

急性淋巴细胞白血病细胞及分子遗传学改变与预后

急性淋巴细胞白血病（Acute Lymphoblastic Leukemia ,ALL）是一种淋巴细胞系前体细胞恶性克隆性血液病,是儿童最常见的白血病类型.儿童急性白血病中ALL占80%,成人急性白血病中ALL约占25%.其中约有80%儿童ALL和60%-70%成人ALL存在细胞遗传学异常[1].更多的患者能够检测出分子遗传学异常,这些基因异常的发现使我们对于ALL的发病机制认识上升至分子层面,为ALL预后分层提供新的依据,并有助于我们寻找新的分子靶向治疗靶点.……     

急性淋巴细胞白血病发病机理相关的细胞遗传学异常

本文就近年来急性淋巴细胞白血病(ALL)细胞遗传学研究的进展作一简述,并着重讨论细胞遗传学异常和ALL发病机理间的关系。     

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。     

儿童急性淋巴细胞白血病的预后因素

目前在西方规模大的儿童急性淋巴细胞白血病（ALL）治疗中心，其ALL的治愈率已达到80%，此成就归因了依据危险度所确定的多药联合化疗和中枢神经系统预防。患的分层是根据预后因素预测复发危险。研究预后因素间的相互关系是必要的，已被广泛熟知的宿主相关因素包括年龄，性别，种族和药物遗传学。疾病相关预后因素包括白细胞计数，免疫分型，细胞或分子遗传学特征。早期治疗反常是最有力的预后因素。大的，对照的和随机的临床方案的采用大大地改善了儿童急性淋巴细胞白血病的预后。     

表鬼臼毒素和阿糖胞苷联合治疗初次诱导失败的儿童急性淋巴细胞白血病

作者报告应用表鬼臼毒素(VM-26)和阿搪胞苷联合治疗14例儿童急性白血病的结果。其中11例为急性淋巴细胞白血病(ALL),3例为细胞化学染色阴性的急性未分化细胞白血病。诊断时分类,5例属于标准危险白血病,9例为高度危险患者。14例中6例有早期中枢神经系统白血病,3例有纵膈肿块,5例系T细胞ALL。所有病例以往均经强的松、长春新碱、柔毛霉素治疗,13例还用了门冬酰胺酶,有的还加阿糖胞     

Effects of biological response modifiers on childhood ALL being in remission after chemotherapy

Of 125 children with acute lymphoblastic leukemia (ALL), who had been in continuous remission for three years on chemotherapy, 108 patients received biological response modifiers (BRM) such as Bestatin, N-CWS, OK-432 and/or PSK in order to prevent relapse after treatment suspension. From 20 patients who were treated with PSK, 6 relapsed within 13 months. This relapse rate was quite similar to the rate observed with those children who were off therapy (4 relapses in 17 patients within 13 months). In contrast to these 37 patients, only 3 out of 31 patients who received Bestatin (p less than 0.05) and 8 out of 57 patients who received N-CWS or OK-432 relapsed. Based on these findings, BRMs used in the present study seems to be effective to prevent relapse of leukemia among childhood ALL who have electively stopped chemotherapy.     

白血病患者异基因造血干细胞移植后复发的高危因素分析

目的 分别统计分析急性淋巴细胞白血病(ALL)、急性髓系白血病(AML)和慢性髓系白血病(CML)患者行异基因造血干细胞移植(allo-HSCT)后复发的高危因素,比较各高危因素的影响并初步分析其影响机制.方法 单中心回顾性研究,以近8年来接受allo-HSCT的262例可评价的白血病患者为研究对象,其中ALL 69例,AML(除外急性早幼粒细胞白血病)90例,CML 103例,采用COX比例风险模型对移植前多项指标进行单因素及多元分析,筛选移植后复发的高危因素.结果 显著影响移植后复发风险的因素因疾病类型不同有所差异.ALL:染色体危险度分层、初始诱导疗程;AML:染色体危险度分层、移植前微量残留病灶水平、白细胞重建时间和移植物中CD4+/CD8+细胞比值;CML:移植前病期.结论 ALL患者移植后复发风险主要取决于本病的危险度,而AML患者移植后复发与移植过程中的多项指标也密切相关,CML患者在移植前保持病情稳定有利于避免移植后复发.染色体危险度分层是影响移植后复发的主要危险因素.     

改良预处理方案单倍体相合造血干细胞联合脐带间充质干细胞移植治疗高危难治恶性血液病的临床分析

本研究旨在观察应用单倍体相合造血干细胞（hi-HSCT）联合脐带间充质干细胞（脐带MSC）移植治疗高危难治恶性血液病的疗效.对30例难治、复发或高危恶性血液病患者自愿接受单倍体相合造血干细胞联合脐带MSC移植的疗效进行分析,其中复发4例,高危26例.病种包括急性髓性白血病15例,急性淋巴细胞白血病9例,前T淋巴母细胞淋巴瘤/白血病3例,脾边缘带淋巴瘤ⅣB1例,NK/T细胞淋巴瘤1例,Burkitt淋巴瘤ⅣB1例.结果表明,30例全部获得了顺利植入,发生急性移植物抗宿主病（aGVHD） 19例（63％）,其中Ⅲ-Ⅳ6例（20％）;发生慢性移植物抗宿主病（cGVHD） 8/25 （32％）,其中广泛型1例,局限型7例;复发3例,复发时间在移植后中位数300 d（128-455 d）;死亡8例,其中1例死于复发,2例死于Ⅳ aGVHD并同时复发,5例死于感染、脏器衰竭.结论：应用脐带MSC联合单倍体相合造血干细胞移植治疗高危难治恶性血液病可取得良好疗效.     

DNA抑制因子4作为急性淋巴细胞白血病临床复发前报告因子的可行性初探

本研究探讨以DNA抑制因子4作为急性淋巴细胞白血病（ALL）复发前报告因子的可行性。以骨髓持续完全缓解6—8个月的ALL患者为研究对象，应用甲基化特异性聚合酶链反应（MS—PCR）对经诱导缓解和巩固强化后持续完全缓解的32例ALL患者进行DNA抑制因子4启动子区甲基化状况分析，并随诊3个月以上。结果发现，32例完全缓解的ALL患者中20例（62．5％）DNA抑制因子4呈甲基化。12例DNA抑制因子4呈非甲基化的患者中只有1例3个月内复发，复发率8．33％，20例DNA抑制因子4呈甲基化状态的患者中10例3个月内复发，复发率50％。DNA抑制因子4甲基化与ALL患者初诊时是否具有高危因素并不完全相关。结论：DNA抑制因子4可作为ALL患者临床复发前的报告因子。     

Terminal transferase surveillance of remission bone marrows in childhood acute lymphoblastic leukemia: improved sensitivity with countercurrent centrifugal elutriation

In an attempt to better define hematologic remission and relapse in children with TdT positive acute lymphoblastic leukemia (ALL), 101 bone marrow (BM) aspirates were obtained from 74 pediatric patients. The mononuclear cell population of these specimens was isolated using countercurrent centrifugal elutriation (CCE) and characterized by an immunofluorescent terminal deoxynucleotidyl transferase (IF-TdT) assay. Twenty-two children with non-leukemic disorders had a median of 8% (range 0-34%) TdT positive mononuclear bone marrow cells. This was similar to values obtained for 25 children with ALL off therapy and in remission (median 10%, range 1-22%) and 16 children with ALL on continuous anti-leukemic therapy and in remission (median 7%, range 1-26%). Twenty-three BM samples were obtained from 11 children in early or high risk to relapse because of increased immature cells on a routine marrow examination or previous relapse(s). Samples from the early and high risk to relapse groups contained a median of 56% (range 25-80%) and 39% (range 25-72%) TdT positive cells. In contrast, the median percent marrow lymphoblasts identified using standard morphologic criteria for these 2 groups was 12.5% (range 9-23%) and 3% (range 0-5%), respectively. All high risk patients relapsed in their BM 1-4 1/2 months after these TdT determinations. Longitudinal studies in 4 patients at increased risk to relapse consistently demonstrated elevated percentages of TdT positive cells while morphologic surveillance was inadequate in establishing a clinical diagnosis of leukemic relapse. CCE in combination with an IF-TdT assay may enhance detection of recurrent and/or residual leukemia in BM samples from children with TdT positive ALL.     

门冬酰胺合成酶表达水平与儿童急性淋巴细胞白血病预后的相关性研究

目的 探讨儿童急性淋巴细胞白血病(ALL)肿瘤细胞中门冬酰胺合成酶(AS)基因表达水平是否与ALL的治疗反应和预后相关.方法 用实时荧光定量PCR(Real-time Quantitative PCR,RQ-PCR)测定53例初发ALL患儿骨髓单个核细胞(BMMNC)AS mRNA水平,结合其临床资料,统计分析不同预后组患儿初诊时BMMNC中AS表达水平差异及其与预后的关系.结果 未缓解组患儿AS表达水平最高,表达水平中位值为17.25(2.48～46.82),复发组其次,为14.28(3.20～54.47),持续完全缓解组患儿AS表达水平最低,为5.08(0.84～54.92),三组比较差异有统计学意义(P＜0.05).合并未缓解和复发两组患儿,其中位AS mRNA水平为14.93(2.48～54.47),显著高于持续完全缓解组患JL(P＜0.01).AS低表达组患儿白血病持续完全缓解率为84.6%,而AS高表达组患儿持续完全缓解率仅为53.8%(P＜0.05).AS高表达组患儿的2年预计无病生存率为51.6%,显著低于AS低表达组患儿(84.6%)(P＜0.05).结论 AS高表达与患儿预后不良相关.     

酪氨酸激酶抑制剂在儿童Ph阳性急性淋巴细胞白血病的治疗进展

急性淋巴细胞白血病(ALL)是儿童最常见的血液系统恶性疾病,其中有3％～5％患儿存在Ph染色体,即断裂点簇集区/Abelson白血病病毒(BCR/ABL)1融合基因,其分子发病机制是t(9;22)(q34;q11)染色体易位,使得酪氨酸激酶持续活化,细胞无限增殖.携带该融合基因的ALL患儿预后差,复发率高.近年,针对该融合基因的分子靶向药物,酪氨酸激酶抑制剂(TKI)的使用改善了Ph+ ALL治疗效果,完全缓解(CR)率和生存率都得到了大幅提高,一定程度上代替了异基因造血干细胞移植(allo-HSCT).另外,相关研究也探讨了TKI的副作用与耐药机制等安全性和长期有效性问题.笔者拟就TKI治疗儿童Ph+ ALL的临床疗效、不良反应、耐药机制等方面的研究进展进行综述,旨在为TKI的临床广泛应用提供理论基础.     

成人急性淋巴细胞白血病缓解后化疗和自体造血干细胞移植疗效的比较

目的比较联合化疗和自体造血干细胞移植（ASCT）在成人急性淋巴细胞白血病（ALL）缓解后治疗的疗效．方法对我院移植中心1990年7月至2003年12月首次诱导缓解、早期连续强化巩固治疗4个疗程后接受ASCT或联合化疗的74例成人ALL患者的疗效进行回顾性分析。联合化疗患者40例，ASCT患者34例，中位随访时间20．5个月，比较两组患者累积无白血病生存（LFS）率、总生存（OS）率及累积复发率：结果①化疗组患者中位LFS和OS期分别是14．0和20．6个月，而ASCT组中位LFS和OS期均大于53．5个月；②化疗组患者28例（70％）复发，而ASCT组患者移植后11例（32．35％）复发；③ASCT组患者1年LFS、OS率及复发率与化疗组患者相比差异无统计学意义（P值均〉0．05），而3年及5年预期LFS和OS率明显高于化疗组（P值均〈0．05），ASCT组患者的3年及5年复发率显著低于化疗组（P〈0．05）；④ASCT前移植物体外净化和移植后维持治疗（处理组）患者3年以上LFS和OS率高于未处理组患者（P〈0．05），累积复发率低于未处理组患者（P〈0．05）。结论ASCT可以有效降低成人ALL患者在早期连续强化巩固治疗后的远期复发率；ASCT前体外净化和移植后维持治疗可降低复发率，提高长期生存率。     

Methotrexate pharmacokinetics in childhood acute lymphoblastic leukaemia: a prognostic value ?

What is known and Objective: In industrialized countries, acute lymphoblastic leukaemia (ALL) is the most frequent cancer in children aged less than 15 years. High‐dose methotrexate is a common component of many chemotherapeutic protocols for childhood with ALL. Our objective was to retrospectively evaluate the pharmacokinetics and plasma levels of high‐dose methotrexate as it relates to event‐free survival (EFS) in children with ALL. Methods: Relapsed patients and subjects in EFS were compared for MTX serum concentrations 24, 36, 48 and 72 h after the start of 24 h infusion. Clearance (Cl), area under the curve (AUC) and volume of distribution (V_d) of the drug were estimated by the nonmem computer program and also compared between both groups. Results and Discussion:  Among 69 children included, 54 (78·3%) were still in EFS, whereas 15 (21·7%) relapsed. The difference between relapsed and EFS patients for the pharmacokinetic parameters studied was not significant. On the contrary, the cohort studied was representative and known prognostic factors for relapse in ALL were significantly associated with relapse. What is new and Conclusion: Serum concentrations and pharmacokinetic parameters of MTX are not associated with outcome in ALL. Prognoses based on single‐drug pharmacokinetic estimates within a complex multiple‐agent protocol appear to be unreliable. However, therapeutic drug monitoring of high‐dose methotrexate remains a useful tool for early detection of impaired elimination and for avoiding systemic toxicity.     

Therapy for Relapsed Multiple Myeloma: Guidelines From the Mayo Stratification for Myeloma and Risk-Adapted Therapy

Life expectancy in patients with multiple myeloma is increasing because of the availability of an increasing number of novel agents with various mechanisms of action against the disease. However, the disease remains incurable in most patients because of the emergence of resistant clones, leading to repeated relapses of the disease. In 2015, 5 novel agents were approved for therapy for relapsed multiple myeloma. This surfeit of novel agents renders management of relapsed multiple myeloma more complex because of the occurrence of multiple relapses, the risk of cumulative and emergent toxicity from previous therapies, as well as evolution of the disease during therapy. A group of physicians at Mayo Clinic with expertise in the care of patients with multiple myeloma regularly evaluates the evolving literature on the biology and therapy for multiple myeloma and issues guidelines on the optimal care of patients with this disease. In this article, the latest recommendations on the diagnostic evaluation of relapsed multiple myeloma and decision trees on how to treat patients at various stages of their relapse (off study) are provided together with the evidence to support them.