Asparaginase in Acute Lymphoblastic Leukemia

Cure rates in pediatric acute lymphoblastic leukemia have significantly improved over the past decades. Now, almost 90% of children will survive the disease. The cure rates in adolescents, young adults, and adults have not kept pace with the improvements in younger patients, even though almost an equal proportion of adult patients achieve complete remission as their pediatric counterparts. Differences in treatment regimens might be important. Intensive use of asparaginase has been a key component of successful pediatric therapy. In this review, we focus on the use of asparaginase and the potential of optimizing asparaginase use via monitoring to minimize adverse drug events and improve efficacy of the drug.     

急性淋巴细胞白血病TPMT基因多态性的研究

目的 分析急性淋巴细胞白血病TPMT基因多态性与6-MP不良反应的相关性.方法 收取急性淋巴细胞白血病患儿48例作为研究对象,对其TPMT基因型及6-MP不良反应进行分析.结果 48例患儿中31.25％按照常规6-MP使用剂量完成维持治疗,68.75％患儿出现不耐受后调整为低剂量完成维持治疗.常规剂量组重度不良反应发生率高于低剂量组,但差异无统计学意义(P＞0.05).6-MP所致骨髓抑制及肝功能损害发生率分别为93.75％及83.33％.仅有1例患儿发生杂合型TPMT×3C点突变,突变发生率为2.08％,该患儿同时发生4级骨髓抑制及4级肝功能损害.结论 TPMT×3C基因突变可能与6-MP所致重度不良反应有关,但6-MP所致重度不良反应可能是多种因素共同作用的结果.     

Acute Lymphoblastic Leukemia following Treatment with Human Growth Hormone in a Boy with Possible Preanemic Fanconi's Anemia

The patient had a low birth weight and was born with appearenceanomalies including microcephalus, microphthalmia, hypoplasticmandible, double chin due to cutaneous fold, micropenis. Abilityto move and intelligence appeared to develop normally, but growthwas markedly retarded. In June 1982, at the age of 2 yr 4 mo,the patient underwent tolerance tests whereby a deficiency ofhuman growth hormone (GH) was proved by poor GH secretion response.GH was administered until April 1985 when acute lymphoblasticleukemia developed. The patient's younger brother, born in 1986,had similar birth anomalies and was diagnosed as having Fanconi'sanemia. It therefore seems possible that our patient developedhis acute leukemia through the stimulatory effect which GH hadon a predisposition to leukemia.     

血浆miRNAs在儿童急性淋巴细胞白血病(ALL)不同疾病状态中的表达特点

目的 分析3种血浆miRNA在儿童急性淋巴细胞白血病(ALL)不同疾病状态中的表达特点.方法 选取急性淋巴细胞白血病患儿40例,其中初诊患儿12例,完全缓解患儿16例,复发患儿12例,同时收集我院经健康体检的儿童25例作为正常对照组.抽取所有儿童的空腹静脉血,离心后取血浆,采取直接扩增目的microRNA,并反转录为cDNA,qRT-PCR方法检测血浆miR150、miR155、miR233的表达.结果 ALL组中血浆miR150、miR155、miR233的表达均与正常组有统计学差异;血浆miR150和miR233在初诊组和复发组的表达显著低于缓解组和正常组(P<0.05),血浆miR155在初诊组和复发组的表达显著高于缓解组和正常组(P<0.05).3种miRNA在初诊组与复发组之间、缓解组与正常组之间比较均无统计学差异(P>0.05);初诊组中3种血浆miRNA在不同年龄和性别之间表达均无统计学差异(P>0.05);3种血浆miRNA的AUC(曲线下面积)和95%CI(95%可信区间)均有较好的满意度,且3种血浆miRNA联合检测的精确度更高.结论 血浆miR150、miR155、miR233的表达在儿童急性淋巴细胞白血病(ALL)的诊断、治疗和复发监测中有较高的应用价值.     

儿童急性淋巴细胞白血病VDLP方案中应用音乐疗法的疗效观察

目的探讨儿童急性淋巴细胞白血病(ALL)VDLP方案中应用音乐疗法的疗效及对神经元特异性烯醇化酶(NSE)和25羟维生素D(25(OH)D)水平的影响。方法将88例ALL患儿随机分为对照组44例和观察组44例。对照组采取VDLP诱导缓解方案。观察组在对照组基础上加用音乐疗法。比较两组患儿的生存率、近期疗效及不良反应发生率。检测两组儿童ALL血清中NSE和25(OH)D的水平。结果对照组患儿的6个月和1年生存率分别为90.91%和84.09%,观察组为97.73%和93.18%,观察组低于对照组,但两组比较无统计学意义(P>0.05)。观察组近期总缓解率为84.09%,明显高于对照组为(63.64%)(P<0.05)。观察组患儿的肝功能损害、骨髓抑制、皮肤损害、口腔粘膜损害及胃肠道反应发生率低于对照组,其中胃肠道反应的发生率明显低于对照组(P<0.05)。观察组治疗后患儿血清中NSE水平明显低于对照组,25(OH)D明显高于对照组(P<0.01)。结论儿童急性淋巴细胞白血病VDLP方案中应用音乐疗法的疗效明显,且可降低血清中NSE水平和提高25(OH)D水平。     

儿童急性淋巴细胞白血病长期生存的康复管理

急性淋巴细胞白血病占儿童白血病的75%~85%,随着诊疗技术的进步,我国儿童ALL长期无事件生存率达70%~80%。因此,ALL患儿远期躯体功能状态和生活质量越来越受到重视。尽管近20年来肿瘤康复在欧美国家发展迅速,但儿童白血病康复的临床干预措施和学术研究方面仍存在诸多不足,我国儿童白血病康复工作更是落后于西方发达国家。本文中,我们描述了一个相对全面的儿童急性淋巴细胞白血病长期生存康复管理框架,以期更好地提高ALL患儿的远期生存质量。     

正元胶囊辅助甲氨蝶呤治疗儿童急性淋巴细胞白血病的有效性和安全性分析

目的探讨正元胶囊辅助甲氨蝶呤治疗儿童急性淋巴细胞白血病的有效性和安全性以及对血清中B淋巴细胞刺激因子(BAFF)和增殖诱导配体(APRIL)水平的影响。方法 78例儿童急性淋巴细胞白血病随机分为对照组和观察组,各39例。对照组采取甲氨蝶呤治疗,观察组在对照组基础上于缓解期口服正元胶囊,1~3粒/次,3次/天,共治疗8周。比较2组近期疗效、治疗过程中不良反应。检测2组患儿血清中BAFF和APRIL水平。结果观察组近期总缓解率为89.74%,显著高于对照组的61.54%(P<0.01)。观察组患儿的口腔黏膜损害、肝功能损害、感染、骨髓抑制、胃肠道反应及皮肤损害发生少于对照组,但组间差异无统计学意义(P>0.05)。治疗后,观察组患儿血清中BAFF和APRIL水平显著低于对照组,差异有统计学意义(P<0.01)。结论金正元胶囊辅助甲氨蝶呤治疗儿童急性淋巴细胞白血病的疗效确切,安全性好,降低患儿血清中BAFF和APRIL水平可能与其疗效有关。     

Karyotypic Evolution: Cytogenetics Follow-Up Study In Childhood Acute Lymphoblastic Leukemia

Forty seven children affected with acute lymphoblastic leukemia (ALL) were cytogenetically investigated ‍at diagnosis and all through different stages of the disease (remission and relapse). A clonal karyotypic abnormality ‍was found in 32% at diagnosis (mainly comprised of cALLa+). A hyperdiploid mode with chromosome counts ‍ranging from 47-58, was found to be most prominent among cALLa+ patients. The most common numerical ‍aberrations were gain of chromosomes 2, 5, and 21. The structural aberrations at diagnosis were found to be ‍del(9)(p22), inv(9)(p11q13) and del(19)(p12). None of the children showed ph+ chromosome. A good prognosis ‍was found in cALLa+ children with an abnormal karyotype at diagnosis and of these children, those who ‍showed karyotypic instability , had a significantly longer first remission time. The karyotypic evolution ‍through remission(s) and relapse(s) revealed the occurrence of structural alterations , including changes in ‍chromosomes 3, 6, 9, 21 and 22. However, irrespective of the karyotypic clonal nature at diagnosis, ‍chromosome 9 was the most commonly involved chromosome through the course of disease. ‍     

Long-Term Results of Autologous Bone Marrow Transplantation in Adult Acute Lymphoblastic Leukemia

Autologous bone marrow transplantation (BMT) is widely performed in both adult and high-risk pediatric acute lymphoblastic leukemia (ALL). Nevertheless, there is still a lack of definitive data concerning its real effectiveness in prolonging the survival of these patients. Between 1984 and 1992, 20 ALL patients in first, second and third complete remission (CR) underwent autografting in the BMT Unit of the University of Milan. This series included 3 children in CR after one or more hematological relapses while all the other patients were adult. Autologous bone marrow was harvested during the same disease phase as that in which the autologous BMT was performed. The conditioning regimen included high-dose Ara-C, cyclophosphamide and TBI 1000 cGy. Successful engraftment occurred in all patients; no early deaths or deaths in CR were recorded, making disease-free survival and event-free survival (EFS) curves superimposable. The overall chance of EFS at 72 months was 41%: 57% for patients in first CR, 53% for patients autografted after one or more isolated meningeal relapse, 14% for patients autografted after one or more hematological relapse. The present data do not provide any evidence to support a role for autologous BMT in prolonging EFS in first CR ALL patients. Nevertheless, the results after meningeal relapse seem to be favourable when compared with the disappointing prospects of these patients after conventional chemotherapy. The EFS after hematological relapse revealed by this study does not significantly differ from that reported in the majority of other studies: the efficacy of autologous BMT in these ALL patients is doubtful.     

GGLG-08方案联合伊马替尼治疗儿童Ph阳性急性淋巴细胞白血病的疗效与安全性分析

目的 研究GGLG-08方案联合伊马替尼治疗儿童Ph阳性急性淋巴细胞白血病的效果与安全性.方法 回顾性分析51例儿童Ph+急性淋巴细胞白血病患儿的临床资料,给予对照组患儿CCLG-ALL2008化疗方案,治疗组患儿采用伊马替尼联合CCLG-ALL2008化疗方案,比较2组患儿的治疗疗效及不良反应,同时分析影响患儿诱导缓解后5年生存率的主要因素.结果 对照组患儿诱导治疗后完全缓解(CR)率为92.86％,治疗组患儿CR率为95.65％;治疗组患儿1年无事件生存率(EFS)为91.30％,3年无事件生存率(EFS)为69.57％,5年无事件生存率(EFS)为65.22％.与对照组比较,治疗组未增加化疗相关毒性.导致患儿诱导缓解后5年生存率降低的独立风险因素为:患儿对糖皮质激素诱导不敏感、治疗依从性差、治疗中复发以及首次诱导缓解失败.结论 GGLG-08方案与伊马替尼联合使用治疗儿童Ph阳性急性淋巴细胞白血病的临床疗效明显,安全性良好.     

Prognostic Effect of CD20 Expression in Adult B-cell Acute Lymphoblastic Leukemia

Introduction

The expression of the CD20 on adult B-cell acute lymphoblastic leukemia (ALL-B) has generally been associated with a poor prognosis, and several studies have explored the incorporation of rituximab into the therapeutic regimen for adult ALL-B patients, with a positive effect on event-free survival (EFS).

Preliminary Experience with a New Chemotherapy Regimen for Adults with Acute Lymphoblastic Leukemia

We treated 11 consecutive adult patients who presented with acute lymphoblastic leukemia to the University of Chicago with a novel, intensified chemotherapy regimen to evaluate the feasibility and toxicity of this program. Following a 5-drug induction therapy (course A), patients received sequential courses (B and C) of high-dose antimetabolite therapies, in part to replace cranial irradiation for CNS prophylaxis. All patients achieved a complete remission. The regimen was designed with a goal of administering all post-remission therapy in the outpatient setting. With the exception of the initial induction course (A), 31/38 total patient courses were administered in the outpatient clinic. As expected, the induction and consolidation courses (A and B) of this regimen were associated with grade 4 hematologic toxicity and significant but manageable infectious toxicity. Another novel aspect of the regimen included a combined intravenous and oral dosing schedule designed to sustain methotrexate levels × 1.0 μM^-for 30 hours (course C). There was minimal toxicity with the CNS prophylaxis/high-dose methotrexate course (C). Methotrexate levels at 30 hours ranged from 0.31-4.0 μM, with a median of 1.0 μM (n=37). This study demonstrates that this novel post-remission regimen is feasible in adults and that high concentrations of methotrexate can be sustained in the outpatient setting. The Cancer and Leukemia Group B is presently evaluating the efficacy of this regimen in a large phase II trial (CALGB study 19802).     

Progress in the Management of Older Adults with Acute Lymphoblastic Leukemia

Remarkable progress has occurred in understanding the pathophysiology, and in developing improved personalized therapies in pediatric and adult acute lymphoblastic leukemia (ALL). However, these successes were not paralleled in older patients with ALL, who have estimated cure rates of only 10-20%.In older patients with ALL, intensive chemotherapy results in lower response rates than those observed in younger patients with ALL, and high rates of toxicities. One-third of patients achieving     

The Prognostic Implications of an Immunological Classification of Acute Lymphoblastic Leukemia

Summary

Thirty-one patients with newly diagnosed acute lymphoblastic leukemia were examined before receiving any treatment and their clinical and laboratory data were analyzed in order to determine the possible correlation between clinical presentation, morphologic sub-classes, cytochemical reactions, immunological phenotypes and cytogenetic findings. Each of the previous parameters and response to therapy were also examined for correlation.

The analysis of clinical and laboratory characteristics of patients according to their immunological phenotype did not show any significant male sex bias, age distribution, hepatomegaly or splenomegaly at diagnosis.

The analysis of clinical response of patients did not demonstrate any significant influence of sex, age, initial WBC count or the presence of a big tumor mass at diagnosis.

There were no significant differences between our two major immunological subclasses Non-T CALLA⁺ ALL, and Pre-T ALL regarding proportions of patients in continuous remission, and relapse-free survival durations.

The analysis of clinical and laboratory characteristics of patients on the basis of their chromosome categories did not show any significant sex bias, age distribution, initial WBC count, tumoral presentation or morphological subtypes at diagnosis, although there was an apparent male predominance in the pseudodiploid category and female predominance in the hyperdiploid category.

Our results concerning the prognostic implication of CALLA were contradictory to those of several other investigators.     

A Novel Cell Line (NCU-L-1) from a Patient with Acute Lymphoblastic Leukemia, FAB, L3, Burkitt's Type

A novel cultured cell line, NCU-L-1, was established from a 71-year-old Japanese woman with acute lymphoblastic leukemia, L3 FAB, Burkitt's type. The NCU-L-1 cells were shown to have a mature B-cell phenotype on the basis of immunologic surface marker analysis; including IgG Lambda surface immunoglobulins, CD19, CD20 and la-like antigen which were all detected on the cells. Intracytoplasmic immunoglobulin was not detected, but IgG was present in the cell culture supernatant. Cytogenetic studies revealed that the NCU-L-1 cells had t(2; 8) and an additional 14q+, a genotype which has not been identified previously in the usual Burkitt's cell lines.

The NCU-L-1 cell line should prove to be useful for studying oncogenic events associated with the t(2; 8) translocation and karyotype evolution.     

Brain Damage After Treatment for Acute Lymphoblastic Leukemia a Report on 34 Patients with Special Regard to Mri Findings

In 34 patients treated for acute lymphoblastic leukemia (ALL), central nervous system (CNS) damage was assessed by clinical evaluation and brain magnetic resonance imaging (MRI). Twenty-seven of them had been off therapy from 5 to 109 months (median 64 months) while 7 had not completed the maintenance phase of their treatment. All the patients were disease-free when evaluated. None of the 3 patients who showed clinical CNS damage during the follow-up was symptomatic when submitted to MRI, while periventricular hyperintensity in T2-weighted images, suggestive of leukoencephalopathy, was present in 8 of the 34 patients. These subclinical abnormalities appear to be more frequent, transient in nature and treatment-related in patients evaluated shortly after the induction phase. Similar MRI findings seem, on the contrary, to be consequences of the disease on the CNS when appearing in long-term survivors.     

Shedding of CD9 Antigen in Acute Lymphoblastic Leukemia

A leukemia-associated CD9 glycoprotein antigen released into the extracellular milieu from acute lymphoblastic leukemia cells has been detected using a unique lectin-monoclonal antibody immunoassay. It has been demonstrated that the release of CD9 antigen is an active process and is associated with active cell growth. In addition, the difference of carbohydrate moiety, and hence glycosylation, in the CD9 antigen derived from lymphoblasts and neuroblasts was verified using lectin affinity chromatography. The lectin affinity of the carbohydrate moiety of lymphoblast CD9 antigen would indicate the presence of N-linked oligosaccharide chains having groups of N-acetyl glucosamine residues, a mannose core and a terminal D-galactose.

The soluble CD9 antigen is specifically detected in plasma from ALL patients at the time of diagnosis, in cerebrospinal fluid from patients with central nervous system involvement, and spent medium from CD9-positive leukemic blasts obtained at the time of diagnosis. Interestingly when bone marrow cells taken from patients in complete remission were studied, a distinct amount of CD9 antigen was released into spent medium in some of the cases. All of these patients have subsequently developed hematological relapse. The present data suggest that shedding of CD9 antigen by leukemic cells may enable the clinical monitoring of residual leukemic cell burden.     

Month-of-Birth and Incidence of Acute Lymphoblastic Leukemia in Children

As a means of examining the virus-relatedness of acute lymphoblastic leukemia (ALL) in children, we investigated the association between month-of-birth and the occurrence of ALL in 1487 children aged 0-15 years at the time of diagnosis. Our hypothesis being that evidence of seasonal variation in births of ALL cases would suggest exposure to a transmissible etiologic agent during the perinatal period. The data were obtained Surveillance, Epidemiology, and End Results (SEER) Program and consisted of children diagnosed during the years 1973-1986. Aggregate monthly incidence rates of ALL stratified by month-of-birth, for each SEER site, all sites combined, and for broad geographic regions were calculated. No evidence for an association between month-of-birth and childhood ALL was found.