儿童白血病MIC分型及群体生物学特征分析

目的 分析南京及周边地区儿童白血病发病的基本情况和规律.方法 总结性分析2005年10月～2011年10月南京儿童医院住院的200例儿童白血病患儿的流行病学资料.结果 本组患儿中急性淋巴细胞白血病(ALL) 146例(73％),ALL免疫表型中B系124例(85％),初诊白血病细胞核型异常率为44.8％.ALL、急性髓细胞白血病(AML)中男性患儿发病率高于女性.10岁以下白血病患儿占90.5％ (181/200),ALL患儿中1～5岁占57.6％.结论 我院儿童白血病以ALL居多,其免疫表型以B系为主,初诊白血病细胞核型异常率高;ALL、AML患儿中男性高于女性,10岁以下患儿比率高,1～5岁为AML发病高峰期.     

难治性复发性急性淋巴细胞白血病治疗进展

难治和复发是导致急性淋巴细胞白血病(ALL)治疗失败的根本原因,提高难治和复发ALL的疗效无疑将改善ALL的预后.     

急性淋巴细胞白血病患儿肝功能损害相关因素分析及治疗

目的分析急性淋巴细胞白血病（ALL）患儿肝功能损害原因，指导临床治疗。方法对124例ALL患儿于化疗不同阶段进行肝功能和病毒学检测，对引起肝功能损伤的原因、损害程度及保肝治疗效果进行分析。结果124例患儿中58例发生肝功能损害，其中药物性损害发生率（70．69％）明显高于病毒性及白血病浸润性损害，以病毒性损害程度最重，以大剂量甲氨喋呤（HDMTX）庇护所防治期最常见；经复方甘草酸单胺、还原性谷胱甘肽及相应抗病毒治疗后，各组谷草转氨酶和谷丙转氨酶均恢复正常，病毒性损害恢复时间最长。结论针对ALL肝损害病因进行治疗可促进肝功能恢复，利于化疗顺利进行。     

中国儿童急性淋巴细胞白血病GATA3基因单核苷酸多态性与预后的相关性研究

目的 研究中国儿童急性淋巴细胞白血病(ALL)患儿GATA3基因单核苷酸多态性(SNP)分布特点及其对预后的影响.方法 利用TaqMan探针荧光定量PCR法检测上海儿童医学中心2009-05～2014-12收治的678例ALL患者GATA3基因rs3781093和rs3824662两个SNP位点,分析其与早期治疗反应、...     

101例成人急性淋巴细胞白血病(ALL)患者初发病和缓解期脾肿大的意义

脾肿大是 ALL 的一种常见表现,ALL 初发期出现脾大是肿瘤增长的反映,对于患儿则提示较差的预后。获得血液学完全缓解的病人出现脾大,临床上须和白血病复发相鉴别。最近,有人报告缓解期 ALL患儿出现脾大未必由白血病浸润引起,认为脾脏足一抗白血病的保护性宿主反应源,患儿施行脾切除可促使复发。作者对101例成人 ALL 患者,在确诊时和缓解期的脾肿大发生率,其预后的意义和脾切除对存活率的影响作了探讨。101例初发 ALL 患者,男59例,女42例,15～78岁,平均29.1岁。诱导治疗药物包括强的松、长春新硷和 anthracycline,对于严重者加用环磷酰胺。均鞘内注射氨甲喋呤作中枢神经系统(CNS)预防。     

大剂量甲氨喋呤预防小儿急性淋巴细胞白血病髓外浸润

近年来 ,由于化疗方案的不断改进 ,小儿急性淋巴细胞白血病 (ALL)的治疗效果明显改观 ,长期无病生存率大为提高。但随着生存期的延长 ,髓外白血病的发生逐渐增多 ,如何有效防治髓外白血病 ,已成为小儿 ALL治疗中的一大难题。为此 ,我们对应用大剂量甲氨喋呤 (MTX)预防髓外白血病的 2 2例 ALL患儿进行了远期随访观察。报告如下。1　资料与方法1 .1 　 临床资料1 993年 6月～ 1 999年 6月 ,我院共收治 ALL患儿 62例 ,其中完成诱导缓解及巩固治疗后 ,按计划进行大剂量 MTX治疗及维持治疗者 2 2例 ,男1 9例 ,女 3例 ;年龄 3～ 1 4岁 ,中…     

急性淋巴细胞白血病研究的若干进展

近10余年来对急性淋巴细胞白血病(ALL)的治疗已取得了巨大的成绩。在国外,儿童ALL 的5年完全缓解率已达65～70%,预计其中85%的患儿可治愈。但少数病人始终不能缓解,而已缓解的病人也可能很快复发。近来对 ALL 的研究,特别是在免疫学分型、染色体、治疗及远期预后等方面的研究,又取得了一些新的进展。ALL 的免疫学分型ALL 是一种“杂源性”疾病。不少学者从免疫学角度,利用细胞表面标志与血清学方法将、ALL 分为多个亚型,这是70年代 ALL研究的重要进展之一。ALL 大多数属非 T 非     

1182例门诊输液患儿的护理体会

输液是治疗儿童疾病常用的一种方法,但患儿紧张、恐惧及对抗心理常导致静脉穿刺成功率明显下降.近年来,我院对1 182例门诊输液患儿采取了针对性护理,穿刺成功率达98%.现将护理体会报告如下.     

帕洛诺司琼预防儿童急性淋巴细胞白血病化疗恶心呕吐的有效性和安全性研究

<正>白血病是儿童癌症中最常见的恶性疾病,其中急性淋巴细胞白血病(ALL)最常见,约占85%。20世纪80年代以后,有效的化疗方案大大提高了ALL患儿的治愈率。恶心、呕吐是患儿在化疗过程中最常见的不良反应之一,称为化疗性恶心、呕吐(CINV)。在化疗期间,反复、持续的恶心、呕吐引起患儿对治疗的恐惧,并造成生理上的诸多不     

FLAG方案治疗儿童复发性急性淋巴细胞白血病及非霍奇金淋巴瘤短期疗效研究

目的研究FLAG方案治疗儿童复发性急性淋巴细胞白血病(ALL)及非霍奇金淋巴瘤的短期疗效。方法将我院收治的25例儿童复发性ALL和非霍奇金淋巴瘤患儿按照患儿及家属治疗意愿分为FLAG治疗组14例和CAG治疗组10例,比较两组疗效、无病生存期和白细胞计数。结果 FLAG组总有效率为78.6%,高于CAG治疗组的70.0%,差异有统计学意义(P=0.000);治疗7d、14d后CAG治疗组白细胞计数低于FLAG组,差异有统计学意义(P<0.01);FLAG治疗组无病生存高于CAG组,差异有统计学意义(P<0.05);两组不良反应发生率比较,差异无统计学意义(P>0.05)。结论 FLAG治疗儿童复发性ALL及非霍奇金淋巴瘤疗效显著,无病生存期延长,对白细胞总数影响小,可以在临床推广应用。     

Changes in neurocognitive function and central nervous system structure in childhood acute lymphoblastic leukaemia survivors after treatment: a meta-analysis

Acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Although the survival rate has increased dramatically over the last decades, patients struggle with the adverse side effects of treatment. Treatment for ALL includes chemotherapy and irradiation - both of which are linked to cognitive impairments and alterations in central nervous system (CNS) structure and function detected by neuroimaging and in neurocognitive studies. The present article is a meta-analysis of the existing evidence for the mechanisms underlying changes in the CNS and neurocognitive function in ALL survivors after treatment. We found that compared with controls, ALL survivors develop: (i) cognitive sequelae in intelligence, academics, attention, memory, processing speed and executive function domains; (ii) decreased grey and white matter volume in cortical and several subcortical brain regions, with functional changes particularly in frontal regions and the hippocampus; (iii) neurocognitive impairments related to CNS changes; and (iv) reduction, but not resolution, of late neurocognitive sequelae in patients in whom prophylactic irradiation was replaced by systemic/intrathecal chemotherapy. Continued work with advanced functional magnetic resonance imaging techniques will hopefully allow the detection of early CNS changes as biomarkers to help guide early diagnosis and intervention for neurocognitive defects in patients with childhood ALL.     

Rehabilitation for cognitive impairments after cerebral malaria in African children: strategies and limitations

Cerebral malaria results in short- to long-term cognitive impairments in many of its child survivors. Although some of the risk factors for impairments have been identified, no attempts have been made to address the plight of those who develop cognitive impairments. This paper discusses the burden of cognitive impairment caused by cerebral malaria and suggests some rehabilitation strategies based on brain injury and cognitive rehabilitation studies. Potential cognitive rehabilitation solutions such as cognitive exercises, environmental enrichment, nutritional supplementation, physical therapy and speech therapy are highlighted. The limitations of implementing these interventions and solutions are discussed in light of the limited human resources and infrastructure of the developing countries that are malaria endemic.     

Infants with acute lymphoblastic leukemia and a germline MLL gene are highly curable with use of chemotherapy alone: results from the Japan Infant Leukemia Study Group

Although infants with acute lymphoblastic leukemia (ALL) and a germline MLL gene have a better prognosis than comparable infants with a rearranged MLL gene, their optimal therapy is controversial. In 2 consecutive studies, conducted between 1996 and 2002, we treated 22 cases of infant ALL with germline MLL using chemotherapy alone. The 5-year event-free survival rate was 95.5% with a 95% confidence interval of 86.9 to 100%. All 21 infants with precursor B-cell ALL have been in first complete remission for 3.5 to 8.8 years. Most treatment-related toxicities were predictable and well tolerated, and neither secondary malignancies nor physical growth impairments have been observed. These results indicate that chemotherapy of the type described here is both safe and highly effective against infant precursor B-cell ALL with MLL in the germline configuration.     

The clinical relevance of chromosomal and genomic abnormalities in B-cell precursor acute lymphoblastic leukaemia

Acute lymphoblastic leukaemia (ALL) occurs at all ages but is the most common cancer of childhood. The current treatment of paediatric ALL is highly successful with up to 90% children being cured. In contrast, survival rates for adult ALL are significantly lower at around 40%. The discovery and characterisation of genetic abnormalities have increased our understanding of the biology of the disease and provided important prognostic and predictive markers which have improved patient outcome. Not only is the spectrum of these aberrations vast but, due to advances in technology, continually expanding. A wide range of chromosomal and genomic abnormalities have been reported as being associated with patient outcome but only a subset are currently used to risk stratify patients. This review highlights the main genetic abnormalities which are used to manage patients with B-cell precursor ALL and discusses the evidence which has been accumulated on several newly described genomic abnormalities.     

Philadelphia chromosome-positive acute lymphoblastic leukemia in children: new and emerging treatment options

Philadelphia chromosome-positive (Ph(+)) acute lymphoblastic leukemia (ALL) in children and adolescents has, until recently, been considered one of the poorest-risk subgroups of ALL. With chemotherapy alone, only 20-30% of children with Ph(+) ALL are cured. Allogeneic hematopoietic cell transplantation in first complete remission cures 60% of patients with a closely matched donor. Although targeted tyrosine kinase inhibitors (TKIs) have limited activity against Ph(+) ALL as a single agent, they have been evaluated in combination with chemotherapy with promising results. The early results of Children's Oncology Group trial AALL0031 have shown 88% 3-year event-free survival for Ph(+) patients treated with intensive chemotherapy plus continuous-dosing imatinib. This suggests that chemotherapy plus TKIs may be the initial treatment of choice for Ph(+) ALL in children. However, the numbers are small in this trial and confirmatory results are not yet available from the European Intergroup Study on Post Induction Treatment of Philadelphia Positive Acute Lymphoblastic Leukaemia with Imatinib trial. Additional issues include determining the most effective TKI (imatinib, dasatinib or nilotinib) and the most effective, least toxic chemotherapy backbone. The experience of adding a targeted agent such as a TKI to the standard chemotherapy regimen suggests that this strategy might be applied to other ALL subtypes to achieve both increased efficacy and decreased toxicity.     

Physiotherapy for the treatment of articular contractures in haemophilia

Articular contractures in haemophilia are impairments that can not be cured by means of physiotherapy because of the pathophysiology of the joint. Rehabilitation, however, tries to diminish the disabilities and prevent handicaps caused by the impairments. Physiotherapy aims at pain reduction by means of manual traction. Next to manual traction the intensive physiotherapy programme includes mobilization techniques, muscle strengthening exercises and stretching, joint stability training, postural and gait training, and functional training. In all 50 haemophilia patients have undergone this intensive 4-week clinical rehabilitation programme. Data of 20 of these severe haemophilia patients show that the mean range of motion at the start of the rehabilitation period, after 4 weeks and after 5 years do not differ. In spite of progressing arthropathy after 5 years the activities of daily living (ADL), walking range and pain are equal or better according to 13 of 15 patients.     

Immunoglobulin and T cell receptor gene configuration in acute lymphoblastic leukemia of infancy

We examined immunoglobulin (Ig) heavy chain, K light chain, and T cell receptor (TCR) gamma and beta gene configuration in the leukemic cells from a series of infants aged less than 1 year with acute lymphoblastic leukemia (ALL). Each of these 11 cases demonstrated leukemic cell surface antigens that have been correlated with a B cell precursor phenotype. Of the 11, lymphoblasts of 4 retained the germline configuration of both Ig and TCR loci, whereas 7 had rearranged the Ig heavy chain gene. Two of these seven showed light chain gene rearrangement. TCB beta chain rearrangement had occurred in only one of the 11 patients' tumors. No TCR gamma chain rearrangements were identified. These results are in contrast to earlier studies of B cell precursor ALL in children in which Ig heavy chain gene rearrangements were evident in every case and approximately 40% showed Ig light chain rearrangement as well. In addition, 45% of cases of B cell precursor ALL of children had rearranged their gamma TCR genes, and 20% had rearranged beta. These data suggest that ALL in infancy represents an earlier stage of B cell development than is found in B cell precursor ALL of children. ALL in the infant age group has been associated with the worst prognosis of all patients with ALL. This study suggests that the disease in infants differs not only clinically, but also at the molecular genetic level, from the disease in children.     

Adult and childhood acute lymphocytic leukemia: Are they different diseases?

Age has long been recognized as an important factor in predicting response to treatment for acute lymphocytic leukemia (ALL). Specifically, the results of treatment of childhood ALL have been far superior to the treatment of what appears to be the same disease in adults. However, from an analysis of the clinical and biological prognostic factors known to be predictive in childhood ALL, there is a striking difference in their distribution in adults with ALL. It appears that there is a special form of ALL seen in children of some populations with a peak incidence of three to seven years. This treatment responsive leukemia appears to be different clinically, biologically, and epidemiologically from adult ALL. © 1993 Wiley-Liss, Inc.     

Molecular markers in ALL: Clinical implications

Acute lymphoblastic leukemia (ALL) is the most common childhood cancer and remains a main cause of death in children despite recent improvements in cure rates. In the past decade, development of massively parallel sequencing has enabled large scale genome profiling studies of ALL, which not only led to identification of new subtypes in both B-cell precursor ALL (BCP-ALL) and T-cell ALL (T-ALL), but has also identified potential new therapeutic approaches to target vulnerabilities of many subtypes. Several of these approaches have been validated in preclinical models and are now being formally evaluated in prospective clinical trials. In this review, we provide an overview of the recent advances in our knowledge of genomic bases of BCP-ALL, T-ALL, and relapsed ALL, and discuss their clinical implications.     

MTHFR Gene Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Adults and Children: A Case Control Study in India

Genetic polymorphisms in the methylene tetrahydrofolate reductase (MTHFR) gene have been associated with the development of acute leukemias and various malignancies. The role of MTHFR polymorphism in the development of pediatric acute lymphoblastic leukemia (ALL) has been extensively studied among north Indians in various settings, yet its association with acute leukemias remains unresolved. To evaluate the relationship between functional MTHFR polymorphisms, C677T and A1298C and possible effect on risk of ALL in adults and children in North Indian population by comparing them with healthy controls. DNA was isolated from peripheral blood of 184 ALL patients (33 adults, 151 children) and 155 controls and analyzed by a PCR-restriction fragment length polymorphism assay. The frequency of MTHFR 677CT and 1298 AC genotypes were significantly lower among adult ALL cases when compared to the controls. We found a 1.74-fold reduced risk of ALL in individuals with 1298AC polymorphic variant and a 9.17-fold decreased risk of adult ALL. However, no statistically significant difference was evident between the above polymorphisms and susceptibility to ALL in children. Polymorphisms in the MTHFR gene possibly modulate risk of ALL in north Indian adults but not in children, although larger studies are needed.