Intracranial bleeding during therapy with L-asparaginase in childhood acute lymphocytic leukemia

Two patients developed clinical features of intracranial bleeding—which were confirmed by computerized axial tomograms—during their induction therapy for acute lymphocytic leukemia. Coagulation studies showed clotting abnormalities including severe hypofibrinogenemia. These findings most probably were related to the effect of L-asparaginase which was part of the treatment protocol. Central nervous system leukemia, intrathecal chemotherapy, cranial irradiation, extreme leukocytosis, or thrombopenia at the time of diagnosis or day of stroke did not appear to be predisposing factors in these cases.     

Measurement of cerebrospinal fluid protein is unnecessary in children with leukemia

To determine the incidence and importance of abnormal cerebrospinal fluid (CSF) protein in children with acute leukemia, we performed a retrospective chart review. On 160 pediatric patients a total of 2,172 LPs were performed (median per patient = 15; range 1-38). Overall, 314 (14%) of CSF protein measurements were abnormal: 141 (7%) were abnormally low (<15 mg/dL) and 158 (7%) were abnormally high (>45 mg/dL). In no case did an abnormal CSF protein impact patient management. We conclude that routine measurement of CSF protein is not indicated in children with acute leukemia.     

Myelin basic protein in cerebrospinal fluid from children

Forty-one cerebrospinal fluid (CSF) specimens from children were investigated with a radioimmunoassay for their content of myelin basic protein (BP). Eight specimens were regarded as BP-positive (BP1.0 ng/ml). Twenty-nine were BP-negative and 4 could not be analyzed because of an excessive protein content. The BP-positive samples were from 6 children with evidence of severe acute brain damage leading to death in 5 cases: i.e., 2 term newborns with perinatal asphyxia, a 4 week-old child with severe convulsions, a 3 year-old boy with hypoxia due to laryngitis, and a 12 year-old girl with encephalitis. One preterm baby survived severe hypoxia and developed hydrocephalus shortly afterwards. We conclude that BP becomes detectable in CSF of newborns and older children under certain pathological conditions, and that the presence of BP in CSF may be associated with severe brain tissue destruction.Supported by Deutsche Forschungsgemeinschaft, SFB 33     

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。     

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.     

Negative correlation between cerebrospinal fluid tau protein and cognitive functioning in children with acute lymphoblastic leukemia

The aim of the study was to assess whether cerebrospinal fluid tau protein is associated with cognitive changes in children with acute lymphoblastic leukemia (ALL). Examination of 38 ALL patients revealed a statistically significant increase in tau protein on treatment day 59 and at two points during consolidation phase. Cognitive functioning was examined in 19 patients at an average of 3.7 years after diagnosis. The level of tau at the initiation of maintenance therapy was negatively correlated with verbal abilities measured on an intellectual scale. The study suggests that standard ALL treatment may cause a decline in cognitive functioning. Pediatr Blood Cancer 2009;53:105–108. © 2009 Wiley‐Liss, Inc.     

Progress in the treatment of childhood acute leukemia: A review

The dramatic improvements in the survival experience for children diagnosed with acute leukemia are analyzed using data collected through hospitals participating in the National Cancer Institute's End Results Group Program between 1950 and 1973. Children under 15 years of age who were diagnosed with both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) showed moderate improvements in the 1950s, but beginning in the 1960s those with ALL did far better. Statistically significant differences at the 0.05 level were noted between their three-year survival rates for all cohorts analyzed between 1960 and 1973. For the 1970-1973 cohort, three-year survival rates were 49% and 20% for ALL and ANLL, respectively, and five-year survival rates were 34% and 12%. Between 1950 and 1976 the age-adjusted incidence rate for all childhood leukemias remained relatively stable in a sample of five geographic areas, changing from 4.6 per 100,000 children under 15 years of age to 4.3 per 100,000. In contrast, the corresponding age-adjusted mortality rate fell approximately 45% over the same period, from 4.4 per 100,000 to 2.4 per 100,000.     

儿童急性早幼粒细胞白血病的临床研究

目的 　探讨儿童急性早幼粒细胞白血病 (APL)的临床及实验室特征。方法对 4 1例APL初治患儿进行临床分析 ,男 2 3例 ,女 1 8例 ,中位年龄 1 2 ( 3～ 1 8)岁。 2 7例进行了遗传学和PML/RARα融合基因检测。 38例患儿进行了免疫分型。诱导及维持治疗全部应用维甲酸 ;采用HA/D/MA方案强化治疗。结果 　临床及实验室特征 :贫血 31 /41例 ,出血 2 3/41例 ,发热 1 9/41例 ,肝肿大 4 /41例 ,脾肿大 3/41例 ,淋巴结肿大 6 /41例 ;Hb 73( 30～ 1 1 0 )g/L ;WBC 2 9( 1 1～ 90 )× 1 0 9/L ;BPC 4 0 ( 1 4～ 1 2 5)× 1 0 9/L。 2 7例进行细胞遗传学分析 ,t( 1 5;1 7) (q2 2 ,q1 2 )者 1 7例 ,同时检测PML/RARα融合基因 1 6例为阳性 :1 0例为正常核型 ,而PML/RARα融合基因 1 0例均为阳性。 38例患儿免疫分型共同特征表现为CD9、CD13 、CD3 3 高表达 ,而HLA -DR及CD3 4为阴性。临床疗效 :维甲酸治疗的完全缓解 (CR)率为 89 76 % ( 36 /41 )。 3年无复发生存率 95% ( 1 9/2 0 )。结论 　APL的临床表现以贫血、出血、发热为主要特征。免疫分型的共同特征为CD9、CD13 、CD3 3 高表达 ,而HLA -DR及CD3 4为阴性。APL的形态学诊断与PML/Rarα融合基因及染色体的符合率分别为 96 3% ( 2 6 /2 7)和 6 3% ( 1 7/2 7)。?     

Epidemiology of childhood acute myeloid leukemia

Although leukemia is the most common childhood cancer diagnosis, the subtype, acute myeloid leukemia (AML), is less common and fewer etiologic studies exist. This review summarizes the major risk factors for AML. We searched the literature using PubMed for articles on childhood AML and reviewed 180 articles. While few risk factors are definitive, we identified several with consistent evidence of a possible effect. Thorough analysis of genetic and epigenetic factors is missing from this literature and methodological issues are unresolved. Future studies should more closely examine causal mechanisms, improve exposure measurement, and include analysis using genetic and epigenetic factors. Pediatr Blood Cancer 2013; 60: 728–733. © 2013 Wiley Periodicals, Inc.     

Superior treatment results in females with high-risk acute lymphoblastic leukemia in childhood

In this population-based study, 808 children aged 1-15 years from Denmark, Finland, Iceland, Norway and Sweden, were diagnosed between July 1981 and June 1986 as suffering from non-B-cell acute lymphoblastic leukemia (ALL). The total population was 4.5 million children. Remission was achieved in 770/808 of the patients (95%). No sex difference in the remission rate was observed. The event free survival (EFS) at 102 months was 0.47 for males and 0.62 for females (p less than 0.001). There was no difference in EFS between males and females with standard-risk (0.58 and 0.60) or intermediate-risk (0.47 and 0.60) ALL, respectively. The EFS for females with high-risk ALL (0.68) was superior to that of males with high-risk ALL (0.31). Cox multivariant analysis showed that white blood cell count, sex, age and thrombocyte count were significant prognostic factors in all children. The intensified treatment according to the prognostic factors used in this study led to equal EFS for females with ALL from all risk groups. Males with high-risk ALL, however, did not benefit from the intensified treatment.     

Ig/TCR基因重排在儿童急性T淋巴细胞白血病中的表达模式特点

目的 探讨免疫球蛋白(Ig)/ T细胞受体(TCR)基因重排在儿童急性T淋巴细胞白血病(T-ALL)中的表达模式特点及其与临床生物学特征的相关性。方法 回顾性纳入首都医科大学附属北京儿童医院(我院)2005年1月1日至2008年12月31日收治的初治T-ALL患儿,分析其初诊时骨髓单个核细胞的Ig/TCR基因重排情况,根据重排情况分为阳性组和阴性组,比较不同组别的临床生物学特征。结果 ①52例儿童T-ALL中男37例(71.2%),入院时中位年龄8.0(1.8~16.0)岁,初诊时WBC中位数为140.5(2.7~667.1)×10⁹·L^-1,中危38例(73.1%)、高危14例(26.9%)。中位随访时间136.3(1.2~171.7)个月,长期完全缓解38例(73.1%)、复发10例(19.2%),其他原因死亡4例(7.7%)。②TCRB、TCRG、TCRD和IgH克隆性基因重排的发生率分别为85%、85%、38%和21%,94%的患儿检出至少1种基因重排,88%的患儿检出至少2种基因重排。TCRB、TCRD、TCRG和IgH重排分别以完全性V_β-(D_β)-J_β、V_δ-J_δ、V_γⅠ-J_γ1.3/2.3和D_H-J_H不完全重排为主。各种重排的胚系片段使用和连接区序列极具多样性。③ 10例复发患儿中有6例检测了复发时的Ig/TCR基因重排模式,4例与初诊时完全一致,2例发生改变。④SIL-TAL1融合基因阳性率在11例IgH重排阳性患儿中0%(0/14),在41例IgH重排阴性患儿中为34.1%(14/41),P=0.025。⑤TCRB基因重排阳性组高危比例(20.5%,9/44)低于阴性组(62.5%,5/8),P=0.025。TCRB或TCRG基因重排阳性组第33 d缓解率(89.4%,42/44)高于阴性组(10.6%,5/8),P=0.022,第78 d MRD水平≥10^-3的比例(10.8%,4/37)低于阴性组(50.0%,3/6),P=0.045。结论 儿童T-ALL初诊时Ig/TCR克隆性基因重排的胚系片段使用和连接区序列极具多样性,有助于进一步性MRD 检测标志的筛选。     

急性淋巴细胞白血病患儿大剂量静脉滴注门冬酰胺酶治疗后脑脊液门冬酰胺浓度

目的　测定急性淋巴细胞白血病 (ALL)患儿大剂量静注门冬酰胺酶 (ASP)治疗前、后脑脊液 (CSF)中门冬酰胺 (ASN)浓度 ,从临床及药代动力学方面 ,探讨ASP在中枢神经系统 (CNS)白血病治疗中的药理作用及最佳给药方式。方法　 10例ALL患儿分别 4次接受德国小儿白血病协作组多中心协作治疗方案 (COALL 97)中的主要药物ASP(每隔 4～ 6周 1次静脉注射 4 0 0 0 0U/m2 )的联合化疗。在静脉注射L ASP前及给药后第1、3、4、5周采集CSF ,用安捷伦高效流相色谱仪检测CSF中ASN浓度 ,并观察临床疗效。结果　CSF中ASN浓度分别为 :给药前 1.894± 0 .5 8μmol/L ;给药后第 1周 0 .0 5 6± 0 .0 13μmol/L ;第 3周 0 .117± 0 .0 0 0 0 8μmol/L ;第 4周 0 .2 12± 0 .0 13μmol/L ;第 5周 0 .897± 0 .0 89μmol/L。ALL患儿应用L ASP后CSF中ASN浓度明显降低 (P <0 .0 5 ) ,同时测定CSF中谷氨酰胺浓度在给药前后均无显著变化。结论　 1次注射 4 0 0 0 0U/m2 ASP后能使CSF中ASN浓度降低并持续至第 5周后回升。这种用药方法有预防或治疗CNS白血病的作用     

儿童急性髓系白血病163例临床分析

目的分析重庆医科大学附属儿童医院初诊急性髓系白血病（AML）患儿的临床资料,为进一步完善治疗方案提供依据。方法除外急性早幼粒细胞白血病,2008年1月-2012年12月共收治AML患儿163例,分析其临床资料。结果（1）以男性和5～10岁组患儿较多见;中位初诊年龄为5岁4个月,其中有18例患儿初诊年龄≤1岁。（2）骨髓MICM分型检查：FAB分型中以M2亚型最多见;免疫分型除139例患儿单纯表达髓系分化抗原表达以外,21例同时伴有淋巴系抗原表达,3例为未表型;细胞遗传学中异常核型的检出率为66％,以复杂核型最多见;26例患儿检测到AML1-ETO融合基因。（3）本研究治疗率55．2％,总诱导缓解率为87．8％,无诱导缓解化疗相关死亡患儿。（4）90例接受诱导缓解化疗患儿中位生存时间为13个月,中位无复发生存时间为9个月,其中43例接受2个疗程以上根治性缓解后化疗患儿中位生存时间为20个月,中位无复发生存时间为14个月。结论我院AML患儿治疗率仅为52．5％。还需要进一步完善AML患儿临床危险度分组以指导治疗,以中大剂量阿糖胞苷为主的化疗可改善预后。     

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??Childhood acute lymphoblastic leukemia is the first disseminated cancer shown to be curable. Central nervous system leukemia ??CNSL?? is one of reasons that cause leukemia replase and is associated with a poor prognosis. Pediatricians should master the diagnostic techniques??modalities of prophylaxis and therapy of CNSL in patients with childhood acute lymphoblastic leukemia.     

Fatigue in survivors of childhood acute lymphoblastic and myeloid leukemia in Japan

Background: Fatigue in cancer survivors is a serious problem in pediatric oncology, but reports on this issue are limited, especially in Asian countries. Methods: Sixty‐three patients with acute lymphoblastic leukemia and 18 patients with acute myeloid leukemia who attended a follow‐up outpatient clinic were enrolled. Participants were required to be >8 years of age, in remission, and without any cancer treatment for at least the previous 1 year. A control group consisted of 243 subjects whose age and gender were matched with the patient group. A questionnaire consisting of 12 items was devised for fatigue measurement. Results: Principal factor analysis identified three dimensions, defined as physical fatigue, decreased function, and altered mood. The mean total and the three fatigue dimension scores tended to be higher in the control group, but significant differences between the scores were seen only in the total and physical fatigue scores. Multiple regression analysis indicated an association of present older age or shorter duration after completion of treatment with total and physical fatigue, and an association of presence of total body irradiation with decreased function. Conclusion: Pediatric leukemia survivors in Japan experience equal or less fatigue compared with that of controls in different fatigue dimensions. Elucidation of underlying mechanisms of cancer‐related fatigue including the differences of cultural background among different countries is necessary for future study of this issue.     

Infections in cerebrospinal fluid shunts

Bacterial colonization of cerebrospinal fluid shunts is a cause of significant morbidity, causing not only shunt malfunction and chronic ill-health but has also been implicated in an immune-complex glomerulonephritis. Almost all shunt colonizations involve Staphylococcus albus which gains access to the shunt during surgery and grows in microcolonies inside the shunt. The most reliable means of diagnosis at present is serological surveillance. Medical management is usually ineffective in eradicating colonization and colonized shunts must be replaced. Recent work on the impregnation of Silastic with antimicrobial substances to prevent colonization has provided encouraging results.