儿童急性白血病围孕期环境因素影响的循证医学研究进展

儿童急性白血病（acute leukemia,AL）是儿童时期最常见的恶性肿瘤,严重危害着患儿的身心健康,儿童 AL 的病因中环境因素及遗传因素起着重要作用,儿童 AL 发病年龄低,大多数5岁前发病,因此推测父母在备孕期间、母亲怀孕期间以及儿童期不良环境暴露可能都有着重要影响,本文就其环境因素中香烟烟雾、咖啡、茶等的循证医学研究进展进行综述。     

我国小儿急性白血病临床研究进展和今后努力方向

新中国成立以来,由于预防为主的卫生工作方针的开展,传染病的发病与病死率明显下降,某些感染性疾病加肺炎与腹泻由于防治工作的提高也得到了有效地控制。目前小儿急性白血病(AL)已成为我国大城市儿童死亡的主要原因,因此,开展白血病的治疗和科研工作已成为儿科工作者的重要任务。我国儿科从70年代末期在几个大城市如北京,上海等首先开展了小儿AL的临床和实验室的研究工作。今年四月召开了全国第三届小儿血液病     

如何提高我国儿童急性白血病患者的长期无病生存率

近20年来，经我国小儿白血病工作者的不懈努力，急性小儿白血病(AL)的诊疗取得了显著的成绩。尤其近10年来在治疗方面不断改进和完善，采用大剂量多药联合化疗，注重白血病的早期治疗效应，使小儿AL的完全缓解(CR)率和长期无病生存(EFS)率有了显著的提高。北京儿童医院和上海儿童医疗中心等单位已达国际先进水平。……     

Livin蛋白在儿童急性白血病中的表达及临床意义

目的 探讨Livin蛋白在儿童急性白血病(AL)中的表达及临床意义.方法 采用免疫组织化学S-P方法检测Livin蛋白在65例AL患儿骨髓细胞中的表达,其中初治35例,缓解30例;对照组10例为非恶性血液病.结果 AL初治患儿Livin蛋白阳性表达率(65.71%)高于缓解患儿(16.67%)和对照组(10.00%)(P<0.01),初治ALL患儿Livin蛋白阳性表达率(64.00%)与初治AML(60.00%)比较差异无统计学意义(P>0.05).结论 Livin蛋白在AL初治患儿中表达上调,提示其可能参与了儿童AL的发生、发展,为儿童AL的基因治疗提供了新思路.     

G-CSF配合小剂量HA方案治疗低增生性急性白血病

低增生性急性白血病(AL)是临床上治疗的难点之一,1998年6月-2002年6月间,我院用粒细胞集落刺激因子(G-CSF)配合小剂量HA方案治疗低增生性AL32例,取得了满意效果,现报告如下.     

儿童急性白血病心肌酶谱的观察

目的 了解儿童急性白血病(AL)心肌酶谱的变化.方法 对70例AL患儿于入院后第2天早晨空腹取静脉血,采用速率法测定心肌酶谱并观察治疗前及化疗后其变化.结果 AL(各类型)心肌酶在治疗前明显高于对照组,完全缓解后下降,尤其以CK-MB、LDH、HBDH差异尤为显著.当AL心肌酶各项指标异常升高时予后不良.结论 AL对心肌有损害.70例儿童AL心肌酶测定结果 显示LDH、HBDH变化显著.     

我国儿童肿瘤5年生存率超过70% 白血病居儿童肿瘤发病和死亡首位

<正>由首都医科大学附属北京儿童医院主办的中国工程院2014年医学前沿论坛暨第四届小儿肿瘤研究高峰论坛在北京召开。全国肿瘤防治研究办公室、全国肿瘤登记中心主任陈万青在本次论坛上首次发布了我国儿童肿瘤发病、死亡等相关数据。全国肿瘤登记中心2013年共收集了全国145个肿瘤登记处的2 234万0¹4岁儿童数据,分析结果显示,白血病位居我国儿童肿瘤发病和死亡首位,同时,我国儿童肿瘤5年生存率达到72%,略低于美国。白血病位居儿童肿瘤发病死亡首位与成人相比,儿童肿     

吡柔比星与米托蒽醌治疗难治性白血病的疗效比较

吡柔比星(THP)是新一代蒽环类抗癌抗生素.我院自1996年6月-2000年3月采用国产吡柔比星为主方案治疗成人难治性急性白血病(AL)26例,对其疗效和毒副作用进行了观察,并与同期(1993年6月-1998年6月)用米托蒽醌(MTZ)为主方案治疗难治性AL25例进行比较,结果报告如下.     

凋亡抑制蛋白XIAP在儿童急性白血病中的表达及其临床意义

目的探讨凋亡抑制蛋白XIAP在儿童急性白血病（AL）中的表达及其临床意义。方法54例AL患儿,其中初诊未治26例,治疗后完全缓解（CR）23例,复发5例。应用免疫组织化学方法检测其骨髓细胞XIAP蛋白表达。对照组为10例非恶性血液病且骨髓正常患儿。结果初诊未治AL患儿骨髓中XIAP蛋白表达水平高于缓解期（P〈0．05）和对照组（P〈0．05）,和复发组相比差异无统计学意义（P〉0．05）,且缓解期仍高于对照组（P〈0．05）;初诊未治AL患儿骨髓中XIAP蛋白水平在急性淋巴细胞白血病（ALL）和急性非淋巴细胞白血病（ANLL）组比较差异无统计学意义（P〉0．05）。结论XIAP蛋白在儿童AL患者中高表达,提示XIAP可能通过抑制肿瘤细胞的凋亡参与了儿童AL的发生、发展。     

15例存活五年以上儿童急性白血病

本文报告我院儿科1978年1月至1988年1月收治的儿童急性白血病(AL)中获得生存5～15年的15例患儿。除2例死亡外,其余13例体格,智力发育良好,1例已参加工作,他们已停化疗1～10年。血液学及BM检查均无异常发现。现将该15例的临床特征、治疗和随访情况讨论分析如下。临床资料一、病例来源: 15例儿童AL为我院根据临床、血象和骨髓象确诊。经联合化疗获得缓解(按1978年全国血液病会议标准)。发病年龄2～10岁,男12例,女3例。本组生存期自确诊日算起,直至死亡或最后一次来院就诊之日为止。不能坚持治疗两个月以上者不统计在内。     

Granulocytic Sarcoma as the Presenting Manifestation of Acute Leukemia in Childhood

This report describes six cases of acute leukemia in childhoodmanifested initially by granulocytic sarcoma. Solid tumor wasassociated with acute monocytic leukemia in one patient andwith acute myelogenous leukemia in other patients. In two patients,generalized lymphadenopathy was the predominant feature precedingother signs and symptoms of acute leukemia. One case revealedthe clinical course of smoldering acute leukemia characterizedby insidious onset and a small number of myeloblasts in thebone marrow. One case showed Mikulicz's syndrome preceding thesystemic manifestation of leukemia, and the peripheral bloodwas normal at the time of admission. In another patient withan orbital tumor, three months after the biopsy which was reportedto be reticulum cell sarcoma, blood and marrow were typicalof acute leukemia. In this case, peripheral blood picture wasnormal at the time of tumor formation, but marrow examinationwas not performed. The last case was unusual in that myeloblastoma preceded theblood and marrow evidence of acute leukemia by 38 months. Reviewof literature revealed 6 well-documented cases of granulocyticsarcoma preceding the marrow evidence of leukemia. The importance of cytological examination by Peroxidase reactionand May-Giemsa staining on imprints prepared from biopsy specimentogether with histological examination in differentiating acuteleukemia from reticulum cell sarcoma was stressed. Chloromas are green tumor masses composed of primitive whiteblood cells, usually associated with acute myelocytic or myelomonocyticleukemia, occurring more often in childhood than in adults.Myeloblastoma—tumorous masses histologically identicalto chloroma but without greenish pigmentation—is oftenused as a synonym. But the term granulocytic sarcoma may bemore appropriate to describe these tumors (Rappaport, 1966). Occasionally, tumor formation may be the earliest manifestationpreceding other symptoms, signs and bone marrow evidence ofacute leukemia.     

Familial history of cancer and childhood acute leukemia: a French population-based case-control study.

A case-control study was conducted to investigate the role of a familial history of cancer in the etiology of childhood acute leukemia. The history of cancer in the relatives of 472 cases was compared with that of 567 population-based controls. Recruitment was frequency matched on age, sex and region. The familial history of cancer in each child's relatives was reported by the mother in response to a standardized self-administered questionnaire. A familial history of solid tumor in first or second-degree relatives was associated with an increased risk of acute lymphoblastic leukemia (odds ratio (OR)=1.6 [95% confidence interval, 1.2-2.1]), while a familial history of hematopoietic malignancies in first or second-degree relatives was associated with an increased risk of acute myeloid leukemia (OR=4.3 [1.4-13]). The ORs for the histories of cancer increased with the number of relatives with cancer (OR=1.5 [1.1-2.0] for one relative and OR=2.3 [1.3-3.8] for two relatives or more; Ptrend<0.0001). Significant associations between childhood acute leukemia and familial history of genital cancers and brain tumor were also observed (OR=2.7 [1.2-5.8] and OR=10.7 [1.3-86], respectively). This study supports the hypothesis that a familial history of cancer may play a role in the etiology of childhood acute leukemia. It also evidences some specific associations that require further investigation.     

Family cancer history and risk of childhood acute leukemia (France)

OBJECTIVE: A case-control study was carried out to investigate the role of a family history of solid tumor or hematologic neoplasm in the etiology of childhood acute leukemia. METHODS: Family cancer history in first- and second-degree relatives was compared in 279 incident cases (242 cases of acute lymphocytic leukemia and 37 of acute myeloid leukemia) and 285 controls. Recruitment was stratified by age, gender, hospital, area of residence, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. RESULTS: A significant association between childhood acute leukemia and a family history of hematologic neoplasm (OR = 2.7, confidence interval (CI) = 1.1-6.9) was found. This association was particularly clear-cut when the cases were restricted to acute myeloid leukemia (OR = 13.3, CI = 2.5-70.9). Childhood acute leukemia was associated with a family history of solid tumor (OR = 1.5, CI = 1.0-2.2), and elevated odds ratios were observed for family history of gastrointestinal cancer and melanoma. Those results are most unlikely to be explained by socioeconomic status and familial structure, which were very similar for the cases and controls. Differential misclassification is also unlikely for the first-degree relatives, even though it is difficult to rule it out for the second-degree relatives' history. CONCLUSION: The present study supports the hypothesis that a family history of cancer may be a risk factor for childhood acute leukemia.     

The successive development of acute myeloblastic leukemia, secondary non-Hodgkin's lymphoma and secondary myeloid/natural killer cell acute leukemia in a single patient

We report a very rare case of a female patient who was initially diagnosed with acute myeloid leukemia (AML) M2 who achieved complete remission (CR) after chemotherapy. Six years later she was still in continuous complete remission from leukemia, but developed a right nasal obstruction and based on the nasal and nasopharynx biopsies, a secondary B cell non-Hodgkin's lymphoma was diagnosed and treated with chemotherapy and involved field radiotherapy. One year and seven months after the completion of therapy she presented with fever, dyspnea and leukocytosis. The blasts were now negative for myeloperoxidase and immunophenotyping showed that they were positive for CD13 and CD56. Now the diagnosis of a secondary myeloid/NK cell acute leukemia was made. The patient died of multiorgan failure 1 month after the onset of leukemia. As far as we know, no other such patient has been described in the English literature until now.     

Breast-feeding and risk of childhood acute leukemia.

BACKGROUND: Breast-feeding is well known to have a protective effect against infection in infants. Although the long-term effects of breast-feeding on childhood cancer have not been studied extensively, a protective effect against childhood Hodgkin's disease and lymphoma has been suggested previously from small investigations. In this study, we tested the hypothesis that breast-feeding decreases the risk of childhood acute leukemia. METHODS: A total of 1744 children with acute lymphoblastic leukemia (ALL) and 1879 matched control subjects, aged 1-14 years, and 456 children with acute myeloid leukemia (AML) and 539 matched control subjects, aged 1-17 years, were included in the analysis. Information regarding breast-feeding was obtained through telephone interviews with mothers. All leukemias combined, histologic type of leukemia (ALL versus AML), immunophenotype of ALL (early pre-B cell, pre-B cell, or T cell), and morphology of AML were assessed separately in the data analysis. RESULTS: Ever having breast-fed was found to be associated with a 21% reduction in risk of childhood acute leukemias (odds ratio [OR] for all types combined = 0.79; 95% confidence interval [CI] = 0.70-0.91). A reduction in risk was seen separately for AML (OR = 0.77; 95% CI = 0.57-1.03) and ALL (OR = 0.80; 95% CI = 0.69-0.93). The inverse associations were stronger with longer duration of breast-feeding for total ALL and AML; for M0, M1, and M2 morphologic subtypes of AML; and for early pre-B-cell ALL. CONCLUSION: In this study, breast-feeding was associated with a reduced risk of childhood acute leukemia. If confirmed in additional epidemiologic studies, our findings suggest that future epidemiologic and experimental efforts should be directed at investigating the anti-infective and/or immune-stimulatory or immune-modulating effects of breast-feeding on leukemogenesis in children.     

N-ras mutations in myeloid leukemias

The presence of mutations activating the N-ras gene was investigated by the polymerase chain reaction technique in twenty patients with acute myeloblastic leukemia (AML) at onset and in four patients with Ph1 positive chronic myelogeneous leukemia (CML) either in chronic phase or in blast crisis. Four remission samples and four relapses from the AML cases were also studied. Mutations were found in five out of twenty (25%) untreated AML cases at onset. No mutations were detected in the complete remission samples, two of them with N-ras mutations during the leukemic phase. Two out of the four leukemia relapses were positive for the same N-ras mutation shown at presentation, whereas no new mutations were found in the other two initially negative cases. An N-ras mutation appeared during the blast crisis of one of the four CML, which were all negative during the chronic phase. In conclusion, whereas some data appear to be consistent with a role of the N-ras mutations as initiating events in myeloid leukemias, in other cases N-ras activation seems to represent a factor involved in progression. These data suggest that a partial overlapping between initiation and progression factors could exist in naturally occurring tumors.     

婆罗双树样基因4在儿童急性白血病中的表达及临床意义

  目的  探讨婆罗双树样基因4（sal-like 4,SALL4）在儿童急性白血病中的表达及其临床意义。  方法  采用实时荧光定量PCR和免疫组织化学技术检测50例初诊急性白血病患儿SALL4 mRNA及蛋白的表达量,以15例免疫性血小板减少性紫癜（immune thrombocytopenic purpura,ITP）为对照;动态观察5例白血病患儿初诊和完全缓解后SALL4 mRNA的表达变化;分析SALL4 mRNA表达量与临床指标的关系。  结果  SALL4 mRNA在初诊急性B淋巴细胞白血病（B-ALL）、急性髓细胞白血病（AML）中的表达量分别为13.89（1.00~63.15）、11.12（2.31~56.59）,显著高于对照组[1.00（0.29~1.71）（P < 0.01）],在急性T淋巴细胞白血病（T-ALL）中的表达量1.48（0.87~4.81）与对照组无显著差异（P>0.05）;SALL4蛋白表达检测结果与SALL4 mRNA表达结果一致;急性白血病患儿完全缓解后SALL4 mRNA表达量0.98（0.22~1.09）较初诊时[28.64（11.20~87.46）]显著降低（P < 0.01）。SALL4 mRNA的高表达与外周血高白细胞计数、高危分型、诱导化疗末期微小残留病（minimal residual disease,MRD）呈正相关（r=0.424、r=0.403、r=0.393,P均 < 0.05）;与发病年龄,性别,肝、脾、淋巴结肿大等因素无相关性（P>0.05）。  结论  SALL4可能促进了儿童B-ALL、AML的发生发展,并有望成为监测治疗效果和判断预后的新指标。      

Prenatal origin of childhood AML occurs less frequently than in childhood ALL

Background  

While there is enough convincing evidence in childhood acute lymphoblastic leukemia (ALL), the data on the pre-natal origin in childhood acute myeloid leukemia (AML) are less comprehensive. Our study aimed to screen Guthrie cards (neonatal blood spots) of non-infant childhood AML and ALL patients for the presence of their respective leukemic markers.     

Number of siblings and the risk of lymphoma, leukemia, and myeloma by histopathology.

Epidemiologic evidence indicates that several markers of exposure to childhood infections are inversely associated with the risk of childhood leukemia and lymphomas. We used the Swedish Family-Cancer Database to assess the effects of number of siblings on the risk of non-Hodgkin's (n = 7,007) and Hodgkin's lymphomas (n = 3,115), leukemias (n = 7,650), and multiple myeloma (n = 1,492) by histopathology. Poisson regression models included terms for age, sex, family history, period, and socioeconomic index. Having four or more siblings compared with none was associated with an excess risk of childhood acute lymphoblastic leukemia [ALL; rate ratio (RR), 2.11; P(trend) = 0.001], acute monocytic leukemia (RR, 2.51; P(trend) = 0.002), and multiple myeloma (RR, 1.34; P(trend) = 0.006). Having three or more older siblings compared with none decreased the risk of acute monocytic leukemia (RR, 0.35; P(trend) = 0.001) and childhood ALL (RR, 0.69; P(trend) = 0.01). The risk of Hodgkin's lymphoma for five or more older siblings compared with none was 0.41 (P(trend) = 0.003). Acute myeloid leukemia, chronic lymphocytic leukemia, and other lymphoproliferative malignancies were not associated with number of siblings. In conclusion, we found an excess risk of childhood ALL and acute monocytic leukemia in large families. However, for ALL, acute monocytic leukemia, and Hodgkin's lymphoma, younger siblings were strongly protected compared with older siblings. The remarkable protective effect of number of older siblings on acute monocytic leukemia is a novel finding of potential interest. Possible interpretations of our findings in the context of a putative infectious etiology are discussed.     

Effect of GSTM1 null genotype on risk of childhood acute leukemia: a meta-analysis

Glutathione S-transferases are important enzymes in the detoxification of a wide range of reactive oxygen species. Recently, there have been a number of studies on the association between Glutathione S-transferase M1 (GSTM1) null genotype and childhood acute leukemia in Chinese, but the results of previous reports are inconsistent. Thus, we performed a meta-analysis to clarify the effect of GSTM1 null genotype on childhood acute leukemia risk. PubMed, Embase, and Wanfang databases were searched to identify case–control studies investigating the association between GSTM1 null genotype and risk of childhood acute leukemia. Between-study heterogeneity was assessed using the I ² statistic method. Odds ratios (OR) with corresponding 95 % confidence intervals (95 % CI) were pooled to assess the association. Seven case–control studies were finally included in the meta-analysis. There was no between-study heterogeneity among those seven studies (I ²?=?0 %). Overall, the GSTM1 null genotype was significantly associated with increased risk of childhood acute leukemia in Chinese (fixed effect OR?=?2.49; 95 % CI, 1.84–3.37; P?<?0.001). The cumulative meta-analyses showed a trend of more obvious association between GSTM1 null genotype and risk of childhood acute leukemia in Chinese as data accumulated by year. Sensitivity analysis by omitting single study in turns also did not materially alter the pooled ORs. Therefore, the GSTM1 null genotype is significantly associated with increased risk of childhood acute leukemia in Chinese.