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Sample records for childhood leukemia study

  1. Childhood acute lymphoblastic leukemia and indicators of early immune stimulation: a Childhood Leukemia International Consortium study.

    Science.gov (United States)

    Rudant, Jérémie; Lightfoot, Tracy; Urayama, Kevin Y; Petridou, Eleni; Dockerty, John D; Magnani, Corrado; Milne, Elizabeth; Spector, Logan G; Ashton, Lesley J; Dessypris, Nikolaos; Kang, Alice Y; Miller, Margaret; Rondelli, Roberto; Simpson, Jill; Stiakaki, Eftichia; Orsi, Laurent; Roman, Eve; Metayer, Catherine; Infante-Rivard, Claire; Clavel, Jacqueline

    2015-04-15

    The associations between childhood acute lymphoblastic leukemia (ALL) and several proxies of early stimulation of the immune system, that is, day-care center attendance, birth order, maternally reported common infections in infancy, and breastfeeding, were investigated by using data from 11 case-control studies participating in the Childhood Leukemia International Consortium (enrollment period: 1980-2010). The sample included 7,399 ALL cases and 11,181 controls aged 2-14 years. The data were collected by questionnaires administered to the parents. Pooled odds ratios and 95% confidence intervals were estimated by unconditional logistic regression adjusted for age, sex, study, maternal education, and maternal age. Day-care center attendance in the first year of life was associated with a reduced risk of ALL (odds ratio = 0.77, 95% confidence interval: 0.71, 0.84), with a marked inverse trend with earlier age at start (P < 0.0001). An inverse association was also observed with breastfeeding duration of 6 months or more (odds ratio = 0.86, 95% confidence interval: 0.79, 0.94). No significant relationship with a history of common infections in infancy was observed even though the odds ratio was less than 1 for more than 3 infections. The findings of this large pooled analysis reinforce the hypothesis that day-care center attendance in infancy and prolonged breastfeeding are associated with a decreased risk of ALL.

  2. Childhood Leukemia

    Science.gov (United States)

    ... fast growing type while chronic leukemia grows slowly. Children with leukemia usually have one of the acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes ...

  3. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Pui, Ching-Hon; Yang, Jun J; Hunger, Stephen P;

    2015-01-01

    PURPOSE: To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. METHODS: A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was re...

  4. Commentary on "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations"

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    Schmitt, Ara

    2011-01-01

    This commentary pertains to the article, "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations" by D. Scott Hermann, Jill R. Thurber, Kenneth Miles, and Gloria Gilbert in this issue (2011) regarding pediatric leukemia. The authors present a literature review regarding leukemia in childhood,…

  5. Childhood Leukemia and Electromagnetic Fields

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    Alpaslan Türkkan

    2009-12-01

    Full Text Available In this review, the relationship between very low frequency electromagnetic fields, originating from high voltage powerlines, and childhood leukemia was evaluated. Electromagnetic fields have biological effects. Whole populations are effected by different levels of electromagnetic fields but children are more sensible. In urban areas high voltage powerlines are the main sources of electromagnetic fields. The relation of electromagnetic fields due to high voltage powerlines and leukemia with consideration of dose-response and distance is investigated in several studies. There are different opinions on the effects of electromagnetic fields on general health. The relation between electromagnetic fields and childhood leukemia must be considered separately. Although there is no limit value, it is generally accepted that exposure to 0.4 µT and over doubles the risk of leukemia in children 15 years and younger. (Journal of Current Pediatrics 2009; 7: 137-41

  6. Birth Weight and Acute Childhood Leukemia: A Meta-analysis of Observational Studies

    Science.gov (United States)

    2007-11-02

    neurofibromatosis, Shwachman syndrome, Bloom syndrome, ataxia telangiectasia, Langerhans cell histiocytosis, and Klinefelter syndrome Increased...childhood leukemia (both ALL and AML) with maternal history of fetal loss14-16 while one study reported an inverse association.17 Some studies showed...about 1.5 times).124 There is little current insight into the natural history of acute leukemia in children and the likely timing of key

  7. Commentary on "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations"

    Science.gov (United States)

    Schmitt, Ara

    2011-01-01

    This commentary pertains to the article, "Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations" by D. Scott Hermann, Jill R. Thurber, Kenneth Miles, and Gloria Gilbert in this issue (2011) regarding pediatric leukemia. The authors present a literature review regarding leukemia in…

  8. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Childhood AML Treatment Research Childhood Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Childhood Acute ... Myelogenous Leukemia Treatment Hairy Cell Leukemia Treatment Past treatment for cancer and certain genetic conditions affect the ...

  9. Infection and childhood leukemia: review of evidence

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    Raquel da Rocha Paiva Maia

    2013-12-01

    Full Text Available OBJECTIVE : To analyze studies that evaluated the role of infections as well as indirect measures of exposure to infection in the risk of childhood leukemia, particularly acute lymphoblastic leukemia. METHODS : A search in Medline, Lilacs, and SciELO scientific publication databases initially using the descriptors “childhood leukemia” and “infection” and later searching for the words “childhood leukemia” and “maternal infection or disease” or “breastfeeding” or “daycare attendance” or “vaccination” resulted in 62 publications that met the following inclusion criteria: subject aged ≤ 15 years; specific analysis of cases diagnosed with acute lymphoblastic leukemia or total leukemia; exposure assessment of mothers’ or infants’ to infections (or proxy of infection, and risk of leukemia. RESULTS : Overall, 23 studies that assessed infections in children support the hypothesis that occurrence of infection during early childhood reduces the risk of leukemia, but there are disagreements within and between studies. The evaluation of exposure to infection by indirect measures showed evidence of reduced risk of leukemia associated mainly with daycare attendance. More than 50.0% of the 16 studies that assessed maternal exposure to infection observed increased risk of leukemia associated with episodes of influenza, pneumonia, chickenpox, herpes zoster, lower genital tract infection, skin disease, sexually transmitted diseases, Epstein-Barr virus, and Helicobacter pylori . CONCLUSIONS : Although no specific infectious agent has been identified, scientific evidence suggests that exposure to infections has some effect on childhood leukemia etiology.

  10. Supportive care for children with acute leukemia - Report of a survey on supportive care by the Dutch Childhood Leukemia Study Group. Part I

    NARCIS (Netherlands)

    Postma, A; Van Leeuwen, EF; Gerritsen, EJA; Roord, JJ; De vries-Hospers, HG

    1998-01-01

    The Dutch Childhood Leukemia Study Group celebrated its 20th anniversary by conducting a nationwide survey on supportive care for children with leukemia. Pediatricians were asked about daily practice and current perceptions with regard to supportive care. The results are discussed and compared to re

  11. Acute leukemia in early childhood

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    M. Emerenciano

    2007-06-01

    Full Text Available Acute leukemia in early childhood is biologically and clinically distinct. The particular characteristics of this malignancy diagnosed during the first months of life have provided remarkable insights into the etiology of the disease. The pro-B, CD10 negative immunophenotype is typically found in infant acute leukemia, and the most common genetic alterations are the rearrangements of the MLL gene. In addition, the TEL/AML1 fusion gene is most frequently found in children older than 24 months. A molecular study on a Brazilian cohort (age range 0-23 months has detected TEL/AML1+ve (N = 9, E2A/PBX1+ve (N = 4, PML/RARA+ve (N = 4, and AML1/ETO+ve (N = 2 cases. Undoubtedly, the great majority of genetic events occurring in these patients arise prenatally. The environmental exposure to damaging agents that give rise to genetic changes prenatally may be accurately determined in infants since the window of exposure is limited and known. Several studies have shown maternal exposures that may give rise to leukemogenic changes. The Brazilian Collaborative Study Group of Infant Acute Leukemia has found that mothers exposed to dipyrone, pesticides and hormones had an increased chance to give birth to babies with infant acute leukemia [OR = 1.48 (95%CI = 1.05-2.07, OR = 2.27 (95%CI = 1.56-3.31 and OR = 9.08 (95%CI = 2.95-27.96], respectively. This review aims to summarize recent clues that have facilitated the elucidation of the biology of early childhood leukemias, with emphasis on infant acute leukemia in the Brazilian population.

  12. Global characteristics of childhood acute promyelocytic leukemia.

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    Zhang, L; Samad, A; Pombo-de-Oliveira, M S; Scelo, G; Smith, M T; Feusner, J; Wiemels, J L; Metayer, C

    2015-03-01

    Acute promyelocytic leukemia (APL) comprises approximately 5-10% of childhood acute myeloid leukemia (AML) cases in the US. While variation in this percentage among other populations was noted previously, global patterns of childhood APL have not been thoroughly characterized. In this comprehensive review of childhood APL, we examined its geographic pattern and the potential contribution of environmental factors to observed variation. In 142 studies (spanning >60 countries) identified, variation was apparent-de novo APL represented from 2% (Switzerland) to >50% (Nicaragua) of childhood AML in different geographic regions. Because a limited number of previous studies addressed specific environmental exposures that potentially underlie childhood APL development, we gathered 28 childhood cases of therapy-related APL, which exemplified associations between prior exposures to chemotherapeutic drugs/radiation and APL diagnosis. Future population-based studies examining childhood APL patterns and the potential association with specific environmental exposures and other risk factors are needed.

  13. Population-based case-control study of childhood leukemia in Shanghai

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    Shu, X.O.; Gao, Y.T.; Brinton, L.A.; Linet, M.S.; Tu, J.T.; Zheng, W.; Fraumeni, J.F. Jr.

    1988-08-01

    A population-based case-control interview study of 309 childhood leukemia cases and 618 healthy population control children was conducted in urban Shanghai, China. Like some studies in other countries, excess risks for both acute lymphocytic leukemia (ALL) and acute nonlymphocytic leukemia (ANLL) were associated with intrauterine and paternal preconception diagnostic x-ray exposure, and with maternal employment in the chemical and agricultural industries during pregnancy. ANLL was linked to maternal occupational exposure to benzene during pregnancy, whereas both ALL and ANLL were significantly associated with maternal exposure to gasoline and the patient's prior use of chloramphenicol. New findings, previously unsuspected, included an association of ANLL with younger maternal age at menarche (odds ratio (OR) = 4.3; 95% confidence interval (CI) = 1.3-13.9); a protective effect for long-term (greater than 1 year) use of cod liver oil containing vitamins A and D for both ALL (OR = 0.4; 95% CI = 0.2-0.9) and ANLL (OR = 0.3; 95% CI = 0.1-1.0); and excess risks of ANLL among children whose mothers were employed in metal refining and processing (OR = 4.6; 95% CI = 1.3-17.2) and of ALL associated with maternal occupational exposure to pesticides (OR = 3.5; 95% CI = 1.1-11.2). No relationships were found with late maternal age, certain congenital disorders, or familial occurrence, which have been related to childhood leukemia in other studies. In contrast with other reports, an excess of leukemia, primarily ANLL, occurred among second or later-born rather than firstborn children.

  14. Childhood Leukemia Survivors and Their Return to School: A Literature Review, Case Study, and Recommendations

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    Herrmann, D. Scott; Thurber, Jill R.; Miles, Kenneth; Gilbert, Gloria

    2011-01-01

    Leukemias (blood cell cancers) and central nervous system tumors are the most frequently occurring types of cancer in children. Mortality rates from all childhood cancers have decreased over the past 2 decades. As a result, many childhood cancer survivors are now returning to their schools after having been successfully treated. Although most of…

  15. GSTM1 and GSTT1 null polymorphisms and childhood acute leukemia risk: evidence from 26 case-control studies.

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    Qiuqin Tang

    Full Text Available Several molecular epidemiological studies have been conducted to examine the association between glutathione S-transferase mu-1 (GSTM1 and glutathione S-transferase theta-1 (GSTT1 null polymorphisms and childhood acute leukemia; however, the conclusions remain controversial. We performed an extensive meta-analysis on 26 published case-control studies with a total of 3252 cases and 5024 controls. Crude odds ratios (ORs with 95% confidence interval were used to assess the strength of association between childhood acute leukemia risk and polymorphisms of GSTM1 and GSTT1. With respect to GSTM1 polymorphism, significantly increased risk of childhood acute leukemia was observed in the overall analysis (OR = 1.30; 95%CI, 1.11-1.51. Furthermore, a stratification analysis showed that the risk of GSTM1 polymorphism are associated with childhood acute leukemia in group of Asians (OR = 1.94; 95%CI, 1.53-2.46, Blacks (OR = 1.76; 95%CI, 1.07-2.91, ALL (OR = 1.33; 95%CI, 1.13-1.58, '< 100 cases and <100 controls' (OR = 1.79; 95%CI, 1.21-2.64, '≥ 100 cases and ≥ 100 controls' (OR = 1.25; 95%CI, 1.02-1.52, and population-based control source (OR = 1.40; 95%CI, 1.15-1.69. With respect to GSTT1 polymorphism, significant association with childhood acute leukemia risk was only found in subgroup of Asian. This meta-analysis supports that GSTM1 null polymorphism is capable of causing childhood acute leukemia susceptibility.

  16. Exposure to magnetic fields and survival after diagnosis of childhood leukemia: a German cohort study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Weihkopf, Thomas; Kaatsch, Peter

    2007-01-01

    Inspired by a recent U.S. study showing poorer survival among children with acute lymphoblastic leukemia (ALL) exposed to magnetic fields above 0.3 microT, we examine this relationship in a German cohort of childhood leukemia cases derived from previous population-based case-control studies...... conducted between 1992 and 2001. A total of 595 ALL cases with 24-h magnetic field measurements are included in the analysis with a median follow-up of 9.5 years. We calculate the hazard ratios (HR) using the Cox proportional hazards model for overall survival, adjusted for age at diagnosis, calendar year...... of diagnosis, and gender. Elevated hazards are found for exposures between 0.1 and 0.2 microT [HR, 2.6; 95% confidence interval (95% CI), 1.3-5.2], based on 34 cases with 9 deaths as well as for exposures above 0.2 microT (HR, 1.6; 95% CI, 0.6-4.4), based on 18 cases with 4 deaths. After adjustment...

  17. Residential Proximity to Heavy-Traffic Roads, Benzene Exposure, and Childhood Leukemia-The GEOCAP Study, 2002-2007.

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    Houot, Jennifer; Marquant, Fabienne; Goujon, Stéphanie; Faure, Laure; Honoré, Cécile; Roth, Marie-Hélène; Hémon, Denis; Clavel, Jacqueline

    2015-10-15

    Childhood leukemia may be associated with traffic-related environmental exposure to benzene, and additional data are needed. The Géolocalisation des Cancers Pédiatriques (GEOCAP) Study, a nationwide French case-control study, was designed to avoid selection bias due to differential participation and misclassification. The study compared the 2,760 childhood leukemia cases diagnosed in France between 2002 and 2007 (including 2,275 cases of acute lymphoblastic leukemia (ALL) and 418 cases of acute myeloblastic leukemia (AML)) with 30,000 contemporaneous child population controls. The residence addresses were precisely geocoded, and 3 indicators of residential proximity to traffic were considered. Estimates of benzene concentrations were also available for the Île-de-France region (including Paris). A 300-m increase in major road length within 150 m of the geocoded address was significantly associated with AML (odds ratio = 1.2, 95% confidence interval: 1.0, 1.4) but not with ALL (odds ratio = 1.0, 95% confidence interval: 0.9, 1.1), and the association was reinforced in the Île-de-France region when this indicator was combined with benzene estimates. These results, which were free from any participation bias and based on objectively determined indices of exposure, showed an increased incidence of AML associated with heavy-traffic road density near a child's home. The results support a role for traffic-related benzene exposure in the etiology of childhood AML.

  18. Home pesticide exposures and risk of childhood leukemia: Findings from the childhood leukemia international consortium.

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    Bailey, Helen D; Infante-Rivard, Claire; Metayer, Catherine; Clavel, Jacqueline; Lightfoot, Tracy; Kaatsch, Peter; Roman, Eve; Magnani, Corrado; Spector, Logan G; Th Petridou, Eleni; Milne, Elizabeth; Dockerty, John D; Miligi, Lucia; Armstrong, Bruce K; Rudant, Jérémie; Fritschi, Lin; Simpson, Jill; Zhang, Luoping; Rondelli, Roberto; Baka, Margarita; Orsi, Laurent; Moschovi, Maria; Kang, Alice Y; Schüz, Joachim

    2015-12-01

    Some previous studies have suggested that home pesticide exposure before birth and during a child's early years may increase the risk of childhood leukemia. To further investigate this, we pooled individual level data from 12 case-control studies in the Childhood Leukemia International Consortium. Exposure data were harmonized into compatible formats. Pooled analyses were undertaken using multivariable unconditional logistic regression. The odds ratio (ORs) for acute lymphoblastic leukemia (ALL) associated with any pesticide exposure shortly before conception, during pregnancy and after birth were 1.39 (95% confidence interval [CI]: 1.25, 1.55) (using 2,785 cases and 3,635 controls), 1.43 (95% CI: 1.32, 1.54) (5,055 cases and 7,370 controls) and 1.36 (95% CI: 1.23, 1.51) (4,162 cases and 5,179 controls), respectively. Corresponding ORs for risk of acute myeloid leukemia (AML) were 1.49 (95% CI: 1.02, 2.16) (173 cases and 1,789 controls), 1.55 (95% CI: 1.21, 1.99) (344 cases and 4,666 controls) and 1.08 (95% CI: 0.76, 1.53) (198 cases and 2,655 controls), respectively. There was little difference by type of pesticide used. The relative similarity in ORs between leukemia types, time periods and pesticide types may be explained by similar exposure patterns and effects across the time periods in ALL and AML, participants' exposure to multiple pesticides, or recall bias. Although some recall bias is likely, until a better study design can be found to investigate the associations between home pesticide use and childhood leukemia in an equally large sample, it would appear prudent to limit the use of home pesticides before and during pregnancy, and during childhood.

  19. Maternal benzene exposure during pregnancy and risk of childhood acute lymphoblastic leukemia: a meta-analysis of epidemiologic studies.

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    Yanfeng Zhou

    Full Text Available The prevalence of childhood leukemia is increasing rapidly all over the world. However, studies on maternal benzene exposure during pregnancy and childhood acute lymphoblastic leukemia (ALL have not been systematically assessed. Therefore, we performed a meta-analysis to investigate the association between maternal solvent, paint, petroleum exposure, and smoking during pregnancy and risk of childhood ALL.Relevant studies up to September 1st, 2013 were identified by searching the PubMed, EMBASE, Cochrane library and the Web of Science databases. The effects were pooled using either fixed or random effect models based on the heterogeneity of the studies.Twenty-eight case-control studies and one cohort study were included for analysis, with a total of 16,695 cases and 1,472,786 controls involved. Pooled odds ratio (OR with 95% confidence interval (CI for ALL was 1.25 (1.09, 1.45 for solvent, 1.23 (1.02, 1.47 for paint, 1.42 (1.10, 1.84 for petroleum exposure, and 0.99 (0.93, 1.06 for maternal smoking during pregnancy. No publication bias was found in this meta-analysis and consistent results were observed for subgroup and sensitivity analyses.Childhood ALL was associated with maternal solvent, paint, and petroleum exposure during pregnancy. No association was found between ALL and maternal smoking during pregnancy. Avoidance of maternal occupational and environmental benzene exposure during pregnancy could contribute to a decrease in the risk of childhood ALL.

  20. Tobacco smoke and risk of childhood acute non-lymphocytic leukemia: findings from the SETIL study.

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    Stefano Mattioli

    Full Text Available BACKGROUND: Parental smoking and exposure of the mother or the child to environmental tobacco smoke (ETS as risk factors for Acute non-Lymphocytic Leukemia (AnLL were investigated. METHODS: Incident cases of childhood AnLL were enrolled in 14 Italian Regions during 1998-2001. We estimated odds ratios (OR and 95% confidence intervals (95%CI conducting logistic regression models including 82 cases of AnLL and 1,044 controls. Inverse probability weighting was applied adjusting for: age; sex; provenience; birth order; birth weight; breastfeeding; parental educational level age, birth year, and occupational exposure to benzene. RESULTS: Paternal smoke in the conception period was associated with AnLL (OR for ≥ 11 cigarettes/day  = 1.79, 95% CI 1.01-3.15; P trend 0.05. An apparent effect modification by maternal age was identified: only children of mothers aged below 30 presented increased risks. We found weak statistical evidence of an association of AnLL with maternal exposure to ETS (OR for exposure>3 hours/day  = 1.85, 95%CI 0.97-3.52; P trend 0.07. No association was observed between AnLL and either maternal smoking during pregnancy or child exposure to ETS. CONCLUSIONS: This study is consistent with the hypothesis that paternal smoke is associated with AnLL. We observed statistical evidence of an association between maternal exposure to ETS and AnLL, but believe bias might have inflated our estimates.

  1. Evaluation of functional RAGE gene polymorphisms in childhood acute lymphoblastic leukemia-A case-control study from Iran.

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    Eskandari-Nasab, Ebrahim; Hashemi, Mohammad; Hasani, Seyed-Shahab-Adin; Naderi, Majid; Sadeghi-Bojd, Simin; Taheri, Mohsen

    2017-03-04

    We examined the possible relationship between three RAGE polymorphisms, -429C/T, -374 T/A, and 63-bp deletion, and susceptibility to childhood acute lymphoblastic leukemia (ALL) in an Iranian population. This study included 75 ALL patients and 115 healthy subjects. Genotyping was performed using HEXA-ARMS-polymerase chain reaction. We found no significant association among RAGE gene polymorphisms and the risk for ALL at genotype, allelic and haplotype levels (P > 0.05). The hemoglobin levels were higher in patients with RAGE -374 TT than in the TA carriers (P = 0.019). Our results demonstrated that the RAGE gene variations were not associated with risk of pediatrics ALL.

  2. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia : a retrospective international study

    NARCIS (Netherlands)

    Inaba, Hiroto; Zhou, Yinmei; Abla, Oussama; Adachi, Souichi; Auvrignon, Anne; Beverloo, H. Berna; de Bont, Eveline; Chang, Tai-Tsung; Creutzig, Ursula; Dworzak, Michael; Elitzur, Sarah; Fynn, Alcira; Forestier, Erik; Hasle, Henrik; Liang, Der-Cherng; Lee, Vincent; Locatelli, Franco; Masetti, Riccardo; De Moerloose, Barbara; Reinhardt, Dirk; Rodriguez, Laura; Van Roy, Nadine; Shen, Shuhong; Taga, Takashi; Tomizawa, Daisuke; Yeoh, Allen E. J.; Zimmermann, Martin; Raimondi, Susana C.

    2015-01-01

    Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age 50 chromosomes (n=44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%),

  3. FLT3 Gene Mutation in Childhood Acute Leukemia: A Preliminary Study

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    Zefarina Zulkafli

    2014-01-01

    Full Text Available Introduction. FLT3 is a tyrosine kinase receptor involved in the proliferation and differentiation of hematopoietic stem cells. There are two types of common FLT3 gene mutation, internal tandem duplication and the D835 mutation, which are known to be associated with a poor clinical outcome in acute leukemia patients. Methods. This study evaluates the incidence of FMS-like tyrosine kinase 3-internal tandem duplication (FLT3-ITD in 38 pediatric patients diagnosed with acute lymphoblastic leukemia (ALL and acute myeloid leukemia (AML in Hospital Universiti Sains Malaysia. DNA extraction was done from archive bone marrow samples to determine FLT3-ITD mutations using polymerase chain reaction. Results. In this pediatric series, the age ranges were 2–14 years. However, no FLT3-ITD mutations were detected in any of the samples. Conclusion. This preliminary study suggested that the incidence of FLT3 gene mutation most probably was very low in pediatrics patients diagnosed with acute leukemia. A further study with larger number of patient samples is necessary to confirm the findings and to further appreciate the prognostic value of FLT3-ITD mutation among pediatrics patients.

  4. Assessment of corticosteroid-induced osteonecrosis in children undergoing chemotherapy for acute lymphoblastic leukemia: a report from the Japanese Childhood Cancer and Leukemia Study Group.

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    Hyakuna, Nobuyuki; Shimomura, Yasuto; Watanabe, Arata; Taga, Takashi; Kikuta, Atsushi; Matsushita, Takeji; Kogawa, Kazuhiro; Kawakami, Chihiro; Horikoshi, Yasuo; Iwai, Tsuyako; Okamoto, Yasuhiro; Tsurusawa, Masahito; Asami, Keiko

    2014-01-01

    Steroid-induced osteonecrosis (ON) is a challenging complication encountered during modern chemotherapy for childhood acute lymphoblastic leukemia (ALL). We retrospectively assessed the incidence of ON and its risk factors in a total of 1095 patients enrolled in 3 consecutive Japanese Children's Cancer and Leukemia Study Group ALL studies (ALL941 [1994 to 2000], n=464; ALL2000 [2000 to 2004], n=305; and ALL2004 [2004 to 2010], n=326). ON was diagnosed in 16 patients, of whom 15 were symptomatic. The cumulative incidence of ON was 0.76% in ALL941, 0.35% in ALL2000, and 3.6% in ALL2004. The incidence of ON in ALL941/2000, in which only prednisolone was administered as a steroid, was significantly lower than that in ALL2004, in which dexamethasone was used as a partial substitute for prednisolone (P<0.01). In ALL2004, sex and age were significantly correlated with the incidence of ON (1.3% in boys vs. 6.7% in girls, P=0.0132; 0.42% for age <10 y vs. 15.6% for age ≥10 y, P<0.0001), suggesting that girls aged 10 years and above are at a greater risk of ON onset. These results indicate that the risk of ON should be considered when administering dexamethasone as part of ALL protocol treatment in girls aged 10 years and above.

  5. Molecular epidemiology of childhood leukemia with emphasis on chemical exposures

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    Buffler, P.A.; Smith, M.T.; Wood, S. [Univ. of California, Berkeley, CA (United States); Reynolds, P. [California Dept. of Health Services, Emeryville, CA (United States)

    1996-12-31

    Developing markets in the Pacific Basin depend heavily on the production and export of consumer goods. The generation of hazardous waste as a by-product of industrial production can be linked to adverse health outcomes, such as childhood leukemia, in ways that are presently unknown. In California, exposures resulting from hazardous waste disposal are of concern in the etiology of childhood cancer. Approximately 63% of the 57 hazardous waste sites that the U.S. Environmental Protection Agency (USEPA) included in the national priority list under the Comprehensive Environmental Response, Compensation and Liability Act (CERCLA) statute were in the six-county San Francisco Bay area. This area includes California`s Silicon Valley, where a disproportionate majority of these sites are located. Although only one study links hazardous waste disposal to childhood leukemia evidence is accumulating that in utero and maternal pesticide exposures as well as chemical exposures during childhood are important in the etiology of childhood leukemia. This study investigates whether children with leukemia have common genetic changes, whether children with genetic changes experience common chemical exposures, and whether the occurrences of these genetic changes correspond to the same temporal sequence as exposure. The purpose of this paper is to describe the study design and report on the status of research activity. 10 refs., 1 fig., 3 tabs.

  6. Post chemotherapy blood and bone marrow regenerative changes in childhood acute lymphoblastic leukemia a prospective study

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    Rashmi Kushwaha

    2014-01-01

    Full Text Available Context: This study was done to assess the Serial peripheral blood and bone marrow changes in patients of Acute Lymphoblastic Leukemia on chemotherapy. Aims: To assess the therapy related serial bone marrow changes in patients of Acute Lymphoblastic Leukemia. Settings and Design: Prospective study, carried out in Lymphoma- Leukemia Lab, Department of Pathology, K.G.M.U from March 2011 to March 2012. A total of 60 cases were studied Materials and Methods: History, complete hemogram, bone marrow examination at pretherapy (Day-0, intratherapy (Day-14, and end of induction chemotherapy (Day-28 were done. Peripheral blood smears were evaluated at regular interval to assess clearance of blast cells. Statistical analysis used: The statistical analysis was done using SPSS (Statistical Package for Social Sciences Version 15.0 statistical Analysis Software. The values were represented in Number (% and Mean ± SD. The following Statistical formulas were used: Mean, standard deviation, Chi square test, Paired "t" test, Student ′t′ test, Level of significance P Results: Incidence of ALL-L1 (46.7% and ALL-L2 (53.3% was equal. ALL-L2 patients had poor survival.Day 0 (D-0 bone marrow was hypercellular with flooding of marrow by leukemic cells. High levels of tumor load at D′0′ were associated with poor survival. 14 th day of Induction phase showed significant decrease in hemoglobin and TLC as compared to D ′0′ parameters. D28 showed marrow regeneration. Cellularity, Blast%, and Leukemic Index showed significant drop from day ′0′ to day 14 due to myelosupression, whereas regeneration reflected by increased cellularity as per day 28 marrow. Lymphocytosis (>20% at end of induction chemotherapy had better survival and longer remission.Risk of mortality was directly proportional to blast clearance and was a major independent prognostic factor for achievement of complete remission. Conclusions: A bone marrow examination at the end of induction

  7. Distance from residence to power line and risk of childhood leukemia

    DEFF Research Database (Denmark)

    Pedersen, Camilla; Raaschou-Nielsen, Ole; Rod, Naja Hulvej

    2013-01-01

    Epidemiological studies have found an association between exposure to extremely low-frequency magnetic fields (ELF-MF) and childhood leukemia. In 2005, a large British study showed an association between proximity of residence to high-voltage power lines and the risk of childhood leukemia...

  8. Childhood leukemia and residential proximity to industrial and urban sites

    Energy Technology Data Exchange (ETDEWEB)

    García-Pérez, Javier, E-mail: jgarcia@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); López-Abente, Gonzalo, E-mail: glabente@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); Gómez-Barroso, Diana, E-mail: dgomez@externos.isciii.es [CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); Morales-Piga, Antonio, E-mail: amorales@isciii.es [Rare Disease Research Institute (IIER), Carlos III Institute of Health, Madrid (Spain); Consortium for Biomedical Research in Rare Diseases (CIBERER), Madrid (Spain); Pardo Romaguera, Elena, E-mail: elena.pardo@uv.es [Spanish Registry of Childhood Tumors (RETI-SEHOP), University of Valencia, Valencia (Spain); Tamayo, Ibon, E-mail: ibontama@gmail.com [Public Health Division of Gipuzkoa, BIODonostia Research Institute, Department of Health of the Regional Government of the Basque Country, Donostia (Spain); Fernández-Navarro, Pablo, E-mail: pfernandezn@isciii.es [Cancer and Environmental Epidemiology Unit, National Center for Epidemiology, Carlos III Institute of Health, Madrid (Spain); CIBER Epidemiología y Salud Pública (CIBERESP) (Spain); and others

    2015-07-15

    Background: Few risk factors for the childhood leukemia are well established. While a small fraction of cases of childhood leukemia might be partially attributable to some diseases or ionizing radiation exposure, the role of industrial and urban pollution also needs to be assessed. Objectives: To ascertain the possible effect of residential proximity to both industrial and urban areas on childhood leukemia, taking into account industrial groups and toxic substances released. Methods: We conducted a population-based case–control study of childhood leukemia in Spain, covering 638 incident cases gathered from the Spanish Registry of Childhood Tumors and for those Autonomous Regions with 100% coverage (period 1990-2011), and 13,188 controls, individually matched by year of birth, sex, and autonomous region of residence. Distances were computed from the respective subject’s residences to the 1068 industries and the 157 urban areas with ≥10,000 inhabitants, located in the study area. Using logistic regression, odds ratios (ORs) and 95% confidence intervals (95%CIs) for categories of distance to industrial and urban pollution sources were calculated, with adjustment for matching variables. Results: Excess risk of childhood leukemia was observed for children living near (≤2.5 km) industries (OR=1.31; 95%CI=1.03–1.67) – particularly glass and mineral fibers (OR=2.42; 95%CI=1.49–3.92), surface treatment using organic solvents (OR=1.87; 95%CI=1.24–2.83), galvanization (OR=1.86; 95%CI=1.07–3.21), production and processing of metals (OR=1.69; 95%CI=1.22–2.34), and surface treatment of metals (OR=1.62; 95%CI=1.22–2.15) – , and urban areas (OR=1.36; 95%CI=1.02–1.80). Conclusions: Our study furnishes some evidence that living in the proximity of industrial and urban sites may be a risk factor for childhood leukemia. - Highlights: • We studied proximity to both industrial and urban sites on childhood leukemia. • We conducted a case–control study in

  9. Epidemiology of childhood leukemia in the presence and absence of Down syndrome.

    Science.gov (United States)

    Mezei, Gabor; Sudan, Madhuri; Izraeli, Shai; Kheifets, Leeka

    2014-10-01

    Down syndrome (DS) is a common congenital anomaly, and children with DS have a substantially higher risk of leukemia. Although understanding of genetic and epigenetic changes of childhood leukemia has improved, the causes of childhood leukemia and the potential role of environmental exposures in leukemogenesis remain largely unknown. Although many epidemiologic studies have examined a variety of environmental exposures, ionizing radiation remains the only generally accepted environmental risk factor for childhood leukemia. Among suspected risk factors, infections, exposure to pesticides, and extremely low frequency magnetic fields are notable. While there are well-defined differences between leukemia in children with and without DS, studies of risk factors for leukemia among DS children are generally consistent with trends seen among non-DS (NDS) children. We provide background on DS epidemiology and review the similarities and differences in biological and epidemiologic features of leukemia in children with and without DS. We propose that both acute lymphoblastic and acute myeloblastic leukemia among DS children can serve as an informative model for development of childhood leukemia. Further, the high rates of leukemia among DS children make it possible to study this disease using a cohort approach, a powerful method that is unfeasible in the general population due to the rarity of childhood leukemia.

  10. How Is Childhood Leukemia Classified?

    Science.gov (United States)

    ... tissues and organs beyond the bone marrow. These children often have fever, poor appetite, and weight loss. At this point the CML acts much like an aggressive acute leukemia (AML or, less often, ALL). Not ... questions about what phase your child’s CML is in, be sure to have the ...

  11. A childhood acute lymphoblastic leukemia genome-wide association study identifies novel sex-specific risk variants

    Science.gov (United States)

    Singh, Sandeep K.; Lupo, Philip J.; Scheurer, Michael E.; Saxena, Anshul; Kennedy, Amy E.; Ibrahimou, Boubakari; Barbieri, Manuel Alejandro; Mills, Ken I.; McCauley, Jacob L.; Okcu, Mehmet Fatih; Dorak, Mehmet Tevfik

    2016-01-01

    Abstract Childhood acute lymphoblastic leukemia (ALL) occurs more frequently in males. Reasons behind sex differences in childhood ALL risk are unknown. In the present genome-wide association study (GWAS), we explored the genetic basis of sex differences by comparing genotype frequencies between male and female cases in a case-only study to assess effect-modification by sex. The case-only design included 236 incident cases of childhood ALL consecutively recruited at the Texas Children's Cancer Center in Houston, Texas from 2007 to 2012. All cases were non-Hispanic whites, aged 1 to 10 years, and diagnosed with confirmed B-cell precursor ALL. Genotyping was performed using the Illumina HumanCoreExome BeadChip on the Illumina Infinium platform. Besides the top 100 statistically most significant results, results were also analyzed by the top 100 highest effect size with a nominal statistical significance (P pregnancy, at birth, childhood, and adolescence. cg22485289 is one of the hypomethylated CpG sites in ALL compared with pre-B cells. Two missense SNPs, rs12722042 and 12722039, in the HLA-DQA1 gene yielded the highest effect sizes (odds ratio [OR] ∼ 14; P <0.01) for sex-specific results. The HLA-DQA1 SNPs belong to DQA1∗01 and confirmed the previously reported male-specific association with DQA1∗01. This finding supports the proposed infection-related etiology in childhood ALL risk for males. Further analyses revealed that most SNPs (either direct effect or through linkage disequilibrium) were within active enhancers or active promoter regions and had regulatory effects on gene expression levels. Cumulative data suggested that RASSF2 rs4813720, which correlates with increased RASSF2 expression, may counteract the suppressor effect of estrogen-regulated miR-17-92 on RASSF2 resulting in protection in males. Given the amount of sex hormone-related mechanisms suggested by our findings, future studies should examine prenatal or early postnatal programming by

  12. How Is Childhood Leukemia Diagnosed?

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    ... the organs. The echoes are converted by a computer into an image on a computer screen. This is a fairly easy test to ... material. For reprint requests, please see our Content Usage Policy . Early Detection, Diagnosis, and Types Can Childhood ...

  13. Family characteristics as risk factors for childhood acute lymphoblastic leukemia: a population-based case-control study.

    Directory of Open Access Journals (Sweden)

    Martin Feller

    Full Text Available BACKGROUND: To date, few risk factors for childhood acute lymphoblastic leukemia (ALL have been confirmed and the scientific literature is full of controversial "evidence." We examined if family characteristics, particularly maternal and paternal age and number of older siblings, were risk factors for childhood acute lymphoblastic leukemia (ALL. METHODOLOGY/PRINCIPAL FINDINGS: In this population-based nationwide matched case-control study, patients 0-14 years of age with ALL diagnosed 1991-2006 and registered in the Swiss Childhood Cancer Registry were linked with their census records of 1990 and 2000. Eight controls per case were selected from the census. The association between family characteristics and ALL was analyzed by conditional logistic regressions. We found that increasing maternal age was associated with incidence of ALL in the offspring (OR per 5-year increase in maternal age 1.18, 95% CI 1.05-1.31; p = 0.004, remaining stable (trend OR 1.14, 95% CI 0.99-1.31; p = 0.060 after adjustment for other risk factors. The association with paternal age was weaker (OR per 5-year increase 1.14, 95% CI 1.01-1.28, p = 0.032 and disappeared after adjustments. Number of older siblings was not associated with risk of ALL in the overall group of children aged 0-14 years at diagnosis. However, we found a negative trend between number of older siblings and ALL diagnosed at age 0-4 years (OR per sibling 0.85, 95% CI 0.68-1.06; p = 0.141 and a positive trend for ALL diagnosed at age 5-9 (OR 1.34, 95% CI 1.05-1.72; p = 0.019, with some evidence for an effect modification (p-value for interaction  = 0.040. CONCLUSIONS: As in other studies, increasing maternal, but not paternal age was associated with risk of ALL. We found only a weak association with the number of older siblings, suggesting a delay in disease manifestation rather than a decrease in incidence.

  14. Neurocognitive Outcomes Decades After Treatment for Childhood Acute Lymphoblastic Leukemia: A Report From the St Jude Lifetime Cohort Study

    Science.gov (United States)

    Krull, Kevin R.; Brinkman, Tara M.; Li, Chenghong; Armstrong, Gregory T.; Ness, Kirsten K.; Srivastava, Deo Kumar; Gurney, James G.; Kimberg, Cara; Krasin, Matthew J.; Pui, Ching-Hon; Robison, Leslie L.; Hudson, Melissa M.

    2013-01-01

    Purpose To determine rates, patterns, and predictors of neurocognitive impairment in adults decades after treatment for childhood acute lymphoblastic leukemia (ALL). Patients and Methods Survivors of childhood ALL treated at St Jude Children's Research Hospital who were still alive at 10 or more years after diagnosis and were age ≥ 18 years were recruited for neurocognitive testing. In all, 1,014 survivors were eligible, 738 (72.8%) agreed to participate, and 567 (76.8%) of these were evaluated. Mean age was 33 years; mean time since diagnosis was 26 years. Medical record abstraction was performed for data on doses of cranial radiation therapy (CRT) and cumulative chemotherapy. Multivariable modeling was conducted and glmulti package was used to select the best model with minimum Akaike information criterion. Results Impairment rates across neurocognitive domains ranged from 28.6% to 58.9%, and those treated with chemotherapy only demonstrated increased impairment in all domains (all P values < .006). In survivors who received no CRT, dexamethasone was associated with impaired attention (relative risk [RR], 2.12; 95% CI, 1.11 to 4.03) and executive function (RR, 2.42; 95% CI, 1.20 to 4.91). The impact of CRT was dependent on young age at diagnosis for intelligence, academic, and memory functions. Risk for executive function problems increased with survival time in a CRT dose-dependent fashion. In all survivors, self-reported behavior problems increased by 5% (RR, 1.05; 95% CI, 1.01 to 1.09) with each year from diagnosis. Impairment was associated with reduced educational attainment and unemployment. Conclusion This study demonstrates persistent and significant neurocognitive impairment in adult survivors of childhood ALL and warrants ongoing monitoring of brain health to facilitate successful adult development and to detect early onset of decline as survivors mature. PMID:24190124

  15. Surviving childhood leukemia: career, family, and future expectations.

    Science.gov (United States)

    Brown, Chris; Pikler, Vanessa I; Lavish, Lea A; Keune, Kristen M; Hutto, C J

    2008-01-01

    The authors examine the impact of childhood leukemia on the career development of 11 young adult survivors, using consensual qualitative research. They discuss the results and implications of childhood leukemia on the survivor's career, family, and future expectations, and provide recommendations for addressing the critical coping and management challenges encountered by survivors, their families, and the helping professionals who treat them.

  16. Viremia during pregnancy and risk of childhood leukemia and lymphomas in the offspring: Nested case-control study.

    Science.gov (United States)

    Bzhalava, Davit; Hultin, Emilie; Arroyo Mühr, Laila Sara; Ekström, Johanna; Lehtinen, Matti; de Villiers, Ethel-Michele; Dillner, Joakim

    2016-05-01

    A possible role for infections of the pregnant mother in the development of childhood acute leukemias and lymphomas has been suggested. However, no specific infectious agent has been identified. Offspring of 74,000 mothers who had serum samples taken during pregnancy and stored in a large-scale biobank were followed up to the age of 15 years (750,000 person years) through over-generation linkages between the biobank files, the Swedish national population and cancer registers to identify incident leukemia/lymphoma cases in the offspring. First-trimester sera from mothers of 47 cases and 47 matched controls were retrieved and analyzed using next generation sequencing. Anelloviruses were the most common viruses detected, found in 37/47 cases and in 40/47 controls, respectively (OR: 0.6, 95% CI: 0.2-1.9). None of the detected viruses was associated with leukemia/lymphoma in the offspring. Viremia during pregnancy was common, but no association with leukemia/lymphoma risk in the offspring was found.

  17. Heterogeneous cytogenetic subgroups and outcomes in childhood acute megakaryoblastic leukemia: a retrospective international study.

    Science.gov (United States)

    Inaba, Hiroto; Zhou, Yinmei; Abla, Oussama; Adachi, Souichi; Auvrignon, Anne; Beverloo, H Berna; de Bont, Eveline; Chang, Tai-Tsung; Creutzig, Ursula; Dworzak, Michael; Elitzur, Sarah; Fynn, Alcira; Forestier, Erik; Hasle, Henrik; Liang, Der-Cherng; Lee, Vincent; Locatelli, Franco; Masetti, Riccardo; De Moerloose, Barbara; Reinhardt, Dirk; Rodriguez, Laura; Van Roy, Nadine; Shen, Shuhong; Taga, Takashi; Tomizawa, Daisuke; Yeoh, Allen E J; Zimmermann, Martin; Raimondi, Susana C

    2015-09-24

    Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤18 years) with non-Down syndrome de novo AMKL diagnosed from 1989 to 2009. Patients with AMKL (median age 1.53 years) comprised 7.8% of pediatric AML. Five-year event-free (EFS) and overall survival (OS) were 43.7% ± 2.7% and 49.0% ± 2.7%, respectively. Patients diagnosed in 2000 to 2009 were treated with higher cytarabine doses and had better EFS (P = .037) and OS (P = .003) than those diagnosed in 1989 to 1999. Transplantation in first remission did not improve survival. Cytogenetic data were available for 372 (75.9%) patients: hypodiploid (n = 18, 4.8%), normal karyotype (n = 49, 13.2%), pseudodiploid (n = 119, 32.0%), 47 to 50 chromosomes (n = 142, 38.2%), and >50 chromosomes (n = 44, 11.8%). Chromosome gain occurred in 195 of 372 (52.4%) patients: +21 (n = 106, 28.5%), +19 (n = 93, 25.0%), +8 (n = 77, 20.7%). Losses occurred in 65 patients (17.5%): -7 (n = 13, 3.5%). Common structural chromosomal aberrations were t(1;22)(p13;q13) (n = 51, 13.7%) and 11q23 rearrangements (n = 38, 10.2%); t(9;11)(p22;q23) occurred in 21 patients. On the basis of frequency and prognosis, AMKL can be classified to 3 risk groups: good risk-7p abnormalities; poor risk-normal karyotypes, -7, 9p abnormalities including t(9;11)(p22;q23)/MLL-MLLT3, -13/13q-, and -15; and intermediate risk-others including t(1;22)(p13;q13)/OTT-MAL (RBM15-MKL1) and 11q23/MLL except t(9;11). Risk-based innovative therapy is needed to improve patient outcomes.

  18. Childhood acute leukemias are frequent in Mexico City: descriptive epidemiology

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    Bekker-Méndez Vilma

    2011-08-01

    Full Text Available Abstract Background Worldwide, acute leukemia is the most common type of childhood cancer. It is particularly common in the Hispanic populations residing in the United States, Costa Rica, and Mexico City. The objective of this study was to determine the incidence of acute leukemia in children who were diagnosed and treated in public hospitals in Mexico City. Methods Included in this study were those children, under 15 years of age and residents of Mexico City, who were diagnosed in 2006 and 2007 with leukemia, as determined by using the International Classification of Childhood Cancer. The average annual incidence rates (AAIR, and the standardized average annual incidence rates (SAAIR per million children were calculated. We calculated crude, age- and sex-specific incidence rates and adjusted for age by the direct method with the world population as standard. We determined if there were a correlation between the incidence of acute leukemias in the various boroughs of Mexico City and either the number of agricultural hectares, the average number of persons per household, or the municipal human development index for Mexico (used as a reference of socio-economic level. Results Although a total of 610 new cases of leukemia were registered during 2006-2007, only 228 fit the criteria for inclusion in this study. The overall SAAIR was 57.6 per million children (95% CI, 46.9-68.3; acute lymphoblastic leukemia (ALL was the most frequent type of leukemia, constituting 85.1% of the cases (SAAIR: 49.5 per million, followed by acute myeloblastic leukemia at 12.3% (SAAIR: 6.9 per million, and chronic myeloid leukemia at 1.7% (SAAIR: 0.9 per million. The 1-4 years age group had the highest SAAIR for ALL (77.7 per million. For cases of ALL, 73.2% had precursor B-cell immunophenotype (SAAIR: 35.8 per million and 12.4% had T-cell immunophenotype (SAAIR 6.3 per million. The peak ages for ALL were 2-6 years and 8-10 years. More than half the children (58.8% were

  19. Outcome of allogeneic hematopoietic stem cell transplantation for childhood acute lymphoblastic leukemia in second complete remission: a single institution study

    Directory of Open Access Journals (Sweden)

    Eun-Jung Lee

    2012-03-01

    Full Text Available Purpose : The survival rate for childhood acute lymphoblastic leukemia (ALL has improved significantly. However, overall prognosis for the 20 to 25% of patients who relapse is poor, and allogeneic hematopoietic stem cell transplantation (HSCT offers the best chance for cure. In this study, we identified significant prognostic variables by analyzing the outcomes of allogeneic HSCT in ALL patients in second complete remission (CR. Methods : Fifty-three ALL patients (42 men, 79% who received HSCT in second CR from August 1991 to February 2009 were included (26 sibling donor HSCTs, 49%; 42 bone marrow transplantations, 79%. Study endpoints included cumulative incidence of acute and chronic graft-versus-host disease (GVHD, relapse, 1-year transplant-related mortality (TRM, disease-free survival (DFS, and overall survival (OS. Results : Cumulative incidences of acute GVHD (grade 2 or above and chronic GVHD were 45.3% and 28.5%, respectively. The estimated 5-year DFS and OS for the cohort was 45.2¡?#?.8%; and 48.3¡?#?%,; respectively. Only donor type, i.e., sibling versus unrelated, showed significant correlation with DFS in multivariate analysis (P=0.010. The rates of relapse and 1 year TRM were 28.9¡?#?.4%; and 26.4¡?#?.1%;, respectively, and unrelated donor HSCT (P=0.002 and HLA mismatch (P =0.022 were significantly correlated with increased TRM in univariate analysis. Conclusion : In this single institution study spanning more than 17 years, sibling donor HSCT was the only factor predicting a favorable result in multivariate analysis, possibly due to increased TRM resulting from unrelated donor HSCT.

  20. Role of Electromagnetic Field Exposure in Childhood Acute Lymphoblastic Leukemia and No Impact of Urinary Alpha- Amylase--a Case Control Study in Tehran, Iran.

    Science.gov (United States)

    Tabrizi, Maral Mazloomi; Hosseini, Seyed Ahmad

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies which accounts for one fourth of all childhood cancer cases. Exposure to environmental factors around the time of conception or pregnancy can increase the risk of ALL in the offspring. This study aimed to evaluate the influence of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL. It also examines the role of various factors such as environmental factors and alpha-amylase as a marker in the development of leukemia. This cross-sectional case control study was carried out on 22 cases and 100 controls who born and lived in low socioeconomic families in Tehran and were hospitalized for therapeutic purposes in different hospitals of rom 2013-2014. With regard to the underlying risk factors; familial history and parental factors were detected as risk factors of ALL but in this age, socioeconomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factor (p=0.006, OR=3.651, CI 95% 1.692-7.878). As the population study was from low socioeconomic state, use of mobiles, computers and microwaves was negligible. Moreover prenatal and postnatal exposure to all indoor electrically charged objects were not detected as significant environmental factors in the present study. This work defined the risk of environmental especially continuous pre and postnatal exposure to high voltage power lines and living in pollutant regions through the parents or children as well as the previously described risk factors of ALL for the first time in low socioeconomic status Iranian population.

  1. Parental and infant characteristics and childhood leukemia in Minnesota

    Directory of Open Access Journals (Sweden)

    Ross Julie A

    2008-02-01

    Full Text Available Abstract Background Leukemia is the most common childhood cancer. With the exception of Down syndrome, prenatal radiation exposure, and higher birth weight, particularly for acute lymphoid leukemia (ALL, few risk factors have been firmly established. Translocations present in neonatal blood spots and the young age peak of diagnosis suggest that early-life factors are involved in childhood leukemia etiology. Methods We investigated the association between birth characteristics and childhood leukemia through linkage of the Minnesota birth and cancer registries using a case-cohort study design. Cases included 560 children with ALL and 87 with acute myeloid leukemia (AML diagnoses from 28 days to 14 years. The comparison group was comprised of 8,750 individuals selected through random sampling of the birth cohort from 1976–2004. Cox proportional hazards regression specific for case-cohort studies was used to compute hazard ratios (HR and 95% confidence intervals (CIs. Results Male sex (HR = 1.41, 95% CI 1.16–1.70, white race (HR = 2.32, 95% CI 1.13–4.76, and maternal birth interval ≥ 3 years (HR = 1.31, 95% CI 1.01–1.70 increased ALL risk, while maternal age increased AML risk (HR = 1.21/5 year age increase, 95% CI 1.0–1.47. Higher birth weights (>3798 grams (HRALL = 1.46, 1.08–1.98; HRAML = 1.97, 95% CI 1.07–3.65, and one minute Apgar scores ≤ 7 (HRALL = 1.30, 95% CI 1.05–1.61; HRAML = 1.62, 95% CI 1.01–2.60 increased risk for both types of leukemia. Sex was not a significant modifier of the association between ALL and other covariates, with the exception of maternal education. Conclusion We confirmed known risk factors for ALL: male sex, high birth weight, and white race. We have also provided data that supports an increased risk for AML following higher birth weights, and demonstrated an association with low Apgar scores.

  2. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2011-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health care services...

  3. Quality of health in survivors of childhood acute myeloid leukemia treated with chemotherapy only: A NOPHO-AML study

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Glosli, Heidi; Jahnukainen, Kirsi;

    2010-01-01

    BACKGROUND: More than 60% of children with acute myeloid leukemia (AML) become long-term survivors, and approximately 50% are cured with chemotherapy only. Limited data exist about their long-term morbidity and social outcomes. The aim of the study was to compare the self-reported use of health...

  4. Maternal and perinatal risk factors for childhood leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Zack, M.; Adami, H.O.; Ericson, A. (Centers for Disease Control, Atlanta, GA (USA))

    1991-07-15

    This report describes an exploratory population-based study of maternal and perinatal risk factors for childhood leukemia in Sweden. The Swedish National Cancer Registry ascertained 411 cases in successive birth cohorts from 1973 through 1984 recorded in the Swedish Medical Birth Registry. Using the latter, we matched five controls without cancer to each case by sex and month and year of birth. Mothers of children with leukemia were more likely to have been exposed to nitrous oxide anesthesia during delivery than mothers of controls (odds ratio (OR) = 1.3; 95% confidence interval (CI) = 1.0, 1.6). Children with leukemia were more likely than controls to have Down's syndrome (OR = 32.5; 95% CI = 7.3, 144.0) or cleft lip or cleft palate (OR = 5.0; 95% CI = 1.0, 24.8); to have had a diagnosis associated with difficult labor but unspecified complications (OR = 4.5; 95% CI = 1.1, 18.2) or with other conditions of the fetus or newborn (OR = 1.5; 95% CI = 1.1, 2.1), specifically, uncomplicated physiological jaundice (OR = 1.9; 95% CI = 1.2, 2.9); or to have received supplemental oxygen (OR = 2.6; 95% CI = 1.3, 1.3, 4.9). Because multiple potential risk factors were analyzed in this study, future studies need to check these findings. The authors did not confirm the previously reported higher risks for childhood leukemia associated with being male, having a high birth weight, or being born to a woman of advanced maternal age.

  5. Parental Tobacco Smoking and Acute Myeloid Leukemia: The Childhood Leukemia International Consortium.

    Science.gov (United States)

    Metayer, Catherine; Petridou, Eleni; Aranguré, Juan Manuel Mejía; Roman, Eve; Schüz, Joachim; Magnani, Corrado; Mora, Ana Maria; Mueller, Beth A; de Oliveira, Maria S Pombo; Dockerty, John D; McCauley, Kathryn; Lightfoot, Tracy; Hatzipantelis, Emmanouel; Rudant, Jérémie; Flores-Lujano, Janet; Kaatsch, Peter; Miligi, Lucia; Wesseling, Catharina; Doody, David R; Moschovi, Maria; Orsi, Laurent; Mattioli, Stefano; Selvin, Steve; Kang, Alice Y; Clavel, Jacqueline

    2016-08-15

    The association between tobacco smoke and acute myeloid leukemia (AML) is well established in adults but not in children. Individual-level data on parental cigarette smoking were obtained from 12 case-control studies from the Childhood Leukemia International Consortium (CLIC, 1974-2012), including 1,330 AML cases diagnosed at age <15 years and 13,169 controls. We conducted pooled analyses of CLIC studies, as well as meta-analyses of CLIC and non-CLIC studies. Overall, maternal smoking before, during, or after pregnancy was not associated with childhood AML; there was a suggestion, however, that smoking during pregnancy was associated with an increased risk in Hispanics (odds ratio = 2.08, 95% confidence interval (CI): 1.20, 3.61) but not in other ethnic groups. By contrast, the odds ratios for paternal lifetime smoking were 1.34 (95% CI: 1.11, 1.62) and 1.18 (95% CI: 0.92, 1.51) in pooled and meta-analyses, respectively. Overall, increased risks from 1.2- to 1.3-fold were observed for pre- and postnatal smoking (P < 0.05), with higher risks reported for heavy smokers. Associations with paternal smoking varied by histological type. Our analyses suggest an association between paternal smoking and childhood AML. The association with maternal smoking appears limited to Hispanic children, raising questions about ethnic differences in tobacco-related exposures and biological mechanisms, as well as study-specific biases.

  6. Steinmaus and Smith Respond to "Proximity to Gasoline Stations and Childhood Leukemia".

    Science.gov (United States)

    Steinmaus, Craig; Smith, Martyn T

    2017-01-01

    Benzene is an established cause of adult leukemia, but its role in childhood leukemia is less clear. In a recent meta-analysis, we identified associations of childhood leukemia with occupational and household product benzene exposure and traffic-related pollution. Residential proximity to gasoline stations or automobile repair facilities may be another source of benzene, and in 3 studies assessing these sources, we identified a summary relative risk of 1.59 (95% confidence interval: 0.70, 3.62). Although not statistically significant, this summary relative risk was of a magnitude similar to that of our other positive findings. In this issue of the Journal (Am J Epidemiol 2017;185(1):5-7), Dr. Infante suggested that meta-analyses of studies on childhood leukemia and proximity to gasoline stations should involve some criteria that differ from those we used. These suggested criteria involved combining leukemia subtypes, excluding automobile repair facilities, and using nonleukemia cancers as control subjects. We redid our meta-analysis using these new criteria and obtained a summary relative risk of 2.42 (95% confidence interval: 1.51, 3.89). Overall, although this result should be interpreted in light of the relatively small sample size (3 studies) and its post-hoc nature, it provides additional new evidence for associations of childhood leukemia with both residential proximity to gasoline stations and exposure to benzene.

  7. Osteogenic toxicity in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet)

    2013-01-01

    textabstractBone mineral density (BMD) Our multi-center study in children treated according to the Dutch Childhood Oncology Group (DCOG)-ALL9 protocol showed a three-years cumulative incidence of fractures of 18%. BMD of ALL patients was lower than of healthy peers. The year after treatment disconti

  8. Therapy-Related Myelodysplastic Syndrome Following Treatment for Childhood Acute Lymphoblastic Leukemia: Outcome of Patients Registered in the EWOG-MDS 98/06 Studies

    DEFF Research Database (Denmark)

    Strahm, Birgitte; Amann, Roland; De Moerloose, Barbara

    Objective: Therapy-related myelodysplastic syndrome (tMDS) following treatment of childhood acute lymphoblastic leukemia (ALL) is one of the most frequently observed secondary malignancies in survivors of childhood cancer. Allogeneic stem cell transplantation (SCT) is the only curative treatment....... This analysis was performed to asses the outcome of patients with tMDS following treatment for childhood ALL reported to the EWOG-MDS study group. Patients and Transplant Procedure: Forty-three patients (19 male/24 female) were diagnosed with tMDS between August 1989 and August 2009. The median age at diagnosis...... was 8.9 yrs (3.4–20.5). The median interval from diagnosis of ALL to the diagnosis of tMDS was 3.3 yrs (1.7–7.0). Five patients did not receive SCT and died due to progressive disease at a median of 5.6 mo after diagnosis. Thirty-eight patients were transplanted. One patient was excluded from...

  9. Renal, gastrointestinal, and hepatic late effects in survivors of childhood acute myeloid leukemia treated with chemotherapy only--a NOPHO-AML study

    DEFF Research Database (Denmark)

    Skou, Anne-Sofie; Glosli, Heidi; Jahnukainen, Kirsi;

    2014-01-01

    BACKGROUND: We investigated the spectrum, frequency, and risk factors for renal, gastrointestinal, and hepatic late adverse effects in survivors of childhood acute myeloid leukemia (AML) without relapse treated with chemotherapy alone according to three consecutive AML trials by the Nordic Society...... with chemotherapy only experienced few renal, gastrointestinal, and hepatic late effects....

  10. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Howard, Scott C.; Pui, Ching-Hon

    2009-01-01

    Although most children with acute lymphoblastic leukemia (ALL) are cured, certain subsets have a high risk of relapse. Relapse risk can be predicted by early response to therapy, clinical and pharmacogenetic features of the host, and genetic characteristics of leukemic cells. Though early treatment response can be assessed by the peripheral blast cell count after 1 week of single-agent glucocorticoid treatment or percent of bone marrow blasts by morphology after 1 or 2 weeks of multiagent induction treatment, determination of minimal residual disease by polymerase chain reaction (PCR) or flow cytometry after 2 to 6 weeks of induction is the most precise and useful measure. Augmented therapy has improved outcome for the poor responders to initial treatment. Infants with mixed-lineage leukemia (MLL)–rearranged ALL comprise a very poor-risk group wherein further intensification of chemotherapy causes significant toxicity. Hybrid protocols incorporating drugs effective for acute myeloid leukemia could improve survival, a strategy being tested in international trials. Studies on the biology of MLL-induced leukemogenesis have prompted the development of novel targeted agents, currently under evaluation in clinical trials. Short-term outcomes of patients with Philadelphia chromosome (Ph)–positive ALL have improved significantly by adding tyrosine kinase inhibitors to standard chemotherapy regimens. New agents and methods to overcome resistance are under investigation, and allogeneic stem cell transplantation is recommended for certain subsets of patients, for example those with Ph+ and T-cell ALL with poor early response. Genome-wide interrogation of leukemic cell genetic abnormalities and germline genetic variations promise to identify new molecular targets for therapy. PMID:19778845

  11. GLUCOCORTICOID RECEPTOR IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    YANG Ping; LIAO Qing-kui; LUO Chun-hua

    1999-01-01

    Objective: To investigate the relationship among glucocorticoid receptor (GCR) level, immunological classification and clinical efficacy of chemotherapy in acute lymphoblastic leukemia (ALL) children. Methods: The GCR level of venous blood lymphocytes was measured by receptor radioligand binding assay in 50 cases with childhood ALL and 41 normal children. The immunological classification of 32 children with ALL was analyzed by ABC immunoenzymatic method. Results: The GCR number in venous blood lymphocytes of normal children was 4651±1617 binding sites/cell. The normal range (95%) was 1482-7800 binding sites/cell. The GCR level of 50 cases with ALL (6695±5256 binding sites/cell) was significantly higher than that of the normal ones (t=2.50, P<0.05). The GCR level of the ALL children with good prognosis was significantly higher than that of bad prognosis (t=4.39,P<0.001). The relationship between immunological classification and GCR level of 32 cases with children ALL was as follows: GCR level of T-ALL and B-ALL were significantly lower than AUL, C-ALL and pre-B-ALL; the prognosis of T-ALL and B-ALL was also bad; the GCR level of the group with good prognosis was significantly higher than that with bad prognosis in all immunological types. Conclusion: The GCR level of the peripheral venous blood lymphocytes in children ALL may be an important biochemistry indicator and used to predict prognosis and guide combination chemotherapy. The relationship between GCR and immunological classification can be useful to the expectation of prognosis.

  12. A 50-Year Journey to Cure Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

    The 50th anniversary of Seminars in Hematology coincides with the 50th of St. Jude Children’s Research Hospital, and both milestones are inexorably linked to studies contributing to the cure of childhood acute lymphoblastic leukemia (ALL). We thought it fitting, therefore, to mark these events by traveling back in time to point out some of the achievements, institutions, study groups and individuals that have made cure of childhood ALL a reality. In many instances, progress was driven by new ideas, while in others it was driven by new experimental tools that allowed more precise assessment of the biology of leukemic blasts and their utility in selecting therapy. We also discuss a number of contemporary advances that point the way to exciting future directions. Whatever pathways are taken, a clear challenge will be to use emerging genome-based or immunologic-based treatment options in ways that will enhance, rather than duplicate or compromise, recent gains in outcome with classic cytotoxic chemotherapy. The theme of this journey serves as a reminder of the chief ingredient of any research directed to a catastrophic disease such as ALL. It is the audacity of a small group of investigators who confronted a childhood cancer with the goal of cure, not palliation, as their mindset. PMID:23953334

  13. Parental occupational pesticide exposure and the risk of childhood leukemia in the offspring: findings from the childhood leukemia international consortium.

    Science.gov (United States)

    Bailey, Helen D; Fritschi, Lin; Infante-Rivard, Claire; Glass, Deborah C; Miligi, Lucia; Dockerty, John D; Lightfoot, Tracy; Clavel, Jacqueline; Roman, Eve; Spector, Logan G; Kaatsch, Peter; Metayer, Catherine; Magnani, Corrado; Milne, Elizabeth; Polychronopoulou, Sophia; Simpson, Jill; Rudant, Jérémie; Sidi, Vasiliki; Rondelli, Roberto; Orsi, Laurent; Kang, Alice Y; Petridou, Eleni; Schüz, Joachim

    2014-11-01

    Maternal occupational pesticide exposure during pregnancy and/or paternal occupational pesticide exposure around conception have been suggested to increase risk of leukemia in the offspring. With a view to providing insight in this area we pooled individual level data from 13 case-control studies participating in the Childhood Leukemia International Consortium (CLIC). Occupational data were harmonized to a compatible format. Pooled individual analyses were undertaken using unconditional logistic regression. Using exposure data from mothers of 8,236 cases, and 14,850 controls, and from fathers of 8,169 cases and 14,201 controls the odds ratio (OR) for maternal exposure during pregnancy and the risk of acute lymphoblastic leukemia (ALL) was 1.01 [95% confidence interval (CI) 0.78, 1.30] and for paternal exposure around conception 1.20 (95% 1.06, 1.38). For acute myeloid leukemia (AML), the OR for maternal exposure during pregnancy was 1.94 (CI 1.19, 3.18) and for paternal exposure around conception 0.91 (CI 0.66, 1.24.) based on data from 1,329 case and 12,141 control mothers, and 1,231 case and 11,383 control fathers. Our finding of a significantly increased risk of AML in the offspring with maternal exposure to pesticides during pregnancy is consistent with previous reports. We also found a slight increase in risk of ALL with paternal exposure around conception which appeared to be more evident in children diagnosed at the age of 5 years or more and those with T cell ALL which raises interesting questions on possible mechanisms.

  14. Decitabine in Treating Children With Relapsed or Refractory Acute Myeloid Leukemia or Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-01-22

    Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  15. Molecular and epidemiologic findings of childhood acute leukemia in Costa Rica.

    Science.gov (United States)

    Santamaría-Quesada, Carlos; Vargas, Mario; Venegas, Patricia; Calvo, Melvin; Obando, Catalina; Valverde, Berta; Cartín, Walter; Carrillo, Juan Manuel; Jimenez, Rafael; González, Marcos

    2009-02-01

    In Central America, nearly 70% of pediatric cancer is related to hemato-oncologic disorders, especially acute lymphoblastic leukemia (ALL). Preliminary studies have described a high incidence of childhood leukemia in these countries; however, no molecular analyses of these malignancies have yet been carried out. We studied diagnostic samples from 84 patients from the National Children's Hospital in San Jose, Costa Rica (65 precursor B-ALL, 5 T-cell ALL, and 14 acute myeloblastic leukemia). Our methodology included cytogenetic, fluorescent in situ hybridization, and polymerase chain reaction approaches. The observed rate of leukemia was 52.2 cases per million children per year. Twelve out of 65 (18.4%) precursor B-ALL tested positive for TEL-AML1 and 3 cases for BCR-ABL (4.6%). In addition, we detected 2 patients carrying an E2A-PBX1 transcript (3.1%) and 1 patient with an MLL-AF4 fusion gene (1.5%). None of the T-cell ALL cases were positive for either SIL-TAL1 or HOX11L2. Within 14 acute myeloblastic leukemia patients, we confirmed 2 cases with FLT3-internal tandem duplication+, 1 patient with AML1-ETO, and only 1 case carrying a PML-RARalpha rearrangement. The present study confirms the relatively high incidence of pediatric leukemia in Costa Rica and constitutes the first report regarding the incidence of the main molecular alterations of childhood leukemia in our region.

  16. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan;

    2016-01-01

    .001) if relapse occurred in the period 1992-2001. Factors independently predicting mortality after relapse included short duration of first remission, bone marrow involvement, age ten years or over, unfavorable cytogenetics, and Down syndrome. T-cell immunophenotype was not an independent prognostic factor unless......Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (P

  17. Physical Activity in Long-term Survivors of Acute Lymphoblastic Leukemia in Childhood and Adolescence: A Cross-sectional Cohort Study.

    Science.gov (United States)

    Nayiager, Trishana; Barr, Ronald D; Anderson, Loretta; Cranston, Amy; Hay, John

    2017-01-01

    Inadequate physical activity (PA) and elevated overweight/obesity (OW/OB) rates are common in survivors of cancer in childhood, especially acute lymphoblastic leukemia (ALL). Bony morbidity, including fractures, is also prevalent among survivors of ALL. This study examined the interrelationships of PA, measured in hours by the Habitual Activity Estimation Scale; OW/OG, defined by body mass index; and fractures (yes/no) in survivors of ALL (n=75) more than 10 years after diagnosis. All had been treated using protocols of the Dana Farber Cancer Institute Childhood ALL Consortium. The median age was 21.15 years and time from diagnosis 15.07 years, and 27 subjects had experienced fractures. More than 30% of the total sample were OW/OB. There was no correlation of body mass index with present PA. There were no significant differences between those with/without fractures in terms of age, sex, time from diagnosis, and the prevalence of OW/OB. Subjects with fractures during treatment reported more total activity on typical weekend days than those without fractures (mean 8.8 vs. 6.9 h, P<0.01). There was no significant difference on weekdays. Higher activity on weekends suggests that fractures may have occurred more commonly in those who had a more active lifestyle before, during, and after treatment.

  18. Pharmacogenetics influence treatment efficacy in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Davidsen, Marie Louise; Dalhoff, Kim; Schmiegelow, Kjeld

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  19. What Are the Risk Factors for Childhood Leukemia?

    Science.gov (United States)

    ... for a possible link to childhood leukemia include: Exposure to electromagnetic fields (such as living near power lines) Living near a nuclear power plant Infections early in life Mother’s age when child is ... history Fetal exposure to hormones such as diethylstilbestrol (DES) or birth ...

  20. Impact of high electromagnetic field levels on childhood leukemia incidence

    NARCIS (Netherlands)

    Teepen, J.C.; Dijck, J.A. van

    2012-01-01

    The increasing exposure to electromagnetic fields (EMFs) has raised concern, as increased exposure may result in an increased risk of childhood leukemia (CL). Besides a short introduction of CL and EMF, our article gives an evaluation of the evidence of a causal relation between EMF and CL by critic

  1. Pharmacogenetics Influence Treatment Efficacy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Devidsen, M.L.; Dalhoff, K.; Schmiegelow, K.

    2008-01-01

    in treatment resistance and toxic side effects. As most childhood acute lymphoblastic leukemia treatment protocols include up to 13 different chemotherapeutic agents, the impact of individual SNPs has been difficult to evaluate. So far Focus has mainly been on the widely used glucocorticosteroids, methotrexate...

  2. Etiology of common childhood acute lymphoblastic leukemia: the adrenal hypothesis

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Vestergaard, T.; Nielsen, S.M.;

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis......--that proposes that the risk of childhood ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis that increase plasma cortisol levels. This may directly eliminate leukemic cells as well as preleukemic cells for the ALL subsets...

  3. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia

    OpenAIRE

    Robien, Kim; Ness, Kirsten K.; Klesges, Lisa M.; Baker, K. Scott; Gurney, James G.

    2008-01-01

    Recent studies indicate that survivors of childhood acute lymphocytic leukemia (ALL) are at increased risk of obesity and cardiovascular disease, conditions that healthy dietary patterns may help ameliorate or prevent. To evaluate the usual dietary intake of adult survivors of childhood ALL, food frequency questionnaire data were collected from 72 participants, and compared with the 2007 WCRF/AICR Cancer Prevention recommendations, the DASH diet, and the 2005 USDA Food Guide. Mean daily energ...

  4. Treatment of isolated testicular relapse in childhood acute lymphoblastic leukemia: an Italian multicenter study. Associazione Italiana Ematologia ed Oncologia Pediatrica.

    Science.gov (United States)

    Uderzo, C; Grazia Zurlo, M; Adamoli, L; Zanesco, L; Aricò, M; Calculli, G; Comelli, A; Cordero di Montezemolo, L; Di Tullio, M T; Guazzelli, C

    1990-04-01

    Between May 1980 and April 1987, 49 children with acute lymphoblastic leukemia (ALL) in isolated testicular and first leukemia relapse (ITR) were enrolled in the Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP) multicenter study REC80-ITR. According to the Rome Workshop criteria, 77% were at standard and 23% at high initial prognostic risk. In 33% of the cases, ITR occurred during first treatment. The REC80-ITR protocol consisted of an induction phase regimen of vincristine (VCR), cytarabine (ARA-C), methotrexate (MTX), and asparaginase (L-asp), and bilateral testicular irradiation, and CNS prophylaxis with intrathecal MTX and a maintenance phase with a multidrug rotating regimen. Total treatment duration was 30 months. The median time of observation after ITR was 51 months. The Kaplan-Meier estimates of survival and disease-free survival (DFS) at 4 years were 67.7% and 41%, respectively. Patients who had an ITR on therapy or within the first off-therapy year showed the poorest outcome. The DFS at 3 years was 20%, 47.6%, and 100%, respectively, for children who had an ITR on treatment (n = 16), within the first year of treatment withdrawal (n = 22), or later (n = 10) (P = .001). Patients with an asymptomatic occult testicular infiltrate at treatment discontinuation had a very unfavorable prognosis. Eighty-one percent of second relapses involved the bone marrow. In our experience, children presenting an early ITR (ie, within 6 months of treatment withdrawal) need a very aggressive treatment because of the high probability of an underlying systemic disease. On the other hand, patients with a late ITR seem to have a truly local recurrence and can apparently be cured by standard protocols, as shown in protocol REC80-ITR.

  5. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Levinsen, Mette Frandsen; Attarbaschi, Andishe

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980...... and 2007. RESULTS: Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival...... estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome...

  6. Treatment Outcome in Older Patients with Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Pounds, Stanley; Cao, Xueyuan; Jenkins, Laura; Dahl, Gary; Bowman, W. Paul; Taub, Jeffrey W; Pui, Ching-Hon; Ribeiro, Raul C.; Campana, Dario; Inaba, Hiroto

    2013-01-01

    Background Older age has historically been an adverse prognostic factor in pediatric acute myeloid leukemia (AML). The impact of age relative to that of other prognostic factors on the outcome of patients treated in recent trials is unknown. Methods Clinical outcome and causes of treatment failure of 351 patients enrolled on three consecutive protocols for childhood AML between 1991 and 2008 were analyzed according to age and protocol. Results The more recent protocol (AML02) produced improved outcomes for 10- to 21-year-old patients compared to 2 earlier studies (AML91 and 97), with 3-year rates of event-free survival (EFS), overall survival (OS) and cumulative incidence of refractory leukemia or relapse (CIR) for this group similar to those of 0- to 9-year old patients: EFS, 58.3% ± 5.4% vs. 66.6% ± 4.9%, P=.20; OS, 68.9% ± 5.1% vs. 75.1% ± 4.5%, P=.36; cumulative incidence of refractory leukemia or relapse, 21.9% ± 4.4%; vs. 25.3% ± 4.1%, P=.59. EFS and OS estimates for 10–15-year-old patients overlapped those for 16–21-year-old patients. However, the cumulative incidence of toxic death was significantly higher for 10- to 21-year-old patients compared to younger patients (13.2% ± 3.6 vs. 4.5% ± 2.0%, P=.028). Conclusion The survival rate for older children with AML has improved on our recent trial and is now similar to that of younger patients. However, deaths from toxicity remain a significant problem in the older age group. Future trials should focus on improving supportive care while striving to develop more effective antileukemic therapy. PMID:22674050

  7. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

    Full Text Available Abstract Acute lymphoblastic leukemia is the most common malignancy in childhood. Continuous progress in risk-adapted treatment for childhood acute lymphoblastic leukemia has secured 5-year event-free survival rates of approximately 80% and 8-year survival rates approaching 90%. Almost 75% of survivors, however, have a chronic health condition negatively impacting on cardiovascular morbidity and mortality. Obesity can be considered one of the most important health chronic conditions in the general population, with an increasing incidence in patients treated for childhood cancers and especially in acute lymphoblastic leukemia survivors who are, at the same time, more at risk of experiencing precocious cardiovascular and metabolic co-morbidities. The hypothalamic-pituitary axis damage secondary to cancer therapies (cranial irradiation and chemotherapy or to primary tumor together with lifestyle modifications and genetic factors could affect long-term outcomes. Nevertheless, the etiology of obesity in acute lymphoblastic leukemia is not yet fully understood. The present review has the aim of summarizing the published data and examining the most accepted mechanisms and main predisposing factors related to weight gain in this particular population.

  8. Living near overhead high voltage transmission power lines as a risk factor for childhood acute lymphoblastic leukemia: a case-control study.

    Science.gov (United States)

    Sohrabi, Mohammad-Reza; Tarjoman, Termeh; Abadi, Alireza; Yavari, Parvin

    2010-01-01

    This study aimed to investigate association of living near high voltage power lines with occurrence of childhood acute lymphoblastic leukemia (ALL). Through a case-control study 300 children aged 1-18 years with confirmed ALL were selected from all referral teaching centers for cancer. They interviewed for history of living near overhead high voltage power lines during at least past two years and compared with 300 controls which were individually matched for sex and approximate age. Logistic regression, chi square and paired t-tests were used for analysis when appropriate. The case group were living significantly closer to power lines (Plines (Plines against more than 600 meters. This ratio estimated as 9.93 (95%CI: 3.47 to 28.5) for 123 KV, 10.78 (95%CI: 3.75 to 31) for 230 KV and 2.98 (95%CI: 0.93 to 9.54) for 400 KV lines. Odds of ALL decreased 0.61 for every 600 meters from the nearest power line. This study emphasizes that living close to high voltage power lines is a risk for ALL.

  9. Novel prognostic subgroups in childhood 11q23/MLL-rearranged acute myeloid leukemia: results of an international retrospective study.

    Science.gov (United States)

    Balgobind, Brian V; Raimondi, Susana C; Harbott, Jochen; Zimmermann, Martin; Alonzo, Todd A; Auvrignon, Anne; Beverloo, H Berna; Chang, Myron; Creutzig, Ursula; Dworzak, Michael N; Forestier, Erik; Gibson, Brenda; Hasle, Henrik; Harrison, Christine J; Heerema, Nyla A; Kaspers, Gertjan J L; Leszl, Anna; Litvinko, Nathalia; Nigro, Luca Lo; Morimoto, Akira; Perot, Christine; Pieters, Rob; Reinhardt, Dirk; Rubnitz, Jeffrey E; Smith, Franklin O; Stary, Jan; Stasevich, Irina; Strehl, Sabine; Taga, Takashi; Tomizawa, Daisuke; Webb, David; Zemanova, Zuzana; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M

    2009-09-17

    Translocations involving chromosome 11q23 frequently occur in pediatric acute myeloid leukemia (AML) and are associated with poor prognosis. In most cases, the MLL gene is involved, and more than 50 translocation partners have been described. Clinical outcome data of the 11q23-rearranged subgroups are scarce because most 11q23 series are too small for meaningful analysis of subgroups, although some studies suggest that patients with t(9;11)(p22;q23) have a more favorable prognosis. We retrospectively collected outcome data of 756 children with 11q23- or MLL-rearranged AML from 11 collaborative groups to identify differences in outcome based on translocation partners. All karyotypes were centrally reviewed before assigning patients to subgroups. The event-free survival of 11q23/MLL-rearranged pediatric AML at 5 years from diagnosis was 44% (+/- 5%), with large differences across subgroups (11% +/- 5% to 92% +/- 5%). Multivariate analysis identified the following subgroups as independent prognostic predictors: t(1;11)(q21;q23) (hazard ratio [HR] = 0.1, P = .004); t(6;11)(q27;q23) (HR = 2.2, P < .001); t(10;11)(p12;q23) (HR = 1.5, P = .005); and t(10;11)(p11.2;q23) (HR = 2.5, P = .005). We could not confirm the favorable prognosis of the t(9;11)(p22;q23) subgroup. We identified large differences in outcome within 11q23/MLL-rearranged pediatric AML and novel subgroups based on translocation partners that independently predict clinical outcome. Screening for these translocation partners is needed for accurate treatment stratification at diagnosis.

  10. Father's occupational exposure to carcinogenic agents and childhood acute leukemia: a new method to assess exposure (a case-control study

    Directory of Open Access Journals (Sweden)

    Rodriguez-Rivera Maria

    2008-01-01

    Full Text Available Abstract Background Medical research has not been able to establish whether a father's occupational exposures are associated with the development of acute leukemia (AL in their offspring. The studies conducted have weaknesses that have generated a misclassification of such exposure. Occupations and exposures to substances associated with childhood cancer are not very frequently encountered in the general population; thus, the reported risks are both inconsistent and inaccurate. In this study, to assess exposure we used a new method, an exposure index, which took into consideration the industrial branch, specific position, use of protective equipment, substances at work, degree of contact with such substances, and time of exposure. This index allowed us to obtain a grade, which permitted the identification of individuals according to their level of exposure to known or potentially carcinogenic agents that are not necessarily specifically identified as risk factors for leukemia. The aim of this study was to determine the association between a father's occupational exposure to carcinogenic agents and the presence of AL in their offspring. Methods From 1999 to 2000, a case-control study was performed with 193 children who reside in Mexico City and had been diagnosed with AL. The initial sample-size calculation was 150 children per group, assessed with an expected odds ratio (OR of three and a minimum exposure frequency of 15.8%. These children were matched by age, sex, and institution with 193 pediatric surgical patients at secondary-care hospitals. A questionnaire was used to determine each child's background and the characteristics of the father's occupation(s. In order to determine the level of exposure to carcinogenic agents, a previously validated exposure index (occupational exposure index, OEI was used. The consistency and validity of the index were assessed by a questionnaire comparison, the sensory recognition of the work area, and an

  11. Dust metal loadings and the risk of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Whitehead, Todd P; Ward, Mary H; Colt, Joanne S; Dahl, Gary; Ducore, Jonathan; Reinier, Kyndaron; Gunier, Robert B; Katharine Hammond, S; Rappaport, Stephen M; Metayer, Catherine

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and the levels of metals in carpet dust. A dust sample was collected from the homes of 142 ALL cases and 187 controls participating in the California Childhood Leukemia Study using a high volume small surface sampler (2001-2006). Samples were analyzed using microwave-assisted acid digestion in combination with inductively coupled plasma mass spectrometry for arsenic, cadmium, chromium, copper, lead, nickel, tin, tungsten, and zinc. Eight metals were detected in at least 85% of the case and control homes; tungsten was detected in nickel: 0.95 (0.82, 1.09), tin: 0.96 (0.86, 1.08), and zinc: 0.94 (0.84, 1.05)). Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL.

  12. Neuroendocrine function in survivors of childhood acute lymphocytic leukemia and non-Hodgkins lymphoma: a study of pulsatile growth hormone and gonadotropin secretions

    Energy Technology Data Exchange (ETDEWEB)

    Mauras, N.; Sabio, H.; Rogol, A.D.

    To assess the neuroendocrine function of long-term survivors of childhood hematologic malignancies, 10 patients who had acute lymphocytic leukemia and two who had non-Hodgkins lymphoma (NHL) (mean age 13.5 +/- 1 year) were studied, who were treated with similar chemotherapeutic regimens with or without 2400 rads of prophylactic cranial irradiation. Pharmacologic growth hormone (GH) stimulation tests and three graded doses of the GH-releasing hormone (1-40-OH-GRH, 0.1, 0.3, and 1 microgram/kg) were administered. Venous sampling for GH and gonadotropin determinations was done at 20-min intervals for 24 h, and a new computerized pulse detection algorithm was used to analyze pulses. All the patients who had neuroendocrine abnormalities were in the cranially irradiated group. Two of the 12 patients were GH deficient, and had abnormal 24-h secretory profiles, blunted GH responses to pharmacologic stimuli, and minimal responses to the three doses of GRH. The pulsatile properties of luteinizing hormone (LH) were normal in 10 of the 12 nongonadally irradiated patients, irrespective of previous cranial irradiation and pubertal stage, when compared with available normative data.

  13. The contributions of the European Medicines Agency and its pediatric committee to the fight against childhood leukemia

    Directory of Open Access Journals (Sweden)

    Rose K

    2015-11-01

    Full Text Available Klaus Rose,1,* Philip D Walson,2,* 1klausrose Consulting, Pediatric Drug Development and More, Riehen, Switzerland; 2Department of Clinical Pharmacology, University Medical School, Goettingen, Germany *These authors contributed equally to this work Background: Although the diagnosis of childhood leukemia is no longer a death sentence, too many patients still die, more with acute myeloid leukemia than with acute lymphoblastic leukemia. The European Union pediatric legislation was introduced to improve pharmaceutical treatment of children, but some question whether the European Medicines Agency (EMA approach is helping children with leukemia. Some have even suggested that the decisions of EMA pediatric committee (PDCO are counterproductive. This study was designed to investigate the impact of PDCO-issued pediatric investigation plans (PIPs for leukemia drugs.Methods: All PIPs listed under “oncology” were downloaded from the EMA website. Non-leukemia decisions including misclassifications, waivers (no PIP, and solid tumors were discarded. The leukemia decisions were analyzed, compared to pediatric leukemia trials in the database http://www.clinicaltrials.gov, and discussed in the light of current literature.Results: The PDCO leukemia decisions demand clinical trials in pediatric leukemia for all new adult drugs without prioritization. However, because leukemia in children is different and much rarer than in adults, these decisions have resulted in proposed studies that are scientifically and ethically questionable. They are also unnecessary, since once promising new compounds are approved for adults, more appropriate, prioritized pediatric leukemia trials are initiated worldwide without PDCO involvement.Conclusion: EMA/PDCO leukemia PIPs do little to advance the treatment of childhood leukemia. The unintended negative effects of the flawed EMA/PDCO's standardized requesting of non-prioritized testing of every new adult leukemia drug in

  14. Obesity and Metabolic Syndrome Among Adult Survivors of Childhood Leukemia.

    Science.gov (United States)

    Gibson, Todd M; Ehrhardt, Matthew J; Ness, Kirsten K

    2016-04-01

    Treatment-related obesity and the metabolic syndrome in adult survivors of childhood acute lymphoblastic leukemia (ALL) are risk factors for cardiovascular disease. Both conditions often begin during therapy. Preventive measures, including dietary counseling and tailored exercise, should be initiated early in the course of survivorship, with referral to specialists to optimize success. However, among adults who develop obesity or the metabolic syndrome and who do not respond to lifestyle therapy, medical intervention may be indicated to manage underlying pathology, such as growth hormone deficiency, or to mitigate risk factors of cardiovascular disease. Because no specific clinical trials have been done in this population to treat metabolic syndrome or its components, clinicians who follow adult survivors of childhood ALL should use the existing American Heart Association/National Heart Lung and Blood Institute Scientific Statement to guide their approach.

  15. Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

    DEFF Research Database (Denmark)

    Bräuner, E.V.; Andersen, Claus Erik; Andersen, H.P.;

    2010-01-01

    Background: In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk. Hypothesis: Traffic exhaust in the air enhances the risk association between radon...... risk within different strata of air pollution and traffic density. Results: The relative risk for childhood leukemia in association with a 103 Bq/m3-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NOx and 1.23 (0.79, 1.91) for those exposed to low levels of NOx...... pollution from traffic may enhance the effect of radon on the risk of childhood leukemia. The observed tendency may also be attributed to chance. © 2010 Springer Science+Business Media B.V....

  16. Second Malignant Neoplasms After Treatment of Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Schmiegelow, Kjeld; Levinsen, Mette Frandsen; Attarbaschi, Andishe; Baruchel, Andre; Devidas, Meenakshi; Escherich, Gabriele; Gibson, Brenda; Heydrich, Christiane; Horibe, Keizo; Ishida, Yasushi; Liang, Der-Cherng; Locatelli, Franco; Michel, Gérard; Pieters, Rob; Piette, Caroline; Pui, Ching-Hon; Raimondi, Susana; Silverman, Lewis; Stanulla, Martin; Stark, Batia; Winick, Naomi; Valsecchi, Maria Grazia

    2013-01-01

    Purpose Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. Patients and Methods We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 1980 and 2007. Results Acute myeloid leukemia (AML; n = 186), myelodysplastic syndrome (MDS; n = 69), and nonmeningioma brain tumor (n = 116) were the most common types of SMNs and had the poorest outcome (5-year survival rate, 18.1% ± 2.9%, 31.1% ± 6.2%, and 18.3% ± 3.8%, respectively). Five-year survival estimates for AML were 11.2% ± 2.9% for 125 patients diagnosed before 2000 and 34.1% ± 6.3% for 61 patients diagnosed after 2000 (P < .001); 5-year survival estimates for MDS were 17.1% ± 6.4% (n = 36) and 48.2% ± 10.6% (n = 33; P = .005). Allogeneic stem-cell transplantation failed to improve outcome of secondary myeloid malignancies after adjusting for waiting time to transplantation. Five-year survival rates were above 90% for patients with meningioma, Hodgkin lymphoma, thyroid carcinoma, basal cell carcinoma, and parotid gland tumor, and 68.5% ± 6.4% for those with non-Hodgkin lymphoma. Eighty-nine percent of patients with brain tumors had received cranial irradiation. Solid tumors were associated with cyclophosphamide exposure, and myeloid malignancy was associated with topoisomerase II inhibitors and starting doses of methotrexate of at least 25 mg/m2 per week and mercaptopurine of at least 75 mg/m2 per day. Myeloid malignancies with monosomy 7/5q− were associated with high hyperdiploid ALL karyotypes, whereas 11q23/MLL-rearranged AML or MDS was associated with ALL harboring translocations of t(9;22), t(4;11), t(1;19), and t(12;21) (P = .03). Conclusion SMNs, except for brain tumors, AML, and MDS, have outcomes similar to their primary counterparts. PMID:23690411

  17. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Science.gov (United States)

    Rudant, Jérémie; Orsi, Laurent; Bonaventure, Audrey; Goujon-Bellec, Stéphanie; Baruchel, André; Petit, Arnaud; Bertrand, Yves; Nelken, Brigitte; Pasquet, Marlène; Michel, Gérard; Saumet, Laure; Chastagner, Pascal; Ducassou, Stéphane; Réguerre, Yves; Hémon, Denis; Clavel, Jacqueline

    2015-01-01

    Genome-wide association studies (GWAS) have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL). These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable). Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012), breastfeeding p = 0.017) and repeated early common infections (p = 0.0070), with allelic odds ratios (OR) which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4), those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5) and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8). The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018) in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by non

  18. ARID5B, IKZF1 and non-genetic factors in the etiology of childhood acute lymphoblastic leukemia: the ESCALE study.

    Directory of Open Access Journals (Sweden)

    Jérémie Rudant

    Full Text Available Genome-wide association studies (GWAS have identified that frequent polymorphisms in ARID5B and IKZF1, two genes involved in lymphoid differentiation, increase the risk of childhood acute lymphoblastic leukemia (ALL. These findings markedly modified the current field of research on the etiology of ALL. In this new context, the present exploratory study investigated the possible interactions between these at-risk alleles and the non-genetic suspected ALL risk factors that were of sufficient prevalence in the French ESCALE study: maternal use of home insecticides during pregnancy, preconception paternal smoking, and some proxies for early immune modulation, i.e. breastfeeding, history of common infections before age one year, and birth order. The analyses were based on 434 ALL cases and 442 controls of European origin, drawn from the nationwide population-based case-control study ESCALE. Information on non-genetic factors was obtained by standardized telephone interview. Interactions between rs10740055 in ARID5B or rs4132601 in IKZF1 and each of the suspected non-genetic factors were tested, with the SNPs coded as counts of minor alleles (trend variable. Statistical interactions were observed between rs4132601 and maternal insecticide use (p = 0.012, breastfeeding p = 0.017 and repeated early common infections (p = 0.0070, with allelic odds ratios (OR which were only increased among the children not exposed to insecticides (OR = 1.8, 95%CI: 1.3, 2.4, those who had been breastfed (OR = 1.8, 95%CI: 1.3, 2.5 and those who had had repeated early common infections (OR = 2.4, 95%CI: 1.5, 3.8. The allelic ORs were close to one among children exposed to insecticides, who had not been breastfed and who had had no or few common infections. Repeated early common infections interacted with rs10740055 (p = 0.018 in the case-only design. Further studies are needed to evaluate whether these observations of a modification of the effect of the at-risk alleles by

  19. Is there any interaction between domestic radon exposure and air pollution from traffic in relation to childhood leukemia risk?

    DEFF Research Database (Denmark)

    Bräuner, Elvira Vaclavik; Andersen, Claus Erik; Andersen, Helle P.;

    2010-01-01

    for different morphological subtypes of leukemia and within different strata of traffic density showed a non-significant pattern of stronger associations between radon and childhood leukemia within strata of higher traffic density at the street address. Air pollution from traffic may enhance the effect of radon...... of air pollution and traffic density. The relative risk for childhood leukemia in association with a 10(3) Bq/m(3)-years increase in radon was 1.77 (1.11, 2.82) among those exposed to high levels of NOx and 1.23 (0.79, 1.91) for those exposed to low levels of NOx (p (interaction,) 0.17). Analyses......In a recent population-based case-control study using 2,400 cases of childhood cancer, we found a statistically significant association between residential radon and acute lymphoblastic leukemia risk. Traffic exhaust in the air enhances the risk association between radon and childhood leukemia. We...

  20. Molecular detection of minimal residual disease is a strong predictive factor of relapse in childhood B-lineage acute lymphoblastic leukemia with medium risk features. A case control study of the International BFM study group

    NARCIS (Netherlands)

    Biondi, A; Valsecchi, MG; Seriu, T; D'Aniello, E; Willemse, MJ; Fasching, K; Pannunzio, A; Gadner, H; Schrappe, M; Kamps, WA; Bartram, CR; van Dongen, JJM; Panzer-Grumayer, ER

    2000-01-01

    The medium-risk B cell precursor acute lymphoblastic leukemia (ALL) accounts for 50-60% of total childhood ALL and comprises the largest number of relapses still unpredictable with diagnostic criteria. To evaluate the prognostic impact of minimal residual disease (MRD) in this specific group, a case

  1. Oral methotrexate/6-mercaptopurine may be superior to a multidrug LSA2L2 Maintenance therapy for higher risk childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Heyman, Mats; Kristinsson, Jon;

    2009-01-01

    The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance th...... significance. These results indicate that oral MTX/6MP maintenance therapy administered after the first year of remission can improve the cure rates of children with T-lineage or with higher risk B-lineage ALL.......The importance of maintenance therapy for higher risk childhood acute lymphoblastic leukemia (ALL) is uncertain. Between 1992 and 2001 the Nordic Society for Pediatric Haematology/Oncology compared in a nonrandomized study conventional oral methotrexate (MTX)/6-mercaptopurine (6MP) maintenance...... therapy with a multidrug cyclic LSA2L2 regimen. 135 children with B-lineage ALL and a white blood count > or =50 x 10/L and 98 children with T-lineage ALL were included. Of the 234 patients, the 135 patients who received MTX/6MP maintenance therapy had a lower relapse risk than the 98 patients who...

  2. Influence of functional polymorphisms of the MDR1 gene on vincristine pharmacokinetics in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Plasschaert, S.L.A.; Groninger, E.; Boezen, M.; Kema, I.P.; Vries, E.G.F. de; Uges, D.R.A.; Veerman, A.J.P.; Kamps, W.A.; Vellenga, E.; Graaf, S.S.N. de; Bont, E.S. de

    2004-01-01

    OBJECTIVE: Our objective was to investigate the effect of single nucleotide polymorphisms (SNPs) in the P-glycoprotein MDR1 gene on vincristine pharmacokinetics and side effects in childhood acute lymphoblastic leukemia. METHODS: From 52 of 70 children who participated in a previous study on vincris

  3. Childhood leukemia and parents' occupational and home exposures.

    Science.gov (United States)

    Lowengart, R A; Peters, J M; Cicioni, C; Buckley, J; Bernstein, L; Preston-Martin, S; Rappaport, E

    1987-07-01

    A case-control study of children of ages 10 years and under in Los Angeles County was conducted to investigate the causes of leukemia. The mothers and fathers of acute leukemia cases and their individually matched controls were interviewed regarding specific occupational and home exposures as well as other potential risk factors associated with leukemia. Analysis of the information from the 123 matched pairs showed an increased risk of leukemia for children whose fathers had occupational exposure after the birth of the child to chlorinated solvents [odds ratio (OR) = 3.5, P = .01], spray paint (OR = 2.0, P = .02), dyes or pigments (OR = 4.5, P = .03), methyl ethyl ketone (CAS: 78-93-3; OR = 3.0, P = .05), and cutting oil (OR = 1.7, P = .05) or whose fathers were exposed during the mother's pregnancy with the child to spray paint (OR = 2.2, P = .03). For all of these, the risk associated with frequent use was greater than for infrequent use. There was an increased risk of leukemia for the child if the father worked in industries manufacturing transportation equipment (mostly aircraft) (OR = 2.5, P = .03) or machinery (OR = 3.0, P = .02). An increased risk was found for children whose parents used pesticides in the home (OR = 3.8, P = .004) or garden (OR = 6.5, P = .007) or who burned incense in the home (OR = 2.7, P = .007). The risk was greater for frequent use. Risk of leukemia was related to mothers' employment in personal service industries (OR = 2.7, P = .04) but not to specified occupational exposures. Risk related to fathers' exposure to chlorinated solvents, employment in the transportation equipment-manufacturing industry, and parents' exposure to household or garden pesticides and incense remains statistically significant after adjusting for the other significant findings.

  4. Cardiac function in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Jarfelt, Marianne; Andersen, Niels Holmark; Glosli, Heidi

    2015-01-01

    OBJECTIVES: We report cardiac function of patients treated for Childhood acute myeloid leukemia with chemotherapy only according to three consecutive Nordic protocols. METHODS: Ninety-eight of 138 eligible patients accepted examination with standardized echocardiography. Results were compared...

  5. Incidence of childhood leukemia and oil exploitation in the Amazon basin of Ecuador.

    Science.gov (United States)

    Hurtig, Anna-Karin; San Sebastián, Miguel

    2004-01-01

    To determine whether there was any difference in childhood leukemia incidence rates between populations living in the proximity to oil fields and those living in areas free from oil exploitation in the Amazon basin of Ecuador, 91 cancer cases among children (0-14 years) from the provinces of Sucumbios, Orellana, Napo, and Pastaza during the period 1985-2000 were studied. The relative risks for all leukemias indicated significantly elevated levels in the youngest age group (0-4 years), both genders combined (RR 3.48, 95% CI 1.25-9.67), and in all age groups (0-14 years) combined for females (RR 2.60, 95% CI 1.11-6.08) and both genders combined (RR 2.56, 95% CI 1.35-4.86). There was no significant difference between the two groups in all other cancer sites combined. Study results are compatible with a relationship between childhood leukemia incidence and living in the proximity of oil fields in the Ecuadorian Amazon.

  6. Treatment of Childhood Acute Lymphoblastic Leukemia Without Prophylactic Cranial Irradiation

    Science.gov (United States)

    Pui, Ching-Hon; Campana, Dario; Pei, Deqing; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Raimondi, Susana C.; Onciu, Mihaela; Coustan-Smith, Elaine; Kun, Larry E.; Jeha, Sima; Cheng, Cheng; Howard, Scott C.; Simmons, Vickey; Bayles, Amy; Metzger, Monika L.; Boyett, James M.; Leung, Wing; Handgretinger, Rupert; Downing, James R.; Evans, William E.; Relling, Mary V.

    2009-01-01

    Background We conducted a clinical trial to test whether prophylactic cranial irradiation could be omitted in all children with newly diagnosed acute lymphoblastic leukemia. Methods A total of 498 evaluable patients were enrolled. Treatment intensity was based on presenting features and the level of minimal residual disease after remission induction treatment. Continuous complete remission was compared between the 71 patients who previously would have received prophylactic cranial irradiation and the 56 historical controls who received it. Results The 5-year event-free and overall survival probabilities (95% confidence interval) for all 498 patients were 85.6% (79.9% to 91.3%) and 93.5% (89.8% to 97.2%), respectively. The 5-year cumulative risk of isolated central-nervous-system (CNS) relapse was 2.7% (1.1% to 4.2%), and that of any CNS relapse (isolated plus combined) was 3.9% (1.9% to 5.9%). The 71 patients had significantly better continuous complete remission than the 56 historical controls (P=0.04). All 11 patients with isolated CNS relapse remain in second remission for 0.4 to 5.5 years. CNS leukemia (CNS-3 status) or a traumatic lumbar puncture with blasts at diagnosis and a high level of minimal residual disease (≥ 1%) after 6 weeks of remission induction were significantly associated with poorer event-free survival. Risk factors for CNS relapse included the presence of the t(1;19)[TCF3-PBX1], any CNS involvement at diagnosis, and T-cell immunophenotype. Common adverse effects included allergic reactions to L-asparaginase, osteonecrosis, thrombosis, and disseminated fungal infection. Conclusions With effective risk-adjusted chemotherapy, prophylactic cranial irradiation can be safely omitted in the treatment of childhood acute lymphoblastic leukemia. PMID:19553647

  7. Nucleophosmin mutations in childhood acute myelogenous leukemia with normal karyotype.

    Science.gov (United States)

    Cazzaniga, Giovanni; Dell'Oro, Maria Grazia; Mecucci, Cristina; Giarin, Emanuela; Masetti, Riccardo; Rossi, Vincenzo; Locatelli, Franco; Martelli, Massimo F; Basso, Giuseppe; Pession, Andrea; Biondi, Andrea; Falini, Brunangelo

    2005-08-15

    Nucleophosmin (NPM) is a nucleocytoplasmic shuttling protein involved in leukemia-associated chromosomal translocations, and it regulates the alternate reading frame (ARF)-p53 tumor-suppressor pathway. Recently, it has been demonstrated that mutations of the NPM1 gene alter the protein at its C-terminal, causing its cytoplasmic localization. Cytoplasmic NPM was detected in 35% of adult patients with primary non-French-American-British (FAB) classification M3 acute myeloid leukemia (AML), associated mainly with normal karyotype. We evaluated the prevalence of the NPM1 gene mutation in non-M3 childhood AML patients enrolled in the ongoing Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP-AML02) protocol in Italy. NPM1 mutations were found in 7 (6.5%) of 107 successfully analyzed patients. NPM1-mutated patients carried a normal karyotype (7/26, 27.1%) and were older in age. Thus, the NPM1 mutation is a frequent abnormality in AML patients without known genetic marker; the mutation may represent a new target to monitor minimal residual disease in AML and a potential candidate for alternative and targeted treatments.

  8. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Schrappe, Martin; Hunger, Stephen P.; Pui, Ching-Hon; Saha, Vaskar; Gaynon, Paul S.; Baruchel, André; Conter, Valentino; Otten, Jacques; Ohara, Akira; Versluys, Anne Birgitta; Escherich, Gabriele; Heyman, Mats; Silverman, Lewis B.; Horibe, Keizo; Mann, Georg; Camitta, Bruce M.; Harbott, Jochen; Riehm, Hansjörg; Richards, Sue; Devidas, Meenakshi; Zimmermann, Martin

    2012-01-01

    BACKGROUND Failure of remission-induction therapy is a rare but highly adverse event in children and adolescents with acute lymphoblastic leukemia (ALL). METHODS We identified induction failure, defined by the persistence of leukemic blasts in blood, bone marrow, or any extramedullary site after 4 to 6 weeks of remission-induction therapy, in 1041 of 44,017 patients (2.4%) 0 to 18 years of age with newly diagnosed ALL who were treated by a total of 14 cooperative study groups between 1985 and 2000. We analyzed the relationships among disease characteristics, treatments administered, and outcomes in these patients. RESULTS Patients with induction failure frequently presented with high-risk features, including older age, high leukocyte count, leukemia with a T-cell phenotype, the Philadelphia chromosome, and 11q23 rearrangement. With a median follow-up period of 8.3 years (range, 1.5 to 22.1), the 10-year survival rate (±SE) was estimated at only 32±1%. An age of 10 years or older, T-cell leukemia, the presence of an 11q23 rearrangement, and 25% or more blasts in the bone marrow at the end of induction therapy were associated with a particularly poor outcome. High hyperdiploidy (a modal chromosome number >50) and an age of 1 to 5 years were associated with a favorable outcome in patients with precursor B-cell leukemia. Allogeneic stem-cell transplantation from matched, related donors was associated with improved outcomes in T-cell leukemia. Children younger than 6 years of age with precursor B-cell leukemia and no adverse genetic features had a 10-year survival rate of 72±5% when treated with chemotherapy only. CONCLUSIONS Pediatric ALL with induction failure is highly heterogeneous. Patients who have T-cell leukemia appear to have a better outcome with allogeneic stem-cell transplantation than with chemotherapy, whereas patients who have precursor B-cell leukemia without other adverse features appear to have a better outcome with chemotherapy. (Funded by Deutsche

  9. Extremely Low Frequency Electromagnetic Field (ELF-EMF and childhood leukemia near transmission lines: a review

    Directory of Open Access Journals (Sweden)

    P. A. Kokate

    2016-04-01

    Full Text Available This article presents a systematic review of most cited studies from developed countries those shed light on the potential relation between childhood leukemia and extremely low frequency electromagnetic field (ELF-EMF. All the findings of articles critically segregated as per some neglected parameters like number of samples, exposure duration, frequency range, distance from the radiation sources, and location during measurement of magnetic field density near power lines. Literature of major 50 studies are divided according to pooled analysis / meta-analysis, residential zone assessment and case-control studies.

  10. Impaired dexamethasone-related increase of anticoagulants is associated with the development of osteonecrosis in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); I.M. Appel (Inge); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2008-01-01

    textabstractCoagulation alterations may be involved in osteonecrosis in childhood acute lymphoblastic leukemia. Retrospectively, we evaluated the available coagulation parameters at diagnosis and during induction treatment of 161 acute lymphoblastic leukemia patients: 24 with symptomatic osteonecros

  11. Paternal Smoking and Risk of Childhood Acute Lymphoblastic Leukemia: Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ruiling Liu

    2011-01-01

    Full Text Available Objective. To investigate the association between paternal smoking and childhood acute lymphoblastic leukemia (ALL. Method. We identified 18 published epidemiologic studies that reported data on both paternal smoking and childhood ALL risk. We performed a meta-analysis and analyzed dose-response relationships on ALL risk for smoking during preconception, during pregnancy, after birth, and ever smoking. Results. The summary odds ratio (OR of childhood ALL associated with paternal smoking was 1.11 (95% Confidence Interval (CI: 1.05–1.18, I2=18% during any time period, 1.25 (95% CI: 1.08–1.46, I2=53% preconception; 1.24 (95% CI: 1.07–1.43, I2=54% during pregnancy, and 1.24 (95% CI: 0.96–1.60, I2=64% after birth, with a dose-response relationship between childhood ALL and paternal smoking preconception or after birth. Conclusion. The evidence supports a positive association between childhood ALL and paternal ever smoking and at each exposure time period examined. Future epidemiologic studies should assess paternal smoking during well-defined exposure windows and should include biomarkers to assess smoking exposure and toxicological mechanisms.

  12. Implications of infectious diseases and the adrenal hypothesis for the etiology of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    F. Azevedo-Silva

    2010-03-01

    Full Text Available Acute leukemia is the most frequent cancer in children. Recently, a new hypothesis was proposed for the pathogenesis of childhood acute lymphoblastic leukemia (ALL. The so-called "adrenal hypothesis" emphasized the role of endogenous cortisol in the etiology of B-cell precursor ALL. The incidence peak of ALL in children between 3 to 5 years of age has been well documented and is consistent with this view. The adrenal hypothesis proposes that the risk of childhood B-cell precursor ALL is reduced when early childhood infections induce qualitative and quantitative changes in the hypothalamus-pituitary-adrenal axis. It suggests that the increased plasma cortisol levels would be sufficient to eliminate all clonal leukemic cells originating during fetal life. Because Brazil is a continental and tropical country, the exposure to infections is diversified with endemic viral and regionally non-viral infections, with some characteristics that support the recent adrenal hypothesis. Here we discuss this new hypothesis in terms of data from epidemiological studies and the possible implications of the diversity of infections occurring in Brazilian children.

  13. Application of FTIR microspectroscopy for the follow-up of childhood leukemia chemotherapy

    Science.gov (United States)

    Mordechai, Shaul; Mordehai, J.; Ramesh, Jagannathan; Levi, C.; Huleihal, Mahmud; Erukhimovitch, Vitaly; Moser, A.; Kapelushnik, J.

    2001-11-01

    Acute Lymphoblastic Leukemia (ALL) accounts for majority of the childhood leukemia. Outcome of children with ALL treatment has improved dramatically. Sensitive techniques are available today for detection of minimal residual disease in children with ALL, which provide insight into the effective cytotoxic treatment. Here, we present a case study, where lymphocytes isolated from two children before and after the treatment were characterized using microscopic Fourier Transform Infrared spectroscopy. Significant changes in the absorbance and spectral pattern in the wavenumber region between 800-1800 cm-1 were found after the treatment. Preliminary analysis of the spectra revealed that the protein content decreased in the T-lymphoma patient before the treatment in comparison to the age matched controls. The chemotherapy treatment resulted in decreased nucleic acids, total carbohydrates and cholesterol contents to a remarkable extent in both B and T lymphoma patients.

  14. Unconventional oil and gas development and risk of childhood leukemia: Assessing the evidence.

    Science.gov (United States)

    Elliott, Elise G; Trinh, Pauline; Ma, Xiaomei; Leaderer, Brian P; Ward, Mary H; Deziel, Nicole C

    2017-01-15

    The widespread distribution of unconventional oil and gas (UO&G) wells and other facilities in the United States potentially exposes millions of people to air and water pollutants, including known or suspected carcinogens. Childhood leukemia is a particular concern because of the disease severity, vulnerable population, and short disease latency. A comprehensive review of carcinogens and leukemogens associated with UO&G development is not available and could inform future exposure monitoring studies and human health assessments. The objective of this analysis was to assess the evidence of carcinogenicity of water contaminants and air pollutants related to UO&G development. We obtained a list of 1177 chemicals in hydraulic fracturing fluids and wastewater from the U.S. Environmental Protection Agency and constructed a list of 143 UO&G-related air pollutants through a review of scientific papers published through 2015 using PubMed and ProQuest databases. We assessed carcinogenicity and evidence of increased risk for leukemia/lymphoma of these chemicals using International Agency for Research on Cancer (IARC) monographs. The majority of compounds (>80%) were not evaluated by IARC and therefore could not be reviewed. Of the 111 potential water contaminants and 29 potential air pollutants evaluated by IARC (119 unique compounds), 49 water and 20 air pollutants were known, probable, or possible human carcinogens (55 unique compounds). A total of 17 water and 11 air pollutants (20 unique compounds) had evidence of increased risk for leukemia/lymphoma, including benzene, 1,3-butadiene, cadmium, diesel exhaust, and several polycyclic aromatic hydrocarbons. Though information on the carcinogenicity of compounds associated with UO&G development was limited, our assessment identified 20 known or suspected carcinogens that could be measured in future studies to advance exposure and risk assessments of cancer-causing agents. Our findings support the need for investigation into

  15. Challenges in implementing individualized medicine illustrated by antimetabolite therapy of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

    2011-01-01

    of acceptable toxicity, an individualized therapeutic approach is indicated. The mapping of the human genome and technological developments in DNA sequencing, gene expression profiling, and proteomics have raised the expectations for implementing genotype-phenotype data into the clinical decision process...... illustrated by studies involving childhood acute lymphoblastic leukemia (ALL), where each patient may receive up to 13 different anticancer agents over a period of 2-3 years. The challenges include i) addressing important, but low-frequency outcomes, ii) difficulties in interpreting the impact of single drug...

  16. Association of Attention Deficit Disorder With Bedside Anti-saccades in Survivors of Childhood Leukemia.

    Science.gov (United States)

    Khan, Raja B; Hudson, Melissa M; Ness, Kirsten K; Liang, Zhu; Srivastava, Deokumar; Krull, Kevin R

    2016-02-01

    Impaired attention is well recognized in childhood cancer survivors. We prospectively evaluated 162 long-term survivors of childhood acute lymphoblastic leukemia to study an association between presence of neurologic soft signs as measured by Zurich Neuromotor Scale, bedside evaluation of anti-saccades, and attention deficit disorder. Attention deficit disorder was recognized in 10.5% of the study cohort. We did not find an association of attention deficit with presence of any soft sign. However, there was an association between presence of abnormal anti-saccades and attention deficit (P = .04). These results will require further validation and if confirmed may introduce a quick bedside method of assessing impaired attention in cancer survivors.

  17. Brain volume and cognitive function in adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Edelmann, Michelle N; Krull, Kevin R

    2013-10-01

    The survival rate for childhood acute lymphoblastic leukemia (ALL) is greater than 80%. However, many of these survivors develop long-term chronic health conditions, with a relatively common late effect being neurocognitive dysfunction. Although neurocognitive impairments have decreased in frequency and severity as treatment has evolved, there is a subset of survivors in the current treatment era that are especially vulnerable to the neurotoxic effects of ALL and its treatment. Additionally, little is known about long-term brain development as survivors mature into adulthood. A recent study by Zeller et al. compared neurocognitive function and brain volume in 130 adult survivors of childhood ALL to 130 healthy adults matched on age and sex. They identified the caudate as particularly sensitive to the neurotoxic effects of chemotherapy. We discuss the implications and limitations of this study, including how their findings support the concept of individual vulnerability to ALL and its treatment.

  18. Clinical and In Vitro Studies on Impact of High-Dose Etoposide Pharmacokinetics Prior Allogeneic Hematopoietic Stem Cell Transplantation for Childhood Acute Lymphoblastic Leukemia on the Risk of Post-Transplant Leukemia Relapse.

    Science.gov (United States)

    Sobiak, Joanna; Kazimierczak, Urszula; Kowalczyk, Dariusz W; Chrzanowska, Maria; Styczyński, Jan; Wysocki, Mariusz; Szpecht, Dawid; Wachowiak, Jacek

    2015-10-01

    The impact of etoposide (VP-16) plasma concentrations on the day of allogeneic hematopoietic stem cell transplantation (allo-HSCT) on leukemia-free survival in children with acute lymphoblastic leukemia (ALL) was studied. In addition, the in vitro effects of VP-16 on the lymphocytes proliferation, cytotoxic activity and on Th1/Th2 cytokine responses were assessed. In 31 children undergoing allo-HSCT, VP-16 plasma concentrations were determined up to 120 h after the infusion using the HPLC-UV method. For mentioned in vitro studies, VP-16 plasma concentrations observed on allo-HSCT day were used. In 84 % of children, VP-16 plasma concentrations (0.1-1.5 μg/mL) were quantifiable 72 h after the end of the drug infusion, i.e. when allo-HSCT should be performed. In 20 (65 %) children allo-HSCT was performed 4 days after the end of the drug infusion, and VP-16 was still detectable (0.1-0.9 μg/mL) in plasma of 12 (39 %) of them. Post-transplant ALL relapse occurred in four children, in all of them VP-16 was detectable in plasma (0.1-0.8 μg/mL) on allo-HSCT day, while there was no relapse in children with undetectable VP-16. In in vitro studies, VP-16 demonstrated impact on the proliferation activity of stimulated lymphocytes depending on its concentration and exposition time. The presence of VP-16 in plasma on allo-HSCT day may demonstrate an adverse effect on graft-versus-leukemia (GvL) reaction and increase the risk of post-transplant ALL relapse. Therefore, if 72 h after VP-16 administration its plasma concentration is still above 0.1 μg/mL then the postponement of transplantation for next 24 h should be considered to protect GvL effector cells from transplant material.

  19. Definition of Cure in Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Inaba, Hiroto; Leung, Wing; Pounds, Stanley; Cao, Xueyuan; Campana, Dario; Ribeiro, Raul C.; Pui, Ching-Hon

    2014-01-01

    Background A better understanding of when cure can be declared in childhood acute myeloid leukemia (AML) would reduce anxiety and improve quality of life of AML survivors. We determined the likelihood of patients with AML to maintain long-term remission after completion of therapy. Patients and Methods The cumulative risk of relapse, time to relapse, event-free survival and overall survival were analyzed for 604 patients with AML enrolled in seven successive clinical trials, divided into 3 treatment eras (1976–1991, 1991–1997, 2002–2008). Results The median time to relapse did not change over time (0.93 years vs. 0.76 vs. 0.8 years for each consecutive era, P = .22) but the risk of relapse decreased significantly (5-year cumulative incidence of relapse 52.6% ± 3.1% vs. 31.5% ± 3.9% vs. 22.0% ± 3.0%, P < .001). Among patients who were in remission 4 years from diagnosis, the probabilities of relapse were 1.7%, 2.9%, and 0.9%, respectively. In the most recent era, all 44 relapses except one occurred within four years of diagnosis. Conclusion Children with AML who are treated with contemporary therapy and remain in remission four years from diagnosis are likely cured. Although late relapses and late deaths from other causes are rare, long-term follow up of survivors is necessary for timely management of late adverse effects. PMID:24798038

  20. Decreased PARP and procaspase-2 protein levels are associated with cellular drug resistance in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Holleman, Amy; den Boer, Monique L; Kazemier, Karin M; Beverloo, H Berna; von Bergh, Anne R M; Janka-Schaub, Gritta E; Pieters, Rob

    2005-09-01

    Drug resistance in childhood acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with impaired ability to induce apoptosis. To elucidate causes of apoptotic defects, we studied the protein expression of Apaf-1, procaspases-2, -3, -6, -7, -8, -10, and poly(adenosine diphosphate [ADP]-ribose) polymerase (PARP) in cells from children with acute lymphoblastic leukemia (ALL; n = 43) and acute myeloid leukemia (AML; n = 10). PARP expression was present in all B-lineage samples, but absent in 4 of 15 T-lineage ALL samples and 3 of 10 AML cases, which was not caused by genomic deletions. PARP expression was a median 7-fold lower in T-lineage ALL (P < .001) and 10-fold lower in AML (P < .001) compared with B-lineage ALL. PARP expression was 4-fold lower in prednisolone, vincristine and L-asparaginase (PVA)-resistant compared with PVA-sensitive ALL patients (P < .001). Procaspase-2 expression was 3-fold lower in T-lineage ALL (P = .022) and AML (P = .014) compared with B-lineage ALL. In addition, procaspase-2 expression was 2-fold lower in PVA-resistant compared to PVA-sensitive ALL patients (P = .042). No relation between apoptotic protease-activating factor 1 (Apaf-1), procaspases-3, -6, -7, -8, -10, and drug resistance was found. In conclusion, low baseline expression of PARP and procaspase-2 is related to cellular drug resistance in childhood acute lymphoblastic leukemia.

  1. TFDP3 confers chemoresistance in minimal residual disease within childhood T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    Chu, Ming; Yin, Kailin; Dong, Yujun; Wang, Pingzhang; Xue, Yun; Zhou, Peng; Wang, Yuqi; Wang, Yuedan

    2017-01-01

    Acquired drug resistance in childhood T-cell acute lymphoblastic leukemia (T-ALL) remains a significant clinical problem. In this study, a novel gene therapy target for childhood T-ALL to overcome chemoresistance was discovered: TFDP3 increased in the minimal residual disease (MRD) positive childhood T-ALL patients. Then, we established a preclinical model of resistance to induction therapy to examine the functional relevance of TFDP3 to chemoresistance in MRD derived from Jurkat/E6-1. Jurkat xenografts in NOD/SCID mice were exposed to a four drug combination (VXLD) of vincristine (VCR), dexamethasone (DEX), L-asparaginase (L-asp) and daunorubicin (DNR). During the 4-week VXLD treatment, the level of TFDP3 increased 4-fold. High expression of TFDP3 was identified in the re-emerging lines (Jurkat/MRD) with increased chemoresistance, which is correlated with partially promoter demethylation of TFDP3. Downregulation of TFDP3 by RNA interference reversed chemoresistance in Jurkat/MRD accompanied by reinstated E2F1 activity that coincided with increased levels of p53, p73, and associated proapoptotic target genes. Importantly, TFDP3 silencing in vivo induced apparent benefit to overcome chemoresistance in combination with VXLD treatment. Collectively, TFDP3 confers chemoresistance in MRD within childhood T-ALL, indicating that TFDP3 is a potential gene therapy target for residual cancer. PMID:27902457

  2. NKAML: A Pilot Study to Determine the Safety and Feasibility of Haploidentical Natural Killer Cell Transplantation in Childhood Acute Myeloid Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Inaba, Hiroto; Ribeiro, Raul C.; Pounds, Stanley; Rooney, Barbara; Bell, Teresa; Pui, Ching-Hon; Leung, Wing

    2010-01-01

    Purpose To conduct a pilot study to determine the safety, feasibility, and engraftment of haploidentical natural killer (NK) cell infusions after an immunosuppressive regimen in children with acute myeloid leukemia (AML). Patients and Methods Ten patients (0.7 to 21 years old) who had completed chemotherapy and were in first complete remission of AML were enrolled on the Pilot Study of Haploidentical Natural Killer Cell Transplantation for Acute Myeloid Leukemia (NKAML) study. They received cyclophosphamide (60 mg/kg on day −7) and fludarabine (25 mg/m2/d on days −6 through −2), followed by killer immunoglobulin-like receptor–human leukocyte antigen (KIR-HLA) mismatched NK cells (median, 29 × 106/kg NK cells) and six doses of interleukin-2 (1 million U/m2). NK cell chimerism, phenotyping, and functional assays were performed on days 2, 7, 14, 21, and 28 after transplantation. Results All patients had transient engraftment for a median of 10 days (range, 2 to 189 days) and a significant expansion of KIR-mismatched NK cells (median, 5,800/mL of blood on day 14). Nonhematologic toxicity was limited, with no graft-versus-host disease. Median length of hospitalization was 2 days. With a median follow-up time of 964 days (range, 569 to 1,162 days), all patients remain in remission. The 2-year event-free survival estimate was 100% (95% CI, 63.1% to 100%). Conclusion Low-dose immunosuppression followed by donor-recipient inhibitory KIR-HLA mismatched NK cells is well tolerated by patients and results in successful engraftment. We propose to further investigate the efficacy of KIR-mismatched NK cells in a phase II trial as consolidation therapy to decrease relapse without increasing mortality in children with AML. PMID:20085940

  3. Polymorphisms in the ABCB1 gene and effect on outcome and toxicity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Gregers, J; Gréen, H; Christensen, I J;

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those...... and prednisolone induction therapy was more prominent in patients with 3435TT variant versus 3435CT/3435CC (P=0.01/P

  4. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

    OpenAIRE

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting fr...

  5. Poor adherence to dietary guidelines among adult survivors of childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Robien, Kim; Ness, Kirsten K; Klesges, Lisa M; Baker, K Scott; Gurney, James G

    2008-11-01

    Recent studies indicate that survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk of obesity and cardiovascular disease, conditions that healthy dietary patterns may help ameliorate or prevent. To evaluate the usual dietary intake of adult survivors of childhood ALL, food frequency questionnaire data were collected from 72 participants, and compared with the 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) Cancer Prevention recommendations, the Dietary Approaches to Stop Hypertension (DASH) diet, and the 2005 United States Department of Agriculture (USDA) Food Guide. Mean daily energy intake was consistent with estimated requirements; however, mean body mass index was 27.1 kg/m2 (overweight). Dietary index scores averaged fewer than half the possible number of points on all 3 scales, indicating poor adherence to recommended guidelines. No study participant reported complete adherence to any set of guidelines. Although half the participants met minimal daily goals for 5 servings of fruits and vegetables (WCRF/AICR recommendations) and Food Guide), participants reported dietary sodium and added sugar intake considerably in excess of recommendations, and suboptimal consumption of whole grains. Guideline adherence was not associated with either body mass index or waist circumference, perhaps due to the low dietary index scores. These findings suggest that dietary intake for many adult survivors of childhood ALL is not concordant with dietary recommendations that may help reduce their risk of obesity, cardiovascular disease, or other treatment-related late effects.

  6. Late recurrence of childhood T-cell acute lymphoblastic leukemia frequently represents a second leukemia rather than a relapse: first evidence for genetic predisposition

    NARCIS (Netherlands)

    Szczepanski, T.; Velden, V.H. van der; Waanders, E.; Kuiper, R.P.; Vlierberghe, P. Van; Gruhn, B.; Eckert, C.; Panzer-Grumayer, R.; Basso, G.; Cave, H.; Stadt, U.Z.; Campana, D.; Schrauder, A.; Sutton, R.; Wering, E. van; Meijerink, J.P.P.; Dongen, J.J. van

    2011-01-01

    PURPOSE: Relapse of childhood T-cell acute lymphoblastic leukemia (T-ALL) often occurs during treatment, but in some cases, leukemia re-emerges off therapy. On the basis of previous analyses of T-cell receptor (TCR) gene rearrangement patterns, we hypothesized that some late recurrences of T-ALL mig

  7. Methotrexate/6-mercaptopurine maintenance therapy influences the risk of a second malignant neoplasm after childhood acute lymphoblastic leukemia: results from the NOPHO ALL-92 study

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld; Al-Modhwahi, Ibrahim; Andersen, Mette Klarskov;

    2009-01-01

    acute myeloid leukemias or myelodysplastic syndromes had monosomy 7 (n = 7) or 7q deletions (n = 2). In Cox multivariate analysis, longer duration of oral 6-mercaptopurine (6MP)/methotrexate (MTX) maintenance therapy (P = .02; longest for standard-risk patients) and presence of high hyperdiploidy (P......Among 1614 children with acute lymphoblastic leukemia (ALL) treated with the Nordic Society for Paediatric Haematology and Oncology (NOPHO) ALL-92 protocol, 20 patients developed a second malignant neoplasm (SMN) with a cumulative risk of 1.6% at 12 years from the diagnosis of ALL. Nine of the 16...

  8. Sleep, fatigue, depression, and quality of life in survivors of childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Huisman, J.; Bierings, M.B.; Hoogerbrugge, P.M.; Kaspers, G.J.L.

    2013-01-01

    BACKGROUND: With the improved survival of childhood acute lymphoblastic leukemia (ALL), the effect of treatment on psychosocial well-being becomes increasingly relevant. Literature on sleep and fatigue during treatment is emerging. However, information on these subjects after treatment is sparse. Th

  9. Health Promotion for Adolescent Childhood Leukemia Survivors: Building on Prevention Science and eHealth

    OpenAIRE

    Elliot, Diane L.; Lindemulder, Susan J; Goldberg, Linn; Stadler, Diane D.; Smith, Jennifer

    2012-01-01

    Teenage survivors of childhood acute lymphoblastic leukemia (ALL) have increased morbidity likely due to their prior multicomponent treatment. Habits established in adolescence can impact individuals’ subsequent adult behaviors. Accordingly, healthy lifestyles, avoiding harmful actions, and appropriate disease surveillance are of heightened importance among teenage survivors. We review the findings from prevention science and their relevance to heath promotion. The capabilities and current us...

  10. Exposure to electromagnetic fields (non-ionizing radiation) and its relationship with childhood leukemia: A systematic review

    Energy Technology Data Exchange (ETDEWEB)

    Calvente, I.; Fernandez, M.F. [Laboratory of Medical Investigations, San Cecilio University Hospital, CIBER de Epidemiologia y Salud Publica (CIBERESP) (Spain); Department of Radiology, University of Granada, Granada (Spain); Villalba, J. [Department of Radiology, University of Granada, Granada (Spain); Olea, N. [Laboratory of Medical Investigations, San Cecilio University Hospital, CIBER de Epidemiologia y Salud Publica (CIBERESP) (Spain); Department of Radiology, University of Granada, Granada (Spain); Nunez, M.I., E-mail: isabeln@ugr.es [Department of Radiology, University of Granada, Granada (Spain)

    2010-07-15

    Childhood exposure to physical contamination, including non-ionizing radiation, has been implicated in numerous diseases, raising concerns about the widespread and increasing sources of exposure to this type of radiation. The primary objective of this review was to analyze the current state of knowledge on the association between environmental exposure to non-ionizing radiation and the risk of childhood leukemia. Scientific publications between 1979 and 2008 that include examination of this association have been reviewed using the MEDLINE/PubMed database. Studies to date have not convincingly confirmed or ruled out an association between non-ionizing radiation and the risk of childhood leukemia. Discrepancies among the conclusions of the studies may also be influenced by confounding factors, selection bias, and misclassification. Childhood defects can result from genetic or epigenetic damage and from effects on the embryo or fetus, which may both be related to environmental exposure of the parent before conception or during the pregnancy. It is therefore critical for researchers to define a priori the type and 'window' of exposure to be assessed. Methodological problems to be solved include the proper diagnostic classification of individuals and the estimated exposure to non-ionizing radiation, which may act through various mechanisms of action. There appears to be an urgent need to reconsider exposure limits for low frequency and static magnetic fields, based on combined experimental and epidemiological research into the relationship between exposure to non-ionizing radiation and adverse human health effects.

  11. Exposure to electromagnetic fields (non-ionizing radiation) and its relationship with childhood leukemia: a systematic review.

    Science.gov (United States)

    Calvente, I; Fernandez, M F; Villalba, J; Olea, N; Nuñez, M I

    2010-07-15

    Childhood exposure to physical contamination, including non-ionizing radiation, has been implicated in numerous diseases, raising concerns about the widespread and increasing sources of exposure to this type of radiation. The primary objective of this review was to analyze the current state of knowledge on the association between environmental exposure to non-ionizing radiation and the risk of childhood leukemia. Scientific publications between 1979 and 2008 that include examination of this association have been reviewed using the MEDLINE/PubMed database. Studies to date have not convincingly confirmed or ruled out an association between non-ionizing radiation and the risk of childhood leukemia. Discrepancies among the conclusions of the studies may also be influenced by confounding factors, selection bias, and misclassification. Childhood defects can result from genetic or epigenetic damage and from effects on the embryo or fetus, which may both be related to environmental exposure of the parent before conception or during the pregnancy. It is therefore critical for researchers to define a priori the type and "window" of exposure to be assessed. Methodological problems to be solved include the proper diagnostic classification of individuals and the estimated exposure to non-ionizing radiation, which may act through various mechanisms of action. There appears to be an urgent need to reconsider exposure limits for low frequency and static magnetic fields, based on combined experimental and epidemiological research into the relationship between exposure to non-ionizing radiation and adverse human health effects.

  12. 农药暴露与儿童急性白血病关系的病例-对照研究%A case-control study on correlation of pesticide exposure with childhood acute leukemia

    Institute of Scientific and Technical Information of China (English)

    张妍; 金萍; 田英; 朱莎; 高宇; 王筱金; 陈涛; 杨友; 汪国权; 胡国华; 施蓉

    2011-01-01

    Objective To evaluate the correlation of pesticide exposure with childhood acute leukemia. Methods An exploratory case-control study was conducted among childhood acute leukemia patients under 15 years old in Shanghai, China. From January 1st,2006 to December 31st,2008, a total of 80 newly diagnosed acute leukemia patients were recruited from Shanghai Children's Medical Center for the case group. Another 96 age-matched patients who visited the hospital for health examination, pediatric treatment or osteological therapy excluding hematological system diseases and neoplastic disease, were recruited for the control group. A questionnaire survey was conducted in both groups; and a 30-40 ml random urine sample was collected from each participant. Five types of organophosphorus pesticide metabolites was then detected among the samples, using Gas Chromatography with Flame Spectrophotometry. Results According to result of the questionnaire survey, more participants (55.0% (44/80)) in case group than in the control group (33.3% (32/96)) reported using mosquitocide, which might increase the risk of childhood acute leukemia (OR = 2.444;95% CI:1. 326-4. 506). At the same time, the detection showed that the concentration (median) of organophosphate metabolites diethyl phosphrate,dimethyl phophrate,dimethyl thiophosphrate,diethyl thiophosphrate and diethyl dithiophosphrate in case group were 0. 0682,0. 0082,0. 0183,0. 0233,0. 4259 μg/g Cr, which were all significantly higher than in control group (0. 0865,0. 0025,0. 0112,0. 0123,0. 1207 μg/g Cr) except the concentration of diethyl phosphrate (Z =-1.081, P = 0. 279). The difference showed statistical significance (Z =-5. 752,-2. 800,-3.316,-8. 120, P < 0. 05). Conclusion Pesticide exposure may be one of the risk factors for childhood acute leukemia.%目的 探讨农药暴露与儿童急性白血病发病之间的关系.方法 选取2006年1月1日至2008年12月31日就诊于上海儿童医学中心,年龄小于15周岁的80

  13. Value of routine bone marrow examination in pediatric acute myeloid leukemia (AML) : A study of the Dutch Childhood Oncology Group (DCOG)

    NARCIS (Netherlands)

    Hageman, Ilse M. G.; Peek, Annemarie M. L.; de Haas, Valerie; Damen-Korbijn, Carin M.; Kaspers, Gertjan J. L.

    2012-01-01

    Background The outcome of the treatment of pediatric acute myeloid leukemia (AML) is still disappointing, due to relatively high treatment-related mortality and relapse rates (3040%). Past treatment protocols have called for routine screening via bone marrow aspiration (BMA) after achievement of fir

  14. Caesarean delivery and risk of childhood leukaemia: a pooled analysis from the Childhood Leukemia International Consortium (CLIC)

    Science.gov (United States)

    Marcotte, Erin L; Thomopoulos, Thomas P; Infante-Rivard, Claire; Clavel, Jacqueline; Petridou, Eleni Th; Schüz, Joachim; Ezzat, Sameera; Dockerty, John D; Metayer, Catherine; Magnani, Corrado; Scheurer, Michael E; Mueller, Beth A; Mora, Ana M; Wesseling, Catharina; Skalkidou, Alkistis; Rashed, Wafaa M; Francis, Stephen S; Ajrouche, Roula; Erdmann, Friederike; Orsi, Laurent; Spector, Logan G

    2017-01-01

    Summary Background Results from case-control studies have shown an increased risk of acute lymphoblastic leukaemia (ALL) in young children born by caesarean delivery, and prelabour caesarean delivery in particular; however, an association of method of delivery with childhood leukaemia subtypes has yet to be established. We therefore did a pooled analysis of data to investigate the association between childhood leukaemia and caesarean delivery. Methods We pooled data from 13 case-control studies from the Childhood Leukemia International Consortium done in nine countries (Canada, Costa Rica, Egypt, France, Germany, Greece, Italy, New Zealand, and the USA) for births from 1970-2013. We analysed caesarean delivery overall and by indications that probably resulted in prelabour caesarean delivery or emergency caesarean delivery. We used multivariable logistic regression models, adjusted for child's birthweight, sex, age, ethnic origin, parental education, maternal age, and study, to estimate odds ratios (ORs) and 95% CIs for the risk of ALL and acute myeloid leukaemia (AML) in children aged 0-14 years at diagnosis. Findings The studies provided data for 8780 ALL cases, 1332 AML cases, and 23 459 controls, of which the birth delivery method was known for 8655 (99%) ALL cases, 1292 (97%) AML cases, and 23 351 (>99%) controls. Indications for caesarean delivery were available in four studies (there were caesarean deliveries for 1061 of 4313 ALL cases, 138 of 664 AML cases, and 1401 of 5884 controls). The OR for all indications of caesarean delivery and ALL was 1.06 (95% CI 0.99–1.13), and was significant for prelabour caesarean delivery and ALL (1.23 [1.04-1.47]; p=0.018). Emergency caesarean delivery was not associated with ALL (OR 1.02 [95% CI 0.81-1.30]). AML was not associated with caesarean delivery (all indications OR 0.99 [95% CI 0.84-1.17]; prelabour caesarean delivery 0.83 [0.54-1.26]; and emergency caesarean delivery 1.05 [0.63-1.77]). Interpretation Our

  15. Childhood central nervous system leukemia: historical perspectives, current therapy, and acute neurological sequelae

    Energy Technology Data Exchange (ETDEWEB)

    Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Kun, Larry E. [St. Jude Children' s Research Hospital, Division of Radiation Oncology, Department of Radiological Sciences, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States); Reddick, Wilburn E.; Ogg, Robert J. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research, Department of Radiological Sciences, Memphis, TN (United States); Morris, E.B. [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States); University of Tennessee Health Sciences Center, Memphis, TN (United States)

    2007-11-15

    During the past three decades, improvements in the treatment of childhood leukemia have resulted in high cure rates, particularly for acute lymphoblastic leukemia (ALL). Unfortunately, successful therapy has come with a price, as significant morbidity can result from neurological affects which harm the brain and spinal cord. The expectation and hope is that chemotherapy, as a primary means of CNS therapy, will result in acceptable disease control with less CNS morbidity than has been observed with combinations of chemotherapy and radiotherapy over the past several decades. In this review we discuss the poignant, historical aspects of CNS leukemia therapy, outline current methods of systemic and CNS leukemia therapy, and present imaging findings we have encountered in childhood leukemia patients with a variety of acute neurological conditions. A major objective of our research is to understand the neuroimaging correlates of acute and chronic effects of cancer and therapy. Specific features related to CNS leukemia and associated short-term toxicities, both disease- and therapy-related, are emphasized in this review with the specific neuroimaging findings. Specific CNS findings are similarly important when treating acute myelogenous leukemia (AML), and details of leukemic involvement and toxicities are also presented in this entity. Despite contemporary treatment approaches which favor the use of chemotherapy (including intrathecal therapy) over radiotherapy in the treatment of CNS leukemia, children still occasionally experience morbid neurotoxicity. Standard neuroimaging is sufficient to identify a variety of neurotoxic sequelae in children, and often suggest specific etiologies. Specific neuroimaging findings frequently indicate a need to alter antileukemia therapy. It is important to appreciate that intrathecal and high doses of systemic chemotherapy are not innocuous and are associated with acute, specific, recognizable, and often serious neurological

  16. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Science.gov (United States)

    Reisi, Nahid; Azhir, Afshin; Hashemipour, Mahin; Raeissi, Pouran; Amini, Abasgholi; Moafi, Alireza

    2009-01-01

    BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran. METHODS: During a 4-year period (2003 to 2007), 55 children (33 male and 22 female) diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this cross-sectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III) crite-ria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR). RESULTS: The mean age of participates was 10.4 years (range 6-19 years) and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55) of survivors (10 male, 1 female) met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004). Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was positively correlated with serum triglycerides (0.543, p ≤ 0.001), systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively), insulin levels (0.914, p < 0.001) and blood sugar (0.398, p = 003). CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors. PMID:21772869

  17. Health-related quality of life assessment in Indonesian childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Sutaryo

    2008-11-01

    Full Text Available Abstract Background Most studies on Health-related Quality of Life (HRQOL in children with cancer were conducted in developed countries. The aims of this study were to assess the HRQOL in childhood acute lymphoblastic leukemia (ALL patients in Indonesia and to assess the influence of demographic and medical characteristics on HRQOL. Methods After cultural linguistic validation, a cross-sectional study of HRQOL was conducted with childhood ALL patients and their guardians in various phases of treatment using the Pediatric Quality of Life Inventory™ (PedsQL™ 4.0 Generic Core Scale and the Pediatric Quality of Life Inventory™ (PedsQL™ 3.0 Cancer Module. Results Ninety-eight guardians and 55 patients participated. The internal consistency of both scales ranged from 0.57 to 0.92. HRQOL of Indonesian patients was comparable with those in developed countries. There were moderate to good correlations between self-reports and proxy-reports, however guardians tended to report worse HRQOL than patients. Children of the 2–5 year-group significantly had more problems in procedural anxiety, treatment anxiety and communication subscales than in older groups (p Conclusion Younger children had more problems in procedural anxiety, treatment anxiety and communication subscales. Therefore, special care during intervention procedures is needed to promote their normal development. Psychosocial support should be provided to children and their parents to facilitate their coping with disease and its treatment.

  18. The Circadian Schedule for Childhood Acute Lymphoblastic Leukemia Maintenance Therapy does not Influence Event-Free Survival in the NOPHO ALL92 Protocol

    DEFF Research Database (Denmark)

    Clemmensen, Kim K. B.; Christensen, Regitse H.; Shabaneh, Diana N.;

    2014-01-01

    BACKGROUND: The event-free survival of childhood acute lymphoblastic leukemia (ALL) has been reported to be superior when oral methotrexate (MTX) and 6-mercaptopurine (6MP) maintenance therapy (MT) is administered in the evening compared to the morning. PROCEDURE: In the ALL92 MT study we prospec...

  19. A comparison of spatial clustering and cluster detection techniques for childhood leukemia incidence in Ohio, 1996 – 2003

    Directory of Open Access Journals (Sweden)

    Wheeler David C

    2007-03-01

    Full Text Available Abstract Background Spatial cluster detection is an important tool in cancer surveillance to identify areas of elevated risk and to generate hypotheses about cancer etiology. There are many cluster detection methods used in spatial epidemiology to investigate suspicious groupings of cancer occurrences in regional count data and case-control data, where controls are sampled from the at-risk population. Numerous studies in the literature have focused on childhood leukemia because of its relatively large incidence among children compared with other malignant diseases and substantial public concern over elevated leukemia incidence. The main focus of this paper is an analysis of the spatial distribution of leukemia incidence among children from 0 to 14 years of age in Ohio from 1996–2003 using individual case data from the Ohio Cancer Incidence Surveillance System (OCISS. Specifically, we explore whether there is statistically significant global clustering and if there are statistically significant local clusters of individual leukemia cases in Ohio using numerous published methods of spatial cluster detection, including spatial point process summary methods, a nearest neighbor method, and a local rate scanning method. We use the K function, Cuzick and Edward's method, and the kernel intensity function to test for significant global clustering and the kernel intensity function and Kulldorff's spatial scan statistic in SaTScan to test for significant local clusters. Results We found some evidence, although inconclusive, of significant local clusters in childhood leukemia in Ohio, but no significant overall clustering. The findings from the local cluster detection analyses are not consistent for the different cluster detection techniques, where the spatial scan method in SaTScan does not find statistically significant local clusters, while the kernel intensity function method suggests statistically significant clusters in areas of central, southern

  20. Ploidy and clinical characteristics of childhood acute myeloid leukemia

    DEFF Research Database (Denmark)

    Sandahl, Julie Damgaard; Kjeldsen, Eigil; Abrahamsson, Jonas;

    2014-01-01

    We report the first large series (n = 596) of pediatric acute myeloid leukemia (AML) focusing on modal numbers (MN) from the population-based NOPHO-AML trials. Abnormal karyotypes were present in 452 cases (76%) and numerical aberrations were present in 40% (n = 237) of all pediatric AML. Among...... with early onset (median age 2 years), female sex (57%), and a dominance of acute megakaryoblastic leukemia (AMKL) (29%). Hypodiploidy constituted 8% of all AML and was associated with older age (median age 9 years), male predominance (60%), FAB M2 (56%), and t(8;21)(q22;q22) (56%) with loss of sex...

  1. The metabolic syndrome in survivors of childhood acute lymphoblastic leukemia in Isfahan, Iran

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2009-04-01

    Full Text Available

    • BACKGROUND: To determine the prevalence of metabolic syndrome in survivors of childhood leukemia in Isfahan, Iran.
    • METHODS: During a 4-year period (2003 to 2007, 55 children (33 male and 22 female diagnosed with ALL at Unit of Hematology/ Oncology, Department of Pediatrics, Isfahan University of Medical Science, were enrolled in this crosssectional study. Metabolic syndrome was defined using the modified version of Adult Treatment Panel (ATP III criteria. Insulin resistance was defined based on the homeostasis model assessment index (HOMA-IR.
    • RESULTS: The mean age of participates was 10.4 years (range 6-19 years and the mean interval since completion of chemotherapy was 35 months. Twenty percent (11/55 of survivors (10 male, 1 female met criteria for diagnosis of metabolic syndrome. Obesity was observed in one forth of patients and nearly 3/4 of obese patients had metabolic syndrome. High serum insulin levels were found in 16% of participants and in 63% of obese survivors. The mean insulin levels in survivors with metabolic syndrome was three-times more than those without (28.3 mu/l vs. 9.57 mu/l, p = 0.004. Insulin resistance was detected in 72.7% of survivors with metabolic syndrome and it was  ositively correlated with serum triglycerides (0.543, p < 0.001, systolic and diastolic BP (0.348, p = 0.01 and 0.368, p = 006 respectively, insulin levels (0.914, p < 0.001 and blood sugar (0.398, p = 003.
    • CONCLUSIONS: The prevalence of metabolic syndrome in survivors of childhood leukemia in Iran is higher than developed countries. Nearly all of the obese patients had metabolic syndrome. Weight control and regular physical exercise are recommended to the survivors.
    • KEYWORDS: Acute lymphoblastic leukemia, metabolic syndrome, obesity, children.

  2. Clinical Utility of Sequential Minimal Residual Disease Measurements in the Context of Risk-based Therapy in Childhood Acute Lymphoblastic Leukemia: a Prospective Study

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Bowman, W Paul; Sandlund, John T; Ribeiro, Raul C; Rubnitz, Jeffrey E; Inaba, Hiroto; Bhojwani, Deepa; Gruber, Tanja A; Leung, Wing H; Downing, James R; Evans, William E; Relling, Mary V; Campana, Dario

    2015-01-01

    Summary Background The level of minimal residual disease (MRD) during remission induction is the most important prognostic indicator in acute lymphoblastic leukemia (ALL). We determined the clinical significance of MRD in the context of a prospective clinical study in which sequential MRD measurements were used to guide treatment decisions. Methods Between 2000 and 2007, 498 evaluable patients with newly diagnosed ALL were enrolled in St. Jude Study XV. Risk of relapse was provisionally classified as low, standard or high according to presenting clinical and laboratory features. Final risk assignment to determine treatment intensity was based mainly on MRD levels measured on days 19 and 46 of remission induction, and on week 7 of continuation treatment. Additional MRD determinations were made on weeks 17, 48 and 120 (end of therapy). Findings Regardless of the provisional risk classification, 10-year event-free survival was significantly inferior for patients with MRD ≥1% on day 19 compared with that of patients having lower MRD levels: 69.2% (95% CI 49.6–82.4, n=36) versus 95.5% (91.7–97.5, n=244) (p<0.001) for the provisional low-risk group and 65.1% (50.7–76.2, n=56) versus 82.9% (75.6–88.2, n=142) (p=0.008) for the provisional standard-risk group. Twelve patients with provisional low-risk ALL and MRD ≥1% on day 19 but negative MRD (<0.01%) on day 46 were treated for standard-risk ALL and had a 10-year event-free survival of 88.9% (43.3–98.4). For the 244 provisional low-risk patients, an MRD level of <1% on day 19 predicted a superior outcome, regardless of the MRD level on day 46. Among provisional standard-risk patients with MRD <1% on day 19, the 15 with persistent MRD on day 46 tended to have an inferior 10-year event-free survival compared with the 126 lacking detectable MRD (72.7% [42.5–88.8] versus 84.0% [76.3–89.4], p=0.06) after receiving the same post-remission treatment for standard-risk ALL. Among patients attaining MRD

  3. Time trends in the incidence of acute lymphoblastic leukemia among children 1976-2002: a population-based Nordic study

    DEFF Research Database (Denmark)

    Svendsen, Anne Louise; Feychting, Maria; Klaeboe, Lars;

    2007-01-01

    We studied the incidence of childhood acute lymphoblastic leukemia in Denmark, Finland, Norway, and Sweden during 1976-2002, on the basis of data from national cancer registries. The incidence of acute lymphoblastic leukemia increased with the calendar period until 1983, and with the birth cohort...

  4. White versus gray matter function as seen on neuropsychological testing following bone marrow transplant for acute leukemia in childhood

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    Fiona S Anderson

    2008-03-01

    Full Text Available Fiona S Anderson1, Alicia S Kunin-Batson1, Joanna L Perkins2, K Scott Baker31Divisions of Pediatric Clinical Neuroscience; 2Department of Pediatric Hematology/Oncology, Children’s Hospitals and Clinics, Minneapolis, MN, USA and 3Hematology/Oncology/BMT, Department of Pediatrics, University of Minnesota, Minneapolis, MN, USAAbstract: Current theory suggests that neurocognitive late effects of treatments for childhood cancer such as difficulties with attention, processing speed and visual-motor ability are the result of white matter damage. Neuroimaging studies have produced a variety of white matter findings. However, although white matter is thought to be differentially affected, previous studies have not demonstrated a discrepancy between white and gray matter function. The present study included 36 children treated for childhood leukemia with hematopoietic stem cell transplant (HCT. Their performance on neurocognitive measures traditionally thought to measure white matter was compared to performance on measures thought to measure gray matter function. Composite white and gray matter standard scores were created based on neuropsychological measures that individuals with known white or gray matter damage perform poorly. As predicted, composite white matter scores (mean = 98.1 were significantly lower (t = 2.26, p = 0.03 than composite gray matter scores (mean = 102.5. Additionally, as gray matter performance increased, the difference between gray and white matter scores increased (R = 0.353, p = 0.035. Overall, the results of this study support the current theory that white matter damage is responsible for the more subtle neurocognitive late effects resulting from treatment for childhood leukemia.Keywords: late effects of cancer treatment, leukemia, neuropsychology, white matter, brain function

  5. Treatment of Childhood Acute Lymphoblastic Leukemia: Prognostic Factors and Clinical Advances.

    Science.gov (United States)

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

    While the majority of children and adolescents with newly diagnosed childhood acute lymphoblastic leukemia (ALL) will be cured, as many as 20 % of patients will experience relapse. On current treatment regimens, the intensity of upfront treatment is stratified based upon prognostic factors with the aim of improving cure rates (for those at the highest risk of relapse) and minimizing treatment-related morbidity (for lower-risk patients). Here we review advances in the understanding of prognostic factors and their application. We also highlight novel treatment approaches aimed at improving outcomes in childhood ALL.

  6. High Throughput Drug Sensitivity Assay and Genomics- Guided Treatment of Patients With Relapsed or Refractory Acute Leukemia

    Science.gov (United States)

    2016-11-14

    Acute Leukemia of Ambiguous Lineage; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  7. Mercaptopurine/Methotrexate Maintenance Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Nielsen, Stine N; Frandsen, Thomas L;

    2014-01-01

    The antileukemic mechanisms of 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy are poorly understood, but the benefits of several years of myelosuppressive maintenance therapy for acute lymphoblastic leukemia are well proven. Currently, there is no international consensus on drug...... intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments, extensive host genome profiling to understand diversity in treatment efficacy and toxicity, and alternative thiopurine dosing regimens...

  8. Cure rates of childhood acute lymphoblastic leukemia in Lithuania and the benefit of joining international treatment protocol

    DEFF Research Database (Denmark)

    Vaitkevičienė, Goda; Matuzevičienė, Rėda; Stoškus, Mindaugas

    2014-01-01

    BACKGROUND: Childhood acute lymphoblastic leukemia (ALL) represents the largest group of pediatric malignancies with long-term survival rates of more than 80% achieved in developed countries. Epidemiological data and survival rates of childhood ALL in Lithuania were lacking. Therefore, the aim of...

  9. Physical activity and late effects in childhood acute lymphoblastic leukemia long-term survivors.

    Science.gov (United States)

    Bertorello, N; Manicone, R; Galletto, C; Barisone, E; Fagioli, F

    2011-08-01

    In the present study the authors evaluated therapy-related long-term adverse effects and physical activity in a cohort of long-term survivors of childhood acute lymphoblastic leukemia (ALL), diagnosed in their center between March 1991 and August 2000, treated according to the AIEOP (Associazione Italiana di Ematologia e Oncologia Pediatrica) ALL 91 or 95 study protocol and regularly seen in the authors' long-term follow-up unit. The authors analyzed the long-term sequelae of major body systems in this cohort of subjects and administered an "ad hoc" questionnaire concerning sport. The authors found that 70 patients out of 102 (68.5%) showed no late effects, 10% presented only instrumental or neuropsychological test abnormalities, and 21.5% had 1 or more clinical late sequelae. None of the evidenced late effects represented a contraindication to do physical activity. Sixty-one percent of survivors do physical activity, most of them regularly. Sixty-one percent of males and 18.5% of females (P < .005) do competitive sport (sports rates are similar to those of the general age-matched population). Nearly all subjects spontaneously choose to do sport and think physical exercise is an important and useful resource for their health. The authors conclude that the more recent therapy regimens for leukemia treatment, excluding bone marrow transplantation, do not seem to cause such late effects as to prevent survivors from doing sport. Therefore, in the care of ALL survivors, physical activity is not only not contraindicated, but should also be promoted as much as possible. The development of specific educational programs is warranted as part of the care of cancer survivors.

  10. Analysis of childhood leukemia mortality trends in Brazil, from 1980 to 2010

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    Franciane F. Silva

    2014-12-01

    Full Text Available OBJECTIVE: Leukemias comprise the most common group of cancers in children and adolescents. Studies conducted in other countries and Brazil have observed a decrease in their mortality.This study aimed to evaluate the trend of mortality from leukemia in children under 19 years of age in Brazil, from 1980 to 2010. METHODS: This was an ecological study, using retrospective time series data from the Mortality Information System, from 1980 to 2010. Calculations of mortality rates were performed, including gross, gender-specific, and age-based. For trend analysis, linear and semi-log regression models were used. The significance level was 5%. RESULTS: Mortality rates for lymphoid and myeloid leukemias presented a growth trend, with the exception of lymphoid leukemia among children under 4 years of age (percentage decrease: 1.21% annually, while in the sub-group "Other types of leukemia", a downward trend was observed. Overall, mortality from leukemia tended to increase for boys and girls, especially in the age groups 10-14 years (annual percentage increase of 1.23% for males and 1.28% for females and 15-19 years (annual percentage increase of 1.40% for males and 1.62% for females. CONCLUSIONS: The results for leukemia generally corroborate the results of other similar studies. A detailed analysis by subgroup of leukemia, age, and gender revealed no trends shown in other studies, thus indicating special requirements for each variable in the analysis.

  11. Psychosocial aspects of survivors of childhood cancer or leukemia.

    Science.gov (United States)

    Massimo, L; Zarri, D; Caprino, D

    2005-12-01

    The majority of childhood cancer patients can expect nowadays to be cured and the percentage is now between 70% and 80%. The number of long-term survivors, off- threatment for at least 5 years, is rising rapidly and is becoming a new population, which needs a special care. It is becoming increasingly important to know how to prevent and treat the physical late effects as well as the psychosocial ones. The oldest among these patients are now in their 40's. How will their old age be like? Are they really cured? The aim of this study is to present a detailed survey of the literature on this topic as well as the authors' personal experience. Several techniques of psychological investigation for this population are highlighted. The semistructured interviews are mostly used for mono-institutional research, while the narrative dialogues are useful for small groups of patients. Questionnaires are usually conducted by epidemiologists for large groups of survivors. Tests are used for specific items such as defense mechanisms, self-esteem, relationships within the family, fear, and panic. The evaluation of the post-traumatic stress disorder is considered and the most important literature data are reported. It is also stressed the need of prevention of any type of psychosocial distress. In conclusion, most of the survivors appear to lead normal adult lives, to have obtained high school degrees, good jobs, and several have families and children. Nevertheless, a small percentage show some psychological or social problems, such as anxiety, depression, fear over the future or over relapse, a second primary, or sterility. The most vulnerable among them are females, people in poor financial conditions, the unemployed and those with poor educations.

  12. The expression of histone deacetylase 4 is associated with prednisone poor-response in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Gruhn, Bernd; Naumann, Thomas; Gruner, Dorothee; Walther, Mario; Wittig, Susan; Becker, Sabine; Beck, James F; Sonnemann, Jürgen

    2013-10-01

    This study aimed at the identification of histone deacetylase (HDAC) isoforms relevant for childhood acute lymphoblastic leukemia (ALL). Expression of HDAC1-11 was determined in 93 primary ALL and eight healthy donor samples. HDAC1, HDAC2 and HDAC8 showed significantly higher expressions in ALL samples. Correlation analysis of HDAC expression with clinicopathological parameters revealed that high HDAC1, HDAC2, HDAC4 and HDAC11 levels were significantly associated with unfavorable prognostic factors. Particularly, high HDAC4 expression was associated with high initial leukocyte count, T cell ALL and prednisone poor-response. siRNA-mediated inhibition of HDAC4 sensitized a T-ALL cell line to etoposide-induced cell death. In conclusion, our data point to HDAC4 as drug target in childhood ALL, especially in prednisone poor-responders.

  13. Temporal changes in water quality at a childhood leukemia cluster

    Science.gov (United States)

    Seiler, R.L.

    2004-01-01

    Since 1997, 15 cases of acute lymphocytic leukemia and one case of acute myelocytic leukemia have been diagnosed in children and teenagers who live, or have lived, in an area centered on the town of Fallon, Nevada. The expected rate for the population is about one case every five years. In 2001, 99 domestic and municipal wells and one industrial well were sampled in the Fallon area. Twenty-nine of these wells had been sampled previously in 1989. Statistical comparison of concentrations of major ions and trace elements in those 29 wells between 1989 and 2001 using the nonparametric Wilcoxon signed-rank test indicate water quality did not substantially change over that period; however, short-term changes may have occurred that were not detected. Volatile organic compounds were seldom detected in ground water samples and those that are regulated were consistently found at concentrations less than the maximum contaminant level (MCL). The MCL for gross-alpha radioactivity and arsenic, radon, and uranium concentrations were commonly exceeded, and sometimes were greatly exceeded. Statistical comparisons using the nonparametric Wilcoxon rank-sum test indicate gross-alpha and -beta radioactivity, arsenic, uranium, and radon concentrations in wells used by families having a child with leukemia did not statistically differ from the remainder of the domestic wells sampled during this investigation. Isotopic measurements indicate the uranium was natural and not the result of a 1963 underground nuclear bomb test near Fallon. In arid and semiarid areas where trace-element concentrations can greatly exceed the MCL, household reverse-osmosis units may not reduce their concentrations to safe levels. In parts of the world where radon concentrations are high, water consumed first thing in the morning may be appreciably more radioactive than water consumed a few minutes later after the pressure tank has been emptied because secular equilibrium between radon and its immediate daughter

  14. CLINICOPATHOLOGICAL STUDY OF ACUTE LYMPHOBLASTIC LEUKEMIA - A MULTIPARAMETER STUDY

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    Jagannath

    2015-11-01

    Full Text Available BACKGROUND Acute Lymphoblastic Leukaemia (ALL, a malignancy of lymphoid lineage cells, has excellent prognosis in children. Leukemia is the most prevalent childhood cancer and Acute Lymphoblastic Leukemia (ALL constitutes 75% of all cases. The most frequent presenting symptoms are fever, weight loss and pallor. Early detection of clinical symptoms positively affects timely diagnosis. AIMS & OBJECTIVES The objectives of the present study were to assess frequency of presenting symptoms, laboratory data and prognostic factors in children with diagnosis of ALL. MATERIALS & METHODS The present study (2014 was performed in the hematology section of Department of Pathology of Gajra Raja Medical College, Gwalior over a period of 12 months from 1st October 2013 to 30th September 2014. This was a prospective study. The blood samples were received from various departments of Jayarogya hospital especially from the Pediatric and Medicine departments. RESULTS Out of the 37 cases diagnosed as Acute Lymphoblastic Leukemia, 25(67.57% were male and 12(32.43%, were female, (male:female ratio: 2.1:1. 43.35% of patients which comprises highest number of cases belonged to 11-20 years of age group. The most frequent presenting symptoms was fever (83.78% followed by weakness (70.27% and loss of appetite (27% while most frequent presenting sign was pallor (86.48% followed by lymphadenopathy (67.57% and splenomegaly (48.65%. Complete blood cell count was abnormal in all of the patients, and pancytopenia was detected in 10.81% of the patients. Of all the patients, 91.89% had abnormal white blood cell (WBC count at presentation, 10.81% had leucopenia and 80% had leucocytosis. FAB L1 subtype was more common as compared to FAB L2 subtype. CONCLUSION In our study (2014, Acute Lymphoblastic Leukemia was more prevalent in males than in females and more common in childhood than in adult. FAB L1 subtype was more common as compared to FAB L2 subtype.

  15. Randomized study of granulocyte colony stimulating factor for childhood B-cell non-Hodgkin lymphoma: a report from the Japanese pediatric leukemia/lymphoma study group B-NHL03 study.

    Science.gov (United States)

    Tsurusawa, Masahito; Watanabe, Tomoyuki; Gosho, Masahiko; Mori, Tetsuya; Mitsui, Tetsuo; Sunami, Shosuke; Kobayashi, Ryoji; Fukano, Reiji; Tanaka, Fumiko; Fujita, Naoto; Inada, Hiroko; Sekimizu, Masahiro; Koh, Katsuyoshi; Kosaka, Yoshiyuki; Komada, Yoshihiro; Saito, Akiko M; Nakazawa, Atsuko; Horibe, Keizo

    2016-07-01

    The objective of this study was to assess the impact of the primary prophylaxis of granulocyte colony-stimulating factor (G-CSF) in the management of childhood B-cell non-Hodgkin lymphoma (B-NHL). Patients with advanced-stage mature B-NHL were randomized to receive prophylactic G-CSF (G-CSF+) or not receive G-CSF (G-CSF-) based on protocols of the B-NHL03 study. The G-CSF group received 5 μg/kg/d Lenograstim from day 2 after each course of six chemotherapy courses. Fifty-eight patients were assessable, 29 G-CSF + and 29 G-CSF-. G-CSF + patients showed a positive impact on the meantime to neutrophil recovery and hospital stay. On the other hand, they had no impact in the incidences of febrile neutropenia, serious infections, stomatitis and total cost. Our study showed that administration of prophylactic G-CSF through all six chemotherapy courses for childhood B-NHL showed no clinical and economic benefits for the management of childhood B-NHL treatment.

  16. Risk-Based Classification System of Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-10-24

    Adult B Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  17. Effects of Maternal Diet During Pregnancy on the Risk of Childhood Acute Lymphoblastic Leukemia: A Systematic Review.

    Science.gov (United States)

    Abiri, Behnaz; Kelishadi, Roya; Sadeghi, Homa; Azizi-Soleiman, Fatemeh

    2016-10-01

    Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children that can be affected by maternal diet. The aim of this study was to evaluate maternal dietary risk factors of ALL. We searched MEDLINE, Cochrane Library, Springer Link, Wiley Online, Science Direct, Mosby, ISI Web of Science, OVID, ProQuest, and Scopus from database inception until February 2, 2016. Two reviewers scanned titles, abstracts, and keywords of articles after excluding duplicates. We included case-control studies evaluating the relationship between maternal diet during pregnancy and childhood ALL. The search resulted in 2,940 papers, of which 11 full-text articles met the criteria for inclusion in the review and were analyzed. The finding of these studies suggest that maternal diet composed largely of vegetables, fruits, and protein sources before and during pregnancy can reduce the risk of ALL in offspring. Maternal alcohol intake had no effect. Nevertheless, inherent limitations of case-control studies like measurement error, random error, recall bias, and selection bias preclude conclusive evidence. Persuading pregnant women to follow a healthy diet rich in fruits, vegetables, and protein may reduce the risk of childhood ALL. Avoiding alcohol intake seems prudent.

  18. High resolution melting curve analysis, a rapid and affordable method for mutation analysis in childhood acute myeloid leukemia

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    Yin eLiu

    2014-09-01

    Full Text Available Background: Molecular genetic alterations with prognostic significance have been described in childhood acute myeloid leukemia (AML. The aim of this study was to establish cost-effective techniques to detect mutations of FMS-like tyrosine kinase 3 (FLT3, Nucleophosmin 1 (NPM1, and a partial tandem duplication within the mixed lineage leukemia (MLL-PTD genes in childhood AML. Procedure: Ninety-nine children with newly diagnosed AML were included in this study. We developed a fluoresent dye SYTO-82 based high resolution melting curve (HRM anaylsis to detect FLT3 internal tandem duplication (FLT3-ITD, FLT3 tyrosine kinase domain (FLT3-TKD and NPM1 mutations. MLL-PTD was screened by real-time quantitative PCR. Results: The HRM methodology correlated well with gold standard Sanger sequencing with less cost. Among the 99 patients studied, the FLT3-ITD mutation was associated with significantly worse event free survival (EFS. Patients with the NPM1 mutation had significantly better EFS and overall survival. However, HRM was not sensitive enough for minimal residual disease monitoring. Conclusions: HRM was a rapid and efficient method for screening of FLT3 and NPM1 gene mutations. It was both affordable and accurate, especially in resource underprivileged regions. Our results indicated that HRM could be a useful clinical tool for rapid and cost effective screening of the FLT3 and NPM1 mutations in AML patients.

  19. Genetic Mediators of Neurocognitive Outcomes in Survivors of Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Krull, Kevin R.; Bhojwani, Deepa; Conklin, Heather M.; Pei, Deqing; Cheng, Cheng; Reddick, Wilburn E.; Sandlund, John T.; Pui, Ching-Hon

    2013-01-01

    Purpose Survivors of childhood acute lymphoblastic leukemia (ALL) are at increased risk for neurocognitive problems, with significant interindividual variability in outcome. This study examined genetic polymorphisms associated with variability in neurocognitive outcome. Patients and Methods Neurocognitive outcomes were evaluated at the end of therapy in 243 survivors treated on an institutional protocol featuring risk-adapted chemotherapy without prophylactic cranial irradiation. Polymorphisms in genes related to pharmacokinetics or pharmacodynamics of antileukemic agents, drug metabolism, oxidative stress, and attention problems in noncancer populations were examined as predictors of outcome, using multiple general linear models and controlling for age at diagnosis, sex, race, and treatment intensity. Results Compared with national norms, the cohort demonstrated significantly higher rates of problems on direct assessment of sustained attention (P = .01) and on parent ratings of attention problems (P = .02). Children with the A2756G polymorphism in methionine synthase (MS) were more likely to demonstrate deficits in attentiveness (P = .03) and response speed (P = .02), whereas those with various polymorphisms in glutathione S-transferase demonstrated increased performance variability (P = .01) and reduced attentiveness (P = .003). Polymorphisms in monoamine oxidase (T1460CA) were associated with increased attention variability (P = .03). Parent-reported attention problems were more common in children with the Cys112Arg polymorphism in apoliopoprotein E4 (P = .01). Conclusion These results are consistent with our previous report of association between attention problems and MS in an independent cohort of long-term survivors of childhood ALL treated with chemotherapy only. The results also raise the possibility of an impact from genetic predispositions related to oxidative stress and CNS integrity. PMID:23650422

  20. Prospective Evaluation of Whole Genome MicroRNA Expression Profiling in Childhood Acute Lymphoblastic Leukemia

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    Muhterem Duyu

    2014-01-01

    Full Text Available Dysregulation of microRNA (miRNA expression contributes to the pathogenesis of several clinical conditions. The aim of this study is to evaluate the associations between miRNAs and childhood acute lymphoblastic leukemia (ALL to discover their role in the course of the disease. Forty-three children with ALL and 14 age-matched healthy controls were included in the study. MicroRNA microarray expression profiling was used for peripheral blood and bone marrow samples. Aberrant miRNA expressions associated with the diagnosis and outcome were prospectively evaluated. Confirmation analysis was performed by real time RT-PCR. miR-128, miR-146a, miR-155, miR-181a, and miR-195 were significantly dysregulated in ALL patients at day 0. Following a six-month treatment period, the change in miRNA levels was determined by real time RT-PCR and expression of miR-146a, miR-155, miR-181a, and miR-195 significantly decreased. To conclude, these miRNAs not only may be used as biomarkers in diagnosis of ALL and monitoring the disease but also provide new insights into the potential roles of them in leukemogenesis.

  1. Differences in Childhood Leukemia Incidence and Survival between Southern Thailand and the United States: A Population-Based Analysis

    Science.gov (United States)

    Demanelis, Kathryn; Sriplung, Hutcha; Meza, Rafael; Wiangnon, Surapon; Rozek, Laura S.; Scheurer, Michael E.; Lupo, Philip J.

    2015-01-01

    BACKGROUND Childhood leukemia incidence and survival varies globally, and this variation may be attributed to environmental risk factors, genetics, and/or disparities in diagnosis and treatment. PROCEDURE We analyzed childhood leukemia incidence and survival trends in children age 0–19 years from 1990 to 2011 in Songkhla, Thailand (n=316) and compared these results to US data from the Surveillance, Epidemiology, and End Results (SEER) registry (n=6,738). We computed relative survival using Ederer II and estimated survival functions using the Kaplan-Meier method. Changes in incidence and five-year survival by year of diagnosis were evaluated using joinpoint regression and are reported as annual percent changes (APC). RESULTS The age-standardized incidence of leukemia was 3.2 and 4.1 cases per 100,000 in Songkhla and SEER-9, respectively. In Songkhla, incidence from 1990–2011 significantly increased for leukemia (APC=1.7%, p=0.031) and acute lymphoblastic leukemia (ALL) (APC=1.8%, p=0.033). Acute myeloid leukemia (AML) incidence significantly increased (APC=4.2%, p=0.044) and was significantly different from the US (p=0.026), where incidence was stable during the same period (APC=0.3%, p=0.541). The overall five-year relative survival for leukemia was lower than that reported in the US (43% vs. 79%). Five-year survival significantly improved by at least 2% per year from 1990–2011 in Songkhla for leukemia, ALL, and AML (p<0.050). CONCLUSIONS While leukemia and ALL incidence increased in Songkhla, differences in leukemia trends, particularly AML incidence, may suggest etiologic or diagnostic differences between Songkhla and the US. This work highlights the importance of evaluating childhood cancer trends in low- and middle-income countries. PMID:25962869

  2. Detection of clonality by polymerase chain reaction in childhood B-lineage acute lymphoblastic leukemia.

    Science.gov (United States)

    Januszkiewicz, D A; Nowak, J S

    1994-09-01

    DNA-based PCR with various sets of primers for TCR gamma/delta, and Ig heavy chain (IgH) genes were used to study clonality in childhood B-lineage acute lymphoblastic leukemia. Amplification of the IgH CDR-III was observed in 75 of 120 analyzed cases (62.5%). From all analyzed groups, the IgH gene rearrangement was most often observed in pre-B ALL (85.7%) and was rather rare in null-ALL (34.5%). TCR delta gene rearrangement was the most common, and was observed in 77 patients (64.2%). The typical pattern of rearrangements was defined as an incomplete V delta 2 to D delta 3, V delta 2 to D delta 2, or D delta 3 to D delta 2 recombination product. Rearrangements of TCR gamma gene we observed in 61 cases (50.8%). TCR gamma gene rearrangements were detected predominantly in null-ALL and early B-ALL (55.2% and 60%, respectively) and were rather rare in other groups. Of all eight V segments of V gamma I group, the most frequent gene usage concerns regions V gamma 2, V gamma 4, and psi V gamma 7. We have confirmed that IgH gene amplification, together with TCR gamma and delta gene amplification, provides a rapid, sensitive approach to assessing clonality in ALL almost in 100% of cases.

  3. More Chemotherapy May Help after Initial Treatment for Childhood Leukemia Fails

    Science.gov (United States)

    A study suggests that at least some children diagnosed with acute lymphoblastic leukemia who respond poorly to initial chemotherapy may do better if they receive additional chemotherapy rather than a stem cell transplant.

  4. FR901228 in Treating Children With Refractory or Recurrent Solid Tumors or Leukemia

    Science.gov (United States)

    2013-01-15

    Blastic Phase Chronic Myelogenous Leukemia; Childhood Central Nervous System Germ Cell Tumor; Childhood Choroid Plexus Tumor; Childhood Chronic Myelogenous Leukemia; Childhood Craniopharyngioma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood High-grade Cerebral Astrocytoma; Childhood Infratentorial Ependymoma; Childhood Low-grade Cerebral Astrocytoma; Childhood Spinal Cord Neoplasm; Childhood Supratentorial Ependymoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Refractory Chronic Lymphocytic Leukemia; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  5. Risk of leukemia in relation to exposure to ambient air toxics in pregnancy and early childhood.

    Science.gov (United States)

    Heck, Julia E; Park, Andrew S; Qiu, Jiaheng; Cockburn, Myles; Ritz, Beate

    2014-07-01

    There are few established causes of leukemia, the most common type of cancer in children. Studies in adults suggest a role for specific environmental agents, but little is known about any effect from exposures in pregnancy to toxics in ambient air. In our case-control study, we ascertained 69 cases of acute lymphoblastic leukemia (ALL) and 46 cases of acute myeloid leukemia (AML) from California Cancer Registry records of children leukemia associated with one interquartile range increase in air toxic exposure. Risk of ALL was elevated with 3(rd) trimester exposure to polycyclic aromatic hydrocarbons (OR=1.16, 95% CI 1.04, 1.29), arsenic (OR=1.33, 95% CI 1.02, 1.73), benzene (OR=1.50, 95% CI 1.08, 2.09), and three other toxics related to fuel combustion. Risk of AML was increased with 3rd trimester exposure to chloroform (OR=1.30, 95% CI 1.00, 1.69), benzene (1.75, 95% CI 1.04, 2.93), and two other traffic-related toxics. During the child's first year, exposure to butadiene, ortho-xylene, and toluene increased risk for AML and exposure to selenium increased risk for ALL. Benzene is an established cause of leukemia in adults; this study supports that ambient exposures to this and other chemicals in pregnancy and early life may also increase leukemia risk in children.

  6. Examination of HFE associations with childhood leukemia risk and extension to other iron regulatory genes.

    Science.gov (United States)

    Kennedy, Amy E; Kamdar, Kala Y; Lupo, Philip J; Okcu, M Fatih; Scheurer, Michael E; Baum, Marianna K; Dorak, M Tevfik

    2014-09-01

    Hereditary hemochromatosis (HFE) variants correlating with body iron levels have shown associations with cancer risk, including childhood acute lymphoblastic leukemia (ALL). Using a multi-ethnic sample of cases and controls from Houston, TX, we examined two HFE variants (rs1800562 and rs1799945), one transferrin receptor gene (TFRC) variant (rs3817672) and three additional iron regulatory gene (IRG) variants (SLC11A2 rs422982; TMPRSS6 rs855791 and rs733655) for their associations with childhood ALL. Being positive for either of the HFE variants yielded a modestly elevated odds ratio (OR) for childhood ALL risk in males (1.40, 95% CI=0.83-2.35), which increased to 2.96 (95% CI=1.29-6.80) in the presence of a particular TFRC genotype for rs3817672 (P interaction=0.04). The TFRC genotype also showed an ethnicity-specific association, with increased risk observed in non-Hispanic Whites (OR=2.54, 95% CI=1.05-6.12; P interaction with ethnicity=0.02). The three additional IRG SNPs all showed individual risk associations with childhood ALL in males (OR=1.52-2.60). A polygenic model based on the number of variant alleles in five IRG SNPs revealed a linear increase in risk among males with the increasing number of variants possessed (OR=2.0 per incremental change, 95% CI=1.29-3.12; P=0.002). Our results replicated previous HFE risk associations with childhood ALL in a US population and demonstrated novel associations for IRG SNPs, thereby strengthening the hypothesis that iron excess mediated by genetic variants contributes to childhood ALL risk.

  7. Disruption of Learning Processes by Chemotherapeutic Agents in Childhood Survivors of Acute Lymphoblastic Leukemia and Preclinical Models

    Directory of Open Access Journals (Sweden)

    Emily B. Bisen-Hersh, Philip N. Hineline, Ellen A. Walker

    2011-01-01

    Full Text Available Objective: With the survival rate of acute lymphoblastic leukemia (ALL surpassing 90 percent within this decade, new research is emerging in the field of late effects. A review of the research investigating the relationship of treatment regimens for ALL to specific late effect deficits, underlying mechanisms, and possible remediation is warranted to support continued studies.Methods: The clinical literature was briefly surveyed to describe the occurrence and topography of late effects, specifically neurocognitive deficits. Additionally, the preclinical literature was reviewed to uncover potential underlying mechanisms of these deficits. The advantages of using rodent models to answer these questions are outlined, as is an assessment of the limited number of rodent models of childhood cancer treatment.Results: The literature supports that childhood survivors of ALL exhibit academic difficulties and are more likely to be placed in a special education program. Behavioral evidence has highlighted impairments in the areas of attention, working memory, and processing speed, leading to a decrease in full scale IQ. Neurophysiological and preclinical evidence for these deficits has implicated white matter abnormalities and acquired brain damage resulting from specific chemotherapeutic agents commonly used during treatment.Conclusions: The exact role of chemotherapeutic agents in learning deficits remains mostly unknown. Recommendations for an improved rodent model of learning deficits in childhood cancer survivors are proposed, along with suggestions for future directions in this area of research, in hopes that forthcoming treatment regimens will reduce or eliminate these types of impairments.

  8. Endocrinological and Cardiological Late Effects Among Survivors of Childhood Acute Lymphoblastic Leukemia

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    Hale Ören

    2013-09-01

    Full Text Available Objective: Survival rates for childhood acute lymphoblastic leukemia (ALL have significantly improved and late effects of therapy have been important in the follow-up of survivors. The objective of this study is to identify the endocrinological and cardiological late effects of ALL patients treated in our pediatric hematology unit. Materials and Methods: Patients treated for ALL with BFM protocols after at least 5 years of diagnosis and not relapsed were included in the study. Endocrinological late effects (growth failure, obesity, insulin resistance, dyslipidemia, thyroid gland disorders, osteopenia/osteoporosis, and pubertal disorders and cardiological late effects were evaluated. The study group was evaluated with anthropometric measurements, body mass index, and laboratory testing of fasting glucose, insulin, serum lipids, thyroid functions, and bone mineral densities. Echocardiography and pulsed wave Doppler imaging were performed for analysis of cardiac functions. Results: Of the 38 ALL survivors, at least 1 adverse event occurred in 23 (60%, with 8 of them (21% having multiple problems. Six (16% of the survivors were obese and 8 (21% of them were overweight. Subjects who were overweight or obese at the time of diagnosis were more likely to be overweight or obese at last follow-up. Obesity was more frequently determined in patients who were younger than 6 years of age at the time of diagnosis. Insulin resistance was observed in 8 (21% subjects. Insulin resistance was more frequently seen in subjects who had family history of type 2 diabetes mellitus. Hyperlipidemia was detected in 8 (21% patients. Hypothyroidism or premature thelarche were detected in 2 children. Two survivors had osteopenia. Cardiovascular abnormalities occurred in one of the subjects with hypertension and cardiac diastolic dysfunction. Conclusion: We point out the necessity of follow-up of these patients for endocrinological and cardiological late effects, since at least

  9. TLR Stimulation of Bone Marrow Lymphoid Precursors from Childhood Acute Leukemia Modifies Their Differentiation Potentials

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    Elisa Dorantes-Acosta

    2013-01-01

    Full Text Available Acute leukemias are the most frequent childhood malignancies worldwide and remain a leading cause of morbidity and mortality of relapsed patients. While remarkable progress has been made in characterizing genetic aberrations that may control these hematological disorders, it has also become clear that abnormalities in the bone marrow microenvironment might hit precursor cells and contribute to disease. However, responses of leukemic precursor cells to inflammatory conditions or microbial components upon infection are yet unexplored. Our previous work and increasing evidence indicate that Toll-like receptors (TLRs in the earliest stages of lymphoid development in mice and humans provide an important mechanism for producing cells of the innate immune system. Using highly controlled co-culture systems, we now show that lymphoid precursors from leukemic bone marrow express TLRs and respond to their ligation by changing cell differentiation patterns. While no apparent contribution of TLR signals to tumor progression was recorded for any of the investigated diseases, the replenishment of innate cells was consistently promoted upon in vitro TLR exposure, suggesting that early recognition of pathogen-associated molecules might be implicated in the regulation of hematopoietic cell fate decisions in childhood acute leukemia.

  10. Methotrexate-Induced Neurotoxicity and Leukoencephalopathy in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Bhojwani, Deepa; Sabin, Noah D.; Pei, Deqing; Yang, Jun J.; Khan, Raja B.; Panetta, John C.; Krull, Kevin R.; Inaba, Hiroto; Rubnitz, Jeffrey E.; Metzger, Monika L.; Howard, Scott C.; Ribeiro, Raul C.; Cheng, Cheng; Reddick, Wilburn E.; Jeha, Sima; Sandlund, John T.; Evans, William E.; Pui, Ching-Hon; Relling, Mary V.

    2014-01-01

    Purpose Methotrexate (MTX) can cause significant clinical neurotoxicity and asymptomatic leukoencephalopathy. We sought to identify clinical, pharmacokinetic, and genetic risk factors for these MTX-related toxicities during childhood acute lymphoblastic leukemia (ALL) therapy and provide data on safety of intrathecal and high-dose MTX rechallenge in patients with neurotoxicity. Patients and Methods Prospective brain magnetic resonance imaging was performed at four time points for 369 children with ALL treated in a contemporary study that included five courses of high-dose MTX and 13 to 25 doses of triple intrathecal therapy. Logistic regression modeling was used to evaluate clinical and pharmacokinetic factors, and a genome-wide association study (GWAS) was performed to identify germline polymorphisms for their association with neurotoxicities. Results Fourteen patients (3.8%) developed MTX-related clinical neurotoxicity. Of 13 patients rechallenged with intrathecal and/or high-dose MTX, 12 did not experience recurrence of neurotoxicity. Leukoencephalopathy was found in 73 (20.6%) of 355 asymptomatic patients and in all symptomatic patients and persisted in 74% of asymptomatic and 58% of symptomatic patients at the end of therapy. A high 42-hour plasma MTX to leucovorin ratio (measure of MTX exposure) was associated with increased risk of leukoencephalopathy in multivariable analysis (P = .038). GWAS revealed polymorphisms in genes enriched for neurodevelopmental pathways with plausible mechanistic roles in neurotoxicity. Conclusion MTX-related clinical neurotoxicity is transient, and most patients can receive subsequent MTX without recurrence of acute or subacute symptoms. All symptomatic patients and one in five asymptomatic patients develop leukoencephalopathy that can persist until the end of therapy. Polymorphisms in genes related to neurogenesis may contribute to susceptibility to MTX-related neurotoxicity. PMID:24550419

  11. Combination Chemotherapy in Treating Young Patients With Down Syndrome and Acute Myeloid Leukemia or Myelodysplastic Syndromes

    Science.gov (United States)

    2017-02-07

    Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  12. Leukemia

    Science.gov (United States)

    Leukemia is cancer of the white blood cells. White blood cells help your body fight infection. Your blood cells form in your bone marrow. In leukemia, the bone marrow produces abnormal white blood cells. ...

  13. Confirmation of childhood acute lymphoblastic leukemia variants, ARID5B and IKZF1, and interaction with parental environmental exposures.

    Directory of Open Access Journals (Sweden)

    Tiffany-Jane Evans

    Full Text Available Genome wide association studies (GWAS have established association of ARID5B and IKZF1 variants with childhood acute lymphoblastic leukemia (ALL. Epidemiological studies suggest that environmental factors alone appear to make a relatively minor contribution to disease risk. The polygenic nature of childhood ALL predisposition together with the timing of environmental triggers may hold vital clues for disease etiology. This study presents results from an Australian GWAS of childhood ALL cases (n = 358 and population controls (n = 1192. Furthermore, we utilised family trio (n = 204 genotypes to extend our investigation to gene-environment interaction of significant loci with parental exposures before conception, and child's sex and age. Thirteen SNPs achieved genome wide significance in the population based case/control analysis; ten annotated to ARID5B and three to IKZF1. The most significant SNPs in these regions were ARID5B rs4245595 (OR 1.63, CI 1.38-1.93, P = 2.13×10(-9, and IKZF1 rs1110701 (OR 1.69, CI 1.42-2.02, p = 7.26×10(-9. There was evidence of gene-environment interaction for risk genotype at IKZF1, whereby an apparently stronger genetic effect was observed if the mother took folic acid or if the father did not smoke prior to pregnancy (respective interaction P-values: 0.04, 0.05. There were no interactions of risk genotypes with age or sex (P-values >0.2. Our results evidence that interaction of genetic variants and environmental exposures may further alter risk of childhood ALL however, investigation in a larger population is required. If interaction of folic acid supplementation and IKZF1 variants holds, it may be useful to quantify folate levels prior to initiating use of folic acid supplements.

  14. Applying molecular epidemiology in pediatric leukemia.

    Science.gov (United States)

    Schiffman, Joshua D

    2016-02-01

    Molecular epidemiology is the study of genetic and environmental risk for disease, with much effort centered on cancer. Childhood leukemia occurs in nearly a third of all patients newly diagnosed with pediatric cancer. only a small percentage of these new cases of childhood leukemia are associated with high penetrant hereditary cancer syndromes. Childhood leukemia, especially acute lymphoblastic leukemia, has been associated with a dysregulated immune system due to delayed infectious exposure at a young age. Identical twins with childhood leukemia suggest that acute lymphoblastic leukemia begins in utero and that the concordant presentation is due to a shared preleukemia subclone via placental transfer. Investigation of single nucleotide polymorphisms within candidate genes find that leukemia risk may be attributed to population-based polymorphisms affecting folate metabolism, xenobiotic metabolism, DNA repair, immunity, and B-cell development. More recently, genome-wide association studies for leukemia risk has led investigators to genes associated with B-cell development. When describing leukemia predisposition due to hereditary cancer syndromes, the following 6 categories become apparent on the basis of biology and clinical presentation: (1) genetic instability/DNA repair syndromes, (2) cell cycle/differentiation syndromes, (3) bone marrow failure syndromes, (4) telomere maintenance syndromes, (5) immunodeficiency syndromes, and (6) transcription factor syndromes and pure familial leukemia. understanding the molecular epidemiology of childhood leukemia can affect the treatment and tumor surveillance strategies for these high risk patients and their family members.

  15. BMS-214662 in Treating Patients With Acute Leukemia, Myelodysplastic Syndrome, or Chronic Myeloid Leukemia

    Science.gov (United States)

    2013-01-22

    Adult Acute Promyelocytic Leukemia (M3); Blastic Phase Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia

  16. The impact of CYP3A5*3 on risk and prognosis in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wallerek, Sandra; Dalhoff, Kim Peder;

    2011-01-01

    Objectives:  Acute lymphoblastic leukemia (ALL) is the most common cancer in childhood; however, little is known of the molecular etiology and environmental exposures causing the disease. Cytochrome P450 3A5 (CYP3A5) plays a crucial role in the catalytic oxidation of endogenous metabolites and to...

  17. Favorable prognostic impact of NPM1 gene mutations in childhood acute myeloid leukemia, with emphasis on cytogenetically normal AML.

    NARCIS (Netherlands)

    Hollink, I.H.; Zwaan, C.M.; Zimmermann, M.; Arentsen-Peters, T.C.; Pieters, R.; Cloos, J.; Kaspers, G.J.L.; Graaf, S.S.N. de; Harbott, J.; Creutzig, U.; Reinhardt, D.; Heuvel-Eibrink, M.M. van den; Thiede, C.

    2009-01-01

    Nucleophosmin (NPM1) mutations occur frequently in adult cytogenetically normal acute myeloid leukemia (CN-AML) and confer favorable outcome. We investigated the frequency and prognostic significance of NPM1 mutations in childhood AML (n=298), specifically focusing on the CN-AML subgroup (n=100). Mu

  18. Medical progress, psychological factors and global care of the patient: lessons from the treatment of childhood leukemia

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    Girolamo Digilio

    2013-03-01

    Full Text Available The history of treatment of childhood leukemia is a meaningful model of ethical, bioethical and organizational repercussions of medical progress. Specifically, it has provided precious indications and very useful tools to cope with several of the more important problems of modern medicine: the value of controlled randomized studies; the risks of intense medicalization impairing the quality of care; the importance of a valid doctor-patient relationship; the psycho-emotive involvement of the pediatric staff; and last but not least, the need of an unrelenting effort of humanization of the procedures and environments, hand in hand with the frequent adjustments of the protocols according to scientific and technological progress. Finally, the authors comment upon the first cures (1962-1966 observed in the Pediatrics Clinic of the Sapienza University of Rome.

  19. Symptomatic osteonecrosis in childhood leukemia survivors: prevalence, risk factors and impact on quality of life in adulthood.

    Science.gov (United States)

    Girard, Pauline; Auquier, Pascal; Barlogis, Vincent; Contet, Audrey; Poiree, Maryline; Demeocq, François; Berbis, Julie; Herrmann, Iris; Villes, Virginie; Sirvent, Nicolas; Kanold, Justyna; Chastagner, Pascal; Chambost, Hervé; Plantaz, Dominique; Michel, Gérard

    2013-07-01

    Corticosteroid can induce osteonecrosis in children with leukemia. Few studies have been designed to assess the influence of a wide range of cumulative steroid dose on this side effect. Prevalence, risk factors of symptomatic osteonecrosis and its impact on adults' Quality of Life were assessed in 943 patients enrolled in the French "Leucémies de l'Enfant et de l'Adolescent" (LEA) cohort of childhood leukemia survivors. During each medical visit, data on previous osteonecrosis diagnosis were retrospectively collected. Patients without a history but with suggestive symptoms were investigated with magnetic resonance imaging. The total steroid dose in equivalent of prednisone was calculated for each patient and its effect on osteonecrosis occurrence was studied in multivariate models. Cumulative incidence was 1.4% after chemotherapy alone versus 6.8% after transplantation (Posteonecrosis. A higher post-transplant steroid dose and age over ten years at time of transplantation were significant factors in the transplanted group. With patients grouped according to steroid dose quartile, cumulative incidence of osteonecrosis reached 3.8% in the chemotherapy group for a dose beyond 5835 mg/m(2) and 23.8% after transplantation for a post-transplant dose higher than 2055 mg/m(2). Mean physical composite score of Quality of Life was 44.3 in patients with osteonecrosis versus 54.8% in patients without (Posteonecrosis, a rare late effect with a strong negative impact on physical domains of Quality of Life.

  20. Using adaptive model predictive control to customize maintenance therapy chemotherapeutic dosing for childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Noble, Sarah L; Sherer, Eric; Hannemann, Robert E; Ramkrishna, Doraiswami; Vik, Terry; Rundell, Ann E

    2010-06-07

    Acute lymphoblastic leukemia (ALL) is a common childhood cancer in which nearly one-quarter of patients experience a disease relapse. However, it has been shown that individualizing therapy for childhood ALL patients by adjusting doses based on the blood concentration of active drug metabolite could significantly improve treatment outcome. An adaptive model predictive control (MPC) strategy is presented in which maintenance therapy for childhood ALL is personalized using routine patient measurements of red blood cell mean corpuscular volume as a surrogate for the active drug metabolite concentration. A clinically relevant mathematical model is developed and used to describe the patient response to the chemotherapeutic drug 6-mercaptopurine, with some model parameters being patient-specific. During the course of treatment, the patient-specific parameters are adaptively identified using recurrent complete blood count measurements, which sufficiently constrain the patient parameter uncertainty to support customized adjustments of the drug dose. While this work represents only a first step toward a quantitative tool for clinical use, the simulated treatment results indicate that the proposed mathematical model and adaptive MPC approach could serve as valuable resources to the oncologist toward creating a personalized treatment strategy that is both safe and effective.

  1. The frequency of NPM1 mutations in childhood acute myeloid leukemia

    Directory of Open Access Journals (Sweden)

    Karamolegou Kalliopi

    2010-10-01

    Full Text Available Abstract Background Mutations in the nucleophosmin (NPM1 gene have been solely associated with childhood acute myeloid leukemia (AML. We evaluated the frequency of NPM1 mutations in childhood AML, their relation to clinical and cytogenetic features and the presence of common FLT3 and RAS mutations. Results NPM1 mutations were found in 8% of cases. They involved the typical type 'A' mutation and one novel mutation characterized by two individual base pair substitutions, which resulted in 2 amino acid changes (W290 and (S293 in the NPM protein. FLT3/ITD mutations were observed in 12% of the cases and in one NPM1-mutated case bearing also t(8;21 (q22;q22. No common RAS mutations were identified. Conclusions A relatively consistent NPM1 mutation rate was observed, but with variations in types of mutations. The role of different types of NPM1 mutations, either individually or in the presence of other common gene mutations may be essential for childhood AML prognosis.

  2. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Vilma Carolina Bekker-Méndez

    2014-01-01

    Full Text Available Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL. The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child’s diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7% patients. ETV6-RUNX1 was detected in 21 (7.4% patients, TCF3-PBX1 in 20 (7.1% patients, BCR-ABL1 in 5 (1.8% patients, and MLL rearrangements in 4 (1.4% patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children.

  3. Prevalence of Gene Rearrangements in Mexican Children with Acute Lymphoblastic Leukemia: A Population Study—Report from the Mexican Interinstitutional Group for the Identification of the Causes of Childhood Leukemia

    Science.gov (United States)

    Bekker-Méndez, Vilma Carolina; Miranda-Peralta, Enrique; Núñez-Enríquez, Juan Carlos; Olarte-Carrillo, Irma; Guerra-Castillo, Francisco Xavier; Pompa-Mera, Ericka Nelly; Ocaña-Mondragón, Alicia; Bernáldez-Ríos, Roberto; Medina-Sanson, Aurora; Jiménez-Hernández, Elva; Amador-Sánchez, Raquel; Peñaloza-González, José Gabriel; de Diego Flores-Chapa, José; Fajardo-Gutiérrez, Arturo; Flores-Lujano, Janet; Rodríguez-Zepeda, María del Carmen; Dorantes-Acosta, Elisa María; Bolea-Murga, Victoria; Núñez-Villegas, Nancy; Velázquez-Aviña, Martha Margarita; Torres-Nava, José Refugio; Reyes-Zepeda, Nancy Carolina; González-Bonilla, Cesar; Mejía-Aranguré, Juan Manuel

    2014-01-01

    Mexico has one of the highest incidences of childhood leukemia worldwide and significantly higher mortality rates for this disease compared with other countries. One possible cause is the high prevalence of gene rearrangements associated with the etiology or with a poor prognosis of childhood acute lymphoblastic leukemia (ALL). The aims of this multicenter study were to determine the prevalence of the four most common gene rearrangements [ETV6-RUNX1, TCF3-PBX1, BCR-ABL1, and MLL rearrangements] and to explore their relationship with mortality rates during the first year of treatment in ALL children from Mexico City. Patients were recruited from eight public hospitals during 2010–2012. A total of 282 bone marrow samples were obtained at each child's diagnosis for screening by conventional and multiplex reverse transcription polymerase chain reaction to determine the gene rearrangements. Gene rearrangements were detected in 50 (17.7%) patients. ETV6-RUNX1 was detected in 21 (7.4%) patients, TCF3-PBX1 in 20 (7.1%) patients, BCR-ABL1 in 5 (1.8%) patients, and MLL rearrangements in 4 (1.4%) patients. The earliest deaths occurred at months 1, 2, and 3 after diagnosis in patients with MLL, ETV6-RUNX1, and BCR-ABL1 gene rearrangements, respectively. Gene rearrangements could be related to the aggressiveness of leukemia observed in Mexican children. PMID:25692130

  4. Clinical Study of Acute Mixed-lineage Leukemia in 14 Children

    Directory of Open Access Journals (Sweden)

    Xiaoling Zhang

    2011-12-01

    Full Text Available Objective: Acute mixed-lineage leukemia (AMLL is characterized as the acute leukemia involved with acute myeloid cells and lymphoid cells at the same time. The AMLL is easily misdiagnosed because of a dual character involved with lymphoid and myeloid cells. At present, researches of AMLL in adults are more common. Only some are reported for children. Therefore, our aim was to study clinical characteristics of the childhood AMLL.Methods: From January 2000 to July 2009, 14 cases of AMLL children were selected by morphological and immunophenotyping methods from 185 cases of childhood acute leukemia admitted to the Department of Pediatrics, Tongji Hospital, Tongji Medical College of Science and Technology of Huazhong University. Medical records of all AMLL cases were reviewed for clinical characteristics.Findings: Fourteen cases of AMLL were screened from 185 cases of acute leukemia by morphology, immunology, cytogenetics and molecular (MICM. The rate of childhood AMLL accounted for 7.57% of pediatric acute leukemia (AL diagnosed in the research period; white blood cell count in most of the patients was normal, the average value being 31.0×109/L in the first visit. In the 14 cases of AMLL, 8 cases were B-Ly+/My+, 2 cases were T-Ly+/My+B, and 4 were T+B-Ly+/My+. Among them, nine cases received treatment. Consequently, 6 cases reached complete remission (CR; 1 case had not complete remission; 2 cases did not complete the treatment. Conclusion: The diagnosis of AMLL should depend on the comprehensive evaluation of MICM. As there are still many problems concerning AMLL, it is very necessary that the research units collaborate with each other to improve the prognosis of childhood AMLL. The limitations and applications of the results are that they are only based on the patients of one hospital.

  5. Health promotion for adolescent childhood leukemia survivors: building on prevention science and ehealth.

    Science.gov (United States)

    Elliot, Diane L; Lindemulder, Susan J; Goldberg, Linn; Stadler, Diane D; Smith, Jennifer

    2013-06-01

    Teenage survivors of childhood acute lymphoblastic leukemia (ALL) have increased morbidity likely due to their prior multicomponent treatment. Habits established in adolescence can impact individuals' subsequent adult behaviors. Accordingly, healthy lifestyles, avoiding harmful actions, and appropriate disease surveillance are of heightened importance among teenage survivors. We review the findings from prevention science and their relevance to heath promotion. The capabilities and current uses of eHealth components including e-learning, serious video games, exergaming, behavior tracking, individual messaging, and social networking are briefly presented. The health promotion needs of adolescent survivors are aligned with those eHealth aspects to propose a new paradigm to enhance the wellbeing of adolescent ALL survivors.

  6. Chemotherapy with cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP) in childhood acute lymphoblastic leukemia (ALL).

    Science.gov (United States)

    Sallan, S E; Camitta, B M; Chan, D M; Traggis, D; Jaffe, N

    1977-01-01

    Three groups of children with acute lymphoblastic leukemia (ALL) were treated with intermittent cyclophosphamide, vincristine, cytosine arabinoside, and prednisone (COAP). Group A (no prior relapse) and Group B (prior single-agent relapse) received COAP after 12 months on another chemotherapy regimen. Children in Group C (prior relapse on multiagent regimens) received COAP following A-COAP (asparaginase plus COAP) reinduction. Median disease-free survival after beginning COAP was not reached for Group A, but was only 7 months for Groups B and C. As of November 1976, there were 8 of 15 Group A patients, 1 of 12 Group B patients, and 1 of 28 Group C patients who had remained disease-free from 38 to 60 (median 54.5) months and were off chemotherapy. COAP has activity in childhood ALL. However, effectiveness is markedly diminished in patients with prior bone marrow relapse.

  7. Quantitative morphologic evaluation of magnetic resonance imaging during and after treatment of childhood leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Reddick, Wilburn E.; Glass, John O. [St. Jude Children' s Research Hospital, Division of Translational Imaging Research (MS 210), Department of Radiological Sciences, Memphis, TN (United States); Laningham, Fred H. [St. Jude Children' s Research Hospital, Division of Diagnostic Imaging, Memphis, TN (United States); Pui, Ching-Hon [St. Jude Children' s Research Hospital, Department of Oncology, Memphis, TN (United States)

    2007-11-15

    Medical advances over the last several decades, including CNS prophylaxis, have greatly increased survival in children with leukemia. As survival rates have increased, clinicians and scientists have been afforded the opportunity to further develop treatments to improve the quality of life of survivors by minimizing the long-term adverse effects. When evaluating the effect of antileukemia therapy on the developing brain, magnetic resonance (MR) imaging has been the preferred modality because it quantifies morphologic changes objectively and noninvasively. Computer-aided detection of changes on neuroimages enables us to objectively differentiate leukoencephalopathy from normal maturation of the developing brain. Quantitative tissue segmentation algorithms and relaxometry measures have been used to determine the prevalence, extent, and intensity of white matter changes that occur during therapy. More recently, diffusion tensor imaging has been used to quantify microstructural changes in the integrity of the white matter fiber tracts. MR perfusion imaging can be used to noninvasively monitor vascular changes during therapy. Changes in quantitative MR measures have been associated, to some degree, with changes in neurocognitive function during and after treatment. In this review, we present recent advances in quantitative evaluation of MR imaging and discuss how these methods hold the promise to further elucidate the pathophysiologic effects of treatment for childhood leukemia. (orig.)

  8. Detection of Fetomaternal Genotype Associations in Early-Onset Disorders: Evaluation of Different Methods and Their Application to Childhood Leukemia

    Directory of Open Access Journals (Sweden)

    Jasmine Healy

    2010-01-01

    Full Text Available Several designs and analytical approaches have been proposed to dissect offspring from maternal genetic contributions to early-onset diseases. However, lack of parental controls halts the direct verification of the assumption of mating symmetry (MS required to assess maternally-mediated effects. In this study, we used simulations to investigate the performance of existing methods under mating asymmetry (MA when parents of controls are missing. Our results show that the log-linear, likelihood-based framework using a case-triad/case-control hybrid design provides valid tests for maternal genetic effects even under MA. Using this approach, we examined fetomaternal associations between 29 SNPs in 12 cell-cycle genes and childhood pre-B acute lymphoblastic leukemia (ALL. We identified putative fetomaternal effects at loci CDKN2A rs36228834 (P=.017 and CDKN2B rs36229158 (P=.022 that modulate the risk of childhood ALL. These data further corroborate the importance of the mother's genotype on the susceptibility to early-onset diseases.

  9. Neurocognitive Outcomes in Long-term Survivors of Childhood Acute Lymphoblastic Leukemia Treated on Contemporary Treatment Protocols: A Systematic Review

    Science.gov (United States)

    Cheung, Yin Ting; Krull, Kevin R.

    2015-01-01

    The intensified administration of chemotherapeutic drugs has gradually replaced cranial radiation therapy (CRT) for the treatment of childhood acute lymphoblastic leukemia (ALL). While CRT is often implicated in neurocognitive impairment in ALL survivors, there is a paucity of literature that evaluates the persistence of neurocognitive deficits in long-term survivors of pediatric ALL who were treated with contemporary chemotherapy-only protocols. Results from this systematic review concurred to the probable cognitive-sparing effect of chemotherapy-based protocols over CRT in long-term survivors. However, coupled with multiple intrinsic and extrinsic factors, survivors who received chemotherapy treatment still suffered from apparent cognitive impairment, particularly in the attention and executive function domains. Notably, there is evidence to suggest that the late neurotoxic effect of methotrexate on survivors’ neurocognitive performance may be dose-related. This review also recommends future pharmacokinetic, neuroimaging and genetic studies to illuminate the multifactorial nature of this subject matter and discusses the potential value of neurochemical, physiological, inflammatory and genetic markers for the prediction of susceptibility to neurocognitive impairment in long-term survivors of childhood ALL. PMID:25857254

  10. Breastfeeding and nutrition to 2 years of age and risk of childhood acute lymphoblastic leukemia and brain tumors.

    Science.gov (United States)

    Greenop, Kathryn R; Bailey, Helen D; Miller, Margaret; Scott, Rodney J; Attia, John; Ashton, Lesley J; Downie, Peter; Armstrong, Bruce K; Milne, Elizabeth

    2015-01-01

    Acute lymphoblastic leukemia (ALL) and childhood brain tumors (CBT) are 2 of the most common forms of childhood cancer, but little is known of their etiology. In 2 nationwide case-control studies we investigated whether breastfeeding, age of food introduction, or early diet are associated with the risk of these cancers. Cases aged 0-14 years were identified from Australian pediatric oncology units between 2003 and 2007 (ALL) and 2005 and 2010 (CBT) and population-based controls through nationwide random-digit dialing. Mothers completed questionnaires giving details of infant feeding up to the age of 2 yr. Data from 322 ALL cases, 679 ALL controls, 299 CBT cases, and 733 CBT controls were analysed using unconditional logistic regression. Breastfeeding was associated with a reduced risk of ALL [odds ratio (OR) = 0.52, 95% confidence interval (CI): 0.32, 0.84), regardless of duration. Introduction of artificial formula within 14 days of birth was positively associated with ALL (OR = 1.57, 95% CI: 1.03, 2.37), as was exclusive formula feeding to 6 mo (OR = 1.81, 95% CI: 1.07, 3.05). No associations were seen between breastfeeding or formula use and risk of CBT. Our results suggest that breastfeeding and delayed introduction of artificial formula may reduce the risk of ALL but not CBT.

  11. Late cardiac effects of anthracycline containing therapy for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Carlsen, Niels L T; Oxhøj, Henrik

    2007-01-01

    At present about 80% of children with acute lymphoblastic leukemia (ALL) will be cured following treatment with multi-drug chemotherapy. A major concern for this growing number of survivors is the risk of late effects of treatment. The aim of this study was to determine whether signs of cardiomyo...

  12. Duration of adrenal insufficiency during treatment for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Vestergaard, Therese Risom; Juul, Anders; Lausten-Thomsen, Ulrik;

    2011-01-01

    Children with acute lymphoblastic leukemia (ALL) recive high doses of glucocorticosteroid as part of their treatment. This may lead to suppression of the hypothalamic-pituitary-adrenal axis, acute adrenal insufficiency, and ultimately to life-threatening conditions. This study explores the adrena...

  13. Expression of multidrug resistance-associated proteins predicts prognosis in childhood and adult acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Plasschaert, SLA; de Bont, ESJM; Boezen, M; vander Kolk, DM; Daenen, SMJG; Faber, KN; Kamps, WA; de Vries, EGE; Vellenga, E

    2005-01-01

    PURPOSE: Patients with acute lymphoblastic leukemia (ALL) are treated with a variety of chemotherapeutic drugs, which can be transported by six multidrug resistance-associated proteins (MRP). These MRPs have strongly overlapping functional activities. The aim of this study was to investigate the exp

  14. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: An Economic Analysis

    Science.gov (United States)

    Gajic-Veljanoski, O.; Pham, B.; Pechlivanoglou, P.; Krahn, M.; Higgins, Caroline; Bielecki, Joanna

    2016-01-01

    Background Minimal residual disease (MRD) testing by higher performance techniques such as flow cytometry and polymerase chain reaction (PCR) can be used to detect the proportion of remaining leukemic cells in bone marrow or peripheral blood during and after the first phases of chemotherapy in children with acute lymphoblastic leukemia (ALL). The results of MRD testing are used to reclassify these patients and guide changes in treatment according to their future risk of relapse. We conducted a systematic review of the economic literature, cost-effectiveness analysis, and budget-impact analysis to ascertain the cost-effectiveness and economic impact of MRD testing by flow cytometry for management of childhood precursor B-cell ALL in Ontario. Methods A systematic literature search (1998–2014) identified studies that examined the incremental cost-effectiveness of MRD testing by either flow cytometry or PCR. We developed a lifetime state-transition (Markov) microsimulation model to quantify the cost-effectiveness of MRD testing followed by risk-directed therapy to no MRD testing and to estimate its marginal effect on health outcomes and on costs. Model input parameters were based on the literature, expert opinion, and data from the Pediatric Oncology Group of Ontario Networked Information System. Using predictions from our Markov model, we estimated the 1-year cost burden of MRD testing versus no testing and forecasted its economic impact over 3 and 5 years. Results In a base-case cost-effectiveness analysis, compared with no testing, MRD testing by flow cytometry at the end of induction and consolidation was associated with an increased discounted survival of 0.0958 quality-adjusted life-years (QALYs) and increased discounted costs of $4,180, yielding an incremental cost-effectiveness ratio (ICER) of $43,613/QALY gained. After accounting for parameter uncertainty, incremental cost-effectiveness of MRD testing was associated with an ICER of $50,249/QALY gained. In

  15. Increased μ-Calpain Activity in Blasts of Common B-Precursor Childhood Acute Lymphoblastic Leukemia Correlates with Their Lower Susceptibility to Apoptosis.

    Directory of Open Access Journals (Sweden)

    Anna Mikosik

    Full Text Available Childhood acute lymphoblastic leukemia (ALL blasts are characterized by inhibited apoptosis promoting fast disease progress. It is known that in chronic lymphocytic and acute myeloid leukemias the reduced apoptosis is strongly related with the activity of calpain-calpastatin system (CCS composed of cytoplasmic proteases--calpains--performing the modulatory proteolysis of key proteins involved in cell proliferation and apoptosis, and of their endogenous inhibitor--calpastatin. Here, the CCS protein abundance and activity was for the first time studied in childhood ALL blasts and in control bone marrow CD19+ B cells by semi-quantitative flow cytometry and western blotting of calpastatin fragments resulting from endogenous calpain activity. Significantly higher μ-calpain (CAPN1 gene transcription, protein amounts and activity (but not those of m-calpain, with calpastatin amount and transcription of its gene (CAST greatly varying were observed in CD19(+ ALL blasts compared to control cells. Significant inverse relation between the amount/activity of calpain and spontaneous apoptosis was noted. Patients older than 10 years (considered at higher risk displayed increased amounts and activities of blast calpain. Finally, treatment of blasts with the tripeptide calpain inhibitors II and IV significantly and in dose-dependent fashion increased the percentage of blasts entering apoptosis. Together, these findings make the CCS a potential new predictive tool and therapeutic target in childhood ALL.

  16. Study Finds Small Increase in Cancer Risk after Childhood CT Scans

    Science.gov (United States)

    A study published in the June 6, 2012, issue of The Lancet shows that radiation exposure from computed tomography (CT) scans in childhood results in very small but increased risks of leukemia and brain tumors in the first decade after exposure.

  17. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model

    Institute of Scientific and Technical Information of China (English)

    Petar Ivanovski; Ivan Ivanovski; Dimitrije Nikoli(c); Ivana Jovanovi(c)

    2012-01-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations.The bottleneck is evidence that leukemia initiation,by in utero acquired chromosome translocations that generate functional fusion genes,is far more common than the incidence rate of corresponding leukemia.For childhood TEL-AML1+ acute lymphoblastic leukemia (ALL) this equates to approximately 100 times.Practically this means that among a hundred children born with TEL-AML1 fusion gene,only one child will later in its life develop ALL.The key data necessary for unraveling of this mystery were discovered in 2002.It was the level of TEL-AML1 + cells' frequency.The bottleneck is caused by the very low body TEL-AML1 + cell count.Only one out of a thousand B cells carries TEL-AML1 fusion gene.TEL-AML1+ body cell count is low because TEL-AML1 fusion is generated at cell level of 10a to 10-4 just during the late fetal lymphopoiesis i.e.after the 36th gestational week.

  18. Childhood leukemia genetic bottleneck phenomenon related to TEL-AML1: the postulation by a mathematical model.

    Science.gov (United States)

    Ivanovski, Petar; Ivanovski, Ivan; Nikolić, Dimitrije; Jovanović, Ivana

    2012-03-01

    Childhood leukemia bottleneck phenomenon is the most mysterious corollary of the prenatal origin discovery of leukemogenic chromosome translocations. The bottleneck is evidence that leukemia initiation, by in utero acquired chromosome translocations that generate functional fusion genes, is far more common than the incidence rate of corresponding leukemia. For childhood TEL-AML1(+) acute lymphoblastic leukemia (ALL) this equates to approximately 100 times. Practically this means that among a hundred children born with TEL-AML1 fusion gene, only one child will later in its life develop ALL. The key data necessary for unraveling of this mystery were discovered in 2002. It was the level of TEL-AML1(+) cells’ frequency. The bottleneck is caused by the very low body TEL-AML1(+) cell count. Only one out of a thousand B cells carries TEL-AML1 fusion gene. TEL-AML1(+) body cell count is low because TEL-AML1 fusion is generated at cell level of 10(-3) to 10(-4) just during the late fetal lymphopoiesis i.e. after the 36th gestational week.

  19. Maternal and offspring genetic variants of AKR1C3 and the risk of childhood leukemia

    OpenAIRE

    Liu, Chen-Yu; Hsu, Yi-Hsiang; Pan, Pi-Chen; Wu, Ming-Tsang; Ho, Chi-Kung; Su, Li; Xu, Xin; Li, Yi; Christiani, David C.

    2008-01-01

    The aldo-keto reductase 1C3 (AKR1C3) gene located on chromosome 10p15-p14, a regulator of myeloid cell proliferation and differentiation, represents an important candidate gene for studying human carcinogenesis. In a prospectively enrolled population-based case–control study of Han Chinese conducted in Kaohsiung in southern Taiwan, a total of 114 leukemia cases and 221 controls

  20. Multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP and lung resistance protein (LRP gene expression in childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Elvis Terci Valera

    Full Text Available CONTEXT: Despite the advances in the cure rate for acute lymphoblastic leukemia, approximately 25% of affected children suffer relapses. Expression of genes for the multiple drug resistance protein (MDR-1, multidrug resistance-related protein (MRP, and lung resistance protein (LRP may confer the phenotype of resistance to the treatment of neoplasias. OBJECTIVE: To analyze the expression of the MDR-1, MRP and LRP genes in children with a diagnosis of acute lymphoblastic leukemia via the semiquantitative reverse transcription polymerase chain reaction (RT-PCR, and to determine the correlation between expression and event-free survival and clinical and laboratory variables. DESIGN: A retrospective clinical study. SETTING: Laboratory of Pediatric Oncology, Department of Pediatrics, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brazil. METHODS: Bone marrow aspirates from 30 children with a diagnosis of acute lymphoblastic leukemia were assessed for the expression of messenger RNA for the MDR-1, MRP and LRP genes by semi-quantitative RT-PCR. RESULTS: In the three groups studied, only the increased expression of LRP was related to worsened event-free survival (p = 0.005. The presence of the common acute lymphoblastic leukemia antigen (CALLA was correlated with increased LRP expression (p = 0.009 and increased risk of relapse or death (p = 0.05. The relative risk of relapse or death was six times higher among children with high LRP expression upon diagnosis (p = 0.05, as confirmed by multivariate analysis of the three genes studied (p = 0.035. DISCUSSION: Cell resistance to drugs is a determinant of the response to chemotherapy and its detection via RT-PCR may be of clinical importance. CONCLUSIONS: Evaluation of the expression of genes for resistance to antineoplastic drugs in childhood acute lymphoblastic leukemia upon diagnosis, and particularly the expression of the LRP gene, may be of clinical relevance, and should be the

  1. Alemtuzumab and Combination Chemotherapy in Treating Patients With Untreated Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2014-03-20

    Acute Undifferentiated Leukemia; B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; L1 Adult Acute Lymphoblastic Leukemia; L1 Childhood Acute Lymphoblastic Leukemia; L2 Adult Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  2. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance

    Science.gov (United States)

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting from articles published inreputable journals from1994 to date and experiments newly performed by our group, a comprehensive review is written about ABCA2 and its role in MDR regarding childhood ALL. ABCA2 transports drugs from the cytoplasm into the lysosomal compartment, where they may become degraded and exported from the cell. The aforementioned mechanism may contribute to MDR. It has been reported that ABCA2 may induce resistance to mitoxantrone, estrogen derivatives and estramustine. It is resistant to the aforementioned compounds. Furthermore, the overexpression ofABCA2 in methotrexate, vinblastine and/or doxorubicin treated Jurkat cells are observed in several publications. The recent study of our group showsthatthe overexpression ofABCA2 gene in children with ALL increases the risk of MDR by 15 times. ABCA2 is the second identified member of the ABCA; ABC transporters' subfamily. ABCA2 gene expression profile is suggested to be an unfavorable prognostic factor in ALL treatment. Better understanding of the MDR mechanisms and the factors involved may improve the therapeutic outcome of ALL by modifying the treatment protocols. PMID:25254091

  3. The role of ATP-binding cassette transporter A2 in childhood acute lymphoblastic leukemia multidrug resistance.

    Science.gov (United States)

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is one of the most prevalent hematologic malignancies in children. Although the cure rate of ALL has improved over the past decades, the most important reason for ALL treatment failure is multidrug resistance (MDR) phenomenon. The current study aims to explain the mechanisms involved in multidrug resistance of childhood ALL, and introduces ATP-binding cassette transporterA2 (ABCA2) as an ABC transporter gene which may have a high impact on MDR. Benefiting from articles published inreputable journals from1994 to date and experiments newly performed by our group, a comprehensive review is written about ABCA2 and its role in MDR regarding childhood ALL. ABCA2 transports drugs from the cytoplasm into the lysosomal compartment, where they may become degraded and exported from the cell. The aforementioned mechanism may contribute to MDR. It has been reported that ABCA2 may induce resistance to mitoxantrone, estrogen derivatives and estramustine. It is resistant to the aforementioned compounds. Furthermore, the overexpression ofABCA2 in methotrexate, vinblastine and/or doxorubicin treated Jurkat cells are observed in several publications. The recent study of our group showsthatthe overexpression ofABCA2 gene in children with ALL increases the risk of MDR by 15 times. ABCA2 is the second identified member of the ABCA; ABC transporters' subfamily. ABCA2 gene expression profile is suggested to be an unfavorable prognostic factor in ALL treatment. Better understanding of the MDR mechanisms and the factors involved may improve the therapeutic outcome of ALL by modifying the treatment protocols.

  4. Nivolumab and Dasatinib in Treating Patients With Relapsed or Refractory Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-08-25

    B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Refractory Adult Acute Lymphoblastic Leukemia; Refractory Childhood Acute Lymphoblastic Leukemia

  5. Treosulfan, Fludarabine Phosphate, and Total-Body Irradiation Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Myelodysplastic Syndrome, Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2013-10-29

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  6. Evaluation of mRNA Expression Profile of ABCG2/BCRP in Childhood Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    M Entezar-e-Ghaem

    2013-12-01

    Conclusion: Results of this study showed no effect of ABCG2/BCRP expression level on MDR development in ALL. Accordingly, clinical value of ABCG2/BCRP expression profile determination was rejected as the prognosis value for childhood ALL in our geographical area.

  7. Chemokines and relapses in childhood acute lymphoblastic leukemia: A role in migration and in resistance to antileukemic drugs.

    Science.gov (United States)

    Gómez, Ana M; Martínez, Carolina; González, Miguel; Luque, Alfonso; Melen, Gustavo J; Martínez, Jesús; Hortelano, Sonsoles; Lassaletta, Álvaro; Madero, Luís; Ramírez, Manuel

    2015-10-01

    We studied whether chemokines may have a role in relapses in childhood acute lymphoblastic leukemia (ALL). We compared the levels of chemokine receptors in marrow samples from 82 children with ALL at diagnosis versus 15 at relapses, and quantified the levels of chemokines in central system fluid (CSF) samples. The functional role of specific chemokines was studied in vitro and in vivo. The expression of some chemokine receptors was upregulated upon leukemic relapse, both in B- and in T-ALL, and in cases of medullary and extramedullary involvement. CXCL10 induced chemotaxis in leukemic cell lines and in primary leukemic cells, depending upon the levels of CXCR3 expression. CXCL10 specifically diminished chemotherapy-induced apoptosis on ALL cells expressing CXCR3, partially inhibiting caspase activation and maintaining the levels of the antiapoptotic protein Bcl-2. Finally, immunodeficient mice engrafted with CXCR3-expressing human leukemic cells showed decreased infiltration of marrow, spleen, and CNS after receiving a CXCR3-antagonist molecule. CXCR3 signaling in ALL may have a dual function: chemotactic for the localisation of leukemic blasts in specific niches, and it may also confer resistance to chemotherapy, enhancing the chances for relapses.

  8. Baicalein Triggers Mitochondria-Mediated Apoptosis and Enhances the Antileukemic Effect of Vincristine in Childhood Acute Lymphoblastic Leukemia CCRF-CEM Cells

    Directory of Open Access Journals (Sweden)

    Yun-Ju Chen

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL accounts for approximately 75% of childhood leukemia, and chemotherapy remains the mainstay therapy. Baicalein is an active flavonoid used in traditional Chinese medicine and has recently been found to have anticancer, anti-inflammatory, and antiallergic properties. This study aims to investigate the molecular apoptotic mechanisms of baicalein in CCRF-CEM leukemic cells and to evaluate the combined therapeutic efficacy of baicalein with several commonly used chemotherapeutic drugs in CCRF-CEM cells. Our results demonstrate that baicalein induces mitochondria-dependent cleavage of caspases-9 and -3 and PARP with concomitant decreases in IAP family proteins, survivin, and XIAP. Furthermore, our results present for the first time that baicalein triggers a convergence of the intrinsic and extrinsic apoptotic pathways via the death receptor-caspase 8-tBid signaling cascade in CCRF-CEM cells. In addition, we also present for the first time that the combination of baicalein and vincristine results in a synergistic therapeutic efficacy. Overall, this combination strategy is recommended for future clinical trials in the treatment of pediatric leukemia owing to baicalein’s beneficial effects in alleviating the vomiting, nausea, and skin rashes caused by chemotherapy.

  9. Spatial analysis of childhood cancer: a case/control study.

    Directory of Open Access Journals (Sweden)

    Rebeca Ramis

    Full Text Available Childhood cancer was the leading cause of death among children aged 1-14 years for 2012 in Spain. Leukemia has the highest incidence, followed by tumors of the central nervous system (CNS and lymphomas (Hodgkin lymphoma, HL, and Non-Hodgkin's lymphoma, NHL. Spatial distribution of childhood cancer cases has been under concern with the aim of identifying potential risk factors.The two objectives are to study overall spatial clustering and cluster detection of cases of the three main childhood cancer causes, looking to increase etiological knowledge.We ran a case-control study. The cases were children aged 0 to 14 diagnosed with leukemia, lymphomas (HL and NHL or CNS neoplasm in five Spanish regions for the period 1996-2011. As a control group, we used a sample from the Birth Registry matching every case by year of birth, autonomous region of residence and sex with six controls. We geocoded and validated the address of the cases and controls. For our two objectives we used two different methodologies. For the first, for overall spatial clustering detection, we used the differences of K functions from the spatial point patterns perspective proposed by Diggle and Chetwynd and the second, for cluster detection, we used the spatial scan statistic proposed by Kulldorff with a level for statistical significance of 0.05.We had 1062 cases of leukemia, 714 cases of CNS, 92 of HL and 246 of NHL. Accordingly we had 6 times the number of controls, 6372 controls for leukemia, 4284 controls for CNS, 552 controls for HL and 1476 controls for NHL. We found variations in the estimated empirical D(s for the different regions and cancers, including some overall spatial clustering for specific regions and distances. We did not find statistically significant clusters.The variations in the estimated empirical D(s for the different regions and cancers could be partially explained by the differences in the spatial distribution of the population; however, according to the

  10. Randomized double blind trial of ciprofloxacin prophylaxis during induction treatment in childhood acute lymphoblastic leukemia in the WK-ALL protocol in Indonesia

    Directory of Open Access Journals (Sweden)

    Widjajanto PH

    2013-02-01

    Full Text Available Pudjo H Widjajanto,1 Sumadiono Sumadiono,1 Jacqueline Cloos,2,3 Ignatius Purwanto,1 Sutaryo Sutaryo,1 Anjo JP Veerman1,21Pediatric Hematology and Oncology Division, Department of Pediatrics, Dr Sardjito Hospital, Medical Faculty, Universitas Gadjah Mada, Yogyakarta, Indonesia; 2Pediatric Oncology/Hematology Division, Department of Pediatrics, 3Department of Hematology, VU University Medical Center, Amsterdam, The NetherlandsObjectives: Toxic death is a big problem in the treatment of childhood acute lymphoblastic leukemia (ALL, especially in low-income countries. Studies of ciprofloxacin as single agent prophylaxis vary widely in success rate. We conducted a double-blind, randomized study to test the effects of ciprofloxacin monotherapy as prophylaxis for sepsis and death in induction treatment of the Indonesian childhood ALL protocol.Methods: Patients were randomized to the ciprofloxacin arm (n = 58 and to the placebo arm (n = 52. Oral ciprofloxacin monotherapy or oral placebo was administered twice a day. All events during induction were recorded: toxic death, abandonment, resistant disease, and complete remission rate.Results: Of 110 patients enrolled in this study, 79 (71.8% achieved CR. In comparison to the placebo arm, the ciprofloxacin arm had lower nadir of absolute neutrophil count during induction with median of 62 (range: 5–884 versus 270 (range: 14–25,480 × 109 cells/L (P > 0.01, greater risks for experiencing fever (50.0% versus 32.7%, P = 0.07, clinical sepsis (50.0% versus 38.5%, P = 0.22, and death (18.9% versus 5.8%, P = 0.05.Conclusion: In our setting, a reduced intensity protocol in a low-income situation, the data warn against using ciprofloxacin prophylaxis during induction treatment. A lower nadir of neutrophil count and higher mortality were found in the ciprofloxacin group.Keywords: ciprofloxacin, prophylaxis, childhood acute lymphoblastic leukemia, randomized trial, low-income country

  11. Vorinostat With or Without Isotretinoin in Treating Young Patients With Recurrent or Refractory Solid Tumors, Lymphoma, or Leukemia

    Science.gov (United States)

    2014-06-16

    Childhood Acute Promyelocytic Leukemia (M3); Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Juvenile Myelomonocytic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent/Refractory Childhood Hodgkin Lymphoma; Relapsing Chronic Myelogenous Leukemia; Unspecified Childhood Solid Tumor, Protocol Specific

  12. Gene Dose Effects of GSTM1, GSTT1 and GSTP1 Polymorphisms on Outcome in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Borst, Louise; Buchard, Anders; Rosthoj, Susanne;

    2012-01-01

    Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing methods...... were applied for genotyping the GSTM1 and GSTT1 genes (distinguishing between 0, 1, or 2 gene copies) and the GSTP1 313 A>G polymorphism, simultaneously. A total of 263 childhood ALL patients were genotyped. No gene dose effect on outcome was demonstrated with either GST polymorphisms. Grouping of GSTM......1 and GSTT1 into poor (0 or 1 gene copy)-and good metabolizers (at least 2 gene copies)-showed that the poor metabolizers had a trend toward a better outcome (event-free survival = 91.8%) compared with the good metabolizers (event-free survival = 83.2%). Similarly, in the adjusted analysis the good...

  13. 长期无病生存白血病儿童情绪、自我意识及个性特征的对照研究%A controlled study on the psychological characteristics of long-term survivors of childhood leukemia

    Institute of Scientific and Technical Information of China (English)

    王红美; 何守森; 陈力军; 陈伟; 任万华

    2009-01-01

    Objective The aim of the study was to evaluate and compare psychosocial functioning of long-term survivors of childhood leukemia, children newly diagnosed as leukemia and age-matched healthy controls. Methods Nineteen long-term survivors of childhood leukemia(Group A), twenty children newly diagnosed as leukemia(Group B) and forty age-matched healthy controls (Group C)completed the questionnaires allowing assessment of symptoms associated with anxiety, depression, self-concept and personality by using the screen for child anxiety related emotional disorders(SCARED), depression self rating scale for children(DSRSC), Piers-Harris children's self-concept scale(PHCSS)and Eysenck personality questionnaire(EPQ), respectively. Results Group A scored significantly higher on subscales of somatization/panic(6.11±4.36), generalized anxiety(5.72±4.56), social phobia(7.67±4.19) and the total scale(25.72±14.72) than Group C(the score was 3.82±1.69,2.84±1.92, 3.95±2.85 and 16.11±11.81, respectively, P<0.05),the depression score was higher than that of the control group, but have no significant difference(P=0.069). The total score of self-concept of both group A (60.06±8.07)and group B(58.25±6.54) were significantly lower than that of the group C(64.90±7.30)(P<0.05). Among which, group A scored significantly higher on subscales of anxiety and gregarization than group C(P<0.05).And Group B scored significantly higher on subscales of behavior, intelligence and anxiety than group C(P<0.05). The extraversion score of EPQ in group A was lower than that in group B and C,whereas the other three dimensions (P,N,L) of EPQ test showed no difference between the three groups. Conclusion The findings of this study suggest that survivors of childhood leukemia are at risk for psychological difficulties.%目的 探讨长期无病生存白血病儿童的情绪、自我意识及个性特征.方法 选用儿童焦虑性情绪障碍筛查表、儿童抑郁障碍自评量表、Piers

  14. Childhood Maltreatment in South Korea: Retrospective Study

    Science.gov (United States)

    Lee, Yanghee; Kim, Sangwon

    2011-01-01

    Objective: This study explored the prevalence of childhood maltreatment in South Korea using the retrospective version of ICAST and the associations between perceptions of abuse experienced during childhood and recent interpersonal problems and depression. Methods: 539 young persons, aged 18-24 years, from various universities, work places, and…

  15. Aurora kinases in childhood acute leukemia: The promise of aurora B as therapeutic target

    NARCIS (Netherlands)

    S.A. Hartsink-Segers (S.); C.M. Zwaan (Michel); C. Exalto (Carla); M.W.J. Luijendijk (M. W J); V. Calvert (V.); E.F. Petricoin (Emanuel F.); W.E. Evans (William); D. Reinhardt (Dirk); V. de Haas (Valerie); M. Hedtjärn (M.); B.R. Hansen (B.); T. Koch (T.); H.N. Caron (Huib); R. Pieters (Rob); M.L. den Boer (Monique)

    2013-01-01

    textabstractWe investigated the effects of targeting the mitotic regulators aurora kinase A and B in pediatric acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML). Aurora protein expression levels in pediatric ALL and AML patient samples were determined by western blot and reverse ph

  16. Post-induction residual leukemia in childhood acute lymphoblastic leukemia quantified by PCR correlates with in vitro prednisolone resistance

    DEFF Research Database (Denmark)

    Schmiegelow, K; Nyvold, C; Seyfarth, J

    2001-01-01

    therapy with a precise and reproducible clone-specific PCR technique. The median MRD-D15 and MRD-PI were 0.50% (75% range 0.0088.1%) and 0.014% (75% range 0.001-2.0%), respectively, and these levels correlated significantly (n = 29, rs = 0.75, P ... combined monitoring of in vitro drug resistance and residual leukemia early during chemotherapy could offer new ways to classify patients and stratify the intensity of therapy. Udgivelsesdato: 2001-Jul...

  17. Tanespimycin in Treating Young Patients With Recurrent or Refractory Leukemia or Solid Tumors

    Science.gov (United States)

    2013-06-03

    Childhood Chronic Myelogenous Leukemia; Childhood Desmoplastic Small Round Cell Tumor; Disseminated Neuroblastoma; Metastatic Childhood Soft Tissue Sarcoma; Metastatic Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Metastatic Osteosarcoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  18. CD+4 Foxp3+调节性T淋巴细胞在儿童急性白血病中的表达及其与微小残留病的关系%The level of CD+4 Foxp3+ regulatory T cells in patients with childhood acute leukemia and its relationship with the minimal residual disease of leukemia

    Institute of Scientific and Technical Information of China (English)

    徐翀; 关明; 蒋黎敏; 江华; 孙婴

    2009-01-01

    Objective To study the regulatory T cells (Treg-cell) frequencies in patients with childhood acute leukemia and evaluate its clinical application value by investigating the relationship between the increasing numbers of Treg cells and minimal residual disease of leukemia (MRD), Methods Foxp3-FITC/CD25-PE/CD4-PerCP/CD3-APC four-color staining flow cytometry was established to identify Treg cells. Treg cells frequencies both in 10 healthy controls and in 33 patients with newly diagnosed childhood acute leukemia ( B-ALL 17 cases, T-ALL 9 cases, AML 7 cases) were detected. The possibility of the accumulation of Treg cells being the prognostic marker for acute leukemia was evaluated by comparing the results of Treg cells frequency with that of MRD. Results The percentage of Treg cells in CD+4 CD+3 T cells was M = 8. 09% in normal bone marrows, which was significantly different from the results in the bone marrows of newly diagnosed childhood acute leukemia ( M = 12.77% , U = 3.41, P 0.05).Treg数量与临床病理学参数无显著相关性.此外,Treg数量在MRD阳性组(M=14.74%)与MRD持续阴性组(M=11.3%)中的差异有统计学意义(t=252.5,P<0.05).结论 白血病初发患儿体内的Treg数量显著增高,且患儿中Treg表达水平与MRD有关联.高水平Treg预示白血病患儿预后较差,存在复发的可能.

  19. Recent advances in the diagnosis and management of childhood acute promyelocytic leukemia

    Directory of Open Access Journals (Sweden)

    Eun Sun Yoo

    2011-03-01

    Full Text Available Since the successful introduction of all-trans-retinoic acid (ATRA and its combination with anthracycline-containing chemotherapy, the prognosis for acute promyelocytic leukemia (APL has markedly improved. With ATRA and anthracycline-based-chemotherapy, the complete remission rate is greater than 90%, and the long-term survival rate is 70&#8210;89%. Moreover, arsenic trioxide (ATO, which was introduced for APL treatment in 1994, resulted in excellent remission rates in relapsed patients with APL, and more recently, several clinical studies have been designed to explore its role in initial therapy either alone or in combination with ATRA. APL is a rare disease in children and is frequently associated with hyperleukocytosis, which is a marker for higher risk of relapse and an increased incidence of microgranular morphology. The frequency of occurrence of the promyelocytic leukemia/ retinoic acid receptor-alpha (PML/RAR?#6752;isoforms bcr 2 and bcr 3 is higher in children than in adults. Although recent clinical studies have reported comparable long-term survival rates in patients with APL, therapy for APL in children is challenging because of the risk of early death and the potential long-term cardiac toxicity resulting from the need to use high doses of anthracyclines. Additional prospective, randomized, large clinical trials are needed to address several issues in pediatric APL and to possibly minimize or eliminate the need for chemotherapy by combining ATRA and ATO. In this review article, we discuss the molecular pathogenesis, diagnostic progress, and most recent therapeutic advances in the treatment of children with APL.

  20. Health-related quality of life in long-term survivors of relapsed childhood acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Stefan Essig

    Full Text Available BACKGROUND: Relapses occur in about 20% of children with acute lymphoblastic leukemia (ALL. Approximately one-third of these children can be cured. Their risk for late effects is high because of intensified treatment, but their health-related quality of life (HRQOL was largely unmeasured. Our aim was to compare HRQOL of ALL survivors with the general population, and of relapsed with non-relapsed ALL survivors. METHODOLOGY/PRINCIPAL FINDINGS: As part of the Swiss Childhood Cancer Survivor Study (SCCSS we sent a questionnaire to all ALL survivors in Switzerland who had been diagnosed between 1976-2003 at age <16 years, survived ≥5 years, and were currently aged ≥16 years. HRQOL was assessed with the Short Form-36 (SF-36, which measures four aspects of physical health and four aspects of mental health. A score of 50 corresponded to the mean of a healthy reference population. We analyzed data from 457 ALL survivors (response: 79%. Sixty-one survivors had suffered a relapse. Compared to the general population, ALL survivors reported similar or higher HRQOL scores on all scales. Survivors with a relapse scored lower in general health perceptions (51.6 compared to those without (55.8;p=0.005, but after adjusting for self-reported late effects, this difference disappeared. CONCLUSION/SIGNIFICANCE: Compared to population norms, ALL survivors reported good HRQOL, even after a relapse. However, relapsed ALL survivors reported poorer general health than non-relapsed. Therefore, we encourage specialists to screen for poor general health in survivors after a relapse and, when appropriate, specifically seek and treat underlying late effects. This will help to improve patients' HRQOL.

  1. Using a Bayesian hierarchical model for identifying single nucleotide polymorphisms associated with childhood acute lymphoblastic leukemia risk in case-parent triads.

    Directory of Open Access Journals (Sweden)

    Ying Cao

    Full Text Available Childhood acute lymphoblastic leukemia (ALL is a condition that arises from complex etiologies. The absence of consistent environmental risk factors and the presence of modest familial associations suggest ALL is a complex trait with an underlying genetic component. The identification of genetic factors associated with disease is complicated by complex genetic covariance structures and multiple testing issues. Both issues can be resolved with appropriate Bayesian variable selection methods. The present study was undertaken to extend our hierarchical Bayesian model for case-parent triads to incorporate single nucleotide polymorphisms (SNPs and incorporate the biological grouping of SNPs within genes. Based on previous evidence that genetic variation in the folate metabolic pathway influences ALL risk, we evaluated 128 tagging SNPs in 16 folate metabolic genes among 118 ALL case-parent triads recruited from the Texas Children's Cancer Center (Houston, TX between 2003 and 2010. We used stochastic search gene suggestion (SSGS in hierarchical Bayesian models to evaluate the association between folate metabolic SNPs and ALL. Using Bayes factors among these variants in childhood ALL case-parent triads, two SNPs were identified with a Bayes factor greater than 1. There was evidence that the minor alleles of NOS3 rs3918186 (OR = 2.16; 95% CI: 1.51-3.15 and SLC19A1 rs1051266 (OR = 2.07; 95% CI: 1.25-3.46 were positively associated with childhood ALL. Our findings are suggestive of the role of inherited genetic variation in the folate metabolic pathway on childhood ALL risk, and they also suggest the utility of Bayesian variable selection methods in the context of case-parent triads for evaluating the role of SNPs on disease risk.

  2. Early loss of teeth after treatment for childhood leukemia; Fruehzeitiger Zahnverlust nach Leukaemiebehandlung im Kindesalter. Fallbericht und Literaturuebersicht

    Energy Technology Data Exchange (ETDEWEB)

    Herrmann, T.; Doerr, W.; Lesche, A.; Lehmann, D. [Klinik und Poliklinik fuer Strahlentherapie und Radioonkologie, Medizinische Fakultaet der Technischen Univ. Dresden (Germany); Koy, S. [Klinik und Poliklinik fuer Mund-, Kiefer- und Gesichtschirurgie, Medizinische Fakultaet der Technischen Univ. Dresden (Germany)

    2004-06-01

    Background: only few reports of effects of radiotherapy in childhood on the dental apparatus are available in the literature. The basis for early loss of teeth appears to be a reduction of the root surface area after radiation exposure. These effects in the periodontium are a consequence of combined radiochemotherapy usually applied for treatment of childhood neoplasia. Chemotherapy alone also results in changes of periodontal development. Case report: a 33-year-old patient is reported, who, at the age of 11 years, received high-dose chemotherapy and radiotherapy of neuroaxis and cranium for acute lymphatic leukemia with relapse. The patient consulted the Implant Section of the Department of Oral and Maxillofacial Surgery because of severe dental changes and tooth loss despite adequate dental care and oral hygiene. Radiation doses given to the superior maxilla and mandible at the age of 11 were estimated to be in the range of 8-25 Gy. Conclusion: intense, life-long dental care and follow-up of patients cured from malignant disease in childhood must hence be postulated in order to minimize dental treatment sequelae by supportive measures, but also to initiate timely adequate dental and prosthetic management. (orig.)

  3. Combination Chemotherapy With or Without PSC 833, Peripheral Stem Cell Transplantation, and/or Interleukin-2 in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; Adult Acute Erythroid Leukemia (M6); Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Basophilic Leukemia; Childhood Acute Eosinophilic Leukemia; Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monoblastic Leukemia and Acute Monocytic Leukemia (M5); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Tretinoin, Cytarabine, and Daunorubicin Hydrochloride With or Without Arsenic Trioxide Followed by Tretinoin With or Without Mercaptopurine and Methotrexate in Treating Patients With Acute Promyelocytic Leukemia

    Science.gov (United States)

    2013-06-04

    Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  5. Lymphoid Progenitor Cells from Childhood Acute Lymphoblastic Leukemia Are Functionally Deficient and Express High Levels of the Transcriptional Repressor Gfi-1

    Directory of Open Access Journals (Sweden)

    Jessica Purizaca

    2013-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34+ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  6. Lymphoid progenitor cells from childhood acute lymphoblastic leukemia are functionally deficient and express high levels of the transcriptional repressor Gfi-1.

    Science.gov (United States)

    Purizaca, Jessica; Contreras-Quiroz, Adriana; Dorantes-Acosta, Elisa; Vadillo, Eduardo; Arriaga-Pizano, Lourdes; Fuentes-Figueroa, Silvestre; Villagomez-Barragán, Horacio; Flores-Guzmán, Patricia; Alvarado-Moreno, Antonio; Mayani, Hector; Meza, Isaura; Hernandez, Rosaura; Huerta-Yepez, Sara; Pelayo, Rosana

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most frequent malignancy of childhood. Substantial progress on understanding the cell hierarchy within ALL bone marrow (BM) has been recorded in the last few years, suggesting that both primitive cell fractions and committed lymphoid blasts with immature stem cell-like properties contain leukemia-initiating cells. Nevertheless, the biology of the early progenitors that initiate the lymphoid program remains elusive. The aim of the present study was to investigate the ability of lymphoid progenitors from B-cell precursor ALL BM to proliferate and undergo multilineage differentiation. By phenotype analyses, in vitro proliferation assays, and controlled culture systems, the lymphoid differentiation potentials were evaluated in BM primitive populations from B-cell precursor ALL pediatric patients. When compared to their normal counterparts, functional stem and progenitor cell contents were substantially reduced in ALL BM. Moreover, neither B nor NK or dendritic lymphoid-cell populations developed recurrently from highly purified ALL-lymphoid progenitors, and their proliferation and cell cycle status revealed limited proliferative capacity. Interestingly, a number of quiescence-associated transcription factors were elevated, including the transcriptional repressor Gfi-1, which was highly expressed in primitive CD34⁺ cells. Together, our findings reveal major functional defects in the primitive hematopoietic component of ALL BM. A possible contribution of high levels of Gfi-1 expression in the regulation of the stem/progenitor cell biology is suggested.

  7. Space-Time Clustering of Childhood Leukemia: Evidence of an Association with ETV6-RUNX1 (TEL-AML1) Fusion

    Science.gov (United States)

    Lupatsch, Judith E.; Niggli, Felix; Egger, Matthias; Kuehni, Claudia E.; Spycher, Ben D.

    2017-01-01

    Background Many studies have observed space-time clustering of childhood leukemia (CL) yet few have attempted to elicit etiological clues from such clustering. We recently reported space-time clustering of CL around birth, and now aim to generate etiological hypotheses by comparing clustered and nonclustered cases. We also investigated whether the clustering resulted from many small aggregations of cases or from a few larger clusters. Methods We identified cases of persons born and diagnosed between 1985 and 2014 at age 0–15 years from the Swiss Childhood Cancer Registry. We determined spatial and temporal lags that maximized evidence of clustering based on the Knox test and classified cases born within these lags from another case as clustered. Using logistic regression adjusted for child population density, we determined whether clustering status was associated with age at diagnosis, immunophenotype, cytogenetic subtype, perinatal and socioeconomic characteristics, and pollution sources. Results Analyses included 1,282 cases of which 242 were clustered (born within 1 km and 2 years from another case). Of all investigated characteristics only the t(12;21)(p13;q22) translocation (resulting in ETV6-RUNX1 fusion) differed significantly in prevalence between clustered and nonclustered cases (40% and 25%, respectively; adjusted OR 2.54 [1.52–4.23]; p = 0.003). Spatio-temporal clustering was driven by an excess of aggregations of two or three children rather than by a few large clusters. Conclusion Our findings suggest ETV6-RUNX1 is associated with space-time clustering of CL and are consistent with an infection interacting with that oncogene in early life leading to clinical leukemia. PMID:28129329

  8. Study on relationship between ApaI site polymorphism of vitamin D receptor gene and hereditary susceptibility to childhood acute leukemia%维生素D受体基因与儿童急性白血病遗传易感性的关系研究

    Institute of Scientific and Technical Information of China (English)

    郑敏; 罗建明; 何云燕

    2011-01-01

    目的 探讨维生素D受体(VDR)基因ApaI位点多态性与儿童急性白血病遗传易感性的关系.方法 采用聚合酶链限制性片段长度多态性技术和基因测序技术,对127例急性白血病患儿和268例健康儿童的VDR基因ApaI位点多态性进行分析.结果 VDR基因ApaI酶切位点基因型和等位基因的频率在急性白血病患儿和正常儿童之间差异无统计学意义.结论 VDR基因ApaI酶切位点的多态性可能与儿童急性白血病的遗传易感性无关.%Objective To investigate the relationship between Apal site gene polymorphism of vitamin D receptor ( VDR) and hereditary susceptibility to acute childhood leukemia.Methods Polymerase chain reaction restrictive fragment length polymorphism analysis technique and DNA sequencing technology were used to detect polymorphisms of VDR gene Apal locus in 127 children with acute leukemia and 268 healthy children (as controls).Results No significant differences in genotype distribution frequencies and the allele gene distribution frequencies of VDR gene Apal locus were found between the two groups.Conclusions The gene polymorphisms of VDR gene Apal enzyme digestion locus may not be related to genetic susceptibility to acute childhood leukemia.

  9. Biological Therapy in Treating Patients With Advanced Myelodysplastic Syndrome, Acute or Chronic Myeloid Leukemia, or Acute Lymphoblastic Leukemia Who Are Undergoing Stem Cell Transplantation

    Science.gov (United States)

    2017-03-27

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; Essential Thrombocythemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  10. Coping Strategies and Locus of Control in Childhood Leukemia: A Multi-Center Research.

    Science.gov (United States)

    Polizzi, Concetta; Fontana, Valentina; Perricone, Giovanna; D'Angelo, Paolo; Jankovic, Momcilo; Taormina, Calogero; Nichelli, Francesca; Burgio, Sofia

    2015-05-25

    Acute lymphoblastic leukemia (ALL) is a very distressing experience for children and requires a special effort of adjustment. Therefore, it seems to be crucial to explore coping resources for the experienced risk condition. In this sense, the study focuses on coping strategies and locus of control in children with ALL during the treatment phase, and on their possible relation. The correlation between children and maternal coping strategies is also investigated. The participants involved were an experimental group of 40 children with ALL and their mothers, and 30 healthy children as the control group. The tools used were: the Child Behavioral Style Scale and the Monitor-Blunter Style Scale to assess the coping strategies of children and mothers; the locus of Control Scale for Children to analyze the children's perception of controlling the events. Both children with ALL and their mothers resorted to monitoring coping strategies with a statistically significant rate of occurrence (children: M=17.8, SD=3.8; mothers: M=10.48, SD=3.4). The data concerning the locus of control show this tendency towards internal causes (M=53.1, SD=4.7). There were statistically significant correlations between monitoring coping strategies and external locus of control (r=0.400, P<0.05). The results gained from the control group are almost equivalent. The outcomes show several interesting resources of the psychological functioning of children as well as of their mothers.

  11. Coping strategies and locus of control in childhood leukemia: a multi-center research

    Directory of Open Access Journals (Sweden)

    Concetta Polizzi

    2015-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a very distressing experience for children and requires a special effort of adjustment. Therefore, it seems to be crucial to explore coping resources for the experienced risk condition. In this sense, the study focuses on coping strategies and locus of control in children with ALL during the treatment phase, and on their possible relation. The correlation between children and maternal coping strategies is also investigated. The participants involved were an experimental group of 40 children with ALL and their mothers, and 30 healthy children as the control group. The tools used were: the Child Behavioral Style Scale and the Monitor-Blunter Style Scale to assess the coping strategies of children and mothers; the locus of Control Scale for Children to analyze the children’s perception of controlling the events. Both children with ALL and their mothers resorted to monitoring coping strategies with a statistically significant rate of occurrence (children: M=17.8, SD=3.8; mothers: M=10.48, SD=3.4. The data concerning the locus of control show this tendency towards internal causes (M=53.1, SD=4.7. There were statistically significant correlations between monitoring coping strategies and external locus of control (r=0.400, P<0.05. The results gained from the control group are almost equivalent. The outcomes show several interesting resources of the psychological functioning of children as well as of their mothers.

  12. Testicular relapse in childhood acute lymphoblastic leukemia: The challenges and lessons

    Directory of Open Access Journals (Sweden)

    K P Kulkarni

    2010-01-01

    Full Text Available Background : Relapse of disease is documented in 15-20% of children with acute lymphoblastic leukemia (ALL. Although testicular relapse is rare with modern risk-adapted treatment protocols, earlier, the testes were a frequently encountered site of relapse and were designated as "drug sanctuaries". Purpose : This descriptive study was designed to assess the pattern of testicular relapse and to identify high-risk factors. Materials and Methods : Data obtained from case records of 407 boys with ALL were analyzed. Fine needle aspiration cytology was carried out in children presenting with painless enlargement of testi(es. Bone marrow aspiration and cerebrospinal fluid examination were performed concomitantly to confirm or exclude disease at these sites. Results : Testicular relapse was documented in 30 boys. It was isolated in 17 patients and associated with bone marrow and/or central nervous system relapse in 13. At relapse, nine boys were over the age of 10 years. The majority were very early and early relapsers. Hyperleucocytosis was documented in five of 30 and seven of 137 relapsers and nonrelapsers, respectively (P = 0.04. Twelve of the 30 boys with testicular relapse were treated with testicular irradiation, reinduction and maintenance therapy. The estimated median overall survival was 33 months. Conclusion : Testicular relapse, which depends on the therapy administered, may manifest several months/years after completion of treatment. The high incidence of testicular relapse in our series implicates the need of revaluation of our protocol and incorporation of high/intermediate dose methotrexate therapy upfront.

  13. Psychological Impact of Chemotherapy for Childhood Acute Lymphoblastic Leukemia on Patients and Their Parents.

    Science.gov (United States)

    Sherief, Laila M; Kamal, Naglaa M; Abdalrahman, Hadel M; Youssef, Doaa M; Abd Alhady, Mohamed A; Ali, Adel S A; Abd Elbasset, Maha Aly; Hashim, Hiatham M

    2015-12-01

    To assess the self-esteem of pediatric patients on chemotherapy for acute lymphoblastic leukemia (ALL) and psychological status of their parents.The psychological status of 178 children receiving chemotherapy for ALL and their parents was assessed using parenting stress index (PSI) to determine the degree of stress the parents are exposed to using parent's and child's domains. Self-esteem Scale was used to determine the psychological status of patients.The study revealed significant low level of self-esteem in 84.83% of patients. Their parents had significant psychological stress. PSI was significantly associated with parents' low sense of competence, negative attachment to their children, feeling of high restriction, high depression, poor relation to spouse, high social isolation variables of parent's domains. It was significantly associated with low distraction, negative parents' reinforcement, low acceptability, and high demanding variables of child's domains. Long duration of disease was the most detrimental factor among demographic data of the patients.Chemotherapy for ALL has a significant impact on the psychological status of both patients and their parents with high prevalence of low self-esteem in children and high degree of stress in their parents.

  14. An adult patient who developed malignant fibrous histiocytoma 9 years after radiation therapy for childhood acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kato, Yasuhiro [National Hiroshima Hospital, Higashi-Hiroshima (Japan); Ohno, Norioki; Horikawa, Yoko; Nishimura, Shin-ichiro; Ueda, Kazuhiro; Shimose, Shoji [Hiroshima Univ. (Japan). School of Medicine

    2002-12-01

    A 24-year-old Japanese man with a history of acute lymphoblastic leukemia, which occurred during childhood, developed malignant fibrous histiocytoma of his left knee. His past history revealed that he had undergone leukemic blast cell invasion of the left knee and subsequent radiation therapy 9 years ago. The total radiation doses for the upper part of the left tibia and the lower part of the left femur were 60 Gy and 40 Gy, respectively. Neither distant metastasis nor a relapse of leukemia occurred. A curative resection of the left femur with a noninvasive margin was performed. Adjuvant chemotherapy including high-dose methotrexate was given successfully before and after surgery; this was followed by relapse-free survival for 3 years. The nature of postirradiation malignant fibrous histiocytoma is highly aggressive. When a patient complains of persistent symptoms in a previously irradiated field, the possibility of this tumor must be taken into account. The importance of early diagnosis cannot be over-emphasized. (author)

  15. Pubertal development and fertility in survivors of childhood acute myeloid leukemia treated with chemotherapy only

    DEFF Research Database (Denmark)

    Molgaard-Hansen, Lene; Skou, Anne-Sofie; Juul, Anders

    2013-01-01

    More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings.......More than 60% of children with acute myeloid leukemia (AML) become long-term survivors. Most are cured using chemotherapy without hematopoietic stem cell transplantation (HSCT). We report on pubertal development and compare self-reported parenthood among AML survivors and their siblings....

  16. Improved flow cytometric detection of minimal residual disease in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Denys, B.; van der Sluijs-Gelling, A. J.; Homburg, C.; van der Schoot, C. E.; de Haas, V.; Philippe, J.; Pieters, R.; van Dongen, J. J. M.; van der Velden, V. H. J.

    2013-01-01

    Most current treatment protocols for acute lymphoblastic leukemia (ALL) include minimal residual disease (MRD) diagnostics, generally based on PCR analysis of rearranged antigen receptor genes. Although flow cytometry (FCM) can be used for MRD detection as well, discordant FCM and PCR results are ob

  17. Chemotherapy-Related Side Effects in Childhood Acute Lymphoblastic Leukemia in Indonesia: Parental Perceptions

    NARCIS (Netherlands)

    Sitaresmi, M.N.; Mostert, S.; Purwanto, I.; Gundy, C.; Sutaryo, N.N.; Veerman, A.J.P.

    2009-01-01

    Noncompliance with prescribed medication has been associated with increased chance of relapse and poor outcome. Side effects may be an important cause of noncompliance. Fifty-one parents of children with acute lymphoblastic leukemia in a tertiary care hospital in Indonesia were interviewed about the

  18. Hypothalamic-pituitary-adrenal axis function in survivors of childhood acute lymphoblastic leukemia and healthy controls.

    NARCIS (Netherlands)

    Gordijn, M.S.; Litsenburg, R.R. van; Gemke, R.J.; Bierings, M.B.; Hoogerbrugge, P.M.; Ven, P.M. van de; Heijnen, C.J.; Kaspers, G.J.L.

    2012-01-01

    Of all malignancies in children, acute lymphoblastic leukemia (ALL) is the most common type. Since survival significantly improves over time, treatment-related side effects become increasingly important. Glucocorticoids play an important role in the treatment of ALL, but they may suppress the hypoth

  19. Hyperglycemia during induction therapy is associated with increased infectious complications in childhood acute lymphocytic leukemia

    Science.gov (United States)

    Children with acute lymphocytic leukemia (ALL) are at high risk for developing hyperglycemia. Hyperglycemic adult ALL patients have shorter remissions, more infections, and increased mortality. No corresponding data are available in children. We hypothesized that children with ALL who become hypergl...

  20. Reduced folate carrier mutations are not the mechanism underlying methotrexate resistance in childhood acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Kaufman, Y; Drori, S.; Cole, PD; Kamen, BA; Sirota, J; Ifergan, I; Arush, MW; Elhasid, R; Sahar, D; Kaspers, G.J.L.; Jansen, G.; Matherly, LH; Rechavi, G; Toren, A; Assaraf, Y.G.

    2004-01-01

    BACKGROUND: Although the majority of children with acute lymphoblastic leukemia (ALL) are cured with combination chemotherapy containing methotrexate (MTX), drug resistance contributes to treatment failure for a substantial fraction of patients. The primary transporter for folates and MTX is the red

  1. Endocrine Effects of the Treatment for Acute Lymphoblastic Leukemia and Hodgkin’s Lymphoma in Childhood

    NARCIS (Netherlands)

    R.D. van Beek (Robert Diederik)

    2010-01-01

    textabstractOne quarter of all cases of pediatric malignancies is acute Lymphoblastic leukemia (ALL). Per year approximately 4 in 100.000 children are diagnosed with ALL. The disease has a peak incidence between the third and sixth year of life. Predisposing factors for ALL are Down syndrome, Fancon

  2. Hairy Cell Leukemia Treatment Option Overview

    Science.gov (United States)

    ... Childhood ALL Treatment Childhood AML Treatment Research Hairy Cell Leukemia Treatment (PDQ®)–Patient Version General Information About Hairy Cell Leukemia Go to Health Professional Version Key Points ...

  3. Caspofungin Acetate or Fluconazole in Preventing Invasive Fungal Infections in Patients With Acute Myeloid Leukemia Who Are Undergoing Chemotherapy

    Science.gov (United States)

    2017-01-31

    Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Minimally Differentiated Myeloid Leukemia (M0); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Minimally Differentiated Myeloid Leukemia (M0); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Fungal Infection; Neutropenia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  4. Combination Chemotherapy With or Without Bone Marrow Transplantation in Treating Children With Acute Myelogenous Leukemia or Myelodysplastic Syndrome

    Science.gov (United States)

    2013-01-15

    Childhood Acute Erythroleukemia (M6); Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myelomonocytic Leukemia (M4); Childhood Myelodysplastic Syndromes; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Secondary Myelodysplastic Syndromes; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  5. Pregnancy, Maternal Tobacco Smoking, and Early Age Leukemia in Brazil

    OpenAIRE

    2012-01-01

    Background: Cigarette smoking has been associated with acute myeloid leukemia but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia is unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (< 2 yr.) leukemia (EAL). Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999-2007. Data were collected by ...

  6. Probability estimates for the unique childhood leukemia cluster in Fallon, Nevada, and risks near other U.S. Military aviation facilities.

    OpenAIRE

    2004-01-01

    A unique cluster of childhood leukemia has recently occurred around the city of Fallon in Churchill County, Nevada. From 1999 to 2001, 11 cases were diagnosed in this county of 23,982 people. Exposures related to a nearby naval air station such as jet fuel or an infectious agent carried by naval aviators have been hypothesized as potential causes. The possibility that the cluster could be attributed to chance was also considered. We used data from the Surveillance, Epidemiology, and End Resul...

  7. Methotrexate resistance in relation to treatment outcome in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Wojtuszkiewicz, Anna; Peters, Godefridus J; van Woerden, Nicole L;

    2015-01-01

    BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblastic...... leukemia (ALL). However, drug resistance phenomena pose major obstacles to efficacious ALL chemotherapy. Moreover, clinically relevant molecular mechanisms underlying chemoresistance remain largely obscure. Several alterations in MTX metabolism, leading to impaired accumulation of this cytotoxic agent...

  8. Gemtuzumab Ozogamicin in Treating Patients With Relapsed or Refractory Acute Myeloid Leukemia or Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-26

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Adult Acute Promyelocytic Leukemia (M3); Childhood Acute Promyelocytic Leukemia (M3); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  9. Prognostic significance of bi/oligoclonality in childhood acute lymphoblastic leukemia as determined by polymerase chain reaction

    Directory of Open Access Journals (Sweden)

    Carlos Alberto Scrideli

    2001-09-01

    Full Text Available CONTEXT: The CDR-3 region of heavy-chain immunoglobulin has been used as a clonal marker in the study of minimal residual disease in children with acute lymphoblastic leukemia. Southern blot and polymerase chain reaction studies have demonstrated the occurrence of bi/oligoclonality in a variable number of cases of B-lineage acute lymphoblastic leukemia, a fact that may strongly interfere with the detection of minimal residual disease. Oligoclonality has also been associated with a poorer prognosis and a higher chance of relapse. OBJECTIVES: To correlate bi/oligoclonality, detected by polymerase chain reaction in Brazilian children with B-lineage acute lymphoblastic leukemia with a chance of relapse, with immunophenotype, risk group, and disease-free survival. DESIGN: Prospective study of patients’ outcome. SETTING: Pediatric Oncology Unit of the University Hospital, Faculty of Medicine of Ribeirão Preto, University of São Paulo. PARTICIPANTS: 47 children with acute lymphoblastic leukemia DIAGNOSTIC TEST: Polymerase chain reaction using consensus primers for the CDR-3 region of heavy chain immunoglobulin (FR3A, LJH and VLJH for the detection of clonality. RESULTS: Bi/oligoclonality was detected in 15 patients (31.9%. There was no significant difference between the groups with monoclonality and biclonality in terms of the occurrence of a relapse (28.1% versus 26.1%, presence of CALLA+ (81.2% versus 80% or risk group (62.5% versus 60%. Disease-free survival was similar in both groups, with no significant difference (p: 0.7695. CONCLUSIONS: We conclude that bi/oligoclonality was not associated with the factors investigated in the present study and that its detection in 31.9% of the patients may be important for the study and monitoring of minimal residual disease.

  10. A multiple-center clinical study on the therapy for childhood acute lymphoblastic leukemia by using GZ-2002 ALL protocol%GZ-2002急性淋巴细胞白血病化疗方案治疗非高危儿童急性淋巴细胞白血病多中心协作临床研究

    Institute of Scientific and Technical Information of China (English)

    方建培; 林愈灯; 柯志勇; 赵玉红; 何岳林; 甄子俊; 何政贤; 周敦华; 官晓清; 张玉明; 何丽雅; 罗学群; 黄绍良; 屠立明; 赖冬波; 吴学东; 孙晓菲; 陈健良; 李志光; 陈纯

    2011-01-01

    Objective To investigate the possibility of multiple-center cooperation on chemotherapy for childhood leukemia, and explore new strategies of enhancing the cure rate of childhood leukemia in Guangzhou, China. Methods Seven main hospitals in Guangzhou attended in our study group, and the Wales Hospital of HongKong Chinese University attended as a consultant. One person was appointed to be in charge of the therapeutic work in each hospital, and another full-time administrator took charge of all the records. All the patients enrolled in the standard risk (SR) group or interim risk (IR) group according to the diagnosis standards were treated with GZ-2002 ALL protocol. The material records were sorted out and analyzed. A discussion meeting was held among our members of the group twice a year.Results Six hundred and seventeen cases were initially enrolled in the seven hospitals from Oct. of 2002 to June of 2009. The children were diagnosed as ALL according to the GZ-2002ALL chemotherapy regimen. All cases were classified into SR, IR, and HR regarding cytomorphology (M), immunology (I), and cytogenetics (C) and response to the first chemotherapy. A total of 446 patients were included in the research and treated with the GZ-BFM2002ALL chemotherapy regimen. They consisted of 227 males and 169 females, ranging in age from one to 14 years, with an average of 6 years. The GZ-2002ALL chemotherapy regimen was established based on the ALLIC-BFM2002 regimen. The regimen lasted for 104 weeks, consisting of induction, consolidation, re-induction and maintenance. The total complete remission rate in induction of SR or IR was 99.8% (445/446). The 3-year EFS was (90.5 ±5.0) % and the 5-year EFS was ( 82.0 ± 4.0) % in the SR group, while they were respectively ( 88.0 ± 6.0) % and (78.0 ± 5.0)% in the IR group. There was a statistically significant difference between groups by Log-rank test (P < 0.05). Four hundred and thirteen ALL children were followed up, accounting

  11. ARID5B Genetic Polymorphisms Contribute to Racial Disparities in the Incidence and Treatment Outcome of Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Xu, Heng; Cheng, Cheng; Devidas, Meenakshi; Pei, Deqing; Fan, Yiping; Yang, Wenjian; Neale, Geoff; Scheet, Paul; Burchard, Esteban G.; Torgerson, Dara G.; Eng, Celeste; Dean, Michael; Antillon, Frederico; Winick, Naomi J.; Martin, Paul L.; Willman, Cheryl L.; Camitta, Bruce M.; Reaman, Gregory H.; Carroll, William L.; Loh, Mignon; Evans, William E.; Pui, Ching-Hon; Hunger, Stephen P.; Relling, Mary V.; Yang, Jun J.

    2012-01-01

    Purpose Recent genome-wide screens have identified genetic variations in ARID5B associated with susceptibility to childhood acute lymphoblastic leukemia (ALL). We sought to determine the contribution of ARID5B single nucleotide polymorphisms (SNPs) to racial disparities in ALL susceptibility and treatment outcome. Patients and Methods We compared the association between ARID5B SNP genotype and ALL susceptibility in whites (> 95% European genetic ancestry; 978 cases and 1,046 controls) versus in Hispanics (> 10% Native American ancestry; 330 cases and 541 controls). We determined the relationships between ARID5B SNP genotype and ALL relapse risk in 1,605 children treated on the Children's Oncology Group (COG) P9904/9905 clinical trials. Results Among 49 ARID5B SNPs interrogated, 10 were significantly associated with ALL susceptibility in both whites and Hispanics (P < .05), with risk alleles consistently more frequent in Hispanics than in whites. rs10821936 exhibited the most significant association in both races (P = 8.4 × 10−20 in whites; P = 1 × 10−6 in Hispanics), and genotype at this SNP was highly correlated with local Native American genetic ancestry (P = 1.8 × 10−8). Multivariate analyses in Hispanics identified an additional SNP associated with ALL susceptibility independent of rs10821936. Eight ARID5B SNPs were associated with both ALL susceptibility and relapse hazard; the alleles related to higher ALL incidence were always linked to poorer treatment outcome and were more frequent in Hispanics. Conclusion ARID5B polymorphisms are important determinants of childhood ALL susceptibility and treatment outcome, and they contribute to racial disparities in this disease. PMID:22291082

  12. Incidence of childhood leukemia around French nuclear sites between 1990 and 1998;Incidence des leucemies de l'enfant aux alentours des sites nucleaires francais entre 1990 et 1998

    Energy Technology Data Exchange (ETDEWEB)

    White-Koning, M.; Hemon, D.; Goubin, A.; Clavel, J. [Inserm-U754, 94 - Villejuif (France); Laurier, D.; Tirmarche, M. [Institut de Radioprotection et de Surete Nucleaire, 92 - Fontenay aux Roses (France); Jougla, E. [Institut National de la Sante et de la Recherche Mrdicale Inserm-CepiDc, 78 - Le Vesinet (France)

    2006-01-15

    The works presented here constitute the first systematic study of the incidence of childhood leukemia around the whole of French nuclear facilities. Globally, the incidence of childhood leukemia does not diverge significantly of the expected incidence during the period 1990-1998. It does not show a decrease of S.I.R. (standardized incidence ratio) in function of the distance from child's home to the nuclear site whatever be the age. This study represents the first analysis of the incidence of leukemia focusing on 29 French nuclear sites, including the whole of the 19 C.N.P.E. ( nuclear power plants that produce electric power), and is based on incidence data rather than mortality. The period, the age groups and the studied area have been all chosen a priori, that gives a statistical validity to the results. The estimation of population at risk have been made with several different methods of interpolation in order to check the stability of estimations. The different methods of statistical analysis used have lead to extremely close results, reinforcing our confidence in the reliability of our estimations. The excess of leukemia incidence observed at Chinon and Civaux and the deficit observed at Bruyere/Saclay/Fontenay loose their statistical significance when the correction of Bonferroni is applied. So, the global analysis of the 29 sites and the analysis by site have not shown statistically significant difference between the numbers of observed and expected cases. The study of the 19 C.N.P.E. gave same results, even in taken into account their electric power or their year of service. The possibility of confounding factors has been excluded. The power of the study to detect excess incidence and a decrease of S.I.R. with distance from the site was examined under different alternative hypotheses through simulation methods. For values of S.I.R. near the site (0-5 km) between 1.5 and 2 and a risk of error of 5%, the power of the study is between 96% and 100

  13. Prognostic value of MRD-dynamics in childhood acute lymphoblastic leukemia treated according to the MB-2002/2008 protocols.

    Science.gov (United States)

    Meleshko, Alexander N; Savva, Natalia N; Fedasenka, Uladzimir U; Romancova, Alexandra S; Krasko, Olga V; Eckert, Cornelia; von Stackelberg, Arend; Aleinikova, Olga V

    2011-10-01

    Detection of minimal residual disease (MRD) during the treatment of acute lymphoblastic leukemia (ALL) by RQ-PCR analysis of clonal Ig/TCR rearrangements is used for risk group stratification in European treatment protocols. In Belarus patients with childhood ALL are treated according to ALL-MB protocols, which do not use MRD-based risk stratification. To evaluate the prognostic significance of MRD for ALL-MB-2002/2008 protocols, MRD was quantified by RQ-PCR in 68 ALL patients at four time points: on day 15, on day 36, before and after maintenance therapy (MT). MRD positivity, as well as quantitative level of MRD were analyzed and compared between patients who stayed in remission and relapsed. Relapse-free survival revealed to be significantly associated with MRD levels at different time points. Unfavorable prognosis was shown for MRD≥10(-3) on day 36 (pPCR in children with ALL treated with ALL-MB protocols is feasible and independently associated with outcome. MRD may be a suitable parameter for treatment stratification in MB protocols in future.

  14. Improving risk stratification of patients with childhood acute lymphoblastic leukemia: Glutathione-S-Transferases polymorphisms are associated with increased risk of relapse

    Science.gov (United States)

    Riccheri, María C.; Nuñez, Myriam; Alfonso, Graciela; Gueron, Geraldine; De Siervi, Adriana; Vazquez, Elba; Cotignola, Javier

    2017-01-01

    The inclusion of genotype at Acute Lymphoblastic Leukemia (ALL) diagnosis as a genetic predictor of disease outcome is under constant study. However, results are inconclusive and seem to be population specific. We analyzed the predictive value of germline polymorphisms for childhood ALL relapse and survival. We retrospectively recruited 140 Argentine patients with de novo ALL. Genotypes were analyzed using PCR-RFLP (GSTP1 c.313A > G, MDR1 c.3435T > C, and MTHFR c.665C > T) and multiplex PCR (GSTT1 null, GSTM1 null). Patients with the GSTP1 c.313GG genotype had an increased risk for relapse in univariate (OR = 2.65, 95% CI = 1.03–6.82, p = 0.04) and multivariate (OR = 3.22, 95% CI = 1.17–8.83, p = 0.02) models. The combined genotype slightly increased risk for relapse in the univariate (OR = 2.82, 95% CI = 1.09–7.32, p = 0.03) and multivariate (OR = 2.98, 95% CI = 1.14–7.79, p = 0.03) models for patients with 2/3-risk-genotypes (GSTT1 null, GSTM1 null, GSTP1 c.313GG). The Recurrence-Free Survival (RFS) was shorter for GSTP1 c.313GG (p = 0.025) and 2/3-risk-genotypes (p = 0.021). GST polymorphisms increased the risk of relapse and RFS of patients with childhood ALL. The inclusion of these genetic markers in ALL treatment protocols might improve risk stratification and reduce the number of relapses and deaths. PMID:27058755

  15. Progress of Studies on Genetics of Childhood Acute Leukemia——Review%儿童急性白血病遗传学研究进展

    Institute of Scientific and Technical Information of China (English)

    岳志霞; 郑胡镛

    2013-01-01

    This study on determination of leukemia-specific chromosomal abnormalities and their relationship with prognosis of childhood acute leukemia(AL) had an important significance for childhood acute leukemia.In recent years,the efficacy of treatment of childhood AL has been greatly improved,but relapse is still a main factor affecting prognosis.Treatment based on the risk stratification by cytogenetic abnormalities can improve the prognosis and survival rate.In the past 3 decades,the genetic techniques have developed rapidly and many new genetic abnormalities have been found.This review highlights the main chromosomal and genomic abnormalities of 3 common childhood AL,including B-cell precursor acute lymphoblastic leukemia(BCP-ALL),T-cell acute lymphoblastic leukemia(T-ALL) and acute myeloid leukemia(AML).%白血病特异染色体异常的确定及其与预后关系的研究对儿童急性白血病(acute leukemia,AL)具有极其重要的意义.近年来,虽然儿童AL的治疗效果有了很大改善,但其复发仍然是影响预后的主要因素.根据遗传学异常进行危险度分层,并指导治疗,可以改善儿童AL预后,提高患儿生存率.在过去的30年中,遗传学检测技术有了突飞猛进的发展,发现了许多新的遗传学异常.本文就三种儿童常见AL,包括前B细胞急性淋巴细胞白血病(B-cell precursor acute lymphoblastic leukemia,BCP-ALL)、T细胞急性淋巴细胞白血病(T-cell acute lymphoblastic leukemia,T-ALL)和急性髓系白血病(acute myeloid leukemia,AML)的最新遗传学研究进展进行综述.

  16. [Long-term survival in childhood acute lymphocitic leukemia (author's transl)].

    Science.gov (United States)

    González-Martín, M C; Muñóz Villa, A; García-Miguel, P; Herrero Díez, A; Hurtado Ruano, T; Fernández Epifanio, J L

    1978-01-01

    Long-term results in the treatment of 116 patients of acute lymphocitic leukemia with ages between six months and seven years are reported. A first group A, formed by 76 patients, was treated with prednisone and vincristine as induction protocol and maintenance therapy with 6-mercaptopurine or methotrexate. No neuromeningeal prophylaxis was made, except some cases in which intratecal methotrexate was applied. 27 patients are alive, 21 of them (27,6%) remain in complete remission for more than three years. A second group B, formed by 40 patients, was treated more recently; with an induction protocol composed by prednisone, vincristine and L-asparaginase. All patients in this group received cranial irradiation and intratecal methotrexate. 31 patients are alive (77,5%), 13 of them (32,5%) remain in complete remission for more than two years. The evolution period in this group B is shorter, but some features are exposed which suggest the possibility of long-term better results.

  17. Long-term outcome of childhood absence epilepsy : Dutch Study of Epilepsy in Childhood

    NARCIS (Netherlands)

    Callenbach, Petra M. C.; Bouma, Paul A. D.; Geerts, Ada T.; Arts, Willem Frans M.; Stroink, Hans; Peeters, Els A. J.; van Donselaar, Cees A.; Peters, A. C. Boudewijn; Brouwer, Oebele F.

    2009-01-01

    We determined long-term outcome and the predictive value of baseline and EEG characteristics on seizure activity evolution in 47 children with newly diagnosed childhood absence epilepsy (CAE) included in the Dutch Study of Epilepsy in Childhood. All children were followed for 12-17 years. The childr

  18. Studies on childhood diabetes mellitus

    NARCIS (Netherlands)

    G.J. Bruining

    1984-01-01

    textabstractThis thesis consists of a number of collaborative studies aimed at the improvement of the diagnosis and care of children with diabetes mellitus. For the reader, who is not familiar with medical problems, a brief account is given of the clinical "behavior" of the disease ( 1) . It is perh

  19. Identification of residual leukemic cells by flow cytometry in childhood B-cell precursor acute lymphoblastic leukemia: verification of leukemic state by flow-sorting and molecular/cytogenetic methods

    OpenAIRE

    2012-01-01

    Reduction in minimal residual disease, measured by real-time quantitative PCR or flow cytometry, predicts prognosis in childhood B-cell precursor acute lymphoblastic leukemia. We explored whether cells reported as minimal residual disease by flow cytometry represent the malignant clone harboring clone-specific genomic markers (53 follow-up bone marrow samples from 28 children with B-cell precursor acute lymphoblastic leukemia). Cell populations (presumed leukemic and non-leukemic) were flow-s...

  20. Residential pesticides and childhood leukemia: a systematic review and meta-analysis Pesticidas residenciais e leucemia na infância: revisão sistemática e meta-análise

    Directory of Open Access Journals (Sweden)

    Michelle C. Turner

    2011-03-01

    Full Text Available It is a systematic review and meta-analysis of previous observational epidemiologic studies examining the relationship between residential pesticide exposures during critical exposure time windows (preconception, pregnancy, and childhood and childhood leukemia. Searches of Medline and other electronic databases were performed (1950-2009. Study selection, data abstraction, and quality assessment were performed by two independent reviewers. Random effects models were used to obtain summary odds ratios (ORs and 95% confidence intervals (Cis. Of the 17 identified studies, 15 were included in the meta-analysis. Exposures during pregnancy to unspecified residential pesticides insecticides, and herbicides were positively associated with childhood leukemia. Exposures during childhood to unspecified residential pesticides and insecticides were also positively associated with childhood leukemia, but there was no association with herbicides. Positive associations were observed between childhood leukemia and residential pesticide exposures. Further work is needed to confirm previous findings based on self-report, to examine potential exposure-response relationships, and to assess specific pesticides and toxicologically related subgroups of pesticides in more detail.Trata-se de uma revisão sistemática e meta-análise de estudos epidemiológicos observacionais anteriores que examinaram a relação entre a exposição de pesticidas residenciais durante as janelas de exposição crítica do tempo (pré-concepção, gravidez e infância e leucemia infantil. Foram realizadas pesquisas de dados em diversas bases de dados eletrônicas como Medline e outras. Dois revisores independentes realizaram o estudo de seleção, abstração de dados e avaliação da qualidade. Foram utilizados modelos de efeitos aleatórios para obtenção de razões chances (odds ratio e intervalos de confiança de 95% (IC. Dos 17 estudos identificados, 15 foram incluídos na meta

  1. Integration of high-resolution methylome and transcriptome analyses to dissect epigenomic changes in childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Busche, Stephan; Ge, Bing; Vidal, Ramon; Spinella, Jean-François; Saillour, Virginie; Richer, Chantal; Healy, Jasmine; Chen, Shu-Huang; Droit, Arnaud; Sinnett, Daniel; Pastinen, Tomi

    2013-07-15

    B-cell precursor acute lymphoblastic leukemia (pre-B ALL) is the most common pediatric cancer. Although the genetic determinants underlying disease onset remain unclear, epigenetic modifications including DNA methylation are suggested to contribute significantly to leukemogenesis. Using the Illumina 450K array, we assessed DNA methylation in matched tumor-normal samples of 46 childhood patients with pre-B ALL, extending single CpG-site resolution analysis of the pre-B ALL methylome beyond CpG-islands (CGI). Unsupervised hierarchical clustering of CpG-site neighborhood, gene, or microRNA (miRNA) gene-associated methylation levels separated the tumor cohort according to major pre-B ALL subtypes, and methylation in CGIs, CGI shores, and in regions around the transcription start site was found to significantly correlate with transcript expression. Focusing on samples carrying the t(12;21) ETV6-RUNX1 fusion, we identified 119 subtype-specific high-confidence marker CpG-loci. Pathway analyses linked the CpG-loci-associated genes with hematopoiesis and cancer. Further integration with whole-transcriptome data showed the effects of methylation on expression of 17 potential drivers of leukemogenesis. Independent validation of array methylation and sequencing-derived transcript expression with Sequenom Epityper technology and real-time quantitative reverse transcriptase PCR, respectively, indicates more than 80% empirical accuracy of our genome-wide findings. In summary, genome-wide DNA methylation profiling enabled us to separate pre-B ALL according to major subtypes, to map epigenetic biomarkers specific for the t(12;21) subtype, and through a combined methylome and transcriptome approach to identify downstream effects on candidate drivers of leukemogenesis.

  2. Alisertib in Treating Young Patients With Recurrent or Refractory Solid Tumors or Leukemia

    Science.gov (United States)

    2016-07-20

    Hepatoblastoma; Previously Treated Childhood Rhabdomyosarcoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Kidney Neoplasm; Recurrent Childhood Malignant Germ Cell Tumor; Recurrent Childhood Rhabdomyosarcoma; Recurrent Childhood Soft Tissue Sarcoma; Recurrent Ewing Sarcoma/Peripheral Primitive Neuroectodermal Tumor; Recurrent Neuroblastoma; Recurrent Osteosarcoma

  3. Identification of a novel molecular partner of the E2A gene in childhood leukemia.

    Science.gov (United States)

    Brambillasca, F; Mosna, G; Colombo, M; Rivolta, A; Caslini, C; Minuzzo, M; Giudici, G; Mizzi, L; Biondi, A; Privitera, E

    1999-03-01

    The 'promiscuous' E2A gene, at 19p13.3, is fused with two different molecular partners, PBX1 and HLF, following two chromosome translocations recurrent in childhood pre-B ALL. We have identified a novel gene, FB1, by virtue of its fusion with E2A and by a combination of molecular techniques. FB1 was localized on 19q13.4, suggesting that the novel chimera originated by a cryptic rearrangement of chromosome 19. Two FB1 transcripts, of 1.2 kb and 1.1 kb, are differentially expressed at low level in a variety of human tissues, including hemopoietic cell lines from different lineages. Accordingly, FB1 cDNA displays high homology with a number of cDNA clones from different human tissues. High homology was found also with cDNA clones from mouse and rat, suggesting that the sequence might be conserved at least among mammals. The function of the putative FB1 protein, however, is currently unknown as database sequence comparisons have failed to reveal strong homology with known proteins. The E2A/FB1 fusion appears to be a recurrent feature of pre-B ALLs, suggesting that it might have a role in the development and/or progression of leukemogenesis.

  4. Study Gaps Relevant to Use of Complementary Medicine in Patients With Leukemia: A Review Study

    Directory of Open Access Journals (Sweden)

    Miladinia

    2016-04-01

    Full Text Available Context A review of the literature of recent decades has shown that few studies have been conducted on the effects of various types of complementary medicine on patients with leukemia. Therefore, the present study aimed to find research gaps in the use of different types of complementary medicine in patients with leukemia to be applied in future studies. Evidence Acquisition The present study was a review-type design based on a review of the literature on different types of complementary medicine in patients with leukemia, up to 2015. The search was conducted through electronic databases and search engines. According to the inclusion and exclusion criteria, 8 studies which had been conducted on the use of complementary medicine in patients with leukemia were selected for the identification of gaps. Results The overall results showed that few studies have been conducted on the use of exercise, massage therapy, music therapy, acupressure, and healing touch in patients with leukemia, and these subjects are potential research areas for many different studies. However, no studies have been carried out on the effects of acupuncture, relaxation, and yoga on these patients. Conclusions The results of this review showed that the number of studies on the use of complementary medicine in leukemia patients is very limited (especially in Iran, and it can be the subject of numerous studies in the future.

  5. Garlic compounds selectively kill childhood pre-B acute lymphoblastic leukemia cells in vitro without reducing T-cell function: Potential therapeutic use in the treatment of ALL

    Directory of Open Access Journals (Sweden)

    Greg Hodge

    2008-03-01

    Full Text Available Greg Hodge1, Stephen Davis2, Michael Rice1, Heather Tapp1, Ben Saxon1, Tamas Revesz11Haematology/Oncology Department, Women’s and Children’s Hospital, North Adelaide, Australia; 2Department of Mycology, Women’s and Children’s Hospital, North Adelaide, AustraliaAbstract: Drugs used for remission induction therapy for childhood precursor-B acute lymphoblastic leukemia (ALL are nonselective for malignant cells. Several garlic compounds have been shown to induce apoptosis of cancer cells and to alter lymphocyte function. To investigate the effect of garlic on the apoptosis of ALL cells and lymphocyte immune function, cells from newly diagnosed childhood ALL patients were cultured with several commonly used chemotherapeutic agents and several garlic compounds. Apoptosis, lymphocyte proliferation and T-cell cytokine production were determined using multiparameter flow cytometry. At concentrations of garlic compounds that did not result in significant increases in Annexin V and 7-AAD staining of normal lymphocytes, there was a significant increase in apoptosis of ALL cells with no alteration of T-cell proliferation as determined by CD25/CD69 upregulation or interferonγ, interleukin-2 or tumor necrosis factor-α intracellular cytokine production. In contrast, the presence of chemotherapeutic agents resulted in nonselective increases in both lymphocyte and ALL apoptosis and a decrease in T-cell proliferation and cytokine production. In conclusion, we show selective apoptosis of malignant cells by garlic compounds that do not alter T-cell immune function and indicate the potential therapeutic benefit of garlic compounds in the treatment of childhood ALL.Keywords: childhood precursor-B acute lymphoblastic leukemia, garlic, apoptosis, immune function, intracellular cytokines

  6. The clinical importance of myeloid antigen coexpression and TEL-AML1 mutation in patients with childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ayşen Türedi Yıldırım

    2013-03-01

    Full Text Available Objective: In this study, we aim to investigate the relationship,if any, between clinical features, prognosis, and thecoexpressions and TEL-AML1 mutation in patients withacute lymphoblastic leukemia (ALL.Methods: Eigthy-three patients with acute lymphoblasticleukemia were retrospectively examined. Age, gender,White blood cell count, hemoglobin level, platelet count,ALL subtypei (B or T ALL, risk groups, surface antigensdeteceted by flow cytometry, existence of TEL-AML1 mutations,response, remission and relapse status at 8., 15.ve 33. Days of treatment were recorded and analyzed.Results: 15 (18% out of 83 were identified with aberrantantigen expression. Of these patients, twelve (14.4%had myeloid antigen coexpression (CD13 and/or CD33,two with B cell ALL had CD2 and CD7 coexpressions respectively,one with T cell ALL had CD19 coexpression.No significant differences were found between patientswith and without myeloid antigen coexpression in terms ofhemoglobin levels, white blood cells and platelet counts,responses given on the 8th, 15th, and 30th days on the treatment,risk groups, and relapse (p>0.05. Myeloid antigencoexpression was found in 4 of 13 patients who were identifiedwith TEL-AML1 mutation. No significant relationshipwas found between this mutation and coexpressions. Norelapse and exitus were observed in four patients with coexpressionand TEL-AML1.Conclusion: The prognosis and clinical features showsno statistically significant relationship with the presence ofneither Myeloid antigen expression nor TEL-AML1 mutation.We believe, however, the future studies involving biggersample sizes will prove to be useful in terms of moreconvincing results. J Clin Exp Invest 2013; 4(1: 90-94Key words: Acute lenfoblastic leukemia, coexpression,TEL-AML1 mutation, prognosis

  7. Writing and Publishing Qualitative Studies in Early Childhood Education

    Science.gov (United States)

    Saracho, Olivia N.

    2017-01-01

    When a study is published in a respected professional journal, it not only verifies that the research has been completed but also that it has been subjected to anonymous peer review. Published results from studies in early childhood education contribute to the field's knowledge and provide direction to guide future early childhood education…

  8. Pain in long-term adult survivors of childhood cancers and their siblings: a report from the Childhood Cancer Survivor Study.

    Science.gov (United States)

    Lu, Qian; Krull, Kevin R; Leisenring, Wendy; Owen, Jason E; Kawashima, Toana; Tsao, Jennie C I; Zebrack, Bradley; Mertens, Ann; Armstrong, Gregory T; Stovall, Marilyn; Robison, Leslie L; Zeltzer, Lonnie K

    2011-11-01

    Little is known about pain among long-term adult survivors of childhood cancers. The study investigated pain prevalence in this population compared with sibling controls and examined pain-related risk factors. Three self-reported pain outcomes including pain conditions, prescription analgesics used, and pain attributed to cancer and treatment were assessed among 10,397 cancer survivors and 3034 sibling controls from the Childhood Cancer Survivor Study. Pain conditions (pain/abnormal sensation, migraines, and other headaches) were reported by 12.3%, 15.5%, and 20.5% of survivors, respectively; 16.7% of survivors reported use of prescription analgesics, and 21% attributed pain to cancer and treatment. Risks of reporting pain conditions and using prescription analgesics were higher among survivors than siblings, adjusting for sociodemographic factors. Younger age at diagnosis and a history of non-Hodgkin lymphoma, Wilms tumor, or neuroblastoma (compared to leukemia) were associated with greater risk of reporting pain conditions. A history of bone cancer or soft tissue sarcoma (compared to leukemia) was associated with greater risks of using prescription analgesics and cancer-related pain attribution. Non-brain-directed scatter irradiation was associated with elevated risk for migraines and cancer-related pain attribution. Female gender and lower educational attainment were associated with increased reports of all 3 pain outcomes; minority status, unemployment, and being single were associated with greater risks for reporting pain conditions. These findings contribute to the understanding of pain and associated risk factors among adult survivors of childhood cancer and suggest areas of focus for pain intervention.

  9. High-throughput DNA methylation analysis in colorectal cancer and childhood leukemia

    NARCIS (Netherlands)

    Roon, Eddy Herman Jasper van

    2012-01-01

    The first study described the colon tumor-specific methylation of a low CG-dense CpG island that is located in the first intron of the PTPRG gene (PTPRGint1). High levels of specificity and sensitivity of this region were observed in sporadic and familial colon cancer which makes this region interes

  10. Domestic Radon and Childhood Cancer in Denmark

    DEFF Research Database (Denmark)

    Raaschou-Nielsen, Ole; Andersen, Claus Erik; Andersen, Helle P.;

    2008-01-01

    Background: Higher incidence rates of childhood cancer and particularly leukemia have been observed in regions with higher radon levels, but case-control studies have given inconsistent results. We tested the hypothesis that domestic radon exposure increases the risk for childhood cancer. Methods......: We identified 2400 incident cases of leukemia, central nervous system tumor, and malignant lymphoma diagnosed in children between 1968 and 1994 in the Danish Cancer Registry. Control children (n = 6697) were selected from the Danish Central Population Registry. Radon levels in residences of children...... and the cumulated exposure of each child were calculated as the product of exposure level and time, for each address occupied during childhood. Results: Cumulative radon exposure was associated with risk for acute lymphoblastic leukemia (ALL), with rate ratios of 1.21 (95% confidence interval = 0...

  11. Bacillus cereus Cerebral Abscess During Induction Chemotherapy for Childhood Acute Leukemia.

    Science.gov (United States)

    Dabscheck, Gabriel; Silverman, Lewis; Ullrich, Nicole J

    2015-10-01

    A 5-year-old boy with standard-risk B-cell acute lymphoblastic anemia developed fever during induction chemotherapy. The patient had no neurological symptoms. Blood cultures grew Bacillus cereus and neuroimaging studies demonstrated a cerebral abscess. Imaging changes resolved after completion of antibiotics. Bacillus cereus bacteremia is increasingly implicated as the cause of life-threatening infections, including cerebral abscesses, in compromised patients. Positive blood cultures for this organism should prompt neuroimaging and consideration of cerebrospinal fluid sampling, as well as catheter removal. Given the worse outcome with central nervous system involvement, there is a need for increased awareness and early diagnosis, particularly in immunocompromised individuals.

  12. Study on subsequent neurologic complications in children with acute leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Kobayashi, Naoaki; Shimazaki, Haruyo; Hoshi, Yasutaka; Akatsuka, Jun-ichi (Jikei Univ., Tokyo (Japan). School of Medicine)

    1989-06-01

    Twenty-seven children with acute leukemia were studied in order to detect the subsequent neurologic complications due to chemotherapy and radiation therapy. Twenty-four patients with ALL received central nervous system prophylaxis including cranial irradiation. The methods of evaluation consisted of electroencephalogram (EEG), computed tomography of the head (CT scan), soft neurological sign, intelligence quotient (IQ) and Bender Gestalt test. The patients with relapse showed severe abnormalities in various kinds of examinations. Younger children at diagnosis were associated with a higher abnormality rate of soft neurological signs and Bender Gestalt test. Factors which were found to be closely associated with a lower IQ score included younger children at diagnosis and longer duration of remission time. These results indicate the need for caution for the dosage of cranial irradiation for younger patients in CNS prophylaxis, and improvement of a lower IQ score in long-term survivors requires further investigation as to the appropriate intellectual environment for their development after remission. (author).

  13. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    Science.gov (United States)

    Marshall, G M; Dalla Pozza, L; Sutton, R; Ng, A; de Groot-Kruseman, H A; van der Velden, V H; Venn, N C; van den Berg, H; de Bont, E S J M; Maarten Egeler, R; Hoogerbrugge, P M; Kaspers, G J L; Bierings, M B; van der Schoot, E; van Dongen, J; Law, T; Cross, S; Mueller, H; de Haas, V; Haber, M; Révész, T; Alvaro, F; Suppiah, R; Norris, M D; Pieters, R

    2013-07-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were identified among 1041 consecutively enrolled patients as high risk (HR) based on clinical features or high MRD. The HR cohort received the AIEOP-BFM (Associazione Italiana di Ematologia ed Oncologia Pediatrica (Italy)-Berlin-Frankfurt-Münster ALL Study Group) 2000 ALL Protocol I, then three novel HR chemotherapy blocks, followed by allogeneic transplant or chemotherapy. Of the 111 HR patients, 91 began HR treatment blocks, while 79 completed the protocol. There were 3 remission failures, 12 relapses, 7 toxic deaths in remission and 10 patients who changed protocol due to toxicity or clinician/parent preference. For the 111 HR patients, 5-year event-free survival (EFS) was 66.8% (±5.5) and overall survival (OS) was 75.6% (±4.3). The 30 patients treated as HR solely on the basis of high MRD levels had a 5-year EFS of 63% (±9.4%). All patients experienced grade 3 or 4 toxicities during HR block therapy. Although cure rates were improved compared with previous studies, high treatment toxicity suggested that novel agents are needed to achieve further improvement.

  14. What Is Childhood Leukemia?

    Science.gov (United States)

    ... Center Volunteer Learning Center Follow Us Twitter Facebook Instagram Cancer Information, Answers, and Hope. Available Every Minute ... 227.2345 Live Chat Follow Us Twitter Facebook Instagram help site map privacy accessibility terms of use ...

  15. t(6;9)(p22;q34)/DEK-NUP214-rearranged pediatric myeloid leukemia: an international study of 62 patients.

    Science.gov (United States)

    Sandahl, Julie Damgaard; Coenen, Eva A; Forestier, Erik; Harbott, Jochen; Johansson, Bertil; Kerndrup, Gitte; Adachi, Souichi; Auvrignon, Anne; Beverloo, H Berna; Cayuela, Jean-Michel; Chilton, Lucy; Fornerod, Maarten; de Haas, Valérie; Harrison, Christine J; Inaba, Hiroto; Kaspers, Gertjan J L; Liang, Der-Cherng; Locatelli, Franco; Masetti, Riccardo; Perot, Christine; Raimondi, Susana C; Reinhardt, Katarina; Tomizawa, Daisuke; von Neuhoff, Nils; Zecca, Marco; Zwaan, C Michel; van den Heuvel-Eibrink, Marry M; Hasle, Henrik

    2014-05-01

    Acute myeloid leukemia with t(6;9)(p22;q34) is listed as a distinct entity in the 2008 World Health Organization classification, but little is known about the clinical implications of t(6;9)-positive myeloid leukemia in children. This international multicenter study presents the clinical and genetic characteristics of 62 pediatric patients with t(6;9)/DEK-NUP214-rearranged myeloid leukemia; 54 diagnosed as having acute myeloid leukemia, representing <1% of all childhood acute myeloid leukemia, and eight as having myelodysplastic syndrome. The t(6;9)/DEK-NUP214 was associated with relatively late onset (median age 10.4 years), male predominance (sex ratio 1.7), French-American-British M2 classification (54%), myelodysplasia (100%), and FLT3-ITD (42%). Outcome was substantially better than previously reported with a 5-year event-free survival of 32%, 5-year overall survival of 53%, and a 5-year cumulative incidence of relapse of 57%. Hematopoietic stem cell transplantation in first complete remission improved the 5-year event-free survival compared with chemotherapy alone (68% versus 18%; P<0.01) but not the overall survival (68% versus 54%; P=0.48). The presence of FLT3-ITD had a non-significant negative effect on 5-year overall survival compared with non-mutated cases (22% versus 62%; P=0.13). Gene expression profiling showed a unique signature characterized by significantly higher expression of EYA3, SESN1, PRDM2/RIZ, and HIST2H4 genes. In conclusion, t(6;9)/DEK-NUP214 represents a unique subtype of acute myeloid leukemia with a high risk of relapse, high frequency of FLT3-ITD, and a specific gene expression signature.

  16. Coherence between data gathering technique and data analysis method in qualitative studies. A research experience based on leukemia survivors’ narratives

    Directory of Open Access Journals (Sweden)

    Lucia Zannini

    2016-02-01

    Full Text Available Framed in the field of human sciences research, this paper is aimed at critically analyzing the issue of consistency between data gathering technique and data analysis method in qualitative research, starting from a study based on written narratives of patients who had suffered from leukemia, during their childhood/adolescence (Zannini et al., 2014. Even if we collected patients’ narratives, we did not choose Narrative Inquiry as research method, but we decided for a Grounded Theory study (Strauss & Corbin, 1990, a method that allow researchers to reconstruct the “theory”, which participants have developed on a certain phenomenon/process. The discussion of the paper is focused on the methodological issues, considering data analysis as a process that does not depend exclusively on data characteristics (i.e. narrative, but also on research questions and, consequently, on the selected research method.

  17. Minimal Residual Disease and Childhood Leukemia: Standard of Care Recommendations From the Pediatric Oncology Group of Ontario MRD Working Group.

    Science.gov (United States)

    Athale, Uma H; Gibson, Paul J; Bradley, Nicole M; Malkin, David M; Hitzler, Johann

    2016-06-01

    Minimal residual disease (MRD) is an independent predictor of relapse risk in children with leukemia and is widely used for risk-adapted treatment. This article summarizes current evidence supporting the use of MRD, including clinical significance, current international clinical practice, impact statement, and recommended indications. The proposed MRD recommendations have been endorsed by the MRD Working Group of the Pediatric Oncology Group of Ontario and provide the foundation for a strategy that aims at equitable access to MRD evaluation for children with leukemia.

  18. Bcl-2 family members in childhood acute lymphoblastic leukemia : relationships with features at presentation, in vitro and in vivo drug response and long-term clinical outcome

    NARCIS (Netherlands)

    Salomons, GS; Smets, LA; Verwijs-Janssen, M; Hart, AAM; Haarman, EG; Kaspers, GJL; Van Wering, ER; Van Der Does-Van Den Berg, A; Kamps, WA

    1999-01-01

    We have found that, in addition to Bcl-2 and Bar, the expression levels of apoptosis inducers (Bad, Bak) and inhibitors (Bcl-x(L), Mcl-1) were highly variable in blasts from 78 children with newly diagnosed acute lymphoblastic leukemia (ALL). The patients were enrolled in the national study ALL-7 of

  19. Monosomy 7 and deletion 7q in children and adolescents with acute myeloid leukemia: an international retrospective study

    DEFF Research Database (Denmark)

    Hasle, Henrik; Alonzo, Todd A; Auvrignon, A

    2007-01-01

    Monosomy 7 (-7) and deletion 7q \\del(7q)] are rare in childhood acute myeloid leukemia (AML). We retrospectively collected data on 258 children with AML or refractory anemia with excess blasts in transformation (RAEB-T) and -7 or del(7q) with or without other cytogenetic aberrations \\+/- other...

  20. Roles of genetic polymorphisms in the folate pathway in childhood acute lymphoblastic leukemia evaluated by Bayesian relevance and effect size analysis.

    Directory of Open Access Journals (Sweden)

    Orsolya Lautner-Csorba

    Full Text Available In this study we investigated whether polymorphisms in the folate pathway influenced the risk of childhood acute lymphoblastic leukemia (ALL or the survival rate of the patients. For this we selected and genotyped 67 SNPs in 15 genes in the folate pathway in 543 children with ALL and 529 controls. The results were evaluated by gender adjusted logistic regression and by the Bayesian network based Bayesian multilevel analysis of relevance (BN-BMLA methods. Bayesian structure based odds ratios for the relevant variables and interactions were also calculated. Altogether 9 SNPs in 8 genes were associated with altered susceptibility to ALL. After correction for multiple testing, two associations remained significant. The genotype distribution of the MTHFD1 rs1076991 differed significantly between the ALL and control population. Analyzing the subtypes of the disease the GG genotype increased only the risk of B-cell ALL (p = 3.52×10(-4; OR = 2.00. The GG genotype of the rs3776455 SNP in the MTRR gene was associated with a significantly reduced risk to ALL (p = 1.21×10(-3; OR = 0.55, which resulted mainly from the reduced risk to B-cell and hyperdiploid-ALL. The TC genotype of the rs9909104 SNP in the SHMT1 gene was associated with a lower survival rate comparing it to the TT genotype (80.2% vs. 88.8%; p = 0.01. The BN-BMLA confirmed the main findings of the frequentist-based analysis and showed structural interactional maps and the probabilities of the different structural association types of the relevant SNPs especially in the hyperdiploid-ALL, involving additional SNPs in genes like TYMS, DHFR and GGH. We also investigated the statistical interactions and redundancies using structural model properties. These results gave further evidence that polymorphisms in the folate pathway could influence the ALL risk and the effectiveness of the therapy. It was also shown that in gene association studies the BN-BMLA could be a useful

  1. mTOR inhibition by everolimus in childhood acute lymphoblastic leukemia induces caspase-independent cell death.

    Directory of Open Access Journals (Sweden)

    Rana Baraz

    Full Text Available Increasingly, anti-cancer medications are being reported to induce cell death mechanisms other than apoptosis. Activating alternate death mechanisms introduces the potential to kill cells that have defects in their apoptotic machinery, as is commonly observed in cancer cells, including in hematological malignancies. We, and others, have previously reported that the mTOR inhibitor everolimus has pre-clinical efficacy and induces caspase-independent cell death in acute lymphoblastic leukemia cells. Furthermore, everolimus is currently in clinical trial for acute lymphoblastic leukemia. Here we characterize the death mechanism activated by everolimus in acute lymphoblastic leukemia cells. We find that cell death is caspase-independent and lacks the morphology associated with apoptosis. Although mitochondrial depolarization is an early event, permeabilization of the outer mitochondrial membrane only occurs after cell death has occurred. While morphological and biochemical evidence shows that autophagy is clearly present it is not responsible for the observed cell death. There are a number of features consistent with paraptosis including morphology, caspase-independence, and the requirement for new protein synthesis. However in contrast to some reports of paraptosis, the activation of JNK signaling was not required for everolimus-induced cell death. Overall in acute lymphoblastic leukemia cells everolimus induces a cell death that resembles paraptosis.

  2. Approaches for cytogenetic and molecular analyses of small flow-sorted cell populations from childhood leukemia bone marrow samples

    DEFF Research Database (Denmark)

    Obro, Nina Friesgaard; Madsen, Hans O.; Ryder, Lars Peter;

    2011-01-01

    defined cell populations with subsequent analyses of leukemia-associated cytogenetic and molecular marker. The approaches described here optimize the use of the same tube of unfixed, antibody-stained BM cells for flow-sorting of small cell populations and subsequent exploratory FISH and PCR-based analyses....

  3. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation

    NARCIS (Netherlands)

    Marshall, G. M.; Dalla Pozza, L.; Sutton, R.; Ng, A.; de Groot-Kruseman, Ha; van der Velden, V. H.; Venn, N. C.; van den Berg, H.; de Bont, E. S. J. M.; Egeler, R. Maarten; Hoogerbrugge, P. M.; Kaspers, G. J. L.; Bierings, M. B.; van der Schoot, E.; van Dongen, J.; Law, T.; Cross, S.; Mueller, H.; de Haas, V.; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M. D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9; 22)-negative ALL, were

  4. High-risk childhood acute lymphoblastic leukemia in first remission treated with novel intensive chemotherapy and allogeneic transplantation.

    NARCIS (Netherlands)

    Marshall, G.M.; Pozza, L. Dalla; Sutton, R.; Ng, A.; Groot-Kruseman, H.A. de; Velden, V.H. van der; Venn, N.C.; Berg, H. van den; Bont, E.S. de; rten Egeler, R. Maa; Hoogerbrugge, P.M.; Kaspers, G.J.L.; Bierings, M.B.; Schoot, E. van der; Dongen, J. Van; Law, T.; Cross, S.; Mueller, H.; Haas, V. de; Haber, M.; Revesz, T.; Alvaro, F.; Suppiah, R.; Norris, M.D.; Pieters, R.

    2013-01-01

    Children with acute lymphoblastic leukemia (ALL) and high minimal residual disease (MRD) levels after initial chemotherapy have a poor clinical outcome. In this prospective, single arm, Phase 2 trial, 111 Dutch and Australian children aged 1-18 years with newly diagnosed, t(9;22)-negative ALL, were

  5. Assessment of Mercaptopurine (6MP) Metabolites and 6MP Metabolic Key-Enzymes in Childhood Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Wojtuszkiewicz, A.; Barcelos, A.; Dubbelman, B.; Abreu, R.A. de; Brouwer, C.; Bökkerink, J.P.M.; Haas, V. de; Groot-Kruseman, H. de; Jansen, Gert; Kaspers, G.L.; Cloos, J.; Peters, G.J.

    2014-01-01

    Pediatric acute lymphoblastic leukemia (ALL) is treated with combination chemotherapy including mercaptopurine (6MP) as an important component. Upon its uptake, 6MP undergoes a complex metabolism involving many enzymes and active products. The prognostic value of all the factors engaged in this path

  6. Complementary and Alternative Medicine in the Pediatrics with Leukemia: A Narrative Review Study

    Directory of Open Access Journals (Sweden)

    Mojtaba Miladinia

    2017-01-01

    Full Text Available BackgroundFor using of complementary and alternative medicine methods (CAM in the leukemia pediatrics than other types of cancer, we have two great challenges; first challenge is their safety and risks and second challenge is study gaps in this field. Regarding to these challenges, this study is a narrative review of some CAM methods in the leukemia pediatrics from the perspective of their safety, risks and study gaps.Materials and MethodsIn this narrative review study searched both international electronic databases including ISI Web of science, PubMed, PsycINFO, CINAHL, ISC, Embase, Scopus, Google Scholar and also, Iranian electronic databases including Magiran, Medlib and SID. Also, searches were performed separately in the specialized journals in the field of leukemia pediatrics and complementary and alternative medicine research.ResultsMusic therapy, gentle yoga movements, gentle massage types are quite safe for leukemia pediatrics. But, use of heavy yoga movements, massages with deep pressure, acupressure and acupuncture can be dangerous for leukemia pediatrics (risks of bleeding and or infection. Also, this study showed that, the number of investigations about the use of CAM in the leukemia pediatrics is very limited; especially in the field of yoga and acupuncture.ConclusionThe results of this study can be a basis both for chose of safe CAM method in these children and a basis for future studies on the basis of identified study gaps in this review study.

  7. Prognostic Impact of Absolute Lymphocyte Counts at the End of Remission Induction in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Rubnitz, Jeffrey E.; Campbell, Patrick; Zhou, Yinmei; Sandlund, John T.; Jeha, Sima; Ribeiro, Raul C.; Inaba, Hiroto; Bhojwani, Deepa; Relling, Mary V.; Howard, Scott C.; Campana, Dario; Pui, Ching-Hon

    2013-01-01

    Background Absolute lymphocyte counts (ALC) during treatment have been associated with outcome in children and adults with hematologic malignancies. However, the impact of ALC relative to that of other prognostic factors on the outcome of children with acute lymphoblastic leukemia (ALL) treated in recent trials is unknown. Methods Outcomes of 399 patients ≤ 18 years of age with newly diagnosed ALL who were enrolled in the Total Therapy XV study at St. Jude Children’s Research Hospital were analyzed according to ALC at the end of remission induction therapy. Results ALC ≥ 500 cell/μL was significantly more prevalent among patients with B-lineage ALL, favorable presenting features and in those who achieved minimal residual disease (MRD) negativity on day 43 of treatment. Both overall survival (OS) and event-free survival (EFS) were superior among patients with higher ALC, but only the association with OS was statistically significant in a univariate analysis. In multivariable analyses, ALC was not a significant predictor of outcome after controlling for age, leukocyte count, lineage, risk group, and MRD at the end of induction (p > 0.1 for all comparisons). However, among MRD-negative patients, those with low ALC had a 5-year OS of 84.2% ± 8.9% versus 97.3 ± 1.0 for patients with higher ALC (P = .036). Conclusion ALC at the end of induction is related to favorable presenting features and good initial treatment response but does not independently predict outcome in the context of contemporary, MRD-guided, therapy. PMID:23456849

  8. Occupation and leukemia in Nordic countries

    DEFF Research Database (Denmark)

    Talibov, Madar; Kautiainen, Susanna; Martinsen, Jan Ivar

    2012-01-01

    We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries.......We studied occupational variation of the risk of acute myeloid leukemia, chronic lymphocytic leukemia, and other leukemia in Nordic countries....

  9. Childhood abuse and fear of childbirth--a population-based study

    DEFF Research Database (Denmark)

    Lukasse, Mirjam; Vangen, Siri; Øian, Pål

    2010-01-01

    Childhood abuse affects adult health. The objective of this study was to examine the association between a self-reported history of childhood abuse and fear of childbirth.......Childhood abuse affects adult health. The objective of this study was to examine the association between a self-reported history of childhood abuse and fear of childbirth....

  10. Acute myeloid leukemia in adults: a case-control study in Yorkshire.

    Science.gov (United States)

    Cartwright, R A; Darwin, C; McKinney, P A; Roberts, B; Richards, I D; Bird, C C

    1988-10-01

    This paper reports the results of a case-control analysis of 161 cases of acute myeloid leukemia and 310 matched hospital controls. The patients were interviewed between 1982 and 1986. The study shows a weak association for cases with previous malignant disease. Furnace workers show excess risks. Urticaria and vertigo are in excess, as well as some aspects of family medical histories, including multiple sclerosis and cases of leukemia/lymphoma in blood relations.

  11. Study of splenic irradiation in chronic lymphocytic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Guiney, M.J.; Liew, K.H.; Quong, G.G.; Cooper, I.A.

    1989-01-01

    A retrospective study was performed to assess the effect of splenic irradiation (SI) on splenomegaly, splenic pain, anemia, and thrombocytopenia in patients with chronic lymphocytic leukemia. Twenty-two patients received 32 courses of SI. Of 31 courses of SI given for splenomegaly there were 19 responders (61%). Ten courses of SI were given for splenic pain resulting in partial relief of pain in 4 courses and complete relief in 4 courses. Only 4 of 16 courses given for anemia resulted in elevations of hemoglobin of 2 g/dL or more. Of the 14 courses of SI given for thrombocytopenia there were only 2 responses with platelet counts decreasing further in another 9 courses. The median duration of response was 14 months (range: 3-116 months). There was no dose-response relationship detected for SI in CLL. Treatment related toxicity was hematologic and secondary to leucopenia and thrombocytopenia. We recommend the use of small fraction sizes of 25 cGy to 50 cGy and close monitoring of hematological parameters. Splenic irradiation effectively palliates splenomegaly and reduces spleen size in CLL. It was of limited value in correcting anemia and thrombocytopenia in this patient population.

  12. Emotional Functioning and School Contentment in Adolescent Survivors of Acute Myeloid Leukemia, Infratentorial Astrocytoma, and Wilms Tumor

    OpenAIRE

    Jóhannsdóttir, Inga M.; Moum, Torbjørn; Hjermstad, Marianne J.; Wesenberg, Finn; Hjorth, Lars; Schrøder, Henrik; Lähteenmäki, Päivi M.; Jónmundsson, Gudmundur; Loge, Jon H.

    2011-01-01

    Purpose: Cancer in childhood may disrupt normal developmental processes and cause psychosocial problems in adolescent survivors of childhood cancers (ACCSs). Previous studies report inconsistent findings. Study aims were to assess subjective well-being (SWB), psychological distress, and school contentment in survivors of three dissimilar childhood cancers. Patients and methods: Nordic patients treated for acute myeloid leukemia (AML), infratentorial astrocytoma (IA), and Wilms tumor (WT) in c...

  13. Vitamin D and bone minerals status in the long-term survivors of childhood acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Nahid Reisi

    2015-01-01

    Conclusions: ALL treatment is associated with the increase in prevalence of vitamin D insufficiency in the childhood ALL survivors and since the low vitamin D level potentially increases the risk of low bone density, subsequent malignancies, and cardiovascular disease in the survivors, close follow-up of such patients are highly recommended to prevent the stated complications.

  14. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia

    Science.gov (United States)

    Eghtedar, Alireza; Verstovsek, Srdan; Estrov, Zeev; Burger, Jan; Cortes, Jorge; Bivins, Carol; Faderl, Stefan; Ferrajoli, Alessandra; Borthakur, Gautam; George, Solly; Scherle, Peggy A.; Newton, Robert C.; Kantarjian, Hagop M.

    2012-01-01

    We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479. PMID:22422826

  15. Phase 2 study of the JAK kinase inhibitor ruxolitinib in patients with refractory leukemias, including postmyeloproliferative neoplasm acute myeloid leukemia.

    Science.gov (United States)

    Eghtedar, Alireza; Verstovsek, Srdan; Estrov, Zeev; Burger, Jan; Cortes, Jorge; Bivins, Carol; Faderl, Stefan; Ferrajoli, Alessandra; Borthakur, Gautam; George, Solly; Scherle, Peggy A; Newton, Robert C; Kantarjian, Hagop M; Ravandi, Farhad

    2012-05-17

    We conducted a phase 2 study of ruxolitinib in patients with relapsed/refractory leukemias. Patients with acceptable performance status (0-2), adequate organ function, and no active infection, received ruxolitinib 25 mg orally twice a day for 4 weeks (1 cycle). Response was assessed after every 2 cycles of treatment, and patients who completed 2 cycles were allowed to continue treatment until disease progression. Dose escalation to 50 mg twice daily was permitted in patients demonstrating a benefit. Thirty-eight patients, with a median age of 69 years (range, 45-88), were treated. The median number of prior therapies was 2 (range, 1-6). Twelve patients had JAK2V617F mutation. Patients received a median of 2 cycles of therapy (range, 1-22). Three of 18 patients with postmyeloproliferative neoplasm (MPN) acute myeloid leukemia (AML) showed a significant response; 2 achieved complete remission (CR) and one achieved a CR with insufficient recovery of blood counts (CRi). The responding patients with palpable spleens also had significant reductions in spleen size. Overall, ruxolitinib was very well tolerated with only 4 patients having grade 3 or higher toxicity. Ruxolitinib has modest antileukemic activity as a single agent, particularly in patients with post-MPN AML. The study was registered at www.clinicaltrials.gov as NCT00674479.

  16. Relationship between Childhood Maltreatment, Suicidality, and Bipolarity: A Retrospective Study

    Science.gov (United States)

    2017-01-01

    Objective The aims of current study were to determine whether childhood maltreatment contributes to the occurrence of major depressive disorder (MDD) with bipolarity or suicidality. Methods In total, 132 outpatients diagnosed with MDD between 2014 and 2015 on the medical records were included. The subjects were divided into two groups according to the presence of childhood maltreatment (CM group) and no childhood maltreatment (NCM group). Depression severity and bipolarity were identified using Beck Depression Inventory (BDI) and the Korean version of Mood Disorder Questionnaire (K-MDQ) respectively on the medical records. In addition, the baseline loud dependence of auditory evoked potentials of 36 patients on medical records were analyzed. Results The mean total BDI, BDI item 9 (suicide ideation), and total K-MDQ score were significantly higher in the CM group than the NCM group. The number of subjects with bipolarity was significantly higher in the CM than in the NCM group. Furthermore two thirds subjects experienced the significant maltreatment during childhood. The central serotonergic activity of the CM group was also lower than that of the NCM group. Conclusion The findings of this study support that there is a relationship between childhood maltreatment and bipolarity or suicidality in patients with MDD.

  17. Risk of Salivary Gland Cancer After Childhood Cancer: A Report From the Childhood Cancer Survivor Study

    Energy Technology Data Exchange (ETDEWEB)

    Boukheris, Houda [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stovall, Marilyn [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Gilbert, Ethel S. [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States); Stratton, Kayla L. [Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington (United States); Smith, Susan A.; Weathers, Rita [Department of Radiation Physics, University of Texas MD Anderson Cancer Center, Houston, Texas (United States); Hammond, Sue [Department of Pathology, Ohio State University School of Medicine, Columbus, Ohio (United States); Mertens, Ann C. [Department of Pediatrics, Emory University, Atlanta, Georgia (United States); Donaldson, Sarah S. [Department of Radiation Oncology, Stanford University Medical Center, Stanford, California (United States); Armstrong, Gregory T.; Robison, Leslie L. [Department of Epidemiology and Cancer Control, St. Jude Children' s Research Hospital, Memphis, Tennessee (United States); Neglia, Joseph P. [Department of Pediatrics, University of Minnesota Medical School, Minneapolis, Minnesota (United States); Inskip, Peter D., E-mail: inskippe@mail.nih.gov [Radiation Epidemiology Branch, Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, Maryland (United States)

    2013-03-01

    Purpose: To evaluate effects of radiation therapy, chemotherapy, cigarette smoking, and alcohol consumption on the risk of second primary salivary gland cancer (SGC) in the Childhood Cancer Survivor Study (CCSS). Methods and Materials: Standardized incidence ratios (SIR) and excess absolute risks (EAR) of SGC in the CCSS were calculated using incidence rates from Surveillance, Epidemiology, and End Results population-based cancer registries. Radiation dose to the salivary glands was estimated based on medical records. Poisson regression was used to assess risks with respect to radiation dose, chemotherapy, smoking, and alcohol consumption. Results: During the time period of the study, 23 cases of SGC were diagnosed among 14,135 childhood cancer survivors. The mean age at diagnosis of the first primary cancer was 8.3 years, and the mean age at SGC diagnosis was 24.8 years. The incidence of SGC was 39-fold higher in the cohort than in the general population (SIR = 39.4; 95% CI = 25.4-57.8). The EAR was 9.8 per 100,000 person-years. Risk increased linearly with radiation dose (excess relative risk = 0.36/Gy; 95% CI = 0.06-2.5) and remained elevated after 20 years. There was no significant trend of increasing risk with increasing dose of chemotherapeutic agents, pack-years of cigarette smoking, or alcohol intake. Conclusion: Although the cumulative incidence of SGC was low, childhood cancer survivors treated with radiation experienced significantly increased risk for at least 2 decades after exposure, and risk was positively associated with radiation dose. Results underscore the importance of long-term follow up of childhood cancer survivors for the development of new malignancies.

  18. Gender and teacher training in Early Childhood Education studies

    Directory of Open Access Journals (Sweden)

    Alfonso Romero Díaz

    2008-12-01

    Full Text Available This paper presents the findings of a research study funded by the European Union that aims to improve early childhood teacher training in gender-related topics. Spain has made considerable headway with the inclusion of gender mainstreaming in the political agenda. However, as we point out in this paper, this issue is still not a priority in vocational training for early childhood education. A series of qualitative interviews and a quantitative questionnaire revealed a lack of training, materials and sensitivity, all needed for the introduction of gender and sexual diversity issues.

  19. Individualized toxicity-titrated 6-mercaptopurine increments during high-dose methotrexate consolidation treatment of lower risk childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Frandsen, Thomas Leth; Abrahamsson, Jonas; Lausen, Birgitte Frederiksen;

    2011-01-01

    This study explored the feasibility and toxicity of individualized toxicity-titrated 6-mercaptopurine (6MP) dose increments during post-remission treatment with High-dose methotrexate (HDM) (5000 mg/m2, ×3) in 38 patients with Childhood (ALL). Patients were increased in steps of 25 mg 6MP/m2 per...

  20. Efficacy and Toxicity of Intrathecal Liposomal Cytarabine in First-line Therapy of Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Harila-Saari, Arja; Grell, Kathrine

    2016-01-01

    We investigated efficacy and toxicity of replacing conventional triple (cytarabine, methotrexate, and hydrocortisone) intrathecal therapy (TIT) with liposomal cytarabine during maintenance therapy among 40 acute lymphoblastic leukemia patients. Twenty-eight of 29 patients in the TIT arm received...... TIT and 9/11 in the liposomal cytarabine arm received liposomal cytarabine. Arachnoiditis occurred in all initial 5 patients given liposomal cytarabine and intrathecal prednisolone succinate. Subsequently liposomal cytarabine was given with systemic dexamethasone. Neurotoxicity occurred at 6....../27 liposomal cytarabine administrations with concomitant dexamethasone (22%). More liposomal cytarabine-treated patients experienced neurotoxicity in relation to intrathecal therapy during at least 1 cycle compared with TIT-treated patients (6/9 [67%] vs. 3/28 [11%], P=0.002). Apart from intermittent lower...

  1. Trajectories of picky eating during childhood : A general population study

    NARCIS (Netherlands)

    Cano, Sebastian Cardona; Tiemeier, Henning; Van Hoeken, Daphne; Tharner, Anne; Jaddoe, Vincent W. V.; Hofman, Albert; Verhulst, Frank C.; Hoek, Hans W.

    2015-01-01

    ObjectiveThis cohort study describes the prevalence of picky eating and examines prognostic factors for picky eating trajectories during childhood. Methods4,018 participants of a population-based cohort with measurements from pregnancy onwards were included. Picky eating was assessed by maternal rep

  2. Childhood Giftedness, Adolescent Agency: A Systemic Multiple-Case Study

    Science.gov (United States)

    Mudrak, Jiri; Zabrodska, Katerina

    2015-01-01

    Although considerable research has addressed development from childhood giftedness to adult excellence, subjective perceptions of this development by gifted individuals themselves have remained largely unexplored. This multiple case study examined the ways in which young adults, who in the past had been identified as gifted, made sense of their…

  3. Free Play in Early Childhood Education: A Phenomenological Study

    Science.gov (United States)

    Aras, Selda

    2016-01-01

    It is aimed to investigate perceptions and implementations of early childhood teachers on free play and their involvement in children's free play. Recent studies focused on that, although there is an increase in the amount of teacher involvement, the quality of this involvement should be clearly examined. Lev Vygotsky examined play as an…

  4. Evaluation Study of Early Childhood Education in Pakistan

    Science.gov (United States)

    Shakeel, Muhammad; Farooq, Muhammad; Umbreen

    2011-01-01

    Early Childhood Education (ECE) was globally and locally an innovation, particularly in third world. The objective of this study was to investigate an impact evaluation of ECE initiated recently in Pakistan. The data of impact evaluation were drawn from three ECE Centers of Islamabad Capital Territory (ICT), Pakistan. Total samples of 65…

  5. Prognostic value of bone marrowhematogones in childhood B-lineage acute lymphoblastic leukemia%原血细胞对于儿童急性B淋巴细胞白血病预后判断的价值

    Institute of Scientific and Technical Information of China (English)

    王月芳; 江咏梅; 高举; 周平; 张鸽

    2016-01-01

    ObjectiveTo study the prognostic value of hematogones (HGs) for childhood B-lineage acute lymphoblastic leukemia (B-ALL) during consolidation chemotherapy.MethodsA retrospective analysis was conducted for 196 children with newly-diagnosed B-ALL. They were divided into high-risk group (n=55), intermediate-risk group (n=69), and low-risk group (n=72) by risk stratiifcation, and into complete remission group (n=165) and relapse group (n=31) by clinical outcome. The European BIOMED-1 standard lfow cytometry for minimal residual disease (MRD) was used to determine the number of HGs during consolidation chemotherapy. The Kaplan-Meier survival curve was used to assess event-free survival (EFS).ResultsThe high-risk group had a signiifcantly lower number of HGs than the intermediate-risk and low-risk groups (P1.0% (P1.0%组,差异有统计学意义(P<0.05)。结论HGs 可反映B-ALL化疗效果,可用于B-ALL患儿疗效及预后的监测。

  6. Gamma-Secretase Inhibitor RO4929097 in Treating Young Patients With Relapsed or Refractory Solid Tumors, CNS Tumors, Lymphoma, or T-Cell Leukemia

    Science.gov (United States)

    2014-11-04

    Childhood Atypical Teratoid/Rhabdoid Tumor; Childhood Central Nervous System Choriocarcinoma; Childhood Central Nervous System Germinoma; Childhood Central Nervous System Mixed Germ Cell Tumor; Childhood Central Nervous System Teratoma; Childhood Central Nervous System Yolk Sac Tumor; Childhood Choroid Plexus Tumor; Childhood Craniopharyngioma; Childhood Ependymoblastoma; Childhood Grade I Meningioma; Childhood Grade II Meningioma; Childhood Grade III Meningioma; Childhood Infratentorial Ependymoma; Childhood Medulloepithelioma; Childhood Mixed Glioma; Childhood Oligodendroglioma; Childhood Supratentorial Ependymoma; Gonadotroph Adenoma; Pituitary Basophilic Adenoma; Pituitary Chromophobe Adenoma; Pituitary Eosinophilic Adenoma; Prolactin Secreting Adenoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Brain Stem Glioma; Recurrent Childhood Central Nervous System Embryonal Tumor; Recurrent Childhood Cerebellar Astrocytoma; Recurrent Childhood Cerebral Astrocytoma; Recurrent Childhood Ependymoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Medulloblastoma; Recurrent Childhood Pineoblastoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Childhood Spinal Cord Neoplasm; Recurrent Childhood Subependymal Giant Cell Astrocytoma; Recurrent Childhood Supratentorial Primitive Neuroectodermal Tumor; Recurrent Childhood Visual Pathway and Hypothalamic Glioma; Recurrent Childhood Visual Pathway Glioma; Recurrent Pituitary Tumor; Recurrent/Refractory Childhood Hodgkin Lymphoma; T-cell Childhood Acute Lymphoblastic Leukemia; T-cell Large Granular Lymphocyte Leukemia; TSH Secreting Adenoma; Unspecified Childhood Solid Tumor, Protocol Specific

  7. Inhibitor of Apoptosis (IAP proteins in pediatric leukemia: Molecular pathways and novel approaches to therapy

    Directory of Open Access Journals (Sweden)

    Simone eFulda

    2014-01-01

    Full Text Available Inhibitor of Apoptosis (IAP proteins are a family of proteins with antiapoptotic functions that contribute to the evasion of apoptosis, a form of programmed cell death. IAP proteins are expressed at high levels in a variety of human cancers including childhood acute leukemia. This elevated expression has been associated with unfavorable prognosis and poor outcome. Therefore, IAP proteins are currently exploited as therapeutic targets for cancer drug discovery. Consequently, small-molecule inhibitors or antisense oligonucleotides directed against IAP proteins have been developed over the last years. Indeed, IAP antagonists proved to exhibit in vitro and in vivo antitumor activities against childhood pediatric leukemia in several preclinical studies. Thus, targeting IAP proteins represents a promising molecular targeted strategy to overcome apoptosis resistance in childhood leukemia which warrants further exploitation.

  8. Danish Childhood Cancer Registry

    DEFF Research Database (Denmark)

    Schrøder, Henrik; Rechnitzer, Catherine; Wehner, Peder Skov

    2016-01-01

    AIM OF DATABASE: The overall aim is to monitor the quality of childhood cancer care in Denmark; to register late effects of treatment; to analyze complications of permanent central venous catheters (CVCs); to study blood stream infections in children with cancer; and to study acute toxicity of high......-dose methotrexate infusions in children with leukemia. STUDY POPULATION: All children below 15 years of age at diagnosis living in Denmark diagnosed after January 1, 1985 according to the International Classification of Diseases 10, including diagnoses DC00-DD48. MAIN VARIABLES: Cancer type, extent of disease......, and outcome of antimicrobial chemotherapy. DESCRIPTIVE DATA: Since 1985, 4,944 children below 15 years of age have been registered in the database. There has been no significant change in the incidence of childhood cancer in Denmark since 1985. The 5-year survival has increased significantly since 1985...

  9. 父母亲化学物质暴露与儿童急性白血病发病关系的探讨%Relationship between parental exposure to chemicals and risk of childhood acute leukemia

    Institute of Scientific and Technical Information of China (English)

    施蓉; 高宇; 张妍; 高怡瑾; 朱莎; 王筱金; 金萍; 田英

    2013-01-01

    目的 探讨父母亲化学物质暴露与儿童急性白血病发病的关系.方法 选取2009年1月1日至2010年12月31日所有就诊于上海地区3家儿童医院年龄小于15周岁的201例新发急性白血病的儿童,在病例所在医院的儿童保健门诊或骨科选取同性别同年龄的对照儿童201例,对其母亲进行面对面的访谈式调查.结果 母亲孕前3个月至孕期总化学物质(柴油、汽油、油漆、杀虫剂、农药、除草剂、化肥)接触史(OR=2.9,95%CI=1.1~7.8)及父亲在母亲孕前3个月接触杀虫剂(OR=10.1,95%CI=1.2~82.9)、化肥(OR=9.5,95%CI=1.1~79.6);母亲孕前从事农业、林业工作(OR=8.4,95%CI=1.4~50.2);孕前及孕期从事纺织、皮革、装潢、汽修(孕前:OR =3.0,95%CI=1.2~7.9;孕期:OR=3.2,95%CI=1.1~9.6);父亲从事农业、林业(OR =9.6,95%CI=2.1~44.8)及纺织、皮革、装潢、汽修工作(OR=2.3,95%CI=1.1~5.0)等因素可能是儿童急性白血病发病的危险因素.结论 父母亲化学物质暴露可能会增加后代患急性白血病的风险.%Objective To investigate the relationship between parental exposure to chemicals and the risk of childhood acute leukemia.Methods An exploratory case-control study was conducted among 201 new cases of childhood acute leukemia under 15 years old who went to 3 children's hospitals in Shanghai,China from January 1,2009 to December 31,2010,as well as 201 sex-and age-matched children (as controls) who went to the child health care clinic or department of orthopedics in the above hospitals.A survey was performed by face-to-face interviews with children's mothers.Results The risk factors for childhood acute leukemia might include maternal exposure to total chemicals (diesel oil,gasoline,paints,insecticides,pesticides,herbicides,and chemical fertilizers) from 3 months before pregnancy to the end of pregnancy (OR=2.9,95%CI=1.1~7.8),paternal exposure to insecticides (OR=10.1,95%CI=1.2~82

  10. A Long-Term Outcome Study of Selective Mutism in Childhood

    Science.gov (United States)

    Steinhausen, Hans-Christoph; Wachter, Miriam; Laimbock, Karin; Metzke, Christa Winkler

    2006-01-01

    Objective: Controlled study of the long-term outcome of selective mutism (SM) in childhood. Method: A sample of 33 young adults with SM in childhood and two age- and gender-matched comparison groups were studied. The latter comprised 26 young adults with anxiety disorders in childhood (ANX) and 30 young adults with no psychiatric disorders during…

  11. Epidemiologic study on survival of chronic myeloid leukemia and Ph(+) acute lymphoblastic leukemia patients with BCR-ABL T315I mutation

    DEFF Research Database (Denmark)

    Nicolini, Franck E; Mauro, Michael J; Martinelli, Giovanni;

    2009-01-01

    The BCR-ABL T315I mutation represents a major mechanism of resistance to tyrosine kinase inhibitors (TKIs). The objectives of this retrospective observational study were to estimate overall and progression-free survival for chronic myeloid leukemia in chronic-phase (CP), accelerated-phase (AP......), or blastic-phase (BP) and Philadelphia chromosome-positive (Ph)(+) acute lymphoblastic leukemia (ALL) patients with T315I mutation. Medical records of 222 patients from 9 countries were reviewed; data were analyzed using log-rank tests and Cox proportional hazard models. Median age at T315I mutation...

  12. AR-42 and Decitabine in Treating Patients With Acute Myeloid Leukemia

    Science.gov (United States)

    2016-04-21

    Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  13. A Phase I Study of Topotecan, Carboplatin and the PARP Inhibitor Veliparib in Acute Leukemias, Aggressive Myeloproliferative Neoplasms, and Chronic Myelomonocytic Leukemia.

    Science.gov (United States)

    Pratz, Keith W; Rudek, Michelle A; Gojo, Ivana; Litzow, Mark R; McDevitt, Michael A; Ji, Jiuping; Karnitz, Larry M; Herman, James G; Kinders, Robert J; Smith, B Douglas; Gore, Steven D; Carraway, Hetty E; Showel, Margaret M; Gladstone, Douglas E; Levis, Mark J; Tsai, Hua-Ling; Rosner, Gary; Chen, Alice; Kaufmann, Scott H; Karp, Judith E

    2017-02-15

    Purpose: The PARP inhibitor veliparib delays DNA repair and potentiates cytotoxicity of multiple classes of chemotherapy drugs, including topoisomerase I inhibitors and platinating agents. This study evaluated veliparib incorporation into leukemia induction therapy using a previously described topotecan/carboplatin backbone.Experimental Design: Employing a 3+3 trial design, we administered escalating doses of veliparib combined with topotecan + carboplatin in relapsed or refractory acute leukemias, aggressive myeloproliferative neoplasms (MPN), and chronic myelomonocytic leukemia (CMML).Results: A total of 99 patients received veliparib 10-100 mg orally twice daily on days 1-8, 1-14, or 1-21 along with continuous infusion topotecan 1.0-1.2 mg/m(2)/d + carboplatin 120-150 mg/m(2)/d on days 3-7. The MTD was veliparib 80 mg twice daily for up to 21 days with topotecan 1.2 mg/m(2)/d + carboplatin 150 mg/m(2)/d. Mucositis was dose limiting and correlated with high veliparib concentrations. The response rate was 33% overall (33/99: 14 CR, 11 CRi, 8 PR) but was 64% (14/22) for patients with antecedent or associated aggressive MPNs or CMML. Leukemias with baseline DNA repair defects, as evidenced by impaired DNA damage-induced FANCD2 monoubiquitination, had improved survival [HR = 0.56 (95% confidence interval, 0.27-0.92)]. A single 80-mg dose of veliparib, as well as veliparib in combination with topotecan + carboplatin, induced DNA damage as manifested by histone H2AX phosphorylation in CD34(+) leukemia cells, with greater phosphorylation in cells from responders.Conclusions: The veliparib/topotecan/carboplatin combination warrants further investigation, particularly in patients with aggressive MPNs, CMML, and MPN- or CMML-related acute leukemias. Clin Cancer Res; 23(4); 899-907. ©2016 AACR.

  14. Sequential treatment with cytarabine and decitabine has an increased anti-leukemia effect compared to cytarabine alone in xenograft models of childhood acute myeloid leukemia.

    Directory of Open Access Journals (Sweden)

    Sarah M Leonard

    Full Text Available The current interest in epigenetic priming is underpinned by the belief that remodelling of the epigenetic landscape will sensitise tumours to subsequent therapy. In this pre-clinical study, paediatric AML cells expanded in culture and primary AML xenografts were treated with decitabine, a DNA demethylating agent, and cytarabine, a frontline cytotoxic agent used in the treatment of AML, either alone or in combination. Sequential treatment with decitabine and cytarabine was found to be more effective in reducing tumour burden than treatment with cytarabine alone suggesting that the sequential delivery of these agents may a have real clinical advantage in the treatment of paediatric AML. However we found no evidence to suggest that this outcome was dependent on priming with a hypomethylating agent, as the benefits observed were independent of the order in which these drugs were administered.

  15. 婴儿出生史相关因素与儿童急性白血病发病风险的Meta分析%Effects of birth order, maternal abortion and mode of delivery on childhood acute leukemia risk: a meta-analysis

    Institute of Scientific and Technical Information of China (English)

    邹国斌; 沙霞

    2014-01-01

    Objective To evaluate the associations between birth order,maternal abortion and mode of delivery and childhood acute leukemia risk.Method Multiple electronic databases were searched to identify relevant studies up to March 2013 using the search terms " childhood leukemia"," acute lymphoblastic leukemia"," acute myeloid leukemia"," birth order"," abortion "," miscarriage ","cesarean","birth characteristics" and "prenatal risk factor".Data from cohort and case-control studies were analyzed using the Stata software.Result Twenty-three studies were included in this meta-analysis according to the selection criteria.No significant associations were identified for birth order and mode of delivery (birth order =2:OR =0.97,95% CI:0.89-1.05 ; birth order =3:OR =1.00,95% CI:0.91-1.11 ; birth order ≥4:OR =1.02,95% CI:0.87-1.20; mode of delivery:OR =1.05,95% CI:0.96-1.15).However,there was a significant association between maternal abortion and childhood acute leukemia risk (spontaneous abortion:OR =1.21,95% CI:1.05-1.41 ; induced abortion:OR =1.23,95% CI:1.07-1.43).Furthermore,the stratified analysis by disease subtypes showed that spontaneous and induced abortions were significantly associated with the risks of childhood acute myeloid leukemia (OR =1.71,95% CI:1.09-2.70) and acute lymphoblastic leukemia (OR =1.23,95% CI:1.05-1.42),respectively.Conclusion This meta-analysis revealed that maternal abortion might contribute to the childhood acute leukemia risk.%目的 综合评价患儿出生顺序、孕妇流产史及分娩方式与儿童急性白血病发病风险之间的关系.方法 在PubMed、Google学术搜索、中国知网(CNKI)、万方数据库中以“childhoodleukemia"、“acute lymphoblastic leukemia"、“acute myeloid leukemia"、“birth order"、“abortion”、“miscarriage”、“caesarean”、“birth characteristics”、“prenatal risk factor”或其对应的中文词目为检索词,收集2013年3月前有关患儿出生顺序

  16. Childhood maltreatment and amygdala connectivity in methamphetamine dependence: a pilot study

    OpenAIRE

    Dean, Andy C.; Kohno, Milky; Hellemann, Gerhard; London, Edythe D

    2014-01-01

    Introduction Childhood maltreatment, a well-known risk factor for the development of substance abuse disorders, is associated with functional and structural abnormalities in the adult brain, particularly in the limbic system. However, almost no research has examined the relationship between childhood maltreatment and brain function in individuals with drug abuse disorders. Methods We conducted a pilot study of the relationship between childhood maltreatment (evaluated with the Childhood Traum...

  17. Very late recurrences of leukemia: why does leukemia awake after many years of dormancy?

    Science.gov (United States)

    Norkin, Maxim; Uberti, Joseph P; Schiffer, Charles A

    2011-02-01

    We report a heterogeneous group of very late recurrences of leukemia occurring more than 10 years after initial treatment including 2 cases of childhood acute lymphoblastic leukemia (ALL) which recurred after more than 20 years of remission, 2 cases of donor cell leukemia which developed more than 10 years after allograft for acute myeloid leukemia (AML) and high risk myelodysplastic syndrome (MDS) and 2 cases of chronic myeloid leukemia (CML) relapsing 13 and 17 years after allograft. Case descriptions are followed by a discussion regarding possible mechanisms leading to leukemia recurrence and a review of the literature.

  18. A Cultural Studies Approach to the Teaching of the Sociology of Children and Childhood

    Directory of Open Access Journals (Sweden)

    Donna King

    2006-04-01

    Full Text Available A cultural studies approach to the teaching of the sociology of childhood is presented, including numerous suggested videos. The course begins with the question, "What is childhood?" and proceeds from there to show how childhood has changed over the years as cultural expectations have changed.

  19. Students' Acquisition of a Threshold Concept in Childhood and Youth Studies

    Science.gov (United States)

    Ashworth, Helen

    2016-01-01

    This paper follows undergraduate students' engagement with the concept of childhood presented to them during a year-long childhood and youth studies module. Through the application of "threshold concepts" as concepts which transform students' understandings of a subject, the challenges of learning new ideas or concepts of childhood are…

  20. Risk of thyroid cancer, brain cancer, and non-Hodgkin lymphoma after adult leukemia

    DEFF Research Database (Denmark)

    Nielsen, Sune F; Bojesen, Stig E; Birgens, Henrik S

    2011-01-01

    Patients with childhood leukemia surviving into adulthood have elevated risk of developing thyroid cancer, brain cancer, and non-Hodgkin lymphoma (NHL); these risks cannot automatically be extrapolated to patients surviving adult leukemia. We tested whether survivors of adult leukemia...... are at increased risk of developing thyroid cancer, brain cancer, and NHL. We included the entire adult Danish population (14 years of age or older), in a 28-year follow-up period from 1980 through 2007, composed of 6 542 639 persons; during this period, 18 834 developed adult leukemia, 4561 developed thyroid...... cancer, 13 362 developed brain cancer, and 15 967 developed NHL. In nested studies using Cox regression models on individual participant data, we found that, after adult leukemia, the multivariate adjusted hazard ratios were 4.9 (95% confidence interval [CI], 2.8-8.5) for thyroid cancer, 1.9 (95% CI, 1...

  1. [Advances of study on prognostic factors of molecular biology in acute myeloid leukemia with normal cytogenetics].

    Science.gov (United States)

    Han, Tian-Jie; Xu, Xiao-Ping

    2010-08-01

    Acute myeloid leukemia (AML) is a group of diseases with a conspicuous heterogeneity. Following the development of cytogenetics, multiple reproducible chromosome aberrations have been discovered in AML, many of which not only are diagnostic markers for specific AML subtypes but also significant prognostic factors for determining complete remission (CR), relapse risk, and overall survival (OS). However, with the foundation of available chromosome analysis, a large group of acute myeloid leukemia (AML) patients, 40% to 49% of adults and 25% of children had not been found abnormality of chromosome karyotype under microscope. These so-called cytogenetically normal acute myeloid leukemia (CN-AML) patients have usually been classified in an intermediate-risk prognostic category. Nevertheless, the outcome of the CN-AML patients are varied in clinical studies, likely because there exist diverse gene mutations in these patients according to recent researches. Those mutations at the molecular level, on basis of which AML could be further classified, are significantly associated with CN-AML patients and offer potential targets for specific therapeutic studies. The review focuses on research advances abroad in this field including gene mutations suggesting bad prognosis such as FMS-related tyrosine kinase 3 gene mutation, Baalc gene and ETS-related gene hyperexpression, Wilms' tumor gene mutation and other gene mutations as well as gene mutations suggesting good prognosis such as nucleophosmin gene mutation, mixed lineage leukemia-partial tandem duplication, CCAAT/enhancer-binding protein α gene mutation.

  2. Autologous Peripheral Blood Stem Cell Transplant Followed by Donor Bone Marrow Transplant in Treating Patients With High-Risk Hodgkin Lymphoma, Non-Hodgkin Lymphoma, Multiple Myeloma, or Chronic Lymphocytic Leukemia

    Science.gov (United States)

    2016-06-17

    B-Cell Prolymphocytic Leukemia; Plasma Cell Leukemia; Progression of Multiple Myeloma or Plasma Cell Leukemia; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Non-Hodgkin Lymphoma; Recurrent Childhood Hodgkin Lymphoma; Recurrent Childhood Non-Hodgkin Lymphoma; Recurrent Chronic Lymphocytic Leukemia; Recurrent Plasma Cell Myeloma; Recurrent Small Lymphocytic Lymphoma; Refractory Childhood Hodgkin Lymphoma; Refractory Chronic Lymphocytic Leukemia; Refractory Non-Hodgkin Lymphoma; Refractory Plasma Cell Myeloma; Refractory Small Lymphocytic Lymphoma; T-Cell Prolymphocytic Leukemia; Waldenstrom Macroglobulinemia

  3. Long-term follow-up study and long-term care of childhood cancer survivors

    Directory of Open Access Journals (Sweden)

    Hyeon Jin Park

    2010-04-01

    Full Text Available The number of long-term survivors is increasing in the western countries due to remarkable improvements in the treatment of childhood cancer. The long-term complications of childhood cancer survivors in these countries were brought to light by the childhood cancer survivor studies. In Korea, the 5-year survival rate of childhood cancer patients is approaching 70%; therefore, it is extremely important to undertake similar long-term follow-up studies and comprehensive long-term care for our population. On the basis of the experiences of childhood cancer survivorship care of the western countries and the current Korean status of childhood cancer survivors, long-term follow-up study and long-term care systems need to be established in Korea in the near future. This system might contribute to the improvement of the quality of life of childhood cancer survivors through effective intervention strategies.

  4. Mixed phenotype acute leukemia

    Institute of Scientific and Technical Information of China (English)

    Ye Zixing; Wang Shujie

    2014-01-01

    Objective To highlight the current understanding of mixed phenotype acute leukemia (MPAL).Data sources We collected the relevant articles in PubMed (from 1985 to present),using the terms "mixed phenotype acute leukemia","hybrid acute leukemia","biphenotypic acute leukemia",and "mixed lineage leukemia".We also collected the relevant studies in WanFang Data base (from 2000 to present),using the terms "mixed phenotype acute leukemia" and "hybrid acute leukemia".Study selection We included all relevant studies concerning mixed phenotype acute leukemia in English and Chinese version,with no limitation of research design.The duplicated articles are excluded.Results MPAL is a rare subgroup of acute leukemia which expresses the myeloid and lymphoid markers simultaneously.The clinical manifestations of MPAL are similar to other acute leukemias.The World Health Organization classification and the European Group for Immunological classification of Leukaemias 1998 cdteria are most widely used.MPAL does not have a standard therapy regimen.Its treatment depends mostly on the patient's unique immunophenotypic and cytogenetic features,and also the experience of individual physician.The lack of effective treatment contributes to an undesirable prognosis.Conclusion Our understanding about MPAL is still limited.The diagnostic criteria have not been unified.The treatment of MPAL remains to be investigated.The prognostic factor is largely unclear yet.A better diagnostic cdteria and targeted therapeutics will improve the therapy effect and a subsequently better prognosis.

  5. Equity and Quality? Challenges for Early Childhood and Primary Education in Ethiopia, India and Peru. Working Papers in Early Childhood Development, No. 55. Studies in Early Childhood Transitions

    Science.gov (United States)

    Woodhead, Martin; Ames, Patricia; Vennam, Uma; Abebe, Workneh; Streuli, Natalia

    2009-01-01

    Part of the "Studies in Early Transitions" series, this Working Paper draws on interviews and observations carried out as part of "Young Lives", a 15-year longitudinal study of childhood poverty in Ethiopia, India, Peru and Vietnam based at the University of Oxford's Department of International Development. This paper focuses…

  6. Tretinoin and Arsenic Trioxide in Treating Patients With Untreated Acute Promyelocytic Leukemia

    Science.gov (United States)

    2016-07-08

    Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Childhood Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Myeloid Neoplasm

  7. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    Science.gov (United States)

    ... Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute ... bleeding and forming blood clots. Smoking, previous chemotherapy treatment, and exposure to radiation may affect the risk ...

  8. Relapse in childhood acute lymphoblastic leukemia after elective cessation of initial treatment: failure of subsequent treatment with cyclophosphamide, cytosine arabinoside, vincristine and prednisone (COAP).

    Science.gov (United States)

    Sallan, S E; Hitchcock-Bryan, S

    1981-01-01

    Although the majority of children with acute lymphoblastic leukemia (ALL) can electively stop treatment after 2 1/2-5 years of continuous disease-free remission, 20-25% of those patients relapse after discontinuation of therapy. We treated 15 patients whose disease recurred after stopping treatment. Fourteen of them attained complete remission, but the median duration of disease-free survival was only 11 months. In this population, the site of initial relapse, bone marrow or testicle, did not influence subsequent outcome. Patients who relapsed within six months of stopping initial therapy had shorter second remissions than those who relapsed after six months. We conclude that the combination chemotherapy utilized in this study was inadequate for the control of relapsed ALL. Future programs will have to use different drug combinations or bone marrow transplantation.

  9. Risk of thyroid cancer in survivors of childhood cancer: results from the British Childhood Cancer Survivor Study.

    Science.gov (United States)

    Taylor, Aliki J; Croft, Adam P; Palace, Aimee M; Winter, David L; Reulen, Raoul C; Stiller, Charles A; Stevens, Michael C G; Hawkins, Mike M

    2009-11-15

    Second primary neoplasms (SPNs) are a recognised late effect of treatment for childhood cancer. Thyroid SPNs can develop after exposure to low-dose radiation, due to the radio-sensitivity of the thyroid gland. The British Childhood Cancer Survivor Study (BCCSS) was set up to directly monitor the late effects of treatment, including risk of SPNs, in childhood cancer survivors and includes 17,980 5-year survivors. We carried out a cohort analysis to determine the risk of thyroid SPNs in the BCCSS, and estimated risk using standardised incidence ratios (SIRs), relative risk (RR) using multivariate Poisson regression and cumulative incidence curves. There were 340,202 person years at risk subsequent to a 5-year survival, median follow-up 17.4 years per survivor. We identified 50 thyroid SPNs including 31 (62%) papillary carcinomas, 15 (30%) follicular carcinomas and 4 (8%) other types. 88% of thyroid SPNs developed after exposure to radiotherapy in or around the thyroid gland. SIR overall was 18.0 (95% confidence interval 13.4-23.8). Risk of thyroid cancer was highest after Hodgkin's disease: RR 3.3 (1.1-10.1) and Non Hodgkin's Lymphoma: RR 3.4 (1.1-10.7) relative to leukaemia (RR 1.0) (p Survivors treated with radiotherapy in childhood had a RR of 4.6 (1.4-15.1) relative to survivors not treated with radiotherapy (RR 1.0), p = 0003. In conclusion, the risk of thyroid cancer in childhood cancer survivors is relatively high in this cohort of childhood cancer survivors. These results will be of use in counselling survivors of childhood cancer exposed to radiation in or around the thyroid area.

  10. High-Dose Busulfan and High-Dose Cyclophosphamide Followed By Donor Bone Marrow Transplant in Treating Patients With Leukemia, Myelodysplastic Syndrome, Multiple Myeloma, or Recurrent Hodgkin or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2010-08-05

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Megakaryoblastic Leukemia (M7); Adult Acute Monoblastic Leukemia (M5a); Adult Acute Monocytic Leukemia (M5b); Adult Acute Myeloblastic Leukemia With Maturation (M2); Adult Acute Myeloblastic Leukemia Without Maturation (M1); Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With Inv(16)(p13;q22); Adult Acute Myeloid Leukemia With T(15;17)(q22;q12); Adult Acute Myeloid Leukemia With T(16;16)(p13;q22); Adult Acute Myeloid Leukemia With T(8;21)(q22;q22); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Adult Pure Erythroid Leukemia (M6b); Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Burkitt Lymphoma; Childhood Acute Erythroleukemia (M6); Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Megakaryocytic Leukemia (M7); Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia With Maturation (M2); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia in Remission; Childhood Acute Myelomonocytic Leukemia (M4); Childhood Acute Promyelocytic Leukemia (M3); Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; De Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Nodal Marginal Zone B-cell Lymphoma; Peripheral T-Cell Lymphoma; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent

  11. Myeloid antigens in childhood lymphoblastic leukemia:clinical data point to regulation of CD66c distinct from other myeloid antigens

    Directory of Open Access Journals (Sweden)

    Madzo Jozef

    2005-04-01

    Full Text Available Abstract Background Aberrant expression of myeloid antigens (MyAgs on acute lymphoblastic leukemia (ALL cells is a well-documented phenomenon, although its regulating mechanisms are unclear. MyAgs in ALL are interpreted e.g. as hallmarks of early differentiation stage and/or lineage indecisiveness. Granulocytic marker CD66c – Carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6 is aberrantly expressed on ALL with strong correlation to genotype (negative in TEL/AML1 and MLL/AF4, positive in BCR/ABL and hyperdiploid cases. Methods In a cohort of 365 consecutively diagnosed Czech B-precursor ALL patients, we analyze distribution of MyAg+ cases and mutual relationship among CD13, CD15, CD33, CD65 and CD66c. The most frequent MyAg (CD66c is studied further regarding its stability from diagnosis to relapse, prognostic significance and regulation of surface expression. For the latter, flow cytometry, Western blot and quantitative RT-PCR on sorted cells is used. Results We show CD66c is expressed in 43% patients, which is more frequent than other MyAgs studied. In addition, CD66c expression negatively correlates with CD13 (p Conclusion In contrast to general notion we show that different MyAgs in lymphoblastic leukemia represent different biological circumstances. We chose the most frequent and tightly genotype-associated MyAg CD66c to show its stabile expression in patients from diagnosis to relapse, which differs from what is known on the other MyAgs. Surface expression of CD66c is regulated at the gene transcription level, in contrast to previous reports.

  12. Risk of leukemia among survivors of testicular cancer: a population-based study of 42,722 patients

    DEFF Research Database (Denmark)

    Howard, R.; Gilbert, E.; Lynch, C.F.

    2008-01-01

    PURPOSE: The aim of this study is to quantify excess absolute risk (EAR) and excess relative risk (ERR) of secondary leukemia among a large population-based group of testicular cancer survivors. METHODS: We identified 42,722 1-year survivors of testicular cancer within 14 population-based cancer...... among patients whose initial management included chemotherapy compared to those receiving radiotherapy alone (p = 0.1). Excess cumulative leukemia risk was approximately 0.23% by 30 years after testicular cancer diagnosis. CONCLUSIONS: Although ERR of leukemia following testicular cancer is large, EAR...

  13. Prospective study on incidence, risk factors, and long-term outcome of osteonecrosis in pediatric acute lymphoblastic leukemia.

    NARCIS (Netherlands)

    Winkel, M.L. te; Pieters, R.; Hop, W.C.J.; Groot-Kruseman, H.A. de; Lequin, M.H.; Sluis, I.M. van der; Bokkerink, J.P.M.; Leeuw, J.A. de; Bruin, M.C.; Egeler, R.M.; Veerman, A.J.P.; Heuvel-Eibrink, M.M. van den

    2011-01-01

    PURPOSE: We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). PATIENTS AND METHODS: Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with

  14. Prospective Study on Incidence, Risk Factors, and Long-Term Outcome of Osteonecrosis in Pediatric Acute Lymphoblastic Leukemia

    NARCIS (Netherlands)

    Winkel, Mariel L. Te; Pieters, Rob; Hop, Wim C. J.; de Groot-Kruseman, Hester A.; Lequin, Maarten H.; van der Sluis, Inge M.; Bokkerink, Jos P. M.; Leeuw, Jan A.; Bruin, Marrie C. A.; Egeler, R. Maarten; Veerman, Anjo J. P.; van den Heuvel-Eibrink, Marry M.

    2011-01-01

    Purpose We studied cumulative incidence, risk factors, therapeutic strategies, and outcome of symptomatic osteonecrosis in pediatric patients with acute lymphoblastic leukemia (ALL). Patients and Methods Cumulative incidence of osteonecrosis was assessed prospectively in 694 patients treated with th

  15. No major cognitive impairment in young children with acute lymphoblastic leukemia using chemotherapy only : A prospective longitudinal study

    NARCIS (Netherlands)

    Kingma, A; Van Dommelen, RI; Mooyaart, EL; Wilmink, JT; Deelman, BG; Kamps, WA

    2002-01-01

    Purpose: To study. using serial neuropsychological assessment and evaluation of school achievement, persistent neuropsychological late effects in children treated for acute lymphoblastic leukemia (ALL) at a young age with chemotherapy only. Patients and Methods: Twenty consecutive patients underwent

  16. Pattern of chromosome involvement in childhood hyperdiploid pre-B-cell acute lymhoblastic leukemia cases from India

    Directory of Open Access Journals (Sweden)

    Lily S. Kerketta

    2014-01-01

    Conclusion: In this study, the pattern of chromosome involvement in hyperdiploid karyotype of ALL patients is same as other studies except some chromosomes like 1, 6, 11, 12, 19 and 22 have some more frequent involvement than other studies. This study also showed the occurrence of TEL/AML1 fusion is more (19.8% than other reports from India.

  17. Course and Long-Term Outcome of Childhood-Onset Epilepsy: Dutch study of epilepsy in childhood

    NARCIS (Netherlands)

    A.T. Geerts (Ada)

    2012-01-01

    textabstractIn a hospital-based study, 494 children with epilepsy were prospectively followed up from the time of diagnosis. The main objective of this study was to investigate the course of childhood-onset epilepsy during a period of 15 years. Generally, medication is withdrawn after a 2-year remis

  18. Response of chronic myelogenous leukemia patients to COAP-splenectomy. A Southwest Oncology Group study.

    Science.gov (United States)

    Hester, J P; Waddell, C C; Coltman, C A; Morrison, F S; Stephens, R L; Balcerzak, S P; Baker, L H; Chen, T T

    1984-11-01

    Eighty-seven patients from 18 institutions with a confirmed diagnosis of chronic myelogenous leukemia were registered on a Southwest Oncology Group protocol for multiagent induction and single-agent maintenance chemotherapy, with randomization to an immunotherapy arm. Elective surgical splenectomy was performed for 42 patients at the completion of 3 months of induction therapy. Final analysis of the study revealed statistically significant survival advantages were correlated with age, splenectomy, the absence of hepatic leukemic infiltrate at the time of splenectomy, and race.

  19. Drugs under preclinical and clinical study for treatment of acute and chronic lymphoblastic leukemia

    OpenAIRE

    Jacob JA; Salmani JMM; Chen B

    2016-01-01

    Joe Antony Jacob, Jumah Masoud Mohammad Salmani, Baoan Chen Department of Hematology and Oncology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, People’s Republic of China Abstract: Targeted therapy has modernized the treatment of both chronic and acute lymphoblastic leukemia. The introduction of monoclonal antibodies and combinational drugs has increased the survival rate of patients. Preclinical studies with various agents have resulted in positive outputs...

  20. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner;

    2015-01-01

    associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups...

  1. Results of external quality control study in flow cytometric acute lymphoblastic leukemia diagnostics

    Directory of Open Access Journals (Sweden)

    A. M. Popov

    2016-01-01

    Full Text Available Comparison of interpretation of acute lymphoblastic leukemia (ALL flow cytometric diagnostics data was the aim of the study. Immunophenotyping data obtained from 10 patients with ALL were analysed separately in 26 laboratories from Russian Federation and Kazahstan. Results comparison showed four main type of discordance: B-lineage ALL diagnostics during heavy bone marrow regeneration, great variability of T-ALL interpretation, complexity of ambiguous lineage acute leukemia and, finally, very different report types, unique for each laboratory. All these problems are the serious obstacles for standardization of flow cytometric ALL diagnostics in multicenter setting. Continuation of similar QC rounds following by consecutive discussions with further development of consensus diagnostic algorithm could be the first step for standardization of ALL immunophenotyping in Russian Federation and CIS countries.

  2. Childhood Precursors of Adult Borderline Personality Disorder Features: A Longitudinal Study.

    Science.gov (United States)

    Cramer, Phebe

    2016-07-01

    This study identifies childhood personality traits that are precursors of adult Borderline Personality Disorder (BPD) features. In a longitudinal study, childhood personality traits were assessed at age 11 (N = 100) using the California Child Q-set (CCQ: Block and Block, 1980). A number of these Q-items were found to be significantly correlated (p features at age 23. Factor analysis of these Q-items suggested that they could be characterized by two underlying personality dimensions: Impulsivity and Nonconformity/Aggression. The findings thus provide evidence that childhood personality traits predict adult BPD features. Identifying such childhood precursors provides an opportunity for early intervention.

  3. Early life predictors of childhood intelligence: evidence from the Aberdeen children of the 1950s study

    OpenAIRE

    Lawlor,D.A.; Batty, G D; Morton, S M B; Deary, I.J.; Macintyre, S.; Ronalds, G.; Leon, D. A.

    2005-01-01

    Objective: To identify the early life predictors of childhood intelligence. \\ud \\ud Design: Cohort study of 10 424 children who were born in Aberdeen (Scotland) between 1950 and 1956. \\ud \\ud Results: Social class of father around the time of birth, gravidity, maternal age, maternal physical condition, whether the child was born outside of marriage, prematurity, intrauterine growth, and childhood height were all independently associated with childhood intelligence at ages 7, 9, and 11. The ef...

  4. Final height and body mass index among adult survivors of childhood brain cancer: childhood cancer survivor study.

    Science.gov (United States)

    Gurney, James G; Ness, Kirsten K; Stovall, Marilyn; Wolden, Suzanne; Punyko, Judy A; Neglia, Joseph P; Mertens, Ann C; Packer, Roger J; Robison, Leslie L; Sklar, Charles A

    2003-10-01

    The objectives of this study were 1) to compare final height and body mass index (BMI) between adult survivors of childhood brain cancer and age- and sex-matched population norms, 2) to quantify the effects of treatment- and cancer-related factors on the risk of final height below the 10th percentile (adult short stature) or having a BMI of 30 kg/m(2) or more (obesity). Treatment records were abstracted and surveys completed by 921 adults aged 20-45 yr who were treated for brain cancer as children and were participants in the multicenter Childhood Cancer Survivor Study. Nearly 40% of childhood brain cancer survivors were below the 10th percentile for height. The strongest risk factors for adult short stature were young age at diagnosis and radiation treatment involving the hypothalamic-pituitary axis (HPA). The multivariate odds ratio for adult short stature among those 4 yr of age or younger at diagnosis, relative to ages 10-20 yr, was 5.67 (95% confidence interval, 3.6-8.9). HPA radiation exposure increased the risk of adult short stature in a dose-response fashion (trend test, P obesity. Except for patients treated with surgery only, survivors of childhood brain cancer are at very high risk for adult short stature, and this risk increases with radiation dose involving the HPA. We did not find a corresponding elevated risk for obesity.

  5. Experiences of mothers on parenting children with leukemia

    Directory of Open Access Journals (Sweden)

    Sheryl Jyothi Cornelio

    2016-01-01

    Full Text Available Introduction: Childhood cancer is the leading cause of death among children. Leukemia is one of the most common childhood cancers. Objective: The objective of this study was to explore the experiences of mothers on parenting children with leukemia. Materials and Methods: A qualitative approach with phenomenological design was used. To collect depth information from the mothers of children with leukemia, purposive sampling technique was adopted. Data were collected from ten mothers. Semi-structured interview schedule was used to collect the data. Data were analyzed using Husserl's method. Result: The themes derived are the pivotal moment in life, the experience of being with a seriously ill child, having to keep distance with the relatives, overcoming the financial and social commitments, responding to challenges, experience of faith as being key to survival, health concerns of the present and future, and optimism. Conclusion: The study concluded that chronic illness such as leukemia in children results in negative impact on the child and on the mother.

  6. Computerized games to study the development of attention in childhood.

    Science.gov (United States)

    Berger, A; Jones, L; Rothbart, M K; Posner, M I

    2000-05-01

    Children enjoy playing games. We can take advantage of this in the designs of computerized tasks that will engage their interest. These designs also serve to advance the study of chronometric measures, such as manual and saccadic reaction times and event related potentials, with young children. The goals of our method development are (1) to allow for comparable tasks across a wide variety of ages, (2) to make possible comparisons of child performance with data gathered in adult cognitive studies, and (3) to help to support inferences about the development of underlying mechanisms. We have designed a battery of computerized tasks in order to study the development of attention functions of alertness, orienting, and executive control during childhood. Our purpose is to describe each of these tasks in detail and present the results that have been obtained so far. The battery was tested using a sample of 5-year-old children as subjects.

  7. 尿中金属元素水平与儿童急性白血病之间的关系%Correlation between level of metallic elements in urine and childhood acute leukemia

    Institute of Scientific and Technical Information of China (English)

    朱莎; 沈晓明; 张妍; 高宇; 王筱金; 陈涛; 杨友; 施蓉; 金萍; 田英

    2011-01-01

    Objective To explore the relation between the level of metallic elements in urine and childhood acute leukemia. Methods A total of 71 patients under 15 years old who were newly diagnosed with acute leukemia between September 2007 and August 2008 without Downs' syndrome or other tumors,and 113 gender-and age-matched controls without tunors or congenital diseases were enrolled for the case-control study.The general data and potential risk factors were obtained by questionnaires.Inductively coupled plasma mass spectrometry (ICP-MS) was used to determine the metal concentrations in urine,which was collected randomly before chemotherapy.Logistic regression model was performed for univariate and multivariate analysis. Results The questionnaire showed that there was significant difference in the proportion of children whose mothers had taken iron supplements during or 3 months before pregnancy between case group and control group,which was 28.2% (20/71) and 14.2% (16/113) respectively (Wald x2 = 5.438,P =0.02).Univariate logistic regression analysis showed that levels of vanadium,manganese,iron,cobalt,copper,arsenic,and barium in urine from case group were all higher than those of control group with significant difference.The median values for vanadium in urine from case and control groups were 5.39 and 3.04 ng/mg creatinine (Wald x2 = 9.03,P < 0.05);the median values for manganese were respectively 4.46 and 2.44 ng/mg creatinine (Wald x2 = 10.57,P <0.05);the median values for iron were separately 58.69 and 14.09 ng/mg creatinine (Wald x2 = 13.41,P < 0.05);the median values for cobalt were respectively 0.98 and 0.77 ng/mg creatinine (Wald x2 = 4.46,P < 0.05);the median values for copper were 61.17 and 10.90 ng/mg creatinine (Wald x2 = 8.15,P < 0.05);the median values for arsenic were respectively 55.93 and 36.11 ng/mg creatinine (Wald x2 = 4.57,P < 0.05);and the median values for barium were 8.55 and 2.87 ng/mg creatinine (Wald x2 = 4.82,P < 0

  8. Childhood Cancer: Leukemia (For Parents)

    Science.gov (United States)

    ... problems — such as Li-Fraumeni syndrome, Down syndrome , Klinefelter syndrome , neurofibromatosis , ataxia telangectasia, or Fanconi's anemia — have ... cancers. The doctor also will take a medical history by asking about symptoms, past health, the family's ...

  9. The Copenhagen Prospective Study on Asthma in Childhood (COPSAC)

    DEFF Research Database (Denmark)

    Bisgaard, Hans

    2004-01-01

    . Exposure assessments comprise respiratory, intestinal, and skin microbiology; the child's diet; indoor and outdoor air quality; allergens; and indicators of lifestyle. Genetic characteristics of probands and parents are evaluated. Quality assurance follows Good Clinical Practice guidelines. RESULTS: Four....... OBJECTIVE: To investigate the relationships among genetic, environmental, and lifestyle factors in the development of atopic diseases in high-risk children with the aim of developing evidence-based prevention strategies. METHODS: The Copenhagen Prospective Study on Asthma in Childhood is a single......-center, birth cohort study of children of asthmatic mothers. Objective assessments begin at birth, with scheduled visits every 6 months and when acute symptoms manifest. Clinical outcomes comprise preasthma, asthma, atopic dermatitis, allergic rhinitis, allergy, lung function, and bronchial responsiveness...

  10. Bullying in Childhood, Externalizing Behaviors, and Adult Offending: Evidence from a 30-Year Study

    Science.gov (United States)

    Fergusson, David M.; Boden, Joseph M.; Horwood, L. John

    2014-01-01

    This study examined the developmental processes linking childhood bullying to criminal offending in adulthood, using data from a 30-year longitudinal study. The linkages between bullying in childhood and three criminal offending outcomes in adulthood were estimated both before and after control for a range of confounding factors. A series of…

  11. Peer Victimization in Childhood and Internalizing Problems in Adolescence: A Prospective Longitudinal Study

    Science.gov (United States)

    Zwierzynska, Karolina; Wolke, Dieter; Lereya, Tanya S.

    2013-01-01

    Traumatic childhood experiences have been found to predict later internalizing problems. This prospective longitudinal study investigated whether repeated and intentional harm doing by peers (peer victimization) in childhood predicts internalizing symptoms in early adolescence. 3,692 children from the Avon Longitudinal Study of Parents and…

  12. Chronic myelogenous leukemia (CML)

    Science.gov (United States)

    CML; Chronic myeloid leukemia; Chronic granulocytic leukemia; Leukemia - chronic granulocytic ... Chronic myelogenous leukemia is grouped into phases: Chronic Accelerated Blast crisis The chronic phase can last for ...

  13. Infections During Induction Therapy of Protocol CCLG-2008 in Childhood Acute Lymphoblastic Leukemia: A Single-center Experience with 256 Cases in China

    Institute of Scientific and Technical Information of China (English)

    Si-Dan Li; Yong-Bing Chen; Zhi-Gang Li; Run-Hui Wu; Mao-Quan Qin; Xuan Zhou; Jin Jiang

    2015-01-01

    Background:Infections remain a major cause of therapy-associated morbidity and mortality in children with acute lymphoblastic leukemia (ALL).Methods:We retrospectively analyzed the medical charts of 256 children treated for ALL under the CCLG-2008 protocol in Beijing Children's Hospital.Results:There were 65 infectious complications in 50 patients during vincristine,daunorubicin,L-asparaginase and dexamethasone induction therapy,including microbiologically documented infections (n =12; 18.5%),clinically documented infections (n =23; 35.3%) and fever of unknown origin (n =30; 46.2%).Neutropenia was present in 83.1% of the infectious episodes.In all,most infections occurred around the 15t1h day of induction treatment (n =28),and no patients died of infection-associated complications.Conclusions:The infections in this study was independent of treatment response,minimal residual diseases at the end of induction therapy,gender,immunophenotype,infection at first visit,risk stratification at diagnosis,unfavorable karyotypes at diagnosis and morphologic type.The infection rate of CCLG-2008 induction therapy is low,and the outcome of patients is favorable.

  14. Cooperating gene mutations in childhood acute myeloid leukemia with special reference on mutations of ASXL1, TET2, IDH1, IDH2, and DNMT3A.

    Science.gov (United States)

    Liang, Der-Cherng; Liu, Hsi-Che; Yang, Chao-Ping; Jaing, Tang-Her; Hung, Iou-Jih; Yeh, Ting-Chi; Chen, Shih-Hsiang; Hou, Jen-Yin; Huang, Ying-Jung; Shih, Yu-Shu; Huang, Yu-Hui; Lin, Tung-Huei; Shih, Lee-Yung

    2013-04-11

    Gene mutations involving epigenetic regulators recently have been described in adult acute myeloid leukemia (AML). Similar studies are limited in children. We analyzed gene mutations and cooperation in pediatric AML with special reference on mutated epigenetic regulators. Nineteen gene mutations, including 8 class I genes, 4 class II genes, WT1 and TP53 (class III), and 5 epigenetic regulator genes (class IV), were analyzed in 206 children with de novo AML. Mutational analysis was performed with polymerase chain reaction-based assay followed by direct sequencing. One hundred seventeen of 206 patients (56.8%) had at least one mutation: 51% class I, 13% class II, 6.8% class III, and 5.6% class IV. FLT3-internal tandem duplication was most frequent, and 29% of patients had more than one gene mutation. Two patients carried ASXL1 mutations, both with t(8;21), 2 had DNMT3A mutations, 2 had IDH1 mutations, 1 had IDH2 mutation, and 3 had TET2 mutations. Both patients with IDH1 mutations had AML-M0 subtype and MLL-partial tandem duplication. Cooperating mutations with mutated epigenetic regulators were observed in 8 of 10 patients. We conclude that mutated epigenetic regulators were much less than those in adult AML but with frequent cooperating mutations. ASXL1, TET2, and IDH1 mutations were associated with specific genetic subtypes.

  15. Renovating Early Childhood Education Pedagogy: A Case Study in Vietnam

    Science.gov (United States)

    Thao, Dang Phuong; Boyd, Wendy Anne

    2014-01-01

    Since 2003, the Vietnamese government has prioritised curriculum reform efforts and commitment to improving the quality of the national curriculum. The Vietnamese early childhood education renovation has encountered considerable changes and challenges, particularly in the area of pedagogical approaches. Many early childhood teachers continue to…

  16. "I Am Not a Babysitter": A Case Study of Five Chinese Mainland Early Childhood Teachers' Identity

    Science.gov (United States)

    Zhang, Limin; Yu, Shulin

    2017-01-01

    Although studies on teacher identity have proliferated in recent years, and examinations of the said topic have been conducted under various educational contexts, limited focus has been given to teacher identity in the early childhood educational context. Drawing upon data from semi-structured interviews with five early childhood teachers, this…

  17. Is Childhood Physical Abuse Associated with Peptic Ulcer Disease? Findings from a Population-Based Study

    Science.gov (United States)

    Fuller-Thomson, Esme; Bottoms, Jennifer; Brennenstuhl, Sarah; Hurd, Marion

    2011-01-01

    This study investigated childhood physical abuse and ulcers in a regionally representative community sample. Age, race and sex were controlled for in addition to five clusters of potentially confounding factors: adverse childhood conditions, adult socioeconomic status, current health behaviors, current stress and marital status, and history of…

  18. Childhood trauma, psychosis liability and social stress reactivity : a virtual reality study

    NARCIS (Netherlands)

    Veling, W.; Counotte, J.; Pot-Kolder, R.; van Os, J.; van der Gaag, M.

    2016-01-01

    Background. Childhood trauma is associated with higher risk for mental disorders, including psychosis. Heightened sensitivity to social stress may be a mechanism. This virtual reality study tested the effect of childhood trauma on level of paranoid ideations and distress in response to social stress

  19. Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.

    Science.gov (United States)

    Aricò, Maurizio; Valsecchi, Maria Grazia; Conter, Valentino; Rizzari, Carmelo; Pession, Andrea; Messina, Chiara; Barisone, Elena; Poggi, Vincenzo; De Rossi, Giulio; Locatelli, Franco; Micalizzi, Maria Concetta; Basso, Giuseppe; Masera, Giuseppe

    2002-07-15

    One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.

  20. Leukemia revisited

    Energy Technology Data Exchange (ETDEWEB)

    Cronkite, E P

    1980-01-01

    Selected features of the historical development of our knowledge of leukemia are discussed. The use of different methodologies for study of the nature of leukemic cell proliferation are analyzed. The differences between older cell kinetic data using tritiated thymidine and autoradiography and the newer cell culture methods are more apparent than real. It is suggested that tritiated thymidine and extracorporeal irradiation of the blood may be useful for therapeutic agents that have not been given an adequate trial. Radiation leukemogenesis presents an opportunity for study of the nature of leukemogenesis that has not been exploited adequately.

  1. Human parvovirus B19 DNA is not detected in Guthrie cards from children who have developed acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Isa, Adiba; Priftakis, Peter; Broliden, Kristina;

    2004-01-01

    BACKGROUND: There has been much speculation about the cause of childhood acute lymphoblastic leukemia (ALL). It has been suggested, on the basis of findings in epidemiological studies, that ALL may be initiated by an in utero infection of the fetus. The human parvovirus B19 (B19) is etiologically...

  2. Allogeneic Transplantation for Patients With Acute Leukemia or Chronic Myelogenous Leukemia (CML)

    Science.gov (United States)

    2016-06-14

    Leukemia, Lymphocytic, Acute; Leukemia; Leukemia Acute Promyelocytic Leukemia (APL); Leukemia Acute Lymphoid Leukemia (ALL); Leukemia Chronic Myelogenous Leukemia (CML); Leukemia Acute Myeloid Leukemia (AML); Leukemia Chronic Lymphocytic Leukemia (CLL)

  3. Leukemia cutis

    Directory of Open Access Journals (Sweden)

    Varuna Mallya

    2015-01-01

    Full Text Available Patients with leukemia may show involvement of the skin. This skin involvement can be due to infiltration of skin by leukemic cells or it may be a part of nonspecific cutaneous manifestations. Leukemia cutis is the infiltration of neoplastic leucocytes or their precursors into the skin resulting in extensive clinical manifestations. Described mostly in acute myeloid leukemia and acute myelocytic monocytic leukemia, it is rare in chronic myeloid leukemia and is seen mostly during the blast crises. Its presence signals poor prognosis.

  4. Pregabalin in childhood epilepsy: a clinical trial study

    Directory of Open Access Journals (Sweden)

    Mohsen MOLLAMOHAMMADI*

    2014-12-01

    Full Text Available How to Cite This Article: Mollamohammadi M, Tonekaboni SH, Pirzadeh Z, Vahedian M . Pregabalin in Childhood Epilepsy: A Clinical TrialIran J Child Neurol. 2014 Autumn;8(4: 62-65.AbstractObjectiveThe prevalence of active epilepsy is about 0.5–1%, and approximately 70% of patients are cured with first anti-epileptic drugs and the remaining patients need multiple drugs. Pregabalin as an add-on therapy has a postive effect on refractory seizures in adults. To the best of our knowledge, there is no research with this drug in childhood epilepsy. We use pregabalin in children with refractory seizures as an add-on therapy. The objective of this study is to evaluate the effects of pregabalin in the reduction of seizures for refractory epilepsy.Material & MethodsForty patients with refractory seizures who were referred to Mofid Children’s Hospital and Hazrat Masoumeh Hospital were selected. A questionnaire based on patient record forms, demographic data (age, gender,…, type of seizure, clinical signs, EEG record, imaging report, drugs that had been used, drugs currently being used, and the number of seizures before and after Pregabalin treatment was completed. We checked the number of seizures after one and four months.ResultsAfter one month, 26.8% of patients had more than a 50% reduction in seizures and 14.6% of these patients were seizure-free; 12.2% had a 25–50% reduction; and approximately 61% had less than a 25% reduction or no change in seizures.After the fourth month, 34.1% of patients had more than a 50% reduction in seizures and 24.4% of these patients were seizure-free. Additionally, 65.9% of patients had less than 50% reduction in seizures (9.8% between 25–50% and 56.1% less than 25% or without improvement.ConclusionWe recommend Pregabalin as an add-on therapy for refractory seizures (except for myoclonic seizures for children.ReferencesKwan P., Brodie MJ. Early identification of refractory epilepsy. N Engl J Med 2000

  5. Genomic profiling of thousands of candidate polymorphisms predicts risk of relapse in 778 Danish and German childhood acute lymphoblastic leukemia patients

    DEFF Research Database (Denmark)

    Wesolowska, Agata; Borst, L.; Dalgaard, Marlene Danner;

    2015-01-01

    defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates...

  6. Flow Cytometric DNA index, G-band Karyotyping, and Comparative Genomic Hybridization in Detection of High Hyperdiploidy in Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Nygaard, Ulrikka; Larsen, Jacob; Kristensen, Tim D;

    2006-01-01

    High hyperdiploid acute lymphoblastic leukemia in children is related to a good outcome. Because these patients may be stratified to a low-intensity treatment, we have investigated the sensitivity of flow cytometry (FCM), G-band karyotyping (GBK), and high-resolution comparative genomic hybridiza...

  7. Personality traits and childhood trauma as correlates of metabolic risk factors : The Netherlands Study of Depression and Anxiety (NESDA)

    NARCIS (Netherlands)

    Dortland, Arianne K. B. van Reedt; Giltay, Erik J.; van Veen, Tineke; Zitman, Frans G.; Penninx, Brenda W. J. H.

    2012-01-01

    Objective: Personality and childhood trauma may affect cardiovascular disease (CVD) risk. However, evidence for an association with metabolic risk factors for CVD is limited and ambiguous. Moreover, despite their interrelatedness, personality and childhood trauma were not yet studied simultaneously.

  8. Pregnancy, maternal exposure to analgesic medicines, and leukemia in Brazilian children below 2 years of age.

    Science.gov (United States)

    Couto, Arnaldo C; Ferreira, Jeniffer D; Pombo-de-Oliveira, Maria S; Koifman, Sérgio

    2015-05-01

    Childhood leukemia etiology, and mainly the interactions of genetic and environmental risk factors, remains largely unexplored. This national hospital-based case-control study was carried out in Brazil among children aged 0-23 months who were recruited at cancer and general hospitals in 13 states. Maternal medicine intake during pregnancy, including analgesic intake, was assessed by face-to-face interviews with the mothers of 231 leukemia patients and 411 controls. Unconditional logistic regression was used to ascertain crude and adjusted odds ratios (ORs), and their 95% confidence intervals (CIs) for the association between maternal analgesic use during pregnancy and early age leukemia. Acetaminophen use during the first trimester of pregnancy showed an OR=0.39 (95% CI 0.17-0.93) for acute lymphocytic leukemia and an OR=0.37 (95% CI 0.16-0.88) for use in the second trimester. For acute myeloid leukemia, an OR=0.11 (95% CI 0.02-0.97) was found following acetaminophen use in the second trimester. For acute lymphocytic leukemia, the exclusive use of dipyrone during preconception showed an OR=1.63 (95% CI 1.06-2.53) and dipyrone intake during lactation showed an OR=2.00 (95% CI 1.18-3.39). These results suggest that acetaminophen use during pregnancy may protect against development of early age leukemia in the offspring, whereas dipyrone use may act as a risk factor for such an outcome.

  9. Exposure to armament wastes and leukemia: a case-control study within a cluster of AML and CML in Germany.

    Science.gov (United States)

    Kilian, P H; Skrzypek, S; Becker, N; Havemann, K

    2001-10-01

    An unusually high incidence of acute myeloid leukemia (AML) and chronic myeloid leukemia (CML) concentrated in a specific locality of a region in Germany motivated a descriptive incidence study in that region which showed a near 10-fold increased risk of CML among males but not among females (Kolb G, Becker N, Scheller S, Zugmaier G, Pralle H, Wahrendorf J, Havemann K. Increased risk of acute myelogenous leukemia (AML) and chronic myelogenous leukemia (CML) in a County of Hesse, Germany, Soc Prev Med 1993;38:190-195). Since a serious environmental contamination of areas in this locality with armament wastes containing toluene-derivatives has been known for a long time, the hypothesis arose that TNT production and the related severe contamination of soil and water might be responsible for the observed higher risk. We carried out a case-control study within the cluster to test this hypothesis. Overall, the results do not confirm the hypothesis. There is an indication of a relationship of an increased odds ratio with the exposure for a small group of persons who lived at a particular site in one of the two communities involved during the peak phase of TNT production during the 1940s. However, this finding is spurious and cannot explain the large majority of cases which occurred in that area in the 1980s. At the moment, no other explanation can be given for the increased risk of leukemias in that area.

  10. Imatinib Mesylate and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome Positive Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-12-28

    B Acute Lymphoblastic Leukemia With t(9;22)(q34.1;q11.2); BCR-ABL1; BCR-ABL1 Fusion Protein Expression; Minimal Residual Disease; Philadelphia Chromosome Positive; T Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  11. Associations between childhood body size, composition, blood pressure and adult cardiac structure: the Fels Longitudinal Study.

    Directory of Open Access Journals (Sweden)

    Roy T Sabo

    Full Text Available To determine whether childhood body size, composition and blood pressure are associated with adult cardiac structure by estimating childhood "age of divergence."385 female and 312 male participants in the Fels Longitudinal Study had echocardiographic measurements of left ventricular mass, relative wall thickness, and interventricular septal thickness. Also available were anthropometric measurements of body mass index, waist circumference, percentage body fat, fat free mass, total body fat, and systolic and diastolic blood pressures, taken in both childhood and adulthood. The age of divergence is estimated as the lowest age at which childhood measurements are significantly different between patients with low and high measurements of adult cardiac structure.Childhood body mass index is significantly associated with adult left ventricular mass (indexed by height in men and women (ages of divergence: 7.5 years and 11.5 years, respectively, and with adult interventricular septal thickness in boys (age of divergence: 9 years. Childhood waist circumference indexed by height is associated with left ventricular mass (indexed by height in boys (age of divergence: 8 years. Cardiac structure was in general not associated with childhood body composition and blood pressure.Though results are affected by adult body size, composition and blood pressure, some aspects of adult cardiac structure may have their genesis in childhood body size.

  12. Temperamental characteristics in childhood migraine without aura: a multicenter study

    Directory of Open Access Journals (Sweden)

    Esposito M

    2013-08-01

    Full Text Available Maria Esposito,1 Rosa Marotta,2 Beatrice Gallai,3 Lucia Parisi,4 Giuseppina Patriciello,1 Serena Marianna Lavano,2 Giovanni Mazzotta,5 Michele Roccella,4 Marco Carotenuto11Center for Childhood Headache, Clinic of Child and Adolescent Neuropsychiatry, Department of Mental Health, Physical and Preventive Medicine, Second University of Naples, Naples, Italy; 2Department of Psychiatry, "Magna Graecia" University of Catanzaro, Catanzaro, Italy; 3Unit of Child and Adolescent Neuropsychiatry, University of Perugia, Perugia, Italy; 4Child Neuropsychiatry, Department of Psychology, University of Palermo, Palermo, Italy; 5Unit of Child and Adolescent Neuropsychiatry, AUSL Umbria 2, Terni, ItalyBackground: Children with migraine seem to be more anxious, sensitive, deliberate, cautious, fearful, vulnerable to frustration, tidy, and less physically enduring than comparisons. To the best our knowledge no studies about the temperamental and the characterial dimension aspects in childhood migraine was conducted. Therefore, the aim of the present study was to describe the temperamental and character aspects in a sample of children affected by migraine without aura (MoA and their relationship with clinical aspects of MoA such as frequency, duration, and severity of attacks.Materials and methods: In our study, 486 children affected by MoA (239 male, 247 female aged 7–12 years, (mean 10.04 ± 2.53 years and 518 typical developing children comparable for age (P = 0.227 and sex (P = 0.892 were enrolled to assess their temperamental characteristics. The mothers of all subjects filled out the Junior Temperament and Character Inventory: Parent Version.Results: Children affected by migraine show a higher prevalence of harm avoidance and persistence temperamental domains (P < 0.001 and significantly lower prevalence of the self-directedness character trait (P = 0.023 with respect to the comparisons, according to Cloninger's model. The Spearman rank correlation analysis

  13. [Donor cell leukemia (DCL): A prospective study of its identification and treatment].

    Science.gov (United States)

    Ruiz-Delgado, Guillermo J; Hernández-Reyes, Jesús; González-Ramírez, Mónica Patricia; Martagón-Herrera, Nora Ángela; Garcés-Eisele, Javier; Ruiz-Argüelles, Alejandro; González-Cortés, Angélica; Ruiz-Argüelles, Guillermo J

    2015-01-01

    Donor-derived malignancies after allogeneic hematopoietic stem cell transplantation and after solid organ transplantation are considered as rare diseases. We have prospectively searched for donor cell leukemia in a 12-year period, in a single institution, in a group of 106 consecutive patients allografted because of leukemia. We have identified seven cases of donor cell leukemia; six were allografted because of relapsed acute lymphoblastic leukemia and one because of paroxysmal nocturnal hemoglobinuria/aplastic anemia. These figures suggest that the real incidence of donor cell leukemia has been underestimated. The six patients with lymphoblastic donor cell leukemia were treated prospectively with a pediatric-inspired combined chemotherapy schedule designed for de novo acute leukemia. A complete response was obtained in three out of six patients with lymphoblastic donor cell leukemia. It is possible to obtain favorable responses in donor cell leukemia patients employing combined chemotherapy. The long-term donor cell leukemia survivors remain as full chimeras and have not needed a second transplant.

  14. Childhood alopecia areata: A study of 89 patients

    Directory of Open Access Journals (Sweden)

    Sibel Doğan

    2014-09-01

    Full Text Available Background and Design: Alopecia areata (AA is a frequent type of acquired hair loss with a sudden onset. The aim of this study was to investigate the epidemiological and clinical features of AA and diseases associated with AA in the Turkish pediatric population. Materials and Methods: We retrospectively evaluated the medical data of patients under 16 years of age who were admitted to the pediatric dermatology outpatient clinic at Hacettepe University Hospital between 2006 and 2011 with a diagnosis of AA, alopecia totalis (AT and alopecia universalis (AU. Results: A total of 89 patients (34 females and 55 males, were included in this study. The mean age of the subjects was 9.8±3.4 years (range: 18 months-16 years. 9% (n=8 patients had other autoimmune diseases: Hashimoto's thyroiditis in 5, vitiligo in 1, juvenile rheumatoid arthiritis (JRA in 1 and morphea in 1 patient. AA was located on the scalp in 86.5% (n=77 of the patients, 7.9% (n=7 of the patients had AA on the scalp together with eyelashes, eyebrows and the body. AT was noted in 1, AU was noted in 4 patients. Severity of hair loss was <25% in 94.3% (n=84 of the patients according to the involved area. Hashimoto's thyroiditis was diagnosed in 5 patients; these patients had normal thyroid function tests (TFT. TFT abnormalities were detected in 27% (n=24 of the patients. 24.7% (n=22 of these patients were diagnosed with clinically insignificant thyroid disorder, 2 patients had compansated hypothyroidism (n=2. Eight patients (9% patients were found to be positive for anti-thyroid peroxidase antibody (Anti-TPO ab. Antithyroglobulin antibody (Anti-TG Ab elevation was noted in 3.3% (n=3 and antinuclear antibody (ANA positivity was noted in 9% (n=8. Nail changes were detected in 12.3% (n=11 of the patients as leukonychia (n=2, longitudinal striation (n=2, trachyonychia (n=1, onychoschizia (n=1 and pitting (n=1. Conclusion: Childhood AA usually causes limited hair loss. TFT anomalies can

  15. STUDY ON SERUM CERULOPLASMIN LEVELS IN VARIOUS CONDITIONS AND TYPES OF LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

    赵劲秋; 欧阳仁荣; 方智雯; 朱学宏; 邵念贤; 潘瑞彭

    1992-01-01

    Serum ceruloplasmin (CP) was determined by electroimmunodiffusion method in 89 normal persons and 92 leukemic patients. It was found that the serum CP of acute and chronic leukemia was very significantly higher than normal (P<0.01). There were no signifcant difference in elevation of serum CP between various types of leukemia. During remission oJ acute or chronic leukemia, the serum CP decreased significantly (P<0.05), but still higher than normal (P<0.01). In the case of long-term remission, serum CP decreased to normal level. During relapse of acute leukemia or acute blast crisis of chronic leukemia, serum CP raised again significantly (P<0.05). Infection enabled the leukemic patient to further increase serum CP (P<0.01). In acute leukemia, serum CP level correlated positively with the percentage of blast cells in bone marrow (P<0.05).

  16. Experiences of punishment by parents during childhood: A retrospective study

    Directory of Open Access Journals (Sweden)

    Isaković Olivera

    2014-01-01

    Full Text Available The study described perceived differences in the choice of child rearing practices aimed at correcting children’s inappropriate behaviors as remembered by the participants at young adulthood. The sample consisted of 207 students of under-graduate studies of the University of Novi Sad. The most of the participants does not have children and they grew up in complete families. On the Dimensions of Discipline Inventory (A (DDI-A, Straus, Fauchier, 2007, the participants estimated the experience and methods of disciplining which were used by their parents during their childhood. The participants describe uniform discipline behaviors of their parents regarding the estimated discipline techniques. These behaviors are dominated by the punishing ones, and the differences between fathers and mothers are visible in a stronger tendency to describe fathers as the ones who use corporal punishment, abolish privileges and give restorative tasks. The described discipline techniques for both fathers and mothers remain stable and similar, regardless of the socio-demographic characteristics of the families as family completeness, work experience and level of education of the parents, as well as estimated economic status of the family.

  17. Effect of the histone deacetylase inhibitor depsipeptide on B-cell differentiation in both TEL-AML1-positive and negative childhood acute lymphoblastic leukemia.

    Science.gov (United States)

    Stams, Wendy A G; den Boer, Monique L; Beverloo, H Berna; Kazemier, Karin M; van Wering, Elisabeth R; Janka-Schaub, Gritta E; Pieters, Rob

    2005-12-01

    The fusion protein TEL-AML1 in t(12;21)+ acute lymphoblastic leukemia (ALL) recruits co-repressors and histone deacetylases (HDAC), which transrepress AML1 target genes. Normal bone marrow cells were more resistant to HDAC inhibitor FK228 induced cell killing than were cells from ALL patients with or without t(12;21). FK228 induced differentiation in ALL, irrespective of the presence of t(12;21).

  18. Dose-finding study of imatinib in combination with intravenous cytarabine: feasibility in newly diagnosed patients with chronic myeloid leukemia

    NARCIS (Netherlands)

    Deenik, W.; van der Holt, B.; Verhoef, G.E.G.; Smit, W.M.; Kersten, M.J.; Kluin-Nelemans, Hanneke; Verdonck, L.F.; Ferrant, A.; Schattenberg, A.V.M.B.; Janssen, J.J.W.M.; Sonneveld, P.; Kooy, M.V.; Wittebol, S.; Willemze, R.; Wijermans, P.W.; Westveer, P.H.M.; Beverloo, H.B.; Valk, P.; Lowenberg, B.; Ossenkoppele, G.J.; Cornelissen, J.J.

    2008-01-01

    The HOVON cooperative study group performed a feasibility study of escalated imatinib and intravenous cytarabine in 165 patients with early chronic-phase chronic myeloid leukemia (CML). Patients received 2 cycles of intravenous cytarabine (200 mg/m(2) or 1000 mg/m(2) days 1-7) in conjunction with im

  19. Nail changes in childhood psoriasis: a study from Kuwait.

    Science.gov (United States)

    Al-Mutairi, Nawaf; Manchanda, Yashpal; Nour-Eldin, Osama

    2007-01-01

    Psoriasis is a widespread skin disorder in which nail involvement can be seen in up to two-thirds of those affected. Childhood psoriasis is a distinct entity and the literature focused on nail changes associated with childhood psoriasis is scant. Our objectives were to evaluate the frequency of nail involvement in childhood psoriatic patients, assess the types of nail changes in childhood psoriasis, and compare our clinical findings with the few reports available in the literature. Two hundred and one consecutive new patients with childhood (age nail changes. The diagnosis of psoriasis was made on clinical grounds. Each patient underwent a thorough dermatologic examination with special attention paid to the nail changes. If a clinical suspicion of fungal infection of the nails existed, further mycologic investigations were performed. We found the prevalence of nail changes to be 37.81% (boys > girls) in children who had psoriasis. Nail pitting was found to be the most common manifestation (61.84%) followed by onycholysis (30.26%), subungual hyperkeratosis (13.16%), and discoloration of the nail plate (7.90%). Nail involvement had no relationship to the type of psoriasis, patient's sex, or duration or extent of disease.

  20. ALL-2005方案对儿童急性淋巴细胞白血病髓外白血病防治效果分析%Analysis of prevention and therapeutic effectiveness of extramedullary leukemia in children with childhood acute lymphoblastic leukemia with ALL-2005 protocol

    Institute of Scientific and Technical Information of China (English)

    薛惠良; 顾龙君; 汤静燕; 陈静; 潘慈; 周敏; 董璐; 汤燕静; 王坚敏; 叶启东

    2012-01-01

    目的 总结ALL-2005方案对急性淋巴细胞白血病(ALL)患儿髓外白血病,包括中枢神经系统白血病(CNSL)及睾丸白血病(TL)的防治效果.方法 2005年5月-2008年5月共218例ALL患儿,采用ALL2005方案进行治疗,总结其临床及治疗情况.结果 218例ALL患儿中,5例初诊时伴CNSL,1例于诱导治疗期间发生CNSL,4例于维持治疗期间发生CNSL;1例初诊时伴TL发生,4例维持治疗期间发生TL.经治疗,2例CNSL患儿骨髓复发.其余8例均缓解至今;TL患儿1例骨髓复发,1例放弃治疗,3例缓解至今.结论 ALL2005方案疗效良好,有利于提高患儿长期生存质量.%Objective To analyze the prevention and therapeutic effectiveness of extramedullary leukemia including cen.ral nervous system leukemia ( CNSL) and testicular leukemia (TL) in children with childhood acute lymphoblastic leukemia (ALL) with ALL-2005 protocol. The clinical data were summarized. Methods From May 2005 to May 2008, 218 children with ALL were treated with All-2005 protocol. The clinical data were summarized. Results Five of 218 patients were found with CNSL and 1 with TL at the time of initial diagnosis of ALL, One child developed CNSL during treatment, 4 developed CNSL and 4 developed TL during maintenance treatment. After treatment , 2 patients with CNSL and 1 patient with TL relapsed; and 8 patients with CNSL and 3 patients with TL have been relieved and 1 patient with TL abandoned treatment. Conclusions ALL-2005 protocol shows good therapeutic effectiveness in treatment of children with ALL and improves the life quality of long term survival.

  1. Double primary cancers in 2 young sibs, leukemia in another, and dextrocardia in a fourth.

    Science.gov (United States)

    Li, F P; McIntosh, S; Peng-Whang, J

    1977-06-01

    Two brothers developed multiple primary neoplasms in childhood; one had glioblastoma and non-Hodgkin's lymphoma at age 11 years, and the other brain tumor and acute leukemia at six years. A third brother died with myelogenous leukemia at thre years, and a fourth with cyanotic congenital heart disease at 11 weeks. Each child also had at least one hamartomatous lesion of the skin. The clinical features suggested von Recklinghausen's neurofibromatosis or other inherited cancer syndrome, but laboratory studies identified no markers of susceptibility to familial neoplasia.

  2. Cytogenetics of pediatric acute myeloid leukemia.

    Science.gov (United States)

    Manola, Kalliopi N

    2009-11-01

    Acute myeloid leukemia (AML) is a clinically and genetically heterogeneous disease accounting for 15-20% of all childhood acute leukemias, while it is responsible for more than half of the leukemic deaths in these patients. This article focuses on the significance of cytogenetic analysis in pediatric AML supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow-up and treatment selection in childhood AML. It reviews in detail the types and frequencies of most common chromosomal aberrations, their molecular background, their correlation with French American British (FAB) subtypes and age distribution and their prognostic relevance. It also summarizes some less frequent or rare chromosome aberrations in which the prognostic classification has not been determined yet owning to the small number of patients and the variable treatment modalities used in different study groups. Furthermore, it discusses the association of specific chromosome rearrangements with prenatal exposure to carcinogenic agents or therapeutic agents and highlights the ongoing and future research on pediatric AML in the evolving field of Cytogenetics.

  3. Social class in childhood and general health in adulthood: questionnaire study of contribution of psychological attributes

    NARCIS (Netherlands)

    H. Bosma (Hans); H. van de Mheen (Dike); J.P. Mackenbach (Johan)

    1999-01-01

    textabstractOBJECTIVE: To determine the contribution of psychological attributes (personality characteristics and coping styles) to the association between social class in childhood and adult health among men and women. DESIGN: Partly retrospective, partly cross sectional study con

  4. Relationship between Vitamin D and Childhood Asthma: A Case–Control Study

    OpenAIRE

    Hatami, Gissou; Ghasemi, Khadijeh; Motamed, Niloofar; Firoozbakht, Saiideh; Movahed, Ali; Farrokhi, Shokrollah

    2014-01-01

    Objective: Studies determining the relationship between serum vitamin D status and childhood asthma have yielded controversial results. Findings indicated that vitamin D deficiency is associated with asthma and airway hyper responsiveness. The aim of this study was to assess the relationship between serum vitamin D status and childhood asthma. Methods: Data were obtained from 200 asthmatic children (age 3–12 years) and 200 healthy controls. Serum levels of 25(OH) vitamin D, total IgE, calcium...

  5. Laboratory-Treated Donor Cord Blood Cell Infusion Following Combination Chemotherapy in Treating Younger Patients With Relapsed or Refractory Acute Myeloid Leukemia

    Science.gov (United States)

    2016-10-31

    Acute Leukemia of Ambiguous Lineage; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(16;16)(p13.1;q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-MLL; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Alkylating Agent-Related Acute Myeloid Leukemia; Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  6. Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group

    NARCIS (Netherlands)

    T.D. Buitenkamp (Trudy); S. Izraeli (Shai); M. Zimmermann (Martin); E. Forestier (Erik); N.A. Heerema (Nyla); M.M. van den Heuvel-Eibrink (Marry); R. Pieters (Rob); C.M. Korbijn (Carin); L.B. Silverman (Lewis); K. Schmiegelow (Kjeld); D.-C. Liang (Der-Cheng); K. Horibe (Keizo); M. Aricò (Maurizio); A. Biondi (Andrea); G. Basso (Giuseppe); K.R. Rabin (Karin); M. Schrappe (Martin); G. Cario (Gunnar); G. Mann (Georg); M. Morak (Maria); R. Panzer-Grümayer (Renate); V. Mondelaers (Veerle); T. Lammens (Tim); H. Cavé (Hèléne); B. Stark (Batia); I. Ganmore (Ithamar); A.V. Moorman (Anthony); A. Vora (Ajay); S.P. Hunger (Stephen); C.H. Pui (Ching-Hon); C.G. Mullighan (Charles); A. Manabe (Atsushi); G. Escherich (Gabriele); J.R. Kowalczyk (Jerzy R.); J.A. Whitlock (James); C.M. Zwaan (Michel)

    2014-01-01

    textabstractChildren with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials

  7. 急性白血病并肺部真菌感染57例早期诊断与防治策略%Early Diagnosis,Treatment and Prevention of Childhood Acute Leukemia Complicated with Pulmonary Fungal Infection

    Institute of Scientific and Technical Information of China (English)

    邵静波; 蒋慧; 李红; 陆正华; 杨静薇; 杨为群

    2011-01-01

    Objective To analyze the clinical features and investigate the early diagnosis and treatment of childhood acute leukemia complicated with pulmonary fungal infection (PFI). Methods The clinical data of 132 cases of childhood acute leukemia were retrospectively analyzed. Fifty -seven patients, who had the PFI,including 5 times with confirmed diagnosis,30 times with clinical diagnosis,and 25 times with recommended diagnosis were diagnosed according to European Organization for Research and Treatment of Cancer. Results 1. The incidence rate of PFI in the childhood acute leukemia was 43.18% (57/132 cases). The median time from occurring PFI to confirmed leukemia was 7.2 months,among which 70% (42/60 cases) were within 12 months while 30% ( 18/60 cases) more than 12 months. 2. The representation of chest CT was multiform,mainly for inflammatory exudate,interstitial changes,and cloud flocculeut nodules. The severe patients were accompanied by pleural effusion or acute respiratory distress syndrome(ARDS). 3. Seventy -one point seven percent(43/60 cases)of PFI were neutropenia ( < 1.5 × 109 L-1 ) ,in which 40.0% were ngranulocytosis ( < 0. 5 × 109L-1 ). 4. The positive rate of fungal G test was 70.5% ( 31/44 cases) wille negative was 29.5% ( 13/44 cases). Totally 7 candida strains and 2 mierozyme strains were obtained from 57 cases of PFI. 5. The total cure rate was 95.0%. Cure rates of single drug and combined anti fungal were 53.3% and 41.7%. Conclusions 1. Fungal infection is one of the main pathogens in childhood acute leukemia complicated by severe infection. 2. Chest CT shows important value in the diagnosis of PFI. The positive rate of microorganism culture is low in children. 3. Early diagnosis and treatment are the key to improve curative effect. Better prognosis can be gained if those patients with early respiratory failure or ARDS get oxygen or mechanical ventilation in time.%目的 分析急性白血病并肺部真菌感染(PFI)患儿的

  8. 儿童急性白血病误诊二例原因分析%Cause Analysis of Misdiagnosis and missed Diagnosis of 2 Cases of Childhood Acute Leukemia

    Institute of Scientific and Technical Information of China (English)

    王衍晶; 刘艳; 王贞

    2015-01-01

    目的:探讨儿童急性白血病的临床特点,分析误诊原因并提出防范措施。方法回顾分析我院2012—2013年收治并误诊的儿童急性白血病2例的临床资料。结果本文例1因间断髋关节疼痛1个月、加重并发热5 d就诊,疼痛可自行缓解并反复出现,于外院影像学检查诊断为髋关节滑膜炎,予抗感染治疗无好转,我院门诊按儿童类风湿病(多关节型)予抗风湿治疗,热退疼痛缓解,但仍有多关节活动受限。为系统治疗收入我院儿科,入院后诊断为全身型幼年特发性关节炎,予对症治疗症状缓解,复查血常规发现原始及幼稚细胞,行骨髓血细胞形态检查确诊为急性淋巴细胞白血病。例2因发热、盗汗、乏力6 d,其间伴少量鼻出血3 d 就诊,予退热及抗感染治疗好转,后症状反复出现,入院后按上呼吸道感染予对症治疗无效。复查血常规发现原始细胞,经骨髓血细胞形态检查确诊为急性淋巴细胞白血病。结论对久治不愈的发热、骨痛、感染的患儿要警惕白血病,尽早行骨穿血细胞形态学检查是明确诊断的关键。%Objective To explore the clinical characteristics of childhood acute leukemia, analyzes the causes of mis-diagnosis and missed diagnosis and put forward the preventive measures. Methods Retrospective analysis of clinical data of 2 cases of misdiagnosis and missed diagnosis of childhood acute leukemia admitted during 2012-2013 combined with literature a-nalysis were made. Results Case 1 had intermittent hip pain for 1 month and fever for 5 days. The pain was alleviated by it-self but relapsed. The patient was diagnosed as having synovitis of the hip in the other hospital's imaging and was given anti -inflammatory therapy without any improvement. In our outpatient department, the patient was diagnosed as having childhood rheumatism (multi-joint type) and was given anti - rheumatism treatment. The fever and pain were relieved, but

  9. [Peripheral microthrombotic purpura associated with acute promyelocytic leukemia in pregnancy. A light and electron microscopic study].

    Science.gov (United States)

    Beller, F K; Wagner, H; Büchner, T

    1978-06-15

    A case is presented of a pregnant patient in the 28th week of gestation with promyelocytic leukemia and an unusual thrombohemorrhagic skin lesion. Ultrastructural examination revealed a microthrombotic purpura. Reduced coagulation factors increased during heparin treatment. The exacerbation of disseminated intravascular coagulation is explained by a hypercoagulable state in pregnancy in association with the as yet unknown etiology of "promyelocytic fibrinopathic leukemia".

  10. Socioeconomic Status and Trajectory of Overweight from Birth to Mid-Childhood: The Early Childhood Longitudinal Study-Birth Cohort

    OpenAIRE

    Jones-Smith, Jessica C; Marlowe Gates Dieckmann; Laura Gottlieb; Jessica Chow; Fernald, Lia C. H.

    2014-01-01

    OBJECTIVE: Our objective was to use longitudinal data from a US birth cohort to test whether the probability of overweight or obesity during the first 6 years of life varied according to socioeconomic status. DESIGN AND METHODS: Using six waves of longitudinal data from full-term children in the Early Childhood Longitudinal Study-Birth Cohort (2001-2007; n≈4,950), we examined the prevalence of overweight or obesity (Body Mass Index (BMI)>2 standard deviations above age- and sex- specific WHO ...

  11. Treatment of Children with APL (Acute Promyelocytic Leukemia)

    Science.gov (United States)

    ... it can be put into a second remission. Arsenic trioxide is a drug that is very effective ... Childhood Leukemia Causes, Risk Factors, and Prevention Early Detection, Diagnosis, and Staging Treatment After Treatment Back To ...

  12. The dog as a model for comparative studies of lymphoma and leukemia in humans 

    Directory of Open Access Journals (Sweden)

    Aleksandra Pawlak

    2013-05-01

    Full Text Available Dogs have accompanied humankind for thousands of years. They share the same environment, and thus are exposed to the same environmental factors such as air pollution, tobacco smoke, and various chemicals. Recent development of veterinary care has led to a significant extension of dogs’ lifespan and allowed the diagnosis and treatment of a growing number of different diseases in this species. Among all diseases in dogs, cancer is considered the main cause of mortality, with lymphoproliferative disorders accounting for up to 30�0of all canine cancers. Some of them, such as non-Hodgkin lymphoma (NHL and lymphocytic leukemia, are very similar in the etiology, pathogenesis and response to treatment to the diseases occurring in humans. Due to anatomical and physiological similarities to humans, the dog is a useful model for the study of new therapeutic strategies for humans. Studies on the canine neoplasia are currently limited by the lack of well-characterized and widely available cell lines; thus, recently obtained canine NHL cell lines may become a valuable model for such studies. Investigation of their sensitivity to the antiproliferative effects of different factors should allow the creation of a database similar to the existing classification of human leukemias and lymphomas. This should enable quick and accurate diagnosis and selection of appropriate treatment based on phenotypic analysis and histopathological examination of clinical samples. The cooperation between human and veterinary oncologists gives the opportunity to use the dog as a model for the study of certain types of cancers presenting a challenge for modern medicine.

  13. Exercise-induced bronchoconstriction : clinical studies in childhood asthma

    NARCIS (Netherlands)

    W.B. Hofstra (Winfried)

    1997-01-01

    textabstractAt present, astluna is regarded as a chronic inflammatory disorder of the airways, In susceptible individuals, asthma causes symptoms, that are usually associated with variable, but often reversible airflow obstmction. Astlulla is the most conunon lung disease in childhood, with a sympto

  14. Childhood leukaemia in the Netherlands : a register based epidemiologic study

    NARCIS (Netherlands)

    H.A. Moll (Henriëtte)

    1983-01-01

    textabstractLeukaemia, literally "white blood", is the most common type of malignancy in childhood (Birch et al., 1980). The clinical features are caused by abnormal proliferation of one or more of the blood-forming cellular elements. The immature malignant cells usually disturb normal haematopoiesi

  15. Comorbidities of asthma during childhood : possibly important, yet poorly studied

    NARCIS (Netherlands)

    de Groot, E. P.; Duiverman, E. J.; Brand, P. L. P.

    2010-01-01

    Asthma in adults is associated with comorbidities such as obesity, gastro-oesophageal reflux, dysfunctional breathing and mental disorders. Herein, we provide an overview of the current state of evidence on these comorbidities in childhood asthma. The prevalence, known mechanisms and possible treatm

  16. Technology User Groups and Early Childhood Education: A Preliminary Study

    Science.gov (United States)

    Parette, Howard P.; Hourcade, Jack J.; Blum, Craig; Watts, Emily H.; Stoner, Julia B.; Wojcik, Brian W.; Chrismore, Shannon B.

    2013-01-01

    This article presents a preliminary examination of the potential of Technology User Groups as a professional development venue for early childhood education professionals in developing operational and functional competence in using hardware and software components of a Technology toolkit. Technology user groups are composed of varying numbers of…

  17. ZNF384-related fusion genes define a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with a characteristic immunotype

    Science.gov (United States)

    Hirabayashi, Shinsuke; Ohki, Kentaro; Nakabayashi, Kazuhiko; Ichikawa, Hitoshi; Momozawa, Yukihide; Okamura, Kohji; Yaguchi, Akinori; Terada, Kazuki; Saito, Yuya; Yoshimi, Ai; Ogata-Kawata, Hiroko; Sakamoto, Hiromi; Kato, Motohiro; Fujimura, Junya; Hino, Moeko; Kinoshita, Akitoshi; Kakuda, Harumi; Kurosawa, Hidemitsu; Kato, Keisuke; Kajiwara, Ryosuke; Moriwaki, Koichi; Morimoto, Tsuyoshi; Nakamura, Kozue; Noguchi, Yasushi; Osumi, Tomoo; Sakashita, Kazuo; Takita, Junko; Yuza, Yuki; Matsuda, Koich; Yoshida, Teruhiko; Matsumoto, Kenji; Hata, Kenichiro; Kubo, Michiaki; Matsubara, Yoichi; Fukushima, Takashi; Koh, Katsuyoshi; Manabe, Atsushi; Ohara, Akira; Kiyokawa, Nobutaka

    2017-01-01

    Fusion genes involving ZNF384 have recently been identified in B-cell precursor acute lymphoblastic leukemia, and 7 fusion partners have been reported. We further characterized this type of fusion gene by whole transcriptome sequencing and/or polymerase chain reaction. In addition to previously reported genes, we identified BMP2K as a novel fusion partner for ZNF384. Including the EP300-ZNF384 that we reported recently, the total frequency of ZNF384-related fusion genes was 4.1% in 291 B-cell precursor acute lymphoblastic leukemia patients enrolled in a single clinical trial, and TCF3-ZNF384 was the most recurrent, with a frequency of 2.4%. The characteristic immunophenotype of weak CD10 and aberrant CD13 and/or CD33 expression was revealed to be a common feature of the leukemic cells harboring ZNF384-related fusion genes. The signature gene expression profile in TCF3-ZNF384-positive patients was enriched in hematopoietic stem cell features and related to that of EP300-ZNF384-positive patients, but was significantly distinct from that of TCF3-PBX1-positive and ZNF384-fusion-negative patients. However, clinical features of TCF3-ZNF384-positive patients are markedly different from those of EP300-ZNF384-positive patients, exhibiting higher cell counts and a younger age at presentation. TCF3-ZNF384-positive patients revealed a significantly poorer steroid response and a higher frequency of relapse, and the additional activating mutations in RAS signaling pathway genes were detected by whole exome analysis in some of the cases. Our observations indicate that ZNF384-related fusion genes consist of a distinct subgroup of B-cell precursor acute lymphoblastic leukemia with a characteristic immunophenotype, while the clinical features depend on the functional properties of individual fusion partners. PMID:27634205

  18. Epidemiological Study Of The Childhood Disabilities: A Household Survey In Four Egyptian Governorates

    Directory of Open Access Journals (Sweden)

    E. A. El-Moselhy; R. M. El-Azab; H. O. Khalifa; E. S. Abd-Allah

    2005-09-01

    Full Text Available This study was conducted on 1403 children from four Egyptian governorates. These governorates were; Alexandria, Al-Behira, Cairo and Al-Giza. The aim of the study was to define different types of the childhood disabilities, to find out their prevalence's in the selected governorates in Egypt, to define their distribution and to define their risk factors. A cross-sectional study design was chosen to investigate the current research problem. All the children had undergone complete physical examinations. Also, children's parents were interviewed. There were specific inclusions criteria have been considered to include the child as a case in the study. The overall prevalence of the childhood disabilities in these governorates was 8.8%. The most common prevalent childhood disabilities were; visual, speech and hearing (4.5%, 2.1% and 1.9%, respectively. While, the most common prevalent risk factors were mother delivered at home and/or not received antenatal care (7.2% and 6.3%, respectively. Positive consanguinity and baby not strictly received vaccination were the most important risk factors, odds ratio = 3.81 and 3.31, respectively. While, only positive consanguinity was significantly correlated with all types of the childhood disabilities. Furthermore, positive consanguinity had the highest correlation with all types of the childhood disabilities. Also, childhood disabilities tend to be common among males (57.6% and of congenital aetiology (61.8%. The main source of habilitation was the private centers (79.2%.

  19. Analyses of karyotypic characteristics and prognosis in pediatric acute myeloblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    阮敏

    2012-01-01

    Objective Acute myeloblastic leukemia(AML) accounts for 15 to 25 percent of childhood acute leukemias. Cytogenetic information is important for diagnosis,classification and prognosis of AML. Our aim was to analyze the relationship between karyotypic characteristics and prognosis of childhood

  20. Childhood IQ and risk of bipolar disorder in adulthood: prospective birth cohort study

    OpenAIRE

    2015-01-01

    Background Intellectual ability may be an endophenotypic marker for bipolar disorder. Aims Within a large birth cohort, we aimed to assess whether childhood IQ (including both verbal IQ (VIQ) and performance IQ (PIQ) subscales) was predictive of lifetime features of bipolar disorder assessed in young adulthood. Method We used data from the Avon Longitudinal Study of Parents and Children (ALSPAC), a large UK birth cohort, to test for an association between measures of childhood IQ at age 8 yea...

  1. Childhood family income, adolescent violent criminality and substance misuse : a quasi-experimental total population study

    OpenAIRE

    Sariaslan, Amir; Larsson, Henrik; D’Onofrio, Brian; Långström, Niklas; Lichtenstein, Paul

    2013-01-01

    Background: Low socioeconomic status in childhood is a well-known predictor of subsequent criminal and substance misuse behaviors but the causal mechanisms are questioned. Aims: To investigate if the associations between childhood family income and subsequent adolescent criminality and substance misuse are explained by unobserved familial risk factors. Method: Swedish population-based quasi-experimental, family-based study following cohorts born 1989-1993 (ntotal=529,428; ncousins...

  2. Competitive Food Sales in Schools and Childhood Obesity: A Longitudinal Study

    OpenAIRE

    Van Hook, Jennifer; Altman, Claire E.

    2011-01-01

    The vast majority of American middle schools and high schools sell what is known as “competitive foods”, such as soft drinks, candy bars, and chips, to children. The relationship between consumption of sugar-sweetened drinks and snacks and childhood obesity is well established but it remains unknown whether competitive food sales in schools are related to unhealthy weight gain among children. We examined this association using data from the Early Childhood Longitudinal Study Kindergarten Coho...

  3. Risk Factors Associated With Secondary Sarcomas in Childhood Cancer Survivors: A Report From the Childhood Cancer Survivor Study

    Energy Technology Data Exchange (ETDEWEB)

    Henderson, Tara O., E-mail: thenderson@peds.bsd.uchicago.edu [University of Chicago, Chicago, IL (United States); Rajaraman, Preetha [National Cancer Institute, Bethesda, MD (United States); Stovall, Marilyn [M.D. Anderson Cancer Center, University of Texas, Houston, TX (United States); Constine, Louis S. [University of Rochester, Rochester, NY (United States); Olive, Aliza [Drexel University, Philadelphia, PA (United States); Smith, Susan A. [M.D. Anderson Cancer Center, University of Texas, Houston, TX (United States); Mertens, Ann [Emory University, Atlanta, GA (United States); Meadows, Anna [Children' s Hospital of Philadelphia, Philadelphia, PA (United States); Neglia, Joseph P. [University of Minnesota, Minneapolis, MN (United States); Hammond, Sue [Nationwide Children' s Hospital, Columbus, OH (United States); Whitton, John [Fred Hutchinson Cancer Research Center, Seattle, WA (United States); Inskip, Peter D. [National Cancer Institute, Bethesda, MD (United States); Robison, Leslie L. [St. Jude Children' s Research Hospital, Memphis, TN (United States); Diller, Lisa [Dana-Farber Cancer Institute/Children' s Hospital Cancer Center, Boston, MA (United States)

    2012-09-01

    Purpose: Childhood cancer survivors have an increased risk of secondary sarcomas. To better identify those at risk, the relationship between therapeutic dose of chemotherapy and radiation and secondary sarcoma should be quantified. Methods and Materials: We conducted a nested case-control study of secondary sarcomas (105 cases, 422 matched controls) in a cohort of 14,372 childhood cancer survivors. Radiation dose at the second malignant neoplasm (SMN) site and use of chemotherapy were estimated from detailed review of medical records. Odds ratios (ORs) and 95% confidence intervals were estimated by conditional logistic regression. Excess odds ratio (EOR) was modeled as a function of radiation dose, chemotherapy, and host factors. Results: Sarcomas occurred a median of 11.8 years (range, 5.3-31.3 years) from original diagnosis. Any exposure to radiation was associated with increased risk of secondary sarcoma (OR = 4.1, 95% CI = 1.8-9.5). A dose-response relation was observed, with elevated risks at doses between 10 and 29.9 Gy (OR = 15.6, 95% CI = 4.5-53.9), 30-49.9 Gy (OR = 16.0, 95% CI 3.8-67.8) and >50 Gy (OR = 114.1, 95% CI 13.5-964.8). Anthracycline exposure was associated with sarcoma risk (OR = 3.5, 95% CI = 1.6-7.7) adjusting for radiation dose, other chemotherapy, and primary cancer. Adjusting for treatment, survivors with a first diagnosis of Hodgkin lymphoma (OR = 10.7, 95% CI = 3.1-37.4) or primary sarcoma (OR = 8.4, 95% CI = 3.2-22.3) were more likely to develop a sarcoma. Conclusions: Of the risk factors evaluated, radiation exposure was the most important for secondary sarcoma development in childhood cancer survivors; anthracycline chemotherapy exposure was also associated with increased risk.

  4. The role of ZAP70 kinase in acute lymphoblastic leukemia infiltration into the central nervous system

    Science.gov (United States)

    Alsadeq, Ameera; Fedders, Henning; Vokuhl, Christian; Belau, Nele M.; Zimmermann, Martin; Wirbelauer, Tim; Spielberg, Steffi; Vossen-Gajcy, Michaela; Cario, Gunnar; Schrappe, Martin; Schewe, Denis M.

    2017-01-01

    Central nervous system infiltration and relapse are poorly understood in childhood acute lymphoblastic leukemia. We examined the role of zeta-chain-associated protein kinase 70 in preclinical models of central nervous system leukemia and performed correlative studies in patients. Zeta-chain-associated protein kinase 70 expression in acute lymphoblastic leukemia cells was modulated using short hairpin ribonucleic acid-mediated knockdown or ectopic expression. We show that zeta-chain-associated protein kinase 70 regulates CCR7/CXCR4 via activation of extracellular signal-regulated kinases. High expression of zeta-chain-associated protein kinase 70 in acute lymphoblastic leukemia cells resulted in a higher proportion of central nervous system leukemia in xenografts as compared to zeta-chain-associated protein kinase 70 low expressing counterparts. High zeta-chain-associated protein kinase 70 also enhanced the migration potential towards CCL19/CXCL12 gradients in vitro. CCR7 blockade almost abrogated homing of acute lymphoblastic leukemia cells to the central nervous system in xenografts. In 130 B-cell precursor acute lymphoblastic leukemia and 117 T-cell acute lymphoblastic leukemia patients, zeta-chain-associated protein kinase 70 and CCR7/CXCR4 expression levels were significantly correlated. Zeta-chain-associated protein kinase 70 expression correlated with central nervous system disease in B-cell precursor acute lymphoblastic leukemia, and CCR7/CXCR4 correlated with central nervous system involvement in T-cell acute lymphoblastic leukemia patients. In multivariate analysis, zeta-chain-associated protein kinase 70 expression levels in the upper third and fourth quartiles were associated with central nervous system involvement in B-cell precursor acute lymphoblastic leukemia (odds ratio=7.48, 95% confidence interval, 2.06–27.17; odds ratio=6.86, 95% confidence interval, 1.86–25.26, respectively). CCR7 expression in the upper fourth quartile correlated with

  5. Transformation of Myelodysplastic Syndrome to Acute Lymphoblastic Leukemia in a Child

    OpenAIRE

    2010-01-01

    Childhood myelodysplastic syndrome (MDS) is an uncommon condition. Unlike adult MDS, pediatric patients have a more progressive course and rapidly transform to acute myeloid leukemia. Evolution to acute lymphoblastic leukemia is extremely rare. We report a 5 year old female child who presented with refractory anemia with excess blasts and transformed into acute lymphoblastic leukemia 4 months after initial diagnosis.

  6. Childhood immunization and atopic disease into middle-age--a prospective cohort study.

    Science.gov (United States)

    Matheson, Melanie C; Haydn Walters, E; Burgess, John A; Jenkins, Mark A; Giles, Graham G; Hopper, John L; Abramson, Michael J; Dharmage, Shyamali C

    2010-03-01

    The association between childhood immunizations and risk of atopic diseases is unclear. No study has examined possible associations between childhood immunizations and such diseases in middle age. The Tasmanian Longitudinal Health Study (TAHS) is a population based cohort study of respiratory disease. The TAHS participants were followed from 7 to 44 yrs of age. Immunizations during childhood were examined for any association with asthma and atopic disease at age 44 yrs. Multivariable regression models were used to estimate relative risks while adjusting for confounders. Cox regression was used to estimate the association between childhood immunizations and asthma developing after the age of 7 yrs. We found no association between any childhood immunization (Diphtheria, Tetanus, Pertussis, Polio, Smallpox) and asthma (ORs ranged from 0.87 to 1.17 p > 0.05), eczema (ORs ranged from 0.99 to 1.07 p > 0.05), food allergy (ORs ranged from 0.97 to 1.11 p > 0.05), or hay fever (ORs ranged from 1.02 to 1.05 p > 0.05) at age 44. Nor did we find any association between childhood immunizations and an increased risk of incident asthma after the age of 7 yrs (Diphtheria HR = 1.06, 95% CI 0.82, 1.36; Tetanus HR = 1.13, 95% CI 0.88, 1.44; Pertussis HR = 1.03, 95% CI 0.81, 1.30; Polio HR = 1.15, 95% CI 0.86, 1.54; Smallpox HR = 1.21, 95% CI 0.99, 1.48; DTP HR = 1.05, 95% CI 0.85, 1.30). Our analysis does not support any association between common childhood immunizations and risk of asthma and atopic disease in middle-age. Our findings should provide reassurance that in terms of life time risk of asthma and atopic disease, childhood immunization is safe.

  7. EVI1基因阳性儿童急性淋巴细胞性白血病临床特征及免疫表型分析%Clinical and immunophenotypic features of childhood acute lymphocytic leukemia with EVI1 gene positive

    Institute of Scientific and Technical Information of China (English)

    姜敏; 金润铭; 杜雯; 李小青; 胡东; 吴介洪; 蔡莎; 张志泉

    2014-01-01

    目的 研究Evi1基因在儿童急性淋巴细胞性白血病(acute lymphoblastic leukemia,ALL)的表达及免疫表型特点.方法 采用逆转录-聚合酶链反应法和流式细胞仪检测2010年12月至2013年2月华中科技大学同济医学院附属协和医院儿科血液病区262例ALL EVI1基因的表达及免疫表型,比较EVI1基因表达阳性与表达阴性患儿的免疫表型及临床特征的差异.结果 262例ALL患儿有29例EVI1基因表达阳性.EVI1表达阳性与表达阴性的ALL患儿相比,EVI1阳性的ALL患儿初诊外周血白细胞计数增高,血小板下降,女性患儿所占比例高,强的松试验敏感者明显减少,第一疗程诱导缓解率明显降低(P<0.05),而年龄、血红蛋白含量差异无统计学意义(P>0.05).EVI1阳性的B系ALL高表达cCD79a、CD38、CD10、CD19、CD22,CD123、TDT、HLADR、CD34,T系ALL高表达CD2、CD3、CD4、CD5、CD7、CD8、CD38、cCD3.B系EVI1阳性组与阴性组相比,B系EVI1阳性组CD13、CD33、CD11b等髓系相关抗原表达增加,CD19、CD20、CD22等B细胞相关抗原表达减少(P<0.05).结论 EVI1基因表达阳性的ALL是一种特殊类型的白血病亚型,近期预后差.B系EVI1阳性ALL患儿部分髓系相关抗原表达增加,部分B细胞相关抗原表达减少.%Objective To study the expression of Ecotropic viral integration site (EVI1) gene and clinical and immunophenotypic features of childhood acute lymphoblastic leukemia(ALL).Methods The expression of EVI1 gene and immunophenotyping of 262 children with acute lymphocytic leukemia in Department of Pediatric Hematology,Union Hospital,Tongji Medical College,Huazhong University of Science and Technology from Dec.2010 to Feb.2013 were detected by RT-PCR and flow cytometry.Immunophenotypic and clinical features were compared between childhood with EVI1 gene positive and negetive.Results We identified 29 ALL with EVI1 gene positive among 262 childhood acute lymphocytic leukemia,the incidences positive

  8. Normal karyotype is a poor prognostic factor in myeloid leukemia of Down syndrome: a retrospective, international study.

    Science.gov (United States)

    Blink, Marjolein; Zimmermann, Martin; von Neuhoff, Christine; Reinhardt, Dirk; de Haas, Valerie; Hasle, Henrik; O'Brien, Maureen M; Stark, Batia; Tandonnet, Julie; Pession, Andrea; Tousovska, Katerina; Cheuk, Daniel K L; Kudo, Kazuko; Taga, Takashi; Rubnitz, Jeffrey E; Haltrich, Iren; Balwierz, Walentyna; Pieters, Rob; Forestier, Erik; Johansson, Bertil; van den Heuvel-Eibrink, Marry M; Zwaan, C Michel

    2014-02-01

    Myeloid leukemia of Down syndrome has a better prognosis than sporadic pediatric acute myeloid leukemia. Most cases of myeloid leukemia of Down syndrome are characterized by additional cytogenetic changes besides the constitutional trisomy 21, but their potential prognostic impact is not known. We, therefore, conducted an international retrospective study of clinical characteristics, cytogenetics, treatment, and outcome of 451 children with myeloid leukemia of Down syndrome. All karyotypes were centrally reviewed before assigning patients to subgroups. The overall 7-year event-free survival for the entire cohort was 78% (± 2%), with the overall survival rate being 79% (± 2%), the cumulative incidence of relapse 12% (± 2%), and the cumulative incidence of toxic death 7% (± 1%). Outcome estimates showed large differences across the different cytogenetic subgroups. Based on the cumulative incidence of relapse, we could risk-stratify patients into two groups: cases with a normal karyotype (n=103) with a higher cumulative incidence of relapse (21%± 4%) than cases with an aberrant karyotype (n=255) with a cumulative incidence of relapse of 9% (± 2%) (P=0.004). Multivariate analyses revealed that white blood cell count ≥ 20 × 10(9)/L and age >3 years were independent predictors for poor event-free survival, while normal karyotype independently predicted inferior overall survival, event-free survival, and relapse-free survival. In conclusion, this study showed large differences in outcome within patients with myeloid leukemia of Down syndrome and identified novel prognostic groups that predicted clinical outcome and hence may be used for stratification in future treatment protocols.

  9. Management and treatment of osteonecrosis in children and adolescents with acute lymphoblastic leukemia.

    Science.gov (United States)

    Te Winkel, Mariël L; Pieters, Rob; Wind, Ernst-Jan D; Bessems, J H J M Gert; van den Heuvel-Eibrink, Marry M

    2014-03-01

    There is no consensus regarding how to manage osteonecrosis in pediatric acute lymphoblastic leukemia patients. Therefore, we performed a quality assessment of the literature with the result of a search strategy using the MESH terms osteonecrosis, children, childhood cancer, surgery, bisphosphonates, 6 hydroxymethyl-glutaryl CoA reductase inhibitors, anticoagulants and hyperbaric oxygen, and terms related to these MESH terms. A randomized controlled trial showed that osteonecrosis can be prevented by intermittent, instead of continuous, corticosteroid administration. The studies on interventions after onset of osteonecrosis were of low-quality evidence. Seven pediatric acute lymphoblastic leukemia studies described non-surgical interventions; bisphosphonates (n=5), hyperbaric oxygen therapy (n=1), or prostacyclin analogs (n=1). Safety and efficacy studies are lacking. Five studies focused on surgical interventions; none was of sufficient quality to draw definite conclusions. In conclusion, preventing osteonecrosis is feasible in a proportion of the pediatric acute lymphoblastic leukemia patients by discontinuous, instead of continuous, steroid scheduling. The questions as to how to treat childhood acute lymphoblastic leukemia patients with osteonecrosis cannot be answered as good-quality studies are lacking.

  10. Incidence, risk factors, and treatment outcome of symptomatic osteonecrosis in Taiwanese children with acute lymphoblastic leukemia: a retrospective cohort study of 245 patients in a single institution.

    Science.gov (United States)

    Chen, Shih-Hsiang; Chang, Tsung-Yen; Jaing, Tang-Her; Lee, Mel S; Wang, Chao-Jan; Hung, Iou-Jih; Yang, Chao-Ping

    2015-07-01

    Osteonecrosis (ON) is a potentially disabling complication encountered in children who receive chemotherapy for acute lymphoblastic leukemia (ALL). Considering the possible effect of ethnic difference on the clinical features of symptomatic ON in pediatric ALL, we retrospectively evaluated 245 children with ALL who were treated at Chang Gung Memorial Hospital, Linkou, between 2002 and 2011. Six (2.4 %) patients developed symptomatic ON in a total of 17 sites during the follow-up period. Diagnosis of ON was confirmed by X-ray in seven, magnetic resonance imaging in two, and bone scan in three patients. The estimated cumulative incidence of symptomatic ON in newly diagnosed ALL was 3.4 % at 8 years. Four patients received ON-directed surgical interventions, including total hip replacement in three and arthroplasty in one. The incidence of ON was significantly higher among girls (P = 0.03), patients >10 years old (P = 2.2 × 10(-4)), and patients who had received more intensive chemotherapy regimen (P = 0.02). These results indicate that the incidence and risk factors in our institute were similar to those observed in Western countries. Future studies surveying the impact on the quality of life of childhood ALL survivors in Taiwan are warranted.

  11. Childhood meat eating and inflammatory markers: The Guangzhou Biobank Cohort Study

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    Zhang WS

    2011-05-01

    Full Text Available Abstract Background We hypothesized that socio-economic development could, via nutritionally driven levels of pubertal sex-steroids, promote a pro-inflammatory state among men but not women in developing countries. We tested this hypothesis, using recalled childhood meat eating as a proxy for childhood nutrition, in southern China. Methods We used multivariable linear regression in the Guangzhou Biobank Cohort Study phase 3 (2006-8 to examine the adjusted associations of recalled childhood meat eating, Results Adjusted for age, childhood socio-economic position, education and smoking, childhood meat eating had sex-specific associations with white blood cell count and lymphocyte count, but not granulocyte count. Men with childhood meat eating almost daily compared to 9/L, 95% confidence interval (CI 0.10 to 0.56 and higher lymphocyte count (0.16 109/L, 95% CI 0.07 to 0.25. Adjustment for obesity slightly attenuated these associations. Conclusion If confirmed, this hypothesis implies that economic development and the associated improvements in nutrition at puberty may be less beneficial among men than women; consistent with the widening sex differentials in life expectancy with economic development.

  12. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Science.gov (United States)

    Cancela, Camila Silva Peres; Murao, Mitiko; Viana, Marcos Borato; de Oliveira, Benigna Maria

    2012-01-01

    Background Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. Methods This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG) between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99) treatment protocol. Results The estimated probabilities of overall survival and event free survival at 5 years were 69.5% (± 3.6%) and 58.8% (± 4.0%), respectively. The cumulative incidence of central nervous system (isolated or combined) relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis ≥ 50 x 109/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 109/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia. PMID:23323068

  13. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99 treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6% and 58.8% ( 4.0%, respectively. The cumulative incidence of central nervous system (isolated or combined relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  14. The genetic and environmental influences on childhood obesity: a systematic review of twin and adoption studies

    DEFF Research Database (Denmark)

    Silventoinen, K; Rokholm, B; Kaprio, J;

    2010-01-01

    a substantial effect in mid-childhood, but this effect disappeared at adolescence. Adoption studies supported the role of family environment in childhood obesity as correlations were found between adoptees and adoptive parents; however, correlations were substantially stronger between parents......In this systematic review, we aimed to collect together all previous twin and adoption studies on childhood and adolescent obesity up to the age of 18 years. Using several sources, we identified nine twin and five adoption studies; all of these studies had used relative weight as an indicator...... of obesity. Except the two twin studies from the Korean population, all studies represented Caucasian populations. In a meta-analysis of these twin studies, we found that genetic factors had a strong effect on the variation of body mass index (BMI) at all ages. The common environmental factors showed...

  15. Open Label, Phase II Study to Evaluate Efficacy and Safety of Oral Nilotinib in Philadelphia Positive (Ph+) Chronic Myelogenous Leukemia (CML) Pediatric Patients.

    Science.gov (United States)

    2016-10-07

    Leukemia; Leukemia,Pediatric; Leukemia, Myleiod; Leukemia, Mylegenous, Chronic; Leukemia, Mylegenous, Accelerated; BCR-ABL Positive; Myeloproliferative Disorder; Bone Marrow Disease; Hematologic Diseases; Neoplastic Processes; Imatinib; Dasatinib; Enzyme Inhibitor; Protein Kinase Inhibitor

  16. Pneumocystis jiroveci pneumonia prophylaxis during maintenance therapy influences methotrexate/6-mercaptopurine dosing but not event-free survival for childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Shabaneh, Diana; Bohnstedt, Cathrine

    2012-01-01

    Trimethoprim-sulfamethoxazole (TMP/SMX) is used in children with acute lymphoblastic leukemia (ALL) to prevent Pneumocystis pneumonia (PCP). We explored to which extent TMP/SMX influenced methotrexate (MTX)/6-mercaptopurine (6MP) dosage, myelosuppression, and event-free survival (EFS) during.......06) were related to reduced EFS. ANC had no effect on EFS among TMP/SMX2–7 patients (P = 0.40) but did for TMP/SMXnever patients (P = 0.02). The difference in the effect on EFS between TMP/SMX2–7 and TMP/SMXnever patients was not significant (P = 0.46). EFS did not differ between TMP/SMX2–7 and TMP....../SMXnever patients (0.83 vs. 0.83; P = 0.82). These results suggest that TMP/SMX is effective in preventing PCP and may have an antileukemic effect. TMP/SMX should be given the entire duration of maintenance therapy...

  17. Gleevec Keeps a Leukemia in Check for More Than a Decade: Study

    Science.gov (United States)

    ... Dr. Andreas Hochhaus, of Jena University Hospital in Germany. Of more than 500 CML patients given Gleevec ... internal medicine, hematology/oncology, Jena University Hospital, Jena, Germany; Michael Mauro, M.D., clinical director, leukemia service, ...

  18. Splenectomy in children with idiopathic thrombocytopenic purpura : A prospective study of 134 children from the Intercontinental Childhood ITP Study Group

    NARCIS (Netherlands)

    Kuehne, Thomas; Blanchette, Victor; Buchanan, George R.; Ramenghi, Ugo; Donato, Hugo; Tamminga, Rienk Y. J.; Rischewski, Johannes; Berchtold, Willi; Imbach, Paul

    2007-01-01

    Background. Splenectomy is an effective procedure for children and adults with severe or refractory idiopathic thrombocytopenic purpura (ITP). Data regarding pediatric patients are limited. Procedure. Sixty-eight Intercontinental Childhood ITP Study Group (ICIS) investigators from 57 institutions in

  19. The Risk of Cataract among Survivors of Childhood and Adolescent Cancer: A Report from the Childhood Cancer Survivor Study.

    Science.gov (United States)

    Chodick, Gabriel; Sigurdson, Alice J; Kleinerman, Ruth A; Sklar, Charles A; Leisenring, Wendy; Mertens, Ann C; Stovall, Marilyn; Smith, Susan A; Weathers, Rita E; Veiga, Lene H S; Robison, Leslie L; Inskip, Peter D

    2016-04-01

    With therapeutic successes and improved survival after a cancer diagnosis in childhood, increasing numbers of cancer survivors are at risk of subsequent treatment-related morbidities, including cataracts. While it is well known that the lens of the eye is one of the most radiosensitive tissues in the human body, the risks associated with radiation doses less than 2 Gy are less understood, as are the long- and short-term cataract risks from exposure to ionizing radiation at a young age. In this study, we followed 13,902 five-year survivors of childhood cancer in the Childhood Cancer Survivor Study cohort an average of 21.4 years from the date of first cancer diagnosis. For patients receiving radiotherapy, lens dose (mean: 2.2 Gy; range: 0-66 Gy) was estimated based on radiotherapy records. We used unconditional multivariable logistic regression models to evaluate prevalence of self-reported cataract in relationship to cumulative radiation dose both at five years after the initial cancer diagnosis and at the end of follow-up. We modeled the radiation effect in terms of the excess odds ratio (EOR) per Gy. We also analyzed cataract incidence starting from five years after initial cancer diagnosis to the end of follow-up using Cox regression. A total of 483 (3.5%) cataract cases were identified, including 200 (1.4%) diagnosed during the first five years of follow-up. In a multivariable logistic regression model, cataract prevalence at the end of follow-up was positively associated with lens dose in a manner consistent with a linear dose-response relationship (EOR per Gy = 0.92; 95% CI: 0.65-1.20). The odds ratio for doses between 0.5 and 1.5 Gy was elevated significantly relative to doses <0.5 Gy (OR = 2.2; 95% CI: 1.3-3.7). The results from this study indicate a strong association between ocular exposure to ionizing radiation and long-term risk of pre-senile cataract. The risk of cataract increased with increasing exposure, beginning at lens doses as low as 0.5 Gy. Our

  20. Prognostic factors in children with acute lymphoblastic leukemia: a ten year study

    Directory of Open Access Journals (Sweden)

    Oloomi yazdi Z.

    2008-06-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common cancer in the pediatric population. With modern treatments, the chance of the complete recovery is nearly 100%. The most important prognostic factors are appropriate treatment protocol and determination of patient risk factors based on clinical, morphological, immunological and cytological characteristics. In this study we reviewed frequency of these factors, like as age, gender, the primary white blood cell number, sub- group on the base of FAB classification, immunophenotype and the clinical progress. Methods: In this retrospective study, we reviewed 877 pediatric patients with the diagnosis of ALL between the years of 1994 and 2004. In these patients the age, gender, primary WBC count, sub-group based on the FAB classification, immunophenotype and the clinical progress in 177 patient with acute lymphoblastic leukemia at Imam Khomeini Hospital between the years of 1994 to 2004 were determined. Results: Of these patients, 1.6% was younger than one year, 24.8% more than ten years old and 73.6% were between the ages of one and ten years; 63.8% were male. WBC counts were above 50,000/ul in 28.8% of the patients. FAB classifications included L1 in 80.2%, L2 in 17.5% and L3 in 2.3% of the patients. Immunophenotypes included pre-B cell in 63.8%, early pre-B cell in 23.1%, T cell in 12.3% and mature B cell in 0.8% of the patients. Marker CD10+ was detected in 88.1% of the B cell cases. In this study group, 74% of the patients recovered, 16.3% died and 16.5% relapsed.Conclusions: The prevalence of FAB-L1 and pre-B cell cases in this study is greater than a previous study, while the prevalence of FAB-L2 and early pre-B cell cases is less than that of the previous study.

  1. Leukemia cutis

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    Angoori G Rao

    2012-01-01

    Full Text Available Leukemia cutis is the infiltration of neoplastic leukocytes or their precursors into the epidermis, the dermis, or the subcutis, resulting in clinically identifiable cutaneous lesions. Leukemia cutis may follow, precede or occur concomitantly with the diagnosis of systemic leukemia. A 50-year-old woman presented with asymptomatic multiple cutaneous nodules all over the body of 4 months duration. Cutaneous examination showed multiple hyperpigmented nodules and plaques involving face, trunk, and extremities. Peripheral smear showed abnormally elevated leucocyte count (TLC-70,000 with abnormal cells: myeloblasts 40%, promyelocytes 8% and myelocytes 39%. Auer rods were present in few myeloblasts. Bone marrow aspiration showed increased cellularity, erythroid hyperplasia with megaloblastic change, increased myeloblasts with maturation arrest. Immunohistochemistry showed strongly positive myeloperoxidase infiltrating cells and negative for CD20 and CD3 consistent with the diagnosis of AML-M 2 with leukemia cutis. This case is reported for its rarity.

  2. Understanding Leukemia

    Science.gov (United States)

    ... material presented in this publication Jane Liesveld, MD Professor, Department of Medicine, Hematology/Oncology Clinical Director, Blood ... of leukemia cell. The marrow has two main jobs. The first job is to form myeloid cells. ...

  3. "Race" and Early Childhood Education: An International Approach to Identity, Politics, and Pedagogy. Critical Cultural Studies of Childhood

    Science.gov (United States)

    Mac Naughton, Glenda, Ed.; Davis, Karina, Ed.

    2009-01-01

    This book explores the prominence of "race" in the lives of young children and their early childhood educators. It critiques the often presumed racial innocence of young children and shows instead how young children actively engage with the politics of race as they form their own identities. It challenges early childhood educators to engage with…

  4. Self Reported Childhood Difficulties, Adult Multimorbidity and Allostatic Load. A Cross-Sectional Analysis of the Norwegian HUNT Study.

    Directory of Open Access Journals (Sweden)

    Margret Olafia Tomasdottir

    Full Text Available Multimorbidity receives increasing scientific attention. So does the detrimental health impact of adverse childhood experiences (ACE. Aetiological pathways from ACE to complex disease burdens are under investigation. In this context, the concept of allostatic overload is relevant, denoting the link between chronic detrimental stress, widespread biological perturbations and disease development. This study aimed to explore associations between self-reported childhood quality, biological perturbations and multimorbidity in adulthood.We included 37 612 participants, 30-69 years, from the Nord-Trøndelag Health Study, HUNT3 (2006-8. Twenty one chronic diseases, twelve biological parameters associated with allostatic load and four behavioural factors were analysed. Participants were categorised according to the self-reported quality of their childhood, as reflected in one question, alternatives ranging from 'very good' to 'very difficult'. The association between childhood quality, behavioural patterns, allostatic load and multimorbidity was compared between groups.Overall, 85.4% of participants reported a 'good' or 'very good' childhood; 10.6% average, 3.3% 'difficult' and 0.8% 'very difficult'. Childhood difficulties were reported more often among women, smokers, individuals with sleep problems, less physical activity and lower education. In total, 44.8% of participants with a very good childhood had multimorbidity compared to 77.1% of those with a very difficult childhood (Odds ratio: 5.08; 95% CI: 3.63-7.11. Prevalences of individual diseases also differed significantly according to childhood quality; all but two (cancer and hypertension showed a significantly higher prevalence (p<0.05 as childhood was categorised as more difficult. Eight of the 12 allostatic parameters differed significantly between childhood groups.We found a general, graded association between self-reported childhood difficulties on the one hand and multimorbidity, individual

  5. Traumatic experiences in childhood and psychopathy: a study on a sample of violent offenders from Italy

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    Giuseppe Craparo

    2013-12-01

    Full Text Available Background: The link between early traumatic experiences of abuse/neglect and criminal behaviour has been widely demonstrated. Less is known, however, about the relationship between these experiences and the development of psychopathic personality. Objective: This study investigated childhood relational trauma in a group of violent offenders from Italy. We hypothesised a higher level of early relational trauma associated with higher scores on psychopathy. Method: Twenty-two offenders convicted for violent crimes aged 22–60 (M=38, SD=11 participated in this study. Participants were selected by the Italian justice system for an experimental research programme aiming at the evaluation of psychopathic personality traits among violent offenders. Within the group, 14 participants (64% had committed murder, 4 (18% had committed rape, and 4 (18% were convicted child sex offenders. The Traumatic Experience Checklist was used to assess childhood relational trauma; the Hare Psychopathy Checklist—Revised (PCL-R was used to assess psychopathy. Results: There was a high prevalence of childhood experiences of neglect and abuse among the offenders. Higher levels of childhood relational trauma were found among participants who obtained high scores on the PCL-R. There was also a significant negative association between age of first relational trauma and psychopathy scores. Conclusions: Findings of this study suggest that an early exposure to relational trauma in childhood can play a relevant role in the development of more severe psychopathic traits.For the abstract or full text in other languages, please see Supplementary files under Article Tools online

  6. Efficacy of Auto-DC-CIK Adoptive Immunotherapy in Childhood Acute Leukemia%自体DC-CIK过继免疫治疗儿童急性白血病的疗效观察

    Institute of Scientific and Technical Information of China (English)

    周东风; 蔡和花; 潘峰; 白燕; 翟丽娜; 吴耀辉; 金润铭; 孟浦

    2011-01-01

    Objective To evaluate the clinical efficacy and safety of co-cultured dendritic cells with cytokine-induced-killer cells(DC-CIK)adaptive immunotherapy in treating childhood acute leukemia who have attained cellular complete remission after chemotherapy. Methods Forty-seven children with acute leukemia who have attained complete remission after chemotherapy were enrolled in this retrospective analysis. Minimal residual disease(MRD)was positive in 9 out of the 47 cases. DC-CIK were transfused to the children twice after cultivation,amplification and quality test in vilro. The hematological and genetic changes, MRD and cellular immune function were monitored regularly after the treatment. Results Forty-seven patients had successfully received a total of 61 courses of DC-CIK transfusion. The median time of follow-up was 41 months(range from 5 to 72 months). Thirty-six out of the 38 MRD-negative cases stayed continuous complete remission(CCR) including a acute lymphoblastic leu-kemia( ALL) child who had hepatitis B with HbsAg+/eAg+/cAb+. The very child was intolerant to chemotherapy because of liver dysfunction,and then received DC-CIK therapy after 5 courses of chemotherapy. During 60 months of follow-up period,he has always stayed CCR. His liver function recovered while the hepatitis B with HbsAg+/eAg+/cAb+ turned to be HbsAg+/ eAb+/cAb+. The MRD was monitored by flow cytometry or real-time quantitative polymerase chain reaction(RQ-PCR). Of the 9 cases positive for MRD,8 cases turned to be negative after DC-CIK therapy. The peripheral T-lymphocyte subsets showed that the proportion of CD3+ CD8+ cells was increased distinctly. Conclusion DC-CIK therapy in combination with or followed by chemotherapy does great well in MRD clearance for childhood acute leukemia. It is a novel hopeful therapy contributing to the improved clinical management of children with acute leukemia that requires more basic and clinical research.%目的 回顾性评估化疗联合自体共培养

  7. Bovine lymphocytic leukemia: studies of etiology, pathogenesis, and mode of transmission. Progress report No. 19, June 1978-June 1979

    Energy Technology Data Exchange (ETDEWEB)

    Sorensen, D.K.

    1979-07-01

    Bovine leukemia is believed to be caused by an oncogenic RNA virus designated bovine leukemia virus (BLV). The presence of BLV particles in lymphocyte cultures from leukemic cattle and cattle with a persistent lymphocytosis has been consistentily demonstrated. Concentrated, cell free, BLV preparations were used to inoculate 12 late stage bovine fetuses (in utero) and two newborn calves. Current studies involve extensive monitoring of these inoculated animals to detect precancerous changes and obtain a detailed description of the events preceding the development of lymphosarcoma. Ongoing monitoring studies will provide a complete record of all changes in the various leukemia associated parameters. We will then be able to detail when, in what sequence, and to what extent each parameter changes in the course of lymphosarcoma development. Fourteen animals were successfully inoculated during the study. Eleven remain alive, and comprise the current monitoring program. All eleven of these animals are definitely infected with BLV, and in nine the infection has substantially progressed with respect to the parameters being monitored. In addition to transmission and monitoring studies, various lymphocyte subpopulations were examined to determine which cell type(s) are involved in the pathogenesis of bovine lymphosarcoma. These studies have conclusively established that B-lymphocytes are the target cells for BLV infection and that they carry the morphologic nuclear abnormality associated with this disease.

  8. Childhood Trauma and Adult Interpersonal Functioning: A Study Using the Core Conflictual Relationship Theme Method (CCRT)

    Science.gov (United States)

    Drapeau, M.; Perry, J.C.

    2004-01-01

    Objective: This study aimed to examine the long-term correlates of childhood trauma in regard to interpersonal functioning in adulthood. Method: One hundred and nineteen (N=119) subjects from the Austen Riggs Follow-along Study were included in the study. The Traumatic Antecedent Interview scoring method was used to assess 10 types of childhood…

  9. Magnetic fields and acute lymphoblastic leukemia in children: a systematic review of case-control studies Campos magnéticos e leucemia linfocítica aguda em crianças: revisão sistemática de estudos caso-controle

    Directory of Open Access Journals (Sweden)

    Daniele Maria Pelissari

    2009-01-01

    Full Text Available Leukemia incidence in children has increased worldwide in recent decades, particularly due to the rise in acute lymphoblastic leukemia. Studies have associated exposure to non-ionizing radiation generated by low frequency magnetic fields with childhood leukemia. The current article reviews the case-control studies published on this subject. Of 152 articles tracked in different databases, ten studies from North America, Asia, and Europe met the defined selection criteria, with patients diagnosed from 1960 to 2004. Methodological limitations were observed in these articles, including difficulties with the procedures for assessing exposure. An association may exist between exposure to low frequency magnetic fields and acute lymphoblastic leukemia in children, but this association is weak, preventing the observation of consistency in the findings. Future studies from a wider range of geographic regions should focus on the analysis of acute lymphoblastic leukemia, which is the subtype with the greatest impact on the increasing overall incidence of childhood leukemia.A incidência de leucemias em crianças tem aumentado nas últimas décadas no mundo, com influência predominante da leucemia linfocítica aguda, principal subtipo em crianças. Estudos têm relacionado a exposição às radiações não-ionizantes geradas pelos campos magnéticos de baixa freqüência com leucemia infantil. Neste artigo foram revisados os estudos caso-controle publicados sobre essa questão. Dos 152 artigos localizados em diferentes bases de dados, dez estudos da América do Norte, Ásia e Europa preencheram os critérios de seleção, comportando pacientes diagnosticados entre 1960 e 2004. Algumas limitações metodológicas foram observadas como dificuldades nos procedimentos de avaliação da exposição. É possível a existência de associação entre exposição a campos magnéticos de baixa freqüência e leucemia linfocítica aguda em crianças, porém, a for

  10. Socioeconomic disparities in childhood cancer survival in Switzerland.

    Science.gov (United States)

    Adam, Martin; Rueegg, Corina S; Schmidlin, Kurt; Spoerri, Adrian; Niggli, Felix; Grotzer, Michael; von der Weid, Nicolas X; Egger, Matthias; Probst-Hensch, Nicole; Zwahlen, Marcel; Kuehni, Claudia E

    2016-06-15

    In this study, we investigated whether childhood cancer survival in Switzerland is influenced by socioeconomic status (SES), and if disparities vary by type of cancer and definition of SES (parental education, living condition, area-based SES). Using Cox proportional hazards models, we analyzed 5-year cumulative mortality in all patients registered in the Swiss Childhood Cancer Registry diagnosed 1991-2006 below 16 years. Information on SES was extracted from the Swiss census by probabilistic record linkage. The study included 1602 children (33% with leukemia, 20% with lymphoma, 22% with central nervous system (CNS) tumors); with an overall 5-year survival of 77% (95%CI 75-79%). Higher SES, particularly parents' education, was associated with a lower 5-year cumulative mortality. Results varied by type of cancer with no association for leukemia and particularly strong effects for CNS tumor patients, where mortality hazard ratios for the different SES indicators, comparing the highest with the lowest group, ranged from 0.48 (95%CI: 0.28-0.81) to 0.71 (95%CI: 0.44-1.15). We conclude that even in Switzerland with a high quality health care system and mandatory health insurance, socioeconomic differences in childhood cancer survival persist. Factors causing these survival differences have to be further explored, to facilitate universal access to optimal treatment and finally eliminate social inequalities in childhood cancer survival.

  11. The Urban Environment and Childhood Asthma (URECA birth cohort study: design, methods, and study population

    Directory of Open Access Journals (Sweden)

    Sandel Megan T

    2009-05-01

    Full Text Available Abstract Background The incidence and morbidity of wheezing illnesses and childhood asthma is especially high in poor urban areas. This paper describes the study design, methods, and population of the Urban Environment and Childhood Asthma (URECA study, which was established to investigate the immunologic causes of asthma among inner-city children. Methods and Results URECA is an observational prospective study that enrolled pregnant women in central urban areas of Baltimore, Boston, New York City, and St. Louis and is following their offspring from birth through age 7 years. The birth cohort consists of 560 inner-city children who have at least one parent with an allergic disease or asthma, and all families live in areas in which at least 20% of the population has incomes below the poverty line. In addition, 49 inner-city children with no parental history of allergies or asthma were enrolled. The primary hypothesis is that specific urban exposures in early life promote a unique pattern of immune development (impaired antiviral and increased Th2 responses that increases the risk of recurrent wheezing and allergic sensitization in early childhood, and of asthma by age 7 years. To track immune development, cytokine responses of blood mononuclear cells stimulated ex vivo are measured at birth and then annually. Environmental assessments include allergen and endotoxin levels in house dust, pre- and postnatal maternal stress, and indoor air nicotine and nitrogen dioxide. Nasal mucous samples are collected from the children during respiratory illnesses and analyzed for respiratory viruses. The complex interactions between environmental exposures and immune development will be assessed with respect to recurrent wheeze at age 3 years and asthma at age 7 years. Conclusion The overall goal of the URECA study is to develop a better understanding of how specific urban exposures affect immune development to promote wheezing illnesses and asthma.

  12. Phase 2 study of cladribine followed by rituximab in patients with hairy cell leukemia

    Science.gov (United States)

    O'Brien, Susan; Jorgensen, Jeffrey; Pierce, Sherry; Faderl, Stefan; Ferrajoli, Alessandra; Koller, Charles; Challagundla, Pramoda; York, Sergernne; Brandt, Mark; Luthra, Rajyalakshmi; Burger, Jan; Thomas, Deborah; Keating, Michael; Kantarjian, Hagop

    2011-01-01

    We conducted this study to determine the feasibility and safety of cladribine followed by rituximab in patients with hairy cell leukemia including the vari-ant form (HCLv). Cladribine 5.6 mg/m2 given IV over 2 hours daily for 5 days was followed ∼ 1 month later with rituximab 375 mg/m2 IV weekly for 8 weeks. Responses were recorded and BM minimal residual disease (MRD) was evaluated after the completion of rituximab. Thirty-six patients have been treated including 5 with HCLv. Median age was 57 years (range, 37-89). All patients (100%) have achieved complete response (CR), defined as presence of no hairy cells in BM and blood with normalization of counts (absolute neutrophil count [ANC]> 1.5 × 109/L, hemoglobin [Hgb] > 12.0 g/dL, platelets [PLT] > 100 × 109/L), as well as resolution of splenomegaly. There were no grade 3 or 4 nonhematologic adverse events directly related to the treatment. Only 1 patient (with HCLv) has relapsed; median CR duration has not been reached (range,1+-63+ months). Three patients with HCLv died including 1 with relapsed disease and 2 from unrelated malignancies. Median survival duration has not been reached (range, 2+-64+ months). Treatment with clad-ribine followed by rituximab is effective tk;4and may increase CR rate. This study was registered at www.clinicaltrials.gov as NCT00412594. PMID:21821712

  13. Long-term results in the treatment of acute nonlymphocytic leukemia: a Pediatric Oncology Group Study.

    Science.gov (United States)

    Krischer, J P; Steuber, C P; Vietti, T J; Culbert, S J; Ragab, A H; Morgan, S K; Berry, D H; Hvizdala, E; Thomas, P J; Land, V J

    1989-01-01

    Complete remission (CR), 5-year remission duration (RD), and overall 5-year survival rates are 74%, 28% and 25%, respectively, for previously untreated children with acute nonlymphocytic leukemia diagnosed between 1977 and 1981, following induction therapy with vincristine, doxorubicin and prednisone (VAP), consolidation therapy with 6-thioguanine, cytosine arabinoside (TA) and cyclophosphamide/vincristine/cytosine arabinoside/prednisone (COAP), and maintenance therapy of alternating TA and COAP with or without VAP pulses. Approximately 20% are free of their disease for more than 5 years. High white blood cell counts (WBC) at diagnosis and M3 and M6 morphology were associated with lower CR rates, while M5 morphology was associated with higher CR rates. Patients with M1 morphology had shorter remission duration as compared to those with M4 or M5 morphology. Low WBC and age between 2 and 10 years at diagnosis were associated with longer remission durations and survival. Patients with M4 morphology also survived longer. The observed CR rates are comparable to other studies initiated at the same time as this study but survival is less than those reported more recently. Low WBC at diagnosis and M4/M5 morphology may identify relatively favorable prognostic groups.

  14. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia

    Science.gov (United States)

    AZIZI, ZAHRA; RAHGOZAR, SOHEILA; MOAFI, ALIREZA; DABAGHI, MOHAMMAD; NADIMI, MOTAHAREH

    2015-01-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance. PMID:26137238

  15. mRNA overexpression of BAALC: A novel prognostic factor for pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Azizi, Zahra; Rahgozar, Soheila; Moafi, Alireza; Dabaghi, Mohammad; Nadimi, Motahareh

    2015-05-01

    BAALC is a novel molecular marker in leukemia that is highly expressed in patients with acute leukemia. Increased expression levels of BAALC are known as poor prognostic factors in adult acute myeloid and lymphoid leukemia. The purpose of the present study was to evaluate the prognostic significance of the BAALC gene expression levels in pediatric acute lymphoblastic leukemia (ALL) and its association with MDR1. Using reverse transcription-quantitative polymerase chain reaction (RT-qPCR), the mRNA expression levels of BAALC and MRD1 were measured in bone marrow samples of 28 new diagnosed childhood ALL patients and 13 children without cancer. Minimal residual disease (MRD) was measured one year after the initiation of the chemotherapy using the RT-qPCR method. The high level expression of BAALC had a significant association with the pre-B-ALL subtype, leukocytosis and positive MRD after one year of treatment in leukemic patients. In addition, a positive correlation between BAALC and MDR1 mRNA expression was shown in this group. In conclusion, to the best of our knowledge, the increase of BAALC expression as a poor prognostic factor for childhood ALL is shown for the first time. Additionally, the correlation between BAALC and MDR1 in mRNA expression levels can aid for an improved understanding of the mechanism through which BAALC may function in ALL and multidrug resistance.

  16. Examining Childhood Maltreatment and School Bullying Among Adolescents: A Cross-Sectional Study From Anhui Province in China.

    Science.gov (United States)

    Wang, Geng-Fu; Jiang, Liu; Wang, Lu-Han; Hu, Guo-Yun; Fang, Yu; Yuan, Shan-Shan; Wang, Xiu-Xiu; Su, Pu-Yu

    2016-05-03

    Although a body of research has established the relationship between childhood maltreatment and bullying in Western culture backgrounds, few studies have examined the association between childhood maltreatment experiences and bullying in China. Moreover, to date, the relationship between multiple types of childhood maltreatment and cyber bullying is poorly understood. This study examined the association between multiple types of childhood maltreatment (physical abuse, emotional abuse, sexual abuse, physical neglect, and emotional neglect) and multiple forms of school bullying (physical, verbal, relational, and cyber). A cross-sectional study using three-stage random cluster-sampling approach was conducted in Tongling, Chuzhou, and Fuyang, in Anhui Province. Self-reported questionnaires were completed by 5,726 middle school students to assess their school bullying involvement and childhood maltreatment experiences. A multivariable logistic regression analysis was used to explore the relationship between each single type of childhood maltreatment and each single form of school bullying. Each type of childhood maltreatment was associated with increased risk for involvement in each form of bullying as bullies, victims, and bully-victims. Specifically, both childhood physical neglect and emotional neglect were associated with increased risk for involvement in each form of school bullying. Each type of childhood maltreatment was associated with involvement in cyber bullying. Students who experienced multiple types of childhood maltreatment seem to report more forms of school bullying. Furthermore, multiple forms of school bullying caused the co-occurrence of several forms of school bullying. Our results indicated a significant association between school bullying and childhood maltreatment among adolescents. Interventions to reduce school bullying encompassing prevention toward childhood maltreatment might get better results in China.

  17. Novel murine B-cell lymphoma/leukemia model to study BCL2-driven oncogenesis.

    Science.gov (United States)

    Meijerink, Jules P P; Van Lieshout, Esther M M; Beverloo, H Berna; Van Drunen, Ellen; Mensink, Ewald J B M; Macville, Merryn; Pieters, Rob

    2005-05-10

    The BCL-2 family has been implicated in the pathogenesis of various hematopoietic malignancies, including follicular non-Hodgkin lymphoma and B-cell chronic lymphocytic leukemia. To identify genes that act synergistically in BCL2-enforced leukemogenesis, we developed a murine B-cell lymphoma/leukemia model based on the IL-3-dependent Balb/C pro-B line (FL5.12). FL5.12 cells were stably transfected with antiapoptotic BCL-2 alone or in combination with proapoptotic BAX or nonfunctional mutant BAX, thereby creating various levels of imbalance within the BCL-2 family. Transfectants were intravenously injected into normal Balb/C mice. Whereas FL5.12 cells did not provoke leukemia, mice injected with stable transfectants died of leukemia over time. Disease incidence and latency time depended on the degree of imbalance in the BCL-2 family, supporting a model whereby BCL2 drives tumorigenesis. All mice presented with hepatosplenomegaly and leukemic FL5.12 cells in peripheral blood and bone marrow compartments. Leukemic conversion was accompanied by secondary genetic aberrations leading to clonal IL-3-responsive leukemia. Cellular transformation was independent of alterations in c-Myc or downstream apoptotic pathway. Leukemic clones retained a normal DNA damage response leading to elevated P53 and P21 levels and cell cycle arrest upon irradiation. In conclusion, our mouse model may prove a valuable tool to identify genes that cooperate in BCL2-enforced lymphoma/leukemogenesis.

  18. Rapid lung MRI - paradigm shift in evaluation of febrile neutropenia in children with leukemia: a pilot study.

    Science.gov (United States)

    Sodhi, Kushaljit Singh; Khandelwal, Niranjan; Saxena, Akshay Kumar; Bhatia, Anmol; Bansal, Deepak; Trehan, Amita; Singh, Meenu; Agarwal, Ritesh

    2016-01-01

    Immunocompromised children with hematological malignancies are at increased risk of developing potentially fatal pulmonary infections. Early detection and prompt treatment is critical to combat morbidity and mortality in these children. Twenty-six children with leukemia (age range: 5-13years) presenting with fever and neutropenia were included in this prospective study, which was approved by the institutional ethics committee. All patients underwent HRCT and MRI of the chest on the same day. The findings of HRCT and MRI were compared, with HRCT as the standard of reference. There was perfect agreement between MRI and CT examinations findings by kappa test (κ = 1). No significant difference was observed between the two modalities by the McNemar test (p > 0.05). Rapid lung MRI is technically feasible; has a high correlation, sensitivity and specificity to CT scan; and can emerge as the first line modality for the detection of pulmonary nodules in children with leukemia and persistent febrile neutropenia.

  19. Recurrence Risk after a First Remote Symptomatic Unprovoked Seizure in Childhood: A Prospective Study

    Science.gov (United States)

    Ramos-Lizana, J.; Aguirre-Rodriguez, J.; Aguilera-Lopez, P.; Cassinello-Garcia, E.

    2009-01-01

    The aim of this study was to assess recurrence risk after a first remote symptomatic unprovoked seizure in childhood. All consecutive patients younger than 14 years with a first remote symptomatic unprovoked seizure who were seen at our hospital between 1994 and 2006 were included in the study and prospectively followed. Only two patients received…

  20. Attention Problems in Very Preterm Children from Childhood to Adulthood: The Bavarian Longitudinal Study

    Science.gov (United States)

    Breeman, Linda D.; Jaekel, Julia; Baumann, Nicole; Bartmann, Peter; Wolke, Dieter

    2016-01-01

    Background: Very preterm (VP; gestational age attention problems in childhood and adulthood. The stability of these problems into adulthood is not known. Methods: The Bavarian Longitudinal Study is a prospective cohort study that followed 260 VP/VLBW and 229 term-born…

  1. Childhood Behavior Problems Linked to Sexual Risk Taking in Young Adulthood: A Birth Cohort Study

    Science.gov (United States)

    Ramrakha, Sandhya; Bell, Melanie L.; Paul, Charlotte; Dickson, Nigel; Moffitt, Terrie E.; Caspi, Avshalom

    2007-01-01

    Objective: To study whether behavioral and emotional problems during childhood predicted early sexual debut, risky sex at age 21 years, and sexually transmitted infections up to age 21 years. Some possible mediational pathways were also explored. Method: Participants were enrolled in the Dunedin Multidisciplinary Health and Development Study (n =…

  2. The Preschool Nap as a Protective Factor in the Fight against Childhood Obesity: An Exploratory Study

    Science.gov (United States)

    Kihm, Holly Spencer; Rolling, Peggy

    2014-01-01

    Although the prevalence of childhood obesity has not increased in recent years, it remains unacceptably high and warrants continued study. The purpose of this study was to explore the potential relationship between weight status and length of sleep (both daytime and nighttime) among preschool children. Special attention was given to the role…

  3. A Comparative Study of Male and Female Early Childhood Teachers' Job Satisfaction in Turkey

    Science.gov (United States)

    Sahin, Fatma Tezel; Sak, Ramazan

    2016-01-01

    The aim of the present study is to provide a comparative analysis of job satisfaction among male and female teachers in early childhood education. A total of 163 teachers participated in the study, which utilized Tahta's (An analysis of job satisfaction of preschool teachers, Hacettepe University, Ankara, 1995) Job Satisfaction Survey and a…

  4. Childhood cancer incidence and arsenic exposure in drinking water in Nevada.

    Science.gov (United States)

    Moore, Lee E; Lu, Meng; Smith, Allan H

    2002-01-01

    Inorganic arsenic exposure through drinking water causes cancer in adults; however, the carcinogenic potential in children remains unknown. A recent leukemia cluster in Churchill County, Nevada, where arsenic levels in water supplies are relatively high, has prompted concern. The authors investigated the incidence of childhood cancer between 1979 and 1999 in all 17 Nevada counties, grouped by low (i.e., water supplies. The standardized incidence ratios (SIRs) for all childhood cancers combined were 1.00 (95% confidence interval [CI] = 0.94, 1.06), 0.72 (95% CI = 0.43, 1.12), and 1.25 (95% CI = 0.91, 1.69) for low-, medium-, and high-exposure counties, respectively. There was no relationship between arsenic levels in water and childhood leukemia (SIRs = 1.02, 0.61, and 0.86, respectively [95% CIIs = 0.90, 1.15; 0.12, 1.79; and 0.37, 1.70, respectively]). For all childhood cancers, excluding leukemias, the SIRs were 0.99 (95% CI = 0.92, 1.07), 0.82 (95% CI = 0.42, 1.22), and 1.37 (0.92, 1.83), respectively. The excess in 5- to 9-yr-old children and 10- to 14-yr-old children was in bone cancers, and the excess in 15- to 19-yr-old young adults was primarily in lymphomas. The findings in this study are reassuring in that leukemia risks were not increased at the concentrations of arsenic in water found in this study. Nonetheless, the results raise the possibility that there are increased risks for nonleukemic childhood cancers that require confirmation in other studies, particularly those in which higher exposures are addressed.

  5. 儿童急性淋巴细胞白血病预防性血小板输注阈值探讨%The threshold analysis for prophylactic platelet transfusions in childhood acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    周令; 徐学聚; 李欢欢

    2013-01-01

    Objective To investigate the threshold for prophylactic platelet transfusions in childhood acute lymphoblastic leukemia(ALL).Methods To analyze platelet transfusions and bleeding condition during chemotherapy in our department in childhood with ALL.Results 1 10 cases of children with a total 385 cases platelet transfusions.No complication group platelet count < 5 × 109/L,given platelet transfusion,major clinical bleeding events increased,complication group platelet count < 5 × 109/L,the risk of clinical bleeding increased.Conclusions The platelet transfusions threshold of 5 × 109/L for stable ALL patients is safe during chemotherapy.The platelet transfusion trigger was increased to 10 × 109/L or even higher in certain clinical situations.%目的 探讨急性淋巴细胞性白血病患儿化疗过程中预防性血小板输注阈值.方法 分析郑州大学第一附属医院儿科2年间急性淋巴细胞白血病患儿化疗期间血小板输注及出血情况.结果 110例患儿共输注血小板385例次,无合并症组血小板计数<5×109/L时输注血小板,临床主要出血事件增加,有合并症组在血小板计数< 10×109/L时临床出血风险增加.结论 儿童急性淋巴细胞白血病化疗过程中,在患儿一般状态稳定情况下,血小板输注阈值定为5×109/L相对安全,有合并症时血小板输注阈值应为10×109/L或更高.

  6. Raman spectroscopy for the assessment of acute myeloid leukemia: a proof of concept study

    Science.gov (United States)

    Vanna, R.; Tresoldi, C.; Ronchi, P.; Lenferink, A. T. M.; Morasso, C.; Mehn, D.; Bedoni, M.; Terstappen, L. W. M. M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2014-03-01

    Acute myeloid leukemia (AML) is a proliferative neoplasm, that if not properly treated can rapidly cause a fatal outcome. The diagnosis of AML is challenging and the first diagnostic step is the count of the percentage of blasts (immature cells) in bone marrow and blood sample, and their morphological characterization. This evaluation is still performed manually with a bright field light microscope. Here we report results of a study applying Raman spectroscopy for analysis of samples from two patients affected by two AML subtypes characterized by a different maturation stage in the neutrophilic lineage. Ten representative cells per sample were selected and analyzed with high-resolution confocal Raman microscopy by scanning 64x64 (4096) points in a confocal layer through the volume of the whole cell. The average spectrum of each cell was then used to obtain a highly reproducible mean fingerprint of the two different AML subtypes. We demonstrate that Raman spectroscopy efficiently distinguishes these different AML subtypes. The molecular interpretation of the substantial differences between the subtypes is related to granulocytic enzymes (e.g. myeloperoxidase and cytochrome b558), in agreement with different stages of maturation of the two considered AML subtypes . These results are promising for the development of a new, objective, automated and label-free Raman based methods for the diagnosis and first assessment of AML.

  7. Meta-analysis of genome-wide association studies discovers multiple loci for chronic lymphocytic leukemia

    Science.gov (United States)

    Berndt, Sonja I.; Camp, Nicola J.; Skibola, Christine F.; Vijai, Joseph; Wang, Zhaoming; Gu, Jian; Nieters, Alexandra; Kelly, Rachel S.; Smedby, Karin E.; Monnereau, Alain; Cozen, Wendy; Cox, Angela; Wang, Sophia S.; Lan, Qing; Teras, Lauren R.; Machado, Moara; Yeager, Meredith; Brooks-Wilson, Angela R.; Hartge, Patricia; Purdue, Mark P.; Birmann, Brenda M.; Vajdic, Claire M.; Cocco, Pierluigi; Zhang, Yawei; Giles, Graham G.; Zeleniuch-Jacquotte, Anne; Lawrence, Charles; Montalvan, Rebecca; Burdett, Laurie; Hutchinson, Amy; Ye, Yuanqing; Call, Timothy G.; Shanafelt, Tait D.; Novak, Anne J.; Kay, Neil E.; Liebow, Mark; Cunningham, Julie M.; Allmer, Cristine; Hjalgrim, Henrik; Adami, Hans-Olov; Melbye, Mads; Glimelius, Bengt; Chang, Ellen T.; Glenn, Martha; Curtin, Karen; Cannon-Albright, Lisa A.; Diver, W Ryan; Link, Brian K.; Weiner, George J.; Conde, Lucia; Bracci, Paige M.; Riby, Jacques; Arnett, Donna K.; Zhi, Degui; Leach, Justin M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Sala, Núria; Casabonne, Delphine; Becker, Nikolaus; Boffetta, Paolo; Brennan, Paul; Foretova, Lenka; Maynadie, Marc; McKay, James; Staines, Anthony; Chaffee, Kari G.; Achenbach, Sara J.; Vachon, Celine M.; Goldin, Lynn R.; Strom, Sara S.; Leis, Jose F.; Weinberg, J. Brice; Caporaso, Neil E.; Norman, Aaron D.; De Roos, Anneclaire J.; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Kaaks, Rudolph; Masala, Giovanna; Weiderpass, Elisabete; Chirlaque, María- Dolores; Vermeulen, Roel C. H.; Travis, Ruth C.; Southey, Melissa C.; Milne, Roger L.; Albanes, Demetrius; Virtamo, Jarmo; Weinstein, Stephanie; Clavel, Jacqueline; Zheng, Tongzhang; Holford, Theodore R.; Villano, Danylo J.; Maria, Ann; Spinelli, John J.; Gascoyne, Randy D.; Connors, Joseph M.; Bertrand, Kimberly A.; Giovannucci, Edward; Kraft, Peter; Kricker, Anne; Turner, Jenny; Ennas, Maria Grazia; Ferri, Giovanni M.; Miligi, Lucia; Liang, Liming; Ma, Baoshan; Huang, Jinyan; Crouch, Simon; Park, Ju-Hyun; Chatterjee, Nilanjan; North, Kari E.; Snowden, John A.; Wright, Josh; Fraumeni, Joseph F.; Offit, Kenneth; Wu, Xifeng; de Sanjose, Silvia; Cerhan, James R.; Chanock, Stephen J.; Rothman, Nathaniel; Slager, Susan L.

    2016-01-01

    Chronic lymphocytic leukemia (CLL) is a common lymphoid malignancy with strong heritability. To further understand the genetic susceptibility for CLL and identify common loci associated with risk, we conducted a meta-analysis of four genome-wide association studies (GWAS) composed of 3,100 cases and 7,667 controls with follow-up replication in 1,958 cases and 5,530 controls. Here we report three new loci at 3p24.1 (rs9880772, EOMES, P=2.55 × 10−11), 6p25.2 (rs73718779, SERPINB6, P=1.97 × 10−8) and 3q28 (rs9815073, LPP, P=3.62 × 10−8), as well as a new independent SNP at the known 2q13 locus (rs9308731, BCL2L11, P=1.00 × 10−11) in the combined analysis. We find suggestive evidence (P<5 × 10−7) for two additional new loci at 4q24 (rs10028805, BANK1, P=7.19 × 10−8) and 3p22.2 (rs1274963, CSRNP1, P=2.12 × 10−7). Pathway analyses of new and known CLL loci consistently show a strong role for apoptosis, providing further evidence for the importance of this biological pathway in CLL susceptibility. PMID:26956414

  8. Preparation and Ongoing Support for Early Childhood Instructional Coaches: A Case Study Exploration of an Instructional Coaching Program

    Science.gov (United States)

    Allard Agnamba, Lindsey Tara

    2012-01-01

    This study gathers current information about the preparation and ongoing support of instructional coaches who provide professional development to early childhood educators. The case study of one large, urban District early childhood instructional coaching program will be explored with two objectives: to identify strengths and areas of need in the…

  9. Bone marrow ectopic expression of a non-coding RNA in childhood T-cell acute lymphoblastic leukemia with a novel t(2;11(q11.2;p15.1 translocation

    Directory of Open Access Journals (Sweden)

    Leszl Anna

    2008-10-01

    Full Text Available Abstract Chromosomal translocations play a crucial role in tumorigenesis, often resulting in the formation of chimeric genes or in gene deregulation through position effects. T-cell acute lymphoblastic leukemia (T-ALL is associated with a large number of such rearrangements. We report the ectopic expression of the 3' portion of EST DA926692 in the bone marrow of a childhood T-ALL case showing a t(2;11(q11.2;p15.1 translocation as the sole chromosome abnormality. The breakpoints, defined at the sequence level, mapped within HPS5 (Hermansky Pudlak syndrome 5 intron 1 at 11p15.1, and DA926692 exon 2 at 2q11.2. The translocation was accompanied by a submicroscopic inversion that brought the two genes into the same transcriptional orientation. No chimeric trancript was detected. Interestingly, Real-Time Quantitative (RQ-PCR detected, in the patient's bone marrow, expression of a 173 bp product corresponding to the 3' portion of DA926692. Samples from four T-ALL cases with a normal karyotype and normal bone marrow used as controls were negative. It might be speculated that the juxtaposition of this genomic segment to the CpG island located upstream HPS5 activated DA92669 expression. RQ-PCR analysis showed expression positivity in 6 of 23 human tissues examined. Bioinformatic analysis excluded that this small non-coding RNA is a precursor of micro-RNA, although it is conceivable that it has a different, yet unknown, functional role. To the best of our knowledge, this is the first report, in cancer, of the activation of a small non-coding RNA as a result of a chromosomal translocation.

  10. Revisiting the biology of infant t(4;11)/MLL-AF4+ B-cell acute lymphoblastic leukemia

    NARCIS (Netherlands)

    A. Sanjuan-Pla (Alejandra); C. Bueno (C.); C. Prieto (Cristina); P. Acha (Pamela); R.W. Stam (Ronald); R. Marschalek (Rolf); P. Menéndez (Pablo)

    2015-01-01

    textabstractInfant B-cell acute lymphoblastic leukemia (B-ALL) accounts for 10% of childhood ALL. The genetic hallmark of most infant B-ALL is chromosomal rearrangements of the mixed-lineage leukemia (MLL) gene. Despite improvement in the clinicalmanagement and survival (∼85-90%) of childhood B-ALL,

  11. Pregnancy, maternal tobacco smoking and early age leukemia in Brazil

    Directory of Open Access Journals (Sweden)

    Sergio eKoifman

    2012-11-01

    Full Text Available Background: Cigarette smoking has been associated with acute myeloid leukemia but hypothesis on the association between maternal smoking during pregnancy and childhood leukemia is unclear. Objectives: To investigate the association between maternal exposure to tobacco smoking during pregnancy and early age (< 2 yr. leukemia (EAL. Methods: A hospital-based multicenter case-control study aiming to explore EAL risk factors was carried out in Brazil during 1999-2007. Data were collected by direct interview with the biological mothers using a standardized questionnaire. The present study included 675 children, being 193 acute lymphoblastic leukemia (ALL, 59 acute myeloid leukemia (AML, and 423 controls, being the latter age frequency matched and paired by area of residence with the cases. Unconditional logistic regression was performed, and odds ratios (OR on the association between tobacco smoking (3 months before pregnancy, during pregnancy, and 3 months after delivery and EAL were ascertained after adjustment for selected variables (maternal age at birth and education, birth weight, infant skin color, and oral contraceptives use during pregnancy.Results: Smoking was reported by 17.5% of case mothers and 20.6% of controls´. Among women who reported to have smoked 20 or more cigarettes during the index pregnancy, an adjusted OR = 5.28 (95% C.I. 1.40-19.95 for ALL was observed. Heavy smoking during breastfeeding yielded an adjusted risk estimate for ALL, OR = 7.78 (95% C.I. 1.33-45.5. No dose-response effect was observed according to smoking exposure during pregnancy and EAL. An association between secondhand smoking during pregnancy or breastfeeding was not observed. Conclusion: An association between maternal smoking and AAL in the offspring was restricted to women who have reported an intense exposure to tobacco smoke during pregnancy and breastfeeding.

  12. Increasing Choice or Inequality? Pathways through Early Education in Andhra Pradesh, India. Working Papers in Early Childhood Development, No. 58. Studies in Early Childhood Transitions

    Science.gov (United States)

    Streuli, Natalia; Vennam, Uma; Woodhead, Martin

    2011-01-01

    This working paper is part of the Studies in Early Transitions series emerging from "Young Lives", a 15-year longitudinal study of childhood poverty in Ethiopia, India, Peru and Vietnam. It explores recent trends for children growing up in Andhra Pradesh, one of India's most populous states, based on Young Lives survey data collected for…

  13. Continuity and Respect for Diversity: Strengthening Early Transitions in Peru. Working Papers in Early Childhood Development, No. 56. Studies in Early Childhood Transitions

    Science.gov (United States)

    Ames, Patricia; Rojas, Vanessa; Portugal, Tamia

    2010-01-01

    This working paper is part of a series on early transitions from "Young Lives," a 15-year longitudinal study of childhood poverty in Ethiopia, India, Peru and Vietnam. It explores the diverse experiences of 28 children from four contrasting communities in Peru as they start school. These detailed case studies highlight common problems:…

  14. Treatment-associated subsequent neoplasms among long-term survivors of childhood cancer: the experience of the Childhood Cancer Survivor Study

    Energy Technology Data Exchange (ETDEWEB)

    Robison, Leslie L. [St. Jude Children' s Research Hospital, Department of Epidemiology and Cancer Control, Memphis, TN (United States)

    2009-02-15

    With improvements in survival among individuals diagnosed and treated for cancer there is an increasing recognition of the risk of long-term adverse effects of therapy. Second neoplasms represent one of the more serious late effects of treatment and are associated with a substantial level of morbidity and mortality. Survivors of childhood cancers, because of their potential longevity, are at particular risk for this adverse outcome. The Childhood Cancer Survivor Study is a large cohort consisting of adult survivors of childhood cancer diagnosed and treated between 1970 and 1986. The CCSS has provided important data to quantify radiation-associated risk for subsequent cancers including neoplasms of the breast, thyroid and central nervous system. (orig.)

  15. Multiracial Children and Poverty: Evidence from the Early Childhood Longitudinal Study of Kindergartners

    Science.gov (United States)

    Bratter, Jenifer; Kimbro, Rachel Tolbert

    2013-01-01

    Despite the recent growth in multiracial children among American children, we know very little about their well-being. Using the Early Childhood Longitudinal Study, Kindergarten Class (N?=?17,706), we evaluated the likelihood of living in poverty and near poverty for multiracial and monoracial children. Most multiracial groups have poverty or near…

  16. The relationship between parenting, family interaction and childhood dental caries: A case-control study

    NARCIS (Netherlands)

    Jong-Lenters, M. de; Duijster, D.; Bruist, M.A.; Thijssen, J.; Ruiter, C. de

    2014-01-01

    The aim of this case-control study was to explore the relationship between parenting practices, parent-child interaction and childhood dental caries, using a sample of 5-8-year old children from the Netherlands. Cases were defined as children with four or more decayed, missing or filled teeth and co

  17. Benign childhood epilepsy with centrotemporal spikes and the multicomponent model of attention : A matched control study

    NARCIS (Netherlands)

    Cerminara, Caterina; D'Agati, Elisa; Lange, Klaus W.; Kaunzinger, Ivo; Tucha, Oliver; Parisi, Pasquale; Spalice, Alberto; Curatolo, Paolo

    2010-01-01

    Although the high risk of cognitive impairments in benign childhood epilepsy with centrotemporal spikes (BCECTS) is now well established, there is no clear definition of a uniform neurocognitive profile. This study was based on a neuropsychological model of attention that assessed various components

  18. An Exploratory Study of the Application of Early Childhood Environment Rating Scale Criteria

    Science.gov (United States)

    Warash, Barbara G.; Ward, Corina; Rotilie, Sally

    2008-01-01

    This study examined whether attending a one day training on the Early Childhood Environment Rating Scale-Revised (ECERS-R) corresponded to pre-k classroom changes. Teachers attended an ECERS-R module training and six months later completed a questionnaire to report any classroom changes. The questionnaire consisted of listing the subscales and…

  19. The Nature of Professional Learning Communities in New Zealand Early Childhood Education: An Exploratory Study

    Science.gov (United States)

    Cherrington, Sue; Thornton, Kate

    2015-01-01

    Professional learning communities are receiving increasing attention within the schooling sector but empirical research into their development and use within early childhood education contexts is rare. This paper reports initial findings of an exploratory study into the development of professional learning communities in New Zealand's early…

  20. Impact of Childhood Trauma on Treatment Outcome in the Treatment for Adolescents with Depression Study (TADS)

    Science.gov (United States)

    Lewis, Cara C.; Simons, Anne D.; Nguyen, Lananh J.; Murakami, Jessica L.; Reid, Mark W.; Silva, Susan G.; March, John S.

    2010-01-01

    Objective: The impact of childhood trauma was examined in 427 adolescents (54% girls, 74% Caucasian, mean = 14.6, SD = 1.5) with major depressive disorder participating in the Treatment for Adolescents with Depression Study (TADS). Method: TADS compared the efficacy of cognitive behavioral therapy (CBT), fluoxetine (FLX), their combination (COMB),…

  1. A Longitudinal Study of Forms and Functions of Aggressive Behavior in Early Childhood

    Science.gov (United States)

    Murray-Close, Dianna; Ostrov, Jamie M.

    2009-01-01

    The purpose of this study was to investigate the distinct forms (i.e., physical and relational) and functions (i.e., proactive and reactive) of aggressive behavior during early childhood (n = 101; M age = 45.09 months). Forms, but not functions, of aggressive behavior were stable over time. A number of contributors to aggression were associated…

  2. Behaviour problems in childhood and adolescence in psychotic offenders: an exploratory study.

    NARCIS (Netherlands)

    Goethals, K.; Willigenburg, L.; Buitelaar, J.K.; Marle, H Van

    2008-01-01

    BACKGROUND: Several studies have shown that adults who develop schizophrenia and commit a criminal offence may already have shown behaviour problems in childhood or adolescence. It is less clear whether such problems follow a particular pattern in such patients. AIMS: To examine the utility of the C

  3. A Longitudinal Study of Childhood Obesity, Weight Status Change, and Subsequent Academic Performance in Taiwanese Children

    Science.gov (United States)

    Chen, Li-Jung; Fox, Kenneth R.; Ku, Po-Wen; Wang, Ching-Hui

    2012-01-01

    Backround: This study examined the association among childhood obesity, weight status change, and subsequent academic performance at 6-year follow-up. Methods: First-grade students from one elementary school district in Taichung City, Taiwan were followed for 6 years (N = 409). Academic performance was extracted from the school records at the end…

  4. A 15-year longitudinal study on ambulatory blood pressure tracking from childhood to early adulthood

    NARCIS (Netherlands)

    Li, Zhibin; Snieder, Harold; Harshfield, Gregory A.; Treiber, Frank A.; Wang, Xiaoling

    2009-01-01

    This study evaluates the tracking stability of office blood pressure (BP), ambulatory BP (ABP), BP variability (BPV) and nocturnal BP drops (dipping) from childhood to early adulthood, and their dependence on ethnicity, gender and family history (FH) of essential hypertension (EH). Generalized estim

  5. Fear of the beast: a prospective study on the effects of negative information on childhood fear

    NARCIS (Netherlands)

    Muris, P.E.H.M.; Bodden, D.H.M.; Merckelbach, H.L.G.J.; Ollendick, T.H.; King, N.J.

    2003-01-01

    The current study examined the effects of negative information on the enhancement of childhood fear. A large group of normal primary school children aged between 4 and 12 years (N=285) received either negative or positive information about an unknown, doglike animal, called 'the beast'. Children's f

  6. A Longitudinal Study of Childhood Depression and Anxiety in Relation to Weight Gain

    Science.gov (United States)

    Rofey, Dana L.; Kolko, Rachel P.; Iosif, Ana-Maria; Silk, Jennifer S.; Bost, James E.; Feng, Wentao; Szigethy, Eva M.; Noll, Robert B.; Ryan, Neal D.; Dahl, Ronald E.

    2009-01-01

    Adult mood disturbances are highly correlated with obesity, although little is known about the developmental relationship between mood disorders and weight. This study investigated the relationship between childhood psychopathology and weight over the course of 3 years. Body Mass Index (BMI) percentiles and demographic data of children (ages 8-18)…

  7. Prenatal Smoking and Internalizing and Externalizing Problems in Children Studied from Childhood to Late Adolescence

    Science.gov (United States)

    Ashford, Janka; Van Lier, Pol A. C.; Timmermans, Maartje; Cuijpers, Pim; Koot, Hans M.

    2008-01-01

    A study was conducted to evaluate whether prenatal smoking was only related to externalizing or both internalizing and externalizing problems in children from childhood to early adolescence. Results indicated that maternal smoking during pregnancy is an accurate predictor of internalizing and externalizing psychopathology among children.

  8. Maternal first-trimester diet and childhood bone mass: The Generation R Study

    NARCIS (Netherlands)

    D.H.M. Heppe (Denise); C. Medina-Gomez (Carolina); A. Hofman (Albert); O.H. Franco (Oscar); F. Rivadeneira Ramirez (Fernando); V.W.V. Jaddoe (Vincent)

    2013-01-01

    textabstractBackground: Maternal diet during pregnancy has been suggested to influence bone health in later life. Objective: We assessed the association of maternal first-trimester dietary intake during pregnancy with childhood bone mass. Design: In a prospective cohort study in 2819 mothers and the

  9. Association of childhood trauma with cognitive function in healthy adults: a pilot study

    Directory of Open Access Journals (Sweden)

    Lin Jin-Mann S

    2010-07-01

    Full Text Available Abstract Background Animal and human studies suggest that stress experienced early in life has detrimental consequences on brain development, including brain regions involved in cognitive function. Cognitive changes are cardinal features of depression and posttraumatic stress disorder. Early-life trauma is a major risk factor for these disorders. Only few studies have measured the long-term consequences of childhood trauma on cognitive function in healthy adults. Methods In this pilot study, we investigated the relationship between childhood trauma exposure and cognitive function in 47 healthy adults, who were identified as part of a larger study from the general population in Wichita, KS. We used the Cambridge Neuropsychological Test Automated Battery (CANTAB and the Wide-Range-Achievement-Test (WRAT-3 to examine cognitive function and individual achievement. Type and severity of childhood trauma was assessed by the Childhood Trauma Questionnaire (CTQ. Data were analyzed using multiple linear regression on CANTAB measures with primary predictors (CTQ scales and potential confounders (age, sex, education, income. Results Specific CTQ scales were significantly associated with measures of cognitive function. Emotional abuse was associated with impaired spatial working memory performance. Physical neglect correlated with impaired spatial working memory and pattern recognition memory. Sexual abuse and physical neglect were negatively associated with WRAT-3 scores. However, the association did not reach the significance level of p Conclusions Our results suggest that physical neglect and emotional abuse might be associated with memory deficits in adulthood, which in turn might pose a risk factor for the development of psychopathology.

  10. Intervention for Childhood Apraxia of Speech: A Single-Case Study

    Science.gov (United States)

    Martikainen, Anna-Leena; Korpilahti, Pirjo

    2011-01-01

    The underlying nature and diagnosis of childhood apraxia of speech (CAS) still requires clarification. However, the label "CAS" or "suspected CAS" continues to be assigned to a group of children with speech problems, and speech and language therapists need to be aware of effective treatment for these children. The aim of this study was to assess…

  11. The Link between Childhood Sexual Abuse and Myocardial Infarction in a Population-Based Study

    Science.gov (United States)

    Fuller-Thomson, Esme; Bejan, Raluca; Hunter, John T.; Grundland, Tamara; Brennenstuhl, Sarah

    2012-01-01

    Objectives: This study examined the relationship between childhood sexual abuse (CSA) and myocardial infarction in men and women, while controlling for social determinants (i.e., socioeconomic status, social support, mental health) and traditional cardiovascular risk factors (i.e., age, race, obesity, smoking, physical inactivity, diabetes…

  12. The relationship between parenting, family interaction and childhood dental caries: a case-control study

    NARCIS (Netherlands)

    M. de Jong-Lenters; D. Duijster; M.A. Bruist; J. Thijssen; C. de Ruiter

    2014-01-01

    The aim of this case-control study was to explore the relationship between parenting practices, parent-child interaction and childhood dental caries, using a sample of 5-8-year old children from the Netherlands. Cases were defined as children with four or more decayed, missing or filled teeth and co

  13. A multicentre study of air pollution exposure and childhood asthma prevalence: the ESCAPE project

    NARCIS (Netherlands)

    Mölter, Anna; Simpson, Angela; Berdel, Dietrich; Brunekreef, Bert; Custovic, Adnan; Cyrys, Josef; de Jongste, Johan; de Vocht, Frank; Fuertes, Elaine; Gehring, Ulrike; Gruzieva, Olena; Heinrich, Joachim; Hoek, Gerard; Hoffmann, Barbara; Klümper, Claudia; Korek, Michal; Kuhlbusch, Thomas A J; Lindley, Sarah; Postma, Dirkje; Tischer, Christina; Wijga, Alet; Pershagen, Göran; Agius, Raymond

    2015-01-01

    The aim of this study was to determine the effect of six traffic-related air pollution metrics (nitrogen dioxide, nitrogen oxides, particulate matter with an aerodynamic diameter <10 μm (PM10), PM2.5, coarse particulate matter and PM2.5 absorbance) on childhood asthma and wheeze prevalence in five E

  14. The New Wave of Childhood Studies: Breaking the Grip of Bio-Social Dualism?

    Science.gov (United States)

    Ryan, Kevin William

    2012-01-01

    The article takes as its starting point a new wave of researchers who use concepts such as "hybridity" and "multiplicity" in a bid to move the study of childhood beyond the strictures of what Lee and Motzkau call "bio-social dualism", whereby the division between the "natural child" of developmental psychology and the "social child" of…

  15. Early life course risk factors for childhood obesity: the IDEFICS case-control study.

    Directory of Open Access Journals (Sweden)

    Karin Bammann

    Full Text Available BACKGROUND: The early life course is assumed to be a critical phase for childhood obesity; however the significance of single factors and their interplay is not well studied in childhood populations. OBJECTIVES: The investigation of pre-, peri- and postpartum risk factors on the risk of obesity at age 2 to 9. METHODS: A case-control study with 1,024 1:1-matched case-control pairs was nested in the baseline survey (09/2007-05/2008 of the IDEFICS study, a population-based intervention study on childhood obesity carried out in 8 European countries in pre- and primary school settings. Conditional logistic regression was used for identification of risk factors. RESULTS: For many of the investigated risk factors, we found a raw effect in our study. In multivariate models, we could establish an effect for gestational weight gain (adjusted OR = 1.02; 95%CI 1.00-1.04, smoking during pregnancy (adjusted OR = 1.48; 95%CI 1.08-2.01, Caesarian section (adjusted OR = 1.38; 95%CI 1.10-1.74, and breastfeeding 4 to 11 months (adjusted OR = 0.77; 95%CI 0.62-0.96. Birth weight was related to lean mass rather than to fat mass, the effect of smoking was found only in boys, but not in girls. After additional adjustment for parental BMI and parental educational status, only gestational weight gain remained statistically significant. Both, maternal as well as paternal BMI were the strongest risk factors in our study, and they confounded several of the investigated associations. CONCLUSIONS: Key risk factors of childhood obesity in our study are parental BMI and gestational weight gain; consequently prevention approaches should target not only children but also adults. The monitoring of gestational weight seems to be of particular importance for early prevention of childhood obesity.

  16. Academic language in early childhood interactions : a longitudinal study of 3- to 6-year-old Dutch monolingual children

    NARCIS (Netherlands)

    Henrichs, L.F.

    2010-01-01

    This study examines academic language in early childhood. It covers children’s exposure to academic language in early childhood, children’s early production of academic language, the development of academic language proficiency and the co-construction of academic language by children and adults.The

  17. Factors influencing childhood conduct disorders: Study of 43 cases

    Directory of Open Access Journals (Sweden)

    Jalili B

    2000-08-01

    Full Text Available Conduct disorders are a group of behavior disorders in which the basic rights of others or major age appropriate social norms or rules are violated. To evaluate the factors influencing childhood conduct disorders, we reviewed records of 43 cases (84% boys, mean age 11 years referred to Shahid Esmaili psychiatric hospital, Tehran. All patients fulfilled diagnostic criteria of DSMIV. 15 variables were included; Age and sex and step of patient among sibling, parental educational level, social class of the family, medical and psychiatric history of entire family members and the kind of therapy. The most frequent complaints were aggressiveness, stealing and lying. The dominant age group was 10-14 years. The most frequent family members were 5. Most of the children were 2nd child of the family. The most often educational level of the parents were illiteracy followed by primary school educated. Most of the patients were of low to intermediate socioeconomic classes. The most effective therapy was behavior modification along with appropriate medications.

  18. Raman spectroscopy for the assessment of acute myeloid leukemia: a proof of concept study

    NARCIS (Netherlands)

    Vanna, R.; Tresoldi, C.; Lenferink, A.T.M.; Ronchi, P.; Morasso, C.; Mehn, D.; Bedoni, M.; Pignatari, C.; Terstappen, L.W.M.M.; Ciceri, F.; Otto, C.; Gramatica, F.

    2014-01-01

    Acute myeloid leukemia (AML) is a proliferative neoplasm, that if not properly treated can rapidly cause a fatal outcome. The diagnosis of AML is challenging and the first diagnostic step is the count of the percentage of blasts (immature cells) in bone marrow and blood sample, and their morphologic

  19. Study of nucleophosmin (NPM) gene mutation in patients with acute myeloid leukemia and myelodysplastic syndromes

    Institute of Scientific and Technical Information of China (English)

    张悦

    2006-01-01

    Objective To investigate nucleophosmin (NPM) gene mutations in patients with de novo acute myeloid leukemia (AML) with normal cytogenetics and primary myelodysplastic syndromes (MDS). Methods Genomic DNA corresponding to exon 12 of NPM gene was amplified by polymerase chain reaction (PCR) in 40 AML patients (28 case untreated and 12 in first remission) and

  20. Childhood otitis media is associated with dizziness in adulthood: the HUNT cohort study.

    Science.gov (United States)

    Aarhus, Lisa; Tambs, Kristian; Hoffman, Howard J; Engdahl, Bo

    2016-08-01

    The objective of the study was to examine the association between otitis media in childhood and dizziness in adulthood. Longitudinal, population-based cohort study of 21,962 adults (aged 20-59 years, mean 40) who completed a health questionnaire in the Nord-Trøndelag Hearing Loss Study was conducted. At 7, 10 and 13 years of age, the same individuals underwent screening audiometry in a longitudinal school hearing investigation. Children found with hearing loss underwent an ear, nose and throat specialist examination. Adults diagnosed with childhood chronic suppurative otitis media (n = 102) and childhood hearing loss after recurrent acute otitis media (n = 590) were significantly more likely to have increased risk of reported dizziness when compared to adults with normal hearing as children at the school investigation and also a negative history of recurrent otitis media (n = 21,270), p media and childhood hearing loss after recurrent acute otitis media are associated with increased risk of dizziness in adulthood. This might reflect a permanent effect of inflammatory mediators or toxins on the vestibular system. The new finding stresses the importance of treatment and prevention of these otitis media conditions.

  1. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) acute lymphoblastic leukemia studies, 1982-1995.

    Science.gov (United States)

    Conter, V; Aricò, M; Valsecchi, M G; Basso, G; Biondi, A; Madon, E; Mandelli, F; Paolucci, G; Pession, A; Rizzari, C; Rondelli, R; Zanesco, L; Masera, G

    2000-12-01

    The first multicentric approach to childhood acute lymphoblastic leukemia (ALL) treatment in Italy started in the early 1970s when the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) was founded. Since then the AIEOP has conducted nationwide chemotherapy protocols. Results obtained in three different periods (1982-1986, 1987-1990, 1991-1995) are reported here. Treatment schedules have been characterized by a progressive intensification of systemic therapy and by a progressive substitution of protracted intrathecal therapy for cranial irradiation as central nervous system (CNS) preventive therapy. In the third period cranial radiotherapy (CRT) has been administered only to patients at high risk of relapse or with CNS involvement at diagnosis (about 15% of the overall population). A progressive improvement of therapeutic results, with a steady reduction of isolated CNS relapse rates have been obtained in the three periods considered here. The AIEOP experience shows that CRT can be safely omitted in non-high risk patients, unless they are T-ALL patients with WBC count at the diagnosis > or =100,000/mm3, and that intensification of treatment allows the improvement of overall results with a reduction of the impact of NCI prognostic criteria. Over the years, AIEOP has also continued to foster active cooperation at an international level. In the ongoing AIEOP ALL 2000 study, conducted in cooperation with the BFM group, patients are stratified according to the presence of translocations t(9;22) and t(4;11) and to treatment response (either initial steroid therapy or induction) or minimal residual disease). This cooperation will allow an adequate recruitment of patients to answer relevant randomized questions in the context of a study in which patients are stratified according to minimal residual disease findings.

  2. Metronomic therapy with oral 6-mercaptopurine in elderly acute myeloid leukemia: A prospective pilot study

    Directory of Open Access Journals (Sweden)

    Akhil Kapoor

    2016-01-01

    Full Text Available Introduction: Acute myeloid leukemia (AML in elderly patients differs biologically from that in younger patients and is known to have unfavorable chromosomal rearrangements, higher resistance, and lower tolerance to chemotherapy. In such circumstances, instead of giving full-blown chemotherapy, palliative metronomic chemotherapy (MCT could be a treatment option. Patients and Methods: We performed a prospective pilot study of old AML patients (age >60 years not amenable to curative treatment. Thirty-two patients were enrolled into the study and were treated with daily oral 6-mercaptopurine 75 mg/m 2 . The following inclusion criteria were used: age >60 years, nonpromyelocytic AML, the absence of uncontrolled comorbidities, and patient not amenable to curative treatment. Overall survival (OS was calculated using Kaplan-Meier method and Cox regression analysis were used to calculate the hazards ratio of significant factors. Results: The median age of the patients was 69 years (range: 61-86 years with male: female ratio of 2.5:1. About 59.4% of patients had Eastern Cooperative Oncology Group performance status of 2 while rest had the status of 3. The median OS was 6 months (95% confidence interval [CI]: 4.4-7.6. Males had median OS of 7 months (95% CI: 5.4-8.6 versus females with OS of 3 months (95% CI: 1.5-4.4; P = 0.008. There was no survival difference on the basis of baseline hemoglobin or French-American-British class. There were no Grade 4 toxicities and no episode of febrile neutropenia. Conclusions: MCT with oral 6-mercaptopurine is an attractive treatment option in elderly AML patients who are not amenable to curative therapy with minimal toxicities.

  3. Randomized phase 2 study of obinutuzumab monotherapy in symptomatic, previously untreated chronic lymphocytic leukemia.

    Science.gov (United States)

    Byrd, John C; Flynn, Joseph M; Kipps, Thomas J; Boxer, Michael; Kolibaba, Kathryn S; Carlile, David J; Fingerle-Rowson, Guenter; Tyson, Nicola; Hirata, Jamie; Sharman, Jeff P

    2016-01-07

    Obinutuzumab is a glycoengineered, type 2 anti-CD20 humanized antibody with single-agent activity in relapsed chronic lymphocytic leukemia (CLL). With other CD20 antibodies, a dose-response relationship has been shown. We therefore performed a randomized phase 2 study in symptomatic, untreated CLL patients to evaluate if an obinutuzumab dose response exists. Obinutuzumab was given at a dose of 1000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 8 and day 15 of cycle 1; 1000 mg day 1 of cycles 2-8) or 2000 mg (100 mg IV day 1, 900 mg day 2, 1000 mg day 3, 2000 mg day 8 and day 15 of cycle 1; 2000 mg day 1 of cycles 2-8). The primary end point was overall response rate (ORR). Eighty patients were enrolled with similar demographics: median age 67 years, 41% high-risk Rai disease, and 10% del(17p)(13.1). ORR (67% vs 49%, P = .08) and complete response (CR) or CR with incomplete cytopenia response (20% vs 5%) favored 2000 mg obinutuzumab. Overall, therapy was well tolerated, and infusion events were manageable. This study demonstrates significant efficacy of obinutuzumab monotherapy, for 1000 mg as well as for 2000 mg, in untreated CLL patients with acceptable toxicity. Although exploratory, a dose-response relationship may exist, but its relevance to improving progression-free survival is uncertain and will require further follow-up. This trial was registered at www.clinicaltrials.gov as #NCT01414205.

  4. Manifestações músculo-esqueléticas como apresentação inicial das leucemias agudas na infância Musculoskeletal manifestations as the onset of acute leukemias in childhood

    Directory of Open Access Journals (Sweden)

    Cássia Maria Passarelli Lupoli Barbosa

    2002-12-01

    Full Text Available Objetivo: estudar a prevalência e as características clínicas e laboratoriais dos pacientes com manifestações músculo-esqueléticas na apresentação inicial das leucemias agudas. Métodos: estudo de casos prevalentes, retrospectivo, descritivo, no qual foram avaliados pacientes com diagnóstico de leucemia aguda, atendidos no Instituto de Oncologia Pediátrica da UNIFESP, de novembro de 1999 a fevereiro de 2000. As queixas músculo-esqueléticas foram investigadas através de um questionário. Os dados referentes ao exame físico e provas laboratoriais, no início da doença, foram obtidos através da revisão de prontuários. Resultados: sessenta e uma crianças foram incluídas neste estudo, sendo que 93% apresentavam leucemia linfóide aguda, e 7% leucemia mielóide aguda. Trinta e oito crianças (62% apresentaram dor músculo-esquelética no início da doença. Artrite foi observada em 8 casos (13%. A média de articulações acometidas foi 2,5 (variando de 1 a 6, sendo as mais acometidas os joelhos, os tornozelos e os cotovelos. Três pacientes (4,9% apresentavam hemograma normal, 54 (88% hemoglobina baixa (em 6 pacientes foi a única alteração, leucopenia em 14 (22%, leucocitose em 26 (42%, e plaquetopenia em 46 (75% pacientes. Oito pacientes (13% mostravam blastos em sangue periférico. Conclusão: as queixas músculo-esqueléticas são manifestações iniciais freqüentes das leucemias agudas, e devem ser consideradas no diagnóstico diferencial da dor em membros e das artrites agudas ou crônicas da infância. Os exames laboratoriais podem ser inicialmente normais, tornando ainda mais difícil esta diferenciação.Objective: to study the frequency, the clinical features and laboratory exams of patients with musculoskeletal symptoms at the onset of acute leukemia. Methods: retrospective, descriptive study including patients diagnosed with acute leukemia, and treated at the Institute of Pediatric Oncology of UNIFESP, carried out

  5. Cumulative incidence of childhood autism: a total population study of better accuracy and precision.

    Science.gov (United States)

    Honda, Hideo; Shimizu, Yasuo; Imai, Miho; Nitto, Yukari

    2005-01-01

    Most studies on the frequency of autism have had methodological problems. Most notable of these have been differences in diagnostic criteria between studies, degree of cases overlooked by the initial screening, and type of measurement. This study aimed to replicate the first report on childhood autism to address cumulative incidence as well as prevalence, as defined in the International Statistical Classification of Diseases and Related Health Problems, 10th revision (ICD-10) Diagnostic Criteria for Research. Here, the same methodological accuracy (exactness of a measurement to the true value) as the first study was used, but population size was four times larger to achieve greater precision (reduction of random error). A community-oriented system of early detection and early intervention for developmental disorders was established in the northern part of Yokohama, Japan. The city's routine health checkup for 18-month-old children served as the initial mass screening, and all facilities that provided child care services aimed to detect all cases of childhood autism and refer them to the Yokohama Rehabilitation Center. Cumulative incidence up to age 5 years was calculated for childhood autism among a birth cohort from four successive years (1988 to 1991). Cumulative incidence of childhood autism was 27.2 per 10000. Cumulative incidences by sex were 38.4 per 10000 in males, and 15.5 per 10000 in females. The male:female ratio was 2.5:1. The proportions of children with high-functioning autism who had Binet IQs of 70 and over and those with Binet IQs of 85 and over were 25.3% and 13.7% respectively. Data on cumulative incidence of childhood autism derived from this study are the first to be drawn from an accurate, as well as precise, screening methodology.

  6. A phase 2 study of MK-0457 in patients with BCR-ABL T315I mutant chronic myelogenous leukemia and philadelphia chromosome-positive acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Seymour, J F; Kim, D W; Rubin, E;

    2014-01-01

    Aurora kinase overexpression has been observed in patients with hematologic malignancies. MK-0457, a pan-aurora kinase inhibitor that also inhibits the ABL T315I mutant, was evaluated to treat patients with chronic myelogenous leukemia (CML) or Philadelphia chromosome (Ph+) acute lymphoblastic...

  7. Parental smoking, maternal alcohol, coffee and tea consumption during pregnancy and childhood malignant central nervous system tumours: the ESCALE study (SFCE).

    Science.gov (United States)

    Plichart, Matthieu; Menegaux, Florence; Lacour, Brigitte; Hartmann, Olivier; Frappaz, Didier; Doz, François; Bertozzi, Anne-Isabelle; Defaschelles, Anne-Sophie; Pierre-Kahn, Alain; Icher, Céline; Chastagner, Pascal; Plantaz, Dominique; Rialland, Xavier; Hémon, Denis; Clavel, Jacqueline

    2008-08-01

    Parental smoking and maternal alcohol and caffeinated beverage consumption are prevalent exposures which may play a role, either directly or through their influence on metabolism, in the aetiology of childhood malignant central nervous system (CNS) tumours. The hypothesis was investigated in the Epidemiological Study on childhood Cancer and Leukemia ESCALE study, a national population-based case-control study carried out in France in 2003-2004. The study included 209 incident cases of CNS tumours and 1681 population-based controls, frequency matched with the cases by age and sex. The data were collected through a standardized telephone interview of the biological mothers. No association between maternal smoking during pregnancy and CNS tumours [odds ratio (OR): 1.1 (0.8-1.6)] was observed. Paternal smoking during the year before birth was associated with CNS tumours (P for trend=0.04), particularly astrocytomas [OR: 3.1 (1.3-7.6)]. Maternal alcohol consumption during pregnancy was not associated with CNS tumours. Associations between ependymomas and the highest consumption of coffee [OR: 2.7 (0.9-8.1)] and tea [OR: 2.5 (1.1-5.9)] were observed. A strong association between CNS tumours and the highest maternal consumption of both coffee and tea during pregnancy was observed [OR: 4.4 (1.5-13)]. The results constitute additional evidence for a role of paternal smoking and suggest that maternal coffee and tea consumption during pregnancy may also increase the risk of CNS tumours. The study does not suggest an increased risk of CNS tumours related to alcohol consumption during pregnancy.

  8. [Clinical study of 32 patients with adult Philadelphia chromosome-positive acute lymphoblastic leukemia].

    Science.gov (United States)

    Chen, Xiao-Yun; Zheng, Yong-Liang; Chen, Yi-Jian

    2014-12-01

    This study was aimed to evaluate the efficacy and safety of imatinib in the treatment of patients with adult Ph chromosome-positive acute lymphoblastic leukemia (Ph(+)ALL). A total of 32 diagnosed adult Ph(+)ALL patients from July 2007 to February 2014 in our hospital were retrospectively analyzed and were divided into two groups: imatinib plus chemotherapy group and traditional chemotherapy group. The differences between two groups were analysed in disease-free survival time (DFS), overall survival time (OS) and toxicity. The G banding technigue was used to analyse the karyotype, and the flow cytometry was applyed to detect the immune markers on surface of cells. The results showed that all patients expressed B cell and hematopietic stem/progenitor cell immune markers, out of them 21 patients (65.6%) were with myeloid antigens, 27 patients with simple Ph (+) phenotype and 5 patients with additional chromosome abnormality. The DFS and OS of the imatinib group were statistically longer than those of the traditional chemotherapy group (14.3 ± 4.7 months vs 10.7 ± 3.8 months) (P 0.05)). It is concluded that the all cases of adult Ph(+)ALL are with B cell phenotype and express hematopietic stem/progenitor cell antigen. They often accompanied by expression of myeloid antigens and additonal chromosome abnormality in genetics. The combination of imatinib with chemotherapy can prolong remission time and survival time for patients of non-hematopietic stem cell transplantation on the basis of no notably increasing the toxic effects.

  9. Determinants of childhood adiposity: evidence from the Australian LOOK study.

    Directory of Open Access Journals (Sweden)

    Richard D Telford

    Full Text Available BACKGROUND: To contribute to the current debate as to the relative influences of dietary intake and physical activity on the development of adiposity in community-based children. METHODS: Participants were 734 boys and girls measured at age 8, 10 and 12 years for percent body fat (dual emission x-ray absorptiometry, physical activity (pedometers, accelerometers; and dietary intake (1 and 2-day records, with assessments of pubertal development and socioeconomic status. RESULTS: Cross-sectional relationships revealed that boys and girls with higher percent body fat were less physically active, both in terms of steps per day and moderate and vigorous physical activity (both sexes p<0.001 for both measures. However, fatter children did not consume more energy, fat, carbohydrate or sugar; boys with higher percent body fat actually consumed less carbohydrate (p = 0.01 and energy (p = 0.05. Longitudinal analysis (combined data from both sexes was weaker, but supported the cross-sectional findings, showing that children who reduced their PA over the four years increased their percent body fat (p = 0.04. Relationships in the 8 year-olds and also in the leanest quartile of all children, where adiposity-related underreporting was unlikely, were consistent with those of the whole group, indicating that underreporting did not influence our findings. CONCLUSIONS: These data provide support for the premise that physical activity is the main source of variation in the percent body fat of healthy community-based Australian children. General community strategies involving dietary intake and physical activity to combat childhood obesity may benefit by making physical activity the foremost focus of attention.

  10. Childhood myelodysplastic syndrome.

    Science.gov (United States)

    Chatterjee, Tathagata; Choudhry, V P

    2013-09-01

    Myelodysplastic syndrome (MDS) comprises of a heterogeneous group of bone marrow disorders resulting from a clonal stem cell defect characterised by cytopenias despite a relatively hypercellular marrow, ineffective hematopoiesis, morphological dysplasia in the marrow elements, no response to hematinics such as iron, B12 or folic acid and risk of progression to leukemia. Myelodysplastic syndrome in childhood is extremely rare and accounts for less than 5% of all hematopoietic neoplasms in children below the age of 14 y. The primary MDS in children, also known as de novo MDS differs from secondary MDS which generally follows congenital or acquired bone marrow (BM) failure syndromes as well as from therapy related MDS, commonly resulting from cytotoxic therapy. MDS associated with Down syndrome which accounts for approximately one-fourth of cases of childhood MDS is now considered a unique biologic entity synonymous with Down syndrome-related myeloid leukemia and is biologically distinct from other cases of childhood MDS. Refractory cytopenia of childhood (RCC) is the commonest type of MDS. Genetic changes predisposing to MDS in childhood remain largely obscure. Monosomy 7 is by-far the commonest cytogenetic abnormality associated with childhood MDS; however most cases of RCC show a normal karyotype. Complex cytogenetic abnormalities and trisomy 8 and trisomy 21 are also occasionally observed. The most effective and curative treatment is Hematopoietic stem cell transplantation and this is particularly effective in children with the monosomy 7 genetic defect as well as those displaying complex karyotype abnormalities provided it is instituted early in the course of the disease.

  11. What Is Chronic Myeloid Leukemia?

    Science.gov (United States)

    ... Chronic Myeloid Leukemia (CML) About Chronic Myeloid Leukemia What Is Chronic Myeloid Leukemia? Cancer starts when cells ... their treatment is the same as for adults. What is leukemia? Leukemia is a cancer that starts ...

  12. What Is Chronic Lymphocytic Leukemia?

    Science.gov (United States)

    ... Chronic Lymphocytic Leukemia (CLL) About Chronic Lymphocytic Leukemia What Is Chronic Lymphocytic Leukemia? Cancer starts when cells ... body, including the lymph nodes, liver, and spleen. What is leukemia? Leukemia is a cancer that starts ...

  13. Gender nonconformity, childhood rejection, and adult attachment: a study of gay men.

    Science.gov (United States)

    Landolt, Monica A; Bartholomew, Kim; Saffrey, Colleen; Oram, Doug; Perlman, Daniel

    2004-04-01

    Several childhood factors are reported to be associated with a homosexual orientation in men, including gender nonconformity and rejection by parents and peers. The purpose of this study was to explore the associations between these childhood factors and attachment anxiety (the tendency to experience anxiety regarding potential loss and rejection in close relationships) and attachment avoidance (the tendency to avoid versus seek out closeness in relationships) in gay and bisexual men. A community sample of 191 gay and bisexual men completed questionnaires and an attachment interview. Gender nonconformity was significantly associated with paternal, maternal, and peer rejection in childhood. In addition, paternal and peer rejection, but not maternal rejection, independently predicted attachment anxiety. Peer rejection and, to a lesser extent, paternal rejection mediated the association between gender nonconformity and attachment anxiety. Finally, peer rejection mediated the association between paternal rejection and attachment avoidance. Findings highlight the role of gender nonconformity in contributing to childhood rejection and the importance of peer relationships in the socialization of gay men.

  14. Childhood cardiometabolic outcomes of maternal obesity during pregnancy: the Generation R Study.

    Science.gov (United States)

    Gaillard, Romy; Steegers, Eric A P; Duijts, Liesbeth; Felix, Janine F; Hofman, Albert; Franco, Oscar H; Jaddoe, Vincent W V

    2014-04-01

    Maternal prepregnancy obesity is associated with impaired cardiometabolic health in offspring. Whether these associations reflect direct intrauterine causal mechanisms remains unclear. In a population-based prospective cohort study among 4871 mothers, fathers, and their children, we examined the associations of both maternal and paternal prepregnancy body mass index (BMI) with childhood body fat distribution and cardiometabolic outcomes and explored whether any association was explained by pregnancy, birth, and childhood factors. We measured childhood BMI, total body and abdominal fat distribution, blood pressure, and blood levels of lipids, insulin, and C-peptide at the age of 6 years. We observed that higher maternal and paternal prepregnancy BMI were associated with higher childhood BMI, total body and abdominal fat mass measures, systolic blood pressure, and insulin levels and lower high-density lipoprotein cholesterol levels (Peffect estimates for these outcomes were observed for paternal obesity. In conclusion, higher maternal and paternal prepregnancy BMI were associated with an adverse cardiometabolic profile in offspring, with stronger associations present for maternal prepregnancy BMI. These findings suggest that maternal prepregnancy BMI may influence the cardiometabolic health of offspring through direct intrauterine mechanisms.

  15. A longitudinal study on early hospitalized airway infections and subsequent childhood asthma.

    Directory of Open Access Journals (Sweden)

    Mei-Jy Jeng

    Full Text Available Acute airway infections, including bronchiolitis, are common causes of early childhood hospitalization. The development of later asthma may be related to early airway infections in young children. This study is to investigate the relationship between hospitalized airway infections (HAI in young children (< 3 years old and later childhood asthma.Hospitalized children (< 3 years old with bronchiolitis or other acute airway infections (other HAI group from 1997-2000 were retrieved from the National Health Insurance Research Database of Taiwan, and compared to age- and gender-matched subjects with regards to asthma until 10 years of age; and potential comorbidities and medical care conditions.In total, 3,264 children (1,981 with bronchiolitis; 1,283 with other HAIs were compared to 18,527 controls. The incidence of childhood asthma was higher in the study (16.2% than the control (11.7% group, and most cases were diagnosed between 3-5 years old. The hazard ratios were 1.583 (95% CI: 1.414-1.772 and 1.226 (95% CI: 1.053-1.428 for the bronchiolitis and other HAI subgroups, respectively, compared to the control group, and 1.228 (95% CI: 1.075-1.542 in the bronchiolitis subgroup compared to the other HAIs subgroup. A significantly higher odds ratio (1.973, 95% CI: 1.193-3.263 for the children with congenital heart disease (CHD in the bronchiolitis subgroup was found at an age of 3-5 years compared to the control group.Young children (< 3 years old hospitalized due to acute HAIs are at a higher risk of developing childhood asthma at age 3 to 10 years. The parents of children with HAIs at age 0 to 2 years should be informed for the higher risk of developing childhood asthma, especially in children with CHD and bronchiolitis.

  16. Is adult ADHD a childhood-onset neurodevelopmental disorder? Evidence from a 4-decade longitudinal cohort study

    Science.gov (United States)

    Moffitt, Terrie E.; Houts, Renate; Asherson, Philip; Belsky, Daniel W; Corcoran, David L; Hammerle, Maggie; Harrington, Honalee; Hogan, Sean; Meier, Madeline; Polanczyk, Guilherme V.; Poulton, Richie; Ramrakha, Sandhya; Sugden, Karen; Williams, Benjamin; Rohde, Luis Augusto; Caspi, Avshalom

    2015-01-01

    Objective Despite a prevailing assumption that adult ADHD is a childhood-onset neurodevelopmental disorder, no prospective-longitudinal study has described the childhoods of the adult-ADHD population. We report follow-back analyses of ADHD cases diagnosed in adulthood, alongside follow-forward analyses of ADHD cases diagnosed in childhood, in one cohort. Method Participants belonged to a representative birth cohort of 1,037 individuals born in Dunedin, New Zealand in 1972-73 and followed to age 38, with 95% retention. Symptoms of ADHD, associated clinical features, comorbid disorders, neuropsychological deficits, GWAS-derived polygenic risk, and life impairment indicators were assessed. Data sources were participants, parents, teachers, informants, neuropsychological testing, and administrative records. Adult ADHD diagnoses used DSM5 criteria, apart from onset-age and cross-setting corroboration, which were study outcomes. Results As expected, the childhood-ADHD group showed 6% prevalence, male excess, childhood comorbid disorders, neurocognitive deficits, polygenic risk, and, despite having outgrown their ADHD diagnosis, residual adult life impairment. As expected, the adult-ADHD group showed 3% prevalence, gender balance, adult substance dependence, adult life impairment, and treatment contact. Unexpectedly, the childhood-ADHD and adult-ADHD groups comprised virtually non-overlapping sets; 90% of adult-ADHD cases lacked a history of childhood ADHD. Also unexpectedly, the adult-ADHD group did not show tested neuropsychological deficits in childhood or adulthood, nor did they show polygenic risk for childhood ADHD. Conclusion Findings raise the possibility that adults presenting with the ADHD symptom picture may not have a childhood-onset neurodevelopmental disorder. If this finding is replicated, then the disorder's place in the classification system must be reconsidered, and research must investigate the etiology of adult ADHD. PMID:25998281

  17. Study on Taxol in Inhibiting Human Leukemia Cell Proliferation and Inducing Apoptosis

    Institute of Scientific and Technical Information of China (English)

    赵小英; 张晓红; 徐磊; 张行

    2004-01-01

    Objective: To explore the effects of Taxol in inhibiting human leukemia k562 cell proliferation and inducing apoptosis in vitro. Methods: Human leukemia K562 cells were treated with Taxol of different concentrations for 12-72 hrs. Cell proliferation was evaluated by MTT assay and morphological changes of apoptosis were examined by microscopy. Cell apoptosis was determined by flow cytometry (FCM) and DNA gel electrophoresis. Results: Growth of K562 cells was inhibited by Taxol with an IC50 value of 0.84 μg/mi.Typical nuclear condensation and apoptosis bodies were observed as early as 24 hrs after a 0.5 μg/ml Taxol treatment; Apoptotic rate of the Taxol-treated K562 cells increased from 3.7% to 24.0% in 24 hrs. No DNA ladder was observed by DNA gel electrophoresis. Conclusion: Taxol could inhibit K562 cell growth and induce apoptosis in vitro.

  18. Neurobiological pathways to childhood psychopathology : Population-based studies of cognition and behavior

    OpenAIRE

    Ghassabian, Akhgar

    2013-01-01

    textabstractIn the past few decades, considerable advances have been made in understanding childhood psychopathology. This progress is the result of four primary developments in the field. First, both in the research and in the clinical framework, psychopathology has been conceptualized across a spectrum of severity of symptoms and impairment. Second, psychopathology has been studied in the context of young children’s real life parallel to referral settings. Third, studying child psychopathol...

  19. Social class in childhood and general health in adulthood: questionnaire study of contribution of psychological attributes

    OpenAIRE

    Bosma, Hans; Mheen, Dike; Mackenbach, Johan

    1999-01-01

    textabstractOBJECTIVE: To determine the contribution of psychological attributes (personality characteristics and coping styles) to the association between social class in childhood and adult health among men and women. DESIGN: Partly retrospective, partly cross sectional study conducted in the framework of the Dutch GLOBE study. SUBJECTS: Sample of general population from south east Netherlands consisting of 2174 men and women aged 25-74 years. Baseline self reported data from 1991 provided ...

  20. The International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE): design and methods

    OpenAIRE

    Peter T. Katzmarzyk; Barreira, Tiago V.; Stephanie T Broyles; Champagne, Catherine M.; Chaput, Jean-Philippe; Fogelholm, Mikael; Hu, Gang; Johnson, William D.; Kuriyan, Rebecca; Kurpad, Anura; Estelle V. Lambert; Maher, Carol; Maia, José; Matsudo, Victor; Olds, Tim

    2013-01-01

    Background The primary aim of the International Study of Childhood Obesity, Lifestyle and the Environment (ISCOLE) was to determine the relationships between lifestyle behaviours and obesity in a multi-national study of children, and to investigate the influence of higher-order characteristics such as behavioural settings, and the physical, social and policy environments, on the observed relationships within and between countries. Methods/design The targeted sample included 6000 10-year old c...

  1. STUDY ON EFFECTS OF QUERCETIN ON PML GENE AND PROTEIN IN LEUKEMIA CELL LINES

    Institute of Scientific and Technical Information of China (English)

    钟璐; 陈芳源; 韩洁英; 邵念贤; 欧阳仁荣

    2003-01-01

    Objective To investigate the effect of quercetin on PML gene and protein expression and localization in leukemia cell lines. MethodsCell morphology was assayed by Wright,s stain and fluorescence stain, and PML Mrna expression by RT-PCR, PML protein localization by immuno fluorescence.ResultsNB4 and HL-60 cells differentiated morphologically after treatment with all trans retinoic acid (ATRA) while K562 cells did not differentiate. Typical apoptosis was found in each cell line after treatment with quercetin. Immuno fluorescence analysis showed, after treatment with ATRA, the fusion protein disappeared in NB4 cells and PML protein relocated, while HL-60 and K562 cells had no difference from control cells. After treatment with quercetin, the fusion protein disappeared in NB4 cells, PML protein relocated, then degraded. In HL-60 cells and K562 cells, PML protein also located and then degraded. The expression of PML Mrna was not changed in all three cell lines after treatment with ATRA or quercetin. ConclusionPML plays the role of differentiation and apoptosis inducer in leukemia cells at the translational level. PML in POD plays the role of apoptosis inducer and the growth control of leukemia cells.

  2. Late Cardiac Events after Childhood Cancer: Methodological Aspects of the Pan-European Study PanCareSurFup

    Science.gov (United States)

    Feijen, Elizabeth A. M.; Font-Gonzalez, Anna; van Dalen, Elvira C.; van der Pal, Helena J. H.; Reulen, Raoul C.; Winter, David L.; Kuehni, Claudia E.; Haupt, Riccardo; Alessi, Daniela; Byrne, Julianne; Bardi, Edit; Jakab, Zsuzsanna; Grabow, Desiree; Garwicz, Stanislaw; Jankovic, Momcilo; Levitt, Gill A.; Skinner, Roderick; Zadravec Zaletel, Lorna; Hjorth, Lars; Tissing, Wim J. E.; de Vathaire, Florent; Hawkins, Mike M.; Kremer, Leontien C. M.

    2016-01-01

    Background and Aim Childhood cancer survivors are at high risk of long-term adverse effects of cancer and its treatment, including cardiac events. The pan-European PanCareSurFup study determined the incidence and risk factors for cardiac events among childhood cancer survivors. The aim of this article is to describe the methodology of the cardiac cohort and nested case-control study within PanCareSurFup. Methods Eight data providers in Europe participating in PanCareSurFup identified and validated symptomatic cardiac events in their cohorts of childhood cancer survivors. Data on symptomatic heart failure, ischemia, pericarditis, valvular disease and arrhythmia were collected and graded according to the Criteria for Adverse Events. Detailed treatment data, data on potential confounders, lifestyle related risk factors and general health problems were collected. Results The PanCareSurFup cardiac cohort consisted of 59,915 5-year childhood cancer survivors with malignancies diagnosed between 1940 and 2009 and classified according to the International Classification of Childhood Cancer 3. Different strategies were used to identify cardiac events such as record linkage to population/ hospital or regional based databases, and patient- and general practitioner-based questionnaires. Conclusion The cardiac study of the European collaborative research project PanCareSurFup will provide the largest cohort of 5-year childhood cancer survivors with systematically ascertained and validated data on symptomatic cardiac events. The result of this study can provide information to minimize the burden of cardiac events in childhood cancer survivors by tailoring the follow-up of childhood cancer survivors at high risk of cardiac adverse events, transferring this knowledge into evidence-based clinical practice guidelines and providing a platform for future research studies in childhood cancer patients.  PMID:27643694

  3. CD123在儿童急性B淋巴细胞白血病中的表达及其在微小残留病检测中的应用%Expressions of CD123 in childhood B-lineage acute lymphoblastic leukemia and the application of CD123 in minimal residual disease detection

    Institute of Scientific and Technical Information of China (English)

    计雪强; 季正华; 邵惠江; 王红英; 何亚香; 朱宏; 邵雪君

    2012-01-01

    Objective: Detecting the expression of CD123 in childhood B-lineage acute lymphoblastic leukemia ( B-ALL ) and discussing the application and significance of CD123 in minimal residual disease ( MRD ) detection. Methods: With the normal children bone marrow lymphocytes as control, multiparame-ter flow cytometry was used to study the bone marrow lymphocytes immunophenotype and the expression of CD123 in 91 cases of children with B-ALL, 78 cases of which were underwent bone marrow cells chromosome cultivation and cytogenetic analysis. 65 cases of B-ALL children with CD123 positive expression were screened and monitored by CD10/CD123/CD34/CD19 in MRD detection. Results: The expression of CD 123 in normal children bone marrow lymphocytes was negative, while 65 cases of 91 in B-ALL children was positive( positive rate 71.43% ), and the expression level of CD123 was negatively correlated with the leukemic cells maturity. When children had a high expression of CD34, the expression of CD123 was also in a high level. The results of cytogenetic analysis showed that hyperdiploid B-ALL children had a higher level of CD123 expression, when comparing with the non-hyperdiploid cases. Forty-seven cases of B-ALL children ( 51. 65% ) had a high level of CD 123 expression, and CD 123 could be used as an effective marker for MRD monitoring. Conclusion: Most of B-ALL children had an expression of CD123 , which was negatively correlated with the leukemic cells maturity. CD123 can be used as a maker for MRD monitoring in childhood B-ALL.%目的:检测细胞表面抗原CD123在儿童急性B淋巴细胞白血病(B-lineage acute lymphoblastic leukemia,B-ALL)中的表达,并探讨其在儿童B-ALL微小残留病(minimal residual disease,MRD)检测中的应用及意义.方法:以健康儿童骨髓淋巴细胞为对照,应用多参数流式细胞术检测91例儿童B-ALL患者骨髓淋巴细胞免疫表型及CD123的表达,其中78例B-ALL患者进行了骨髓细胞染色体培养及

  4. Maternal depressive symptoms across early childhood and asthma in school children: findings from a Longitudinal Australian Population Based Study.

    Directory of Open Access Journals (Sweden)

    Rebecca Giallo

    Full Text Available There is a growing body of evidence attesting to links between early life exposure to stress and childhood asthma. However, available evidence is largely based on small, genetically high risk samples. The aim of this study was to explore the associations between the course of maternal depressive symptoms across early childhood and childhood asthma in a nationally representative longitudinal cohort study of Australian children. Participants were 4164 children and their biological mothers from the Longitudinal Study of Australian Children. Latent class analysis identified three trajectories of maternal depressive symptoms across four biennial waves from the first postnatal year to when children were 6-7 years: minimal symptoms (74.6%, sub-clinical symptoms (20.8%, and persistent and increasing high symptoms (4.6%. Logistic regression analyses revealed that childhood asthma at age 6-7 years was associated with persistent and increasing high depressive symptoms after accounting for known risk factors including smoking during pregnancy and maternal history of asthma (adjusted OR 2.36, 95% CI 1.61-3.45, p.001. Our findings from a nationally representative sample of Australian children provide empirical support for a relationship between maternal depressive symptoms across the early childhood period and childhood asthma. The burden of disease from childhood asthma may be reduced by strengthening efforts to promote maternal mental health in the early years of parenting.

  5. Maternal depressive symptoms across early childhood and asthma in school children: findings from a Longitudinal Australian Population Based Study.

    Science.gov (United States)

    Giallo, Rebecca; Bahreinian, Salma; Brown, Stephanie; Cooklin, Amanda; Kingston, Dawn; Kozyrskyj, Anita

    2015-01-01

    There is a growing body of evidence attesting to links between early life exposure to stress and childhood asthma. However, available evidence is largely based on small, genetically high risk samples. The aim of this study was to explore the associations between the course of maternal depressive symptoms across early childhood and childhood asthma in a nationally representative longitudinal cohort study of Australian children. Participants were 4164 children and their biological mothers from the Longitudinal Study of Australian Children. Latent class analysis identified three trajectories of maternal depressive symptoms across four biennial waves from the first postnatal year to when children were 6-7 years: minimal symptoms (74.6%), sub-clinical symptoms (20.8%), and persistent and increasing high symptoms (4.6%). Logistic regression analyses revealed that childhood asthma at age 6-7 years was associated with persistent and increasing high depressive symptoms after accounting for known risk factors including smoking during pregnancy and maternal history of asthma (adjusted OR 2.36, 95% CI 1.61-3.45), p.001). Our findings from a nationally representative sample of Australian children provide empirical support for a relationship between maternal depressive symptoms across the early childhood period and childhood asthma. The burden of disease from childhood asthma may be reduced by strengthening efforts to promote maternal mental health in the early years of parenting.

  6. Knowledge Orientations of Prospective Early Childhood Teachers: A Study of Students' Scientific versus Subjective Orientations in Teacher Education Courses in Germany

    Science.gov (United States)

    Mischo, Christoph; Wahl, Stefan; Strohmer, Janina; Hendler, Jessica

    2012-01-01

    Recent changes in the system of early childhood teacher education in Germany raise the question of whether different academic levels of early childhood teacher education lead to different beliefs and orientations. In this study, prospective early childhood teachers' orientations to scientific knowledge and to research were explored. A…

  7. Parental occupation and childhood astrocytoma: results of a case-control study.

    Science.gov (United States)

    Kuijten, R R; Bunin, G R; Nass, C C; Meadows, A T

    1992-02-15

    Parental occupations were investigated as possible risk factors for astrocytoma, the most frequently occurring brain tumor in children. A case-control study of 163 pairs was performed. Cases under 15 years of age at diagnosis in 1980-1986 were identified through the tumor registries of eight hospitals in Pennsylvania, New Jersey, and Delaware. Controls were selected by random-digit dialing and were matched to cases on age, race, and telephone area code. Occupations before the child's conception, during the pregnancy, and after the child's birth were studied separately. We did not observe any strong associations. Significantly more fathers of cases were electrical or electronic repairmen, a subgroup of an occupational category previously associated with increased risk. An excess of case mothers employed as nurses was observed, which was significant for mothers of children diagnosed before 5 years of age. Elevated although not significant odds ratios were observed for some white collar and professional occupations in case parents; for paternal exposure to paint and paternal occupation in the paper and pulp mill industry, both in the period after the child's birth; and for maternal occupation as a hairdresser. The lack of strong associations may have resulted from low statistical power for some job groupings. Our study, unlike previous studies, focused on a single type of brain tumor: childhood astrocytoma. Thus our results suggest that some parental occupations associated with childhood brain tumors in previous studies may not be risk factors for childhood astrocytoma.

  8. Incidence and outcomes for adults diagnosed with acute myeloid leukemia in the north of England: a real world study.

    Science.gov (United States)

    McGregor, Andrew Kenneth; Moulton, Deborah; Bown, Nick; Cuthbert, Gavin; Bourn, David; Mathew, Susanna; Dang, Raymond; Mounter, Philip; Jones, Gail

    2016-07-01

    We conducted a retrospective population-based study of patients diagnosed with acute myeloid leukemia (AML) in northern England (population 3.1 million) in order to assess the impact of age and genetics on outcome. Four hundred and sixteen patients were diagnosed with AML, between 2007 and 2011. In those aged ≤60 years (n = 20) with acute promyelocytic leukemia (APL) overall survival (OS) was 100%. For non-APL patients aged ≤60 years, OS for those with favorable, intermediate and adverse cytogenetics was not reached, 17 and 9.8 months, respectively (p = 0.0001). Of particular note, intensively treated patients aged >60 years with intermediate cytogenetics and FLT3-/NPM1+ status had a five-year survival of 60% versus median OS of 11 months for other subsets (p = 0.04). Population-based studies reduce selection bias and have utility in studying rarer diseases, particularly in populations that recruit poorly to trials. The highly favorable outcome in our subgroup of intensively-treated FLT3-/NPM1+ older patients merits further study.

  9. Childhood Gender-Typed Behavior and Adolescent Sexual Orientation: A Longitudinal Population-Based Study.

    Science.gov (United States)

    Li, Gu; Kung, Karson T F; Hines, Melissa

    2017-02-20

    Lesbian and gay individuals have been reported to show more interest in other-sex, and/or less interest in same-sex, toys, playmates, and activities in childhood than heterosexual counterparts. Yet, most of the relevant evidence comes from retrospective studies or from prospective studies of clinically referred, extremely gender nonconforming children. In addition, findings are mixed regarding the relation between childhood gender-typed behavior and the later sexual orientation spectrum from exclusively heterosexual to exclusively lesbian/gay. The current study drew a sample (2,428 girls and 2,169 boys) from a population-based longitudinal study, and found that the levels of gender-typed behavior at ages 3.5 and 4.75 years, although less so at age 2.5 years, significantly and consistently predicted adolescents' sexual orientation at age 15 years, both when sexual orientation was conceptualized as 2 groups or as a spectrum. In addition, within-individual change in gender-typed behavior during the preschool years significantly related to adolescent sexual orientation, especially in boys. These results suggest that the factors contributing to the link between childhood gender-typed behavior and sexual orientation emerge during early development. Some of those factors are likely to be nonsocial, because nonheterosexual individuals appear to diverge from gender norms regardless of social encouragement to conform to gender roles. (PsycINFO Database Record

  10. Factors associated with incomplete childhood immunization in Arbegona district, southern Ethiopia: a case – control study

    OpenAIRE

    Negussie, Abel; Kassahun, Wondewosen; Assegid, Sahilu; Hagan, Ada K.

    2016-01-01

    Background The prevention of child mortality through immunization is one of the most cost-effective and widely applied public health interventions. In Ethiopia, the Expanded Program on Immunization (EPI) schedule is rarely completed as planned and the full immunization rate is only 24 %. The objective of this study was to identify determinant factors of incomplete childhood immunization in Arbegona district, Sidama zone, southern Ethiopia. Methods A community based unmatched case-control stud...

  11. Studying The Long-term Psychological Effects of Emotional Abuse Experienced in Childhood.

    OpenAIRE

    Newton, Claira; Gavin, Helen

    2016-01-01

    Objectives: In order to study the effect of child emotional abuse (CEA) on adult well-being, a survey was conducted to determine the links. In order to understand how the various forms of abuse are dealt with by the victim, this research examines the different coping strategies employed in both childhood and adulthood. Design: An online survey was developed including questions designed to elicit qualitative and quantitative data. The online survey method was used in order to maintain anonymit...

  12. 环境化学物暴露与儿童急性淋巴细胞白血病风险的关联研究%Association of exposure to environmental chemicals with risk of childhood acute lymphocytic leukemia

    Institute of Scientific and Technical Information of China (English)

    蒋伟超; 吴思英; 柯跃斌

    2016-01-01

    境化学因素的暴露可能增加cALL的发病风险。%Objective This study aimed to investigate the association between exposure to environmental chemicals and the risk of childhood acute lymphocytic leukemia (cALL). Methods A case-controlled study was conducted in Shenzhen Children's Hospital, China from January 2015 to January 2016. The cases were selected from the section of Hematology and Oncology, and the controls were selected from Orthopedics by 1∶2 matching of cases according to sex and age. A questionnaire including population data and chemical exposure characteristics was conducted on the children's parents, and urine and EDTA-blood were collected from the children. Then, we quantitatively measured the internal dose of formaldehyde (i.e., formaldehyde-human serum albumin) by enzyme-linked immunosorbent assay and the doses of metabolites benzene, toluene, and xylene (i.e., trans-muconic acid, hippuric acid, and methylhippuric acid) by high-performance liquid chromatography. Logistic regression models were used to analyze the relationships between exposure factors measured from children and their parents and cALL. Results In the study, 71 cases (average age:6.08 ± 3.61 years), and 142 controls (average age:5.91 ± 3.57 years) were assessed; there were no differences in general demographics between two groups. The self-reported results showed that living in a home that had been painted in the past 10 years (OR=4.39, 95% CI: 1.87-10.31), maternal chemical exposure during pregnancy (OR=11.78, 95% CI: 1.65-83.88), paternal diesel or gasoline exposure (OR=8.15, 95% CI: 2.68-24.83), paternal dye exposure (OR=7.77, 95% CI: 1.52-39.67) and trash burning near the child's residence (OR=6.08, 95% CI: 1.17-31.66) were associated with increased risk of cALL. The positive detection rates of only benzene metabolites were significantly higher in cases (40/44) than controls (81/111) (χ2=5.92, P=0.021). The median formaldehyde and benzene concentrations in cases (32

  13. Characterization of children with FLT3-ITD acute myeloid leukemia: a report from the AIEOP AML-2002 study group.

    Science.gov (United States)

    Manara, E; Basso, G; Zampini, M; Buldini, B; Tregnago, C; Rondelli, R; Masetti, R; Bisio, V; Frison, M; Polato, K; Cazzaniga, G; Menna, G; Fagioli, F; Merli, P; Biondi, A; Pession, A; Locatelli, F; Pigazzi, M

    2017-01-01

    Recurrent molecular markers have been routinely used in acute myeloid leukemia (AML) for risk assessment at diagnosis, whereas their post-induction monitoring still represents a debated issue. We evaluated the prognostic value and biological impact of minimal residual disease (MRD) and of the allelic ratio (AR) of FLT3-internal-tandem duplication (ITD) in childhood AML. We retrospectively screened 494 children with de novo AML for FLT3-ITD mutation, identifying 54 harboring the mutation; 51% of them presented high ITD-AR at diagnosis and had worse event-free survival (EFS, 19.2 versus 63.5% for low ITD-AR, <0.05). Forty-one percent of children with high levels of MRD after the 1st induction course, measured by a patient-specific real-time-PCR, had worse EFS (22.2 versus 59.4% in low-MRD patients, P<0.05). Next, we correlated these parameters with gene expression, showing that patients with high ITD-AR or persistent MRD had characteristic expression profiles with deregulated genes involved in methylation and acetylation. Moreover, patients with high CyclinA1 expression presented an unfavorable EFS (20.3 versus 51.2% in low CyclinA1 group, P<0.01). Our results suggest that ITD-AR levels and molecular MRD should be considered in planning clinical management of FLT3-ITD patients. Different transcriptional activation of epigenetic and oncogenic profiles may explain variability in outcome among these patients, for whom novel therapeutic approaches are desirable.

  14. A Study on Uptake and Localization of Merocyanine 540 (MC540) in Murine Myeloid Leukemia Cells by Confocal Laser Scanning Microscopy (CLSM)

    Institute of Scientific and Technical Information of China (English)

    J. Y. Chen; N. H. Cheung; S. C. Chen; M. C. Fung; W. N. Leung; N. K. Mak

    2000-01-01

    The intracellular localization of merocyanine 540 (MC540), a photosensitizer commonly used in the photo-inactivation of leukemia cells, was studied using confocal laser scanning microscopy. It was found for the first time that MC540 not only localized in the plasma membrane but also in the cytoplasm and the nuclear membrane of the murine myeloid leukemia M1 and WEHI 3B (JCS) cells. Exposure of MC540 treated leukemia cells to light under conditions that could cause photobleaching did not cause the redistribution of cell-bound MC540. Rapid localization of MC540 in the cytoplasm was observed 5 minutes after exposure of leukemia cell to MC540, indicating that MC540 could promptly be internalized by these two leukemia cell lines. In contrast, localization of MC540 was limited only to the plasma membrane of erythrocytes. These results suggest that the binding pattern of MC540 is cell type dependent and may be related to the efficacy of photosenitization in photodynamic therapy.

  15. Effect of supplemental folic acid in pregnancy on childhood asthma: a prospective birth cohort study.

    Science.gov (United States)

    Whitrow, Melissa J; Moore, Vivienne M; Rumbold, Alice R; Davies, Michael J

    2009-12-15

    This study aimed to investigate the effect of the timing, dose, and source of folate during pregnancy on childhood asthma by using data from an Australian prospective birth cohort study (n = 557) from 1998 to 2005. At 3.5 years and 5.5 years, 490 and 423 mothers and children participated in the study, respectively. Maternal folate intake from diet and supplements was assessed by food frequency questionnaire in early (late (30-34 weeks) pregnancy. The primary outcome was physician-diagnosed asthma, obtained by maternal-completed questionnaire. Asthma was reported in 11.6% of children at 3.5 years (n = 57) and in 11.8% of children at 5.5 years (n = 50). Folic acid taken in supplement form in late pregnancy was associated with an increased risk of childhood asthma at 3.5 years (relative risk (RR) = 1.26, 95% confidence interval (CI): 1.08, 1.43) and with persistent asthma (RR = 1.32, 95% CI: 1.03, 1.69). The effect sizes did not change with adjustment for potential confounders. The association was similar at 5.5 years but did not reach statistical significance (RR = 1.17, 95% CI: 0.96, 1.42) in univariable models. These findings on childhood asthma support previous observations that supplementation with folate in pregnancy leads to an allergic asthma phenotype in mice via epigenetic mechanisms and is associated with poorer respiratory outcomes in young children.

  16. Childhood adversity profiles and adult psychopathology in a representative Northern Ireland study.

    Science.gov (United States)

    McLafferty, Margaret; Armour, Cherie; McKenna, Aine; O'Neill, Siobhan; Murphy, Sam; Bunting, Brendan

    2015-10-01

    Childhood adversities are key aetiological factors in the onset and persistence of psychopathology. The aims of this study were to identify childhood adversity profiles, and investigate the relationship between the adversity classes and psychopathology in Northern Ireland. The study utilized data from the Northern Ireland Study of Health and Stress, an epidemiological survey (N=1986), which used the CIDI to examine mental health disorders and associated risk factors. Latent Class Analysis revealed 3 distinct typologies; a low risk class (n=1709; 86%), a poly-adversity class (n=122; 6.1%), and an economic adversity class (n=155; 7.8%). Logistic Regression models revealed that individuals in the economic adversity class had a heightened risk of anxiety and substance disorders, with individuals in the poly-adversity class more likely to have a range of mental health problems and suicidality. The findings indicate the importance of considering the impact of co-occurring childhood adversities when planning treatment, prevention, and intervention programmes.

  17. Nilotinib 300 mg twice daily: an academic single-arm study of newly diagnosed chronic phase chronic myeloid leukemia patients

    Science.gov (United States)

    Castagnetti, Fausto; Breccia, Massimo; Gugliotta, Gabriele; Martino, Bruno; D’Adda, Mariella; Stagno, Fabio; Carella, Angelo Michele; Avanzini, Paolo; Tiribelli, Mario; Trabacchi, Elena; Visani, Giuseppe; Gobbi, Marco; Salvucci, Marzia; Levato, Luciano; Binotto, Gianni; Capalbo, Silvana Franca; Bochicchio, Maria Teresa; Soverini, Simona; Cavo, Michele; Martinelli, Giovanni; Alimena, Giuliana; Pane, Fabrizio; Saglio, Giuseppe; Rosti, Gianantonio; Baccarani, Michele

    2016-01-01

    The introduction and the extended clinical use of nilotinib in the first-line treatment of chronic myeloid leukemia have been based on company-sponsored trials. Independent confirmations are extremely important. We report an investigator-sponsored study of nilotinib 300 mg twice daily in 130 chronic myeloid leukemia patients in early chronic phase. A deep molecular response was achieved in 46% (MR4.0) and 17% (MR4.5) of patients at 2 years; 58% of the enrolled patients achieved a MR4.0 at least once, with a sustained MR4.0 in 52% of them. With a median observation of 29 months (range 24–37 months), 77% of patients were still on treatment with nilotinib. The reasons for permanent discontinuation were: 3% progression, 5% failure or suboptimal response, 8% adverse events, 1% treatment-free remission, and 5% other reasons. Thirteen thrombotic arterial events were reported in 12 patients. A prospective evaluation of metabolic effects showed an increase of fasting glucose without significant variations of glycated hemoglobin, an increase of total cholesterol (both low density lipoprotein and high density lipoprotein fractions) and a decrease of triglycerides. This study confirms a high and rapid efficacy of nilotinib 300 mg twice daily and provides detailed information on the type and incidence of non-hematologic and metabolic adverse events (clinicaltrials.gov identifier: 01535391). PMID:27470600

  18. 'Once upon a time …': Orphanhood, childhood studies and the depoliticisation of childhood poverty in southern Africa.

    Science.gov (United States)

    Ansell, Nicola

    2016-05-01

    Policy, interventions and research concerning southern African children remain dominated by a focus on AIDS-related orphanhood, although the association between orphanhood and disadvantage is highly questionable. I argue that the trope of the AIDS orphan serves a range of agendas, including for academic research. In particular, orphans represent the quintessential child-agent, celebrated in fairytales and fiction. Finally, I examine how this has led to a policy response - education bursaries - that cannot adequately address childhood poverty in the region.

  19. Sex-Specific Effects of Childhood Poverty on Neurocircuitry of Processing of Emotional Cues: A Neuroimaging Study

    Directory of Open Access Journals (Sweden)

    Arash Javanbakht

    2016-12-01

    Full Text Available Background: There is accumulating evidence on the negative impacts of childhood poverty on physical and mental health. Previous work has suggested hyperactive neural response to social fear cues, as well as impairment in neural regulatory functions. However, despite differences found between males and females in stress-related and anxiety disorders, possible sex-specific effects of poverty on emotional processing have not been explored. Methods: We analyzed data from three previously reported experiments of childhood poverty effects on emotional processing and regulation, for sex-specific effects. Participants were 52 healthy Caucasian males and females, from a longitudinal cohort of poverty development study, who were recruited for examining the long-term effects of childhood poverty and stress. The three functional MRI studies included emotion regulation task, emotional face assessment task, and shifted attention emotion appraisal task. Brain activations that associated with childhood poverty previously were entered into a regression analysis with interaction of gender by childhood income-to-need ratio as the independent variable, and age and current income-to-need ratio as variables of no interest, separately for males and females. Results: Amygdala reactivity to implicitly processed fearful faces was positively correlated with childhood income-to-need in adult females but not males. On the other hand, activation in dorsolateral and ventrolateral prefrontal regions during emotion regulation by reappraisal was positively correlated with childhood income-to-need in males. Conclusion: Childhood poverty may exert sex-specific effects in adulthood as presented by hypersensitive emotional reactivity of the amygdala in females, and impaired emotion regulatory function of the prefrontal cortex in males. Results suggest further focus on sex-specific effects of childhood poverty.

  20. Physical activity in childhood and the association with myopia in adolescence – The CHAMPS Eye Study

    DEFF Research Database (Denmark)

    Lundberg, Lars Kristian; Vestergaard, Anders Højslet; Jacobsen, Nina

    Purpose: Myopia is the most frequent eye disease globally and is usually caused by increasing axial growth of the eye during childhood and adolescence. Lifestyle changes such as reduced physical activity (PA) are thought to be the driving force behind the rapid increase of myopia worldwide......-PA prompt a 0.3 mm longer AL (Pphysical activity was associated with a shorter axial length and refractive error for SED-PA and M-PA, consistent with theory....... cohort (Childhood Health, Activity, and Motor Performance School Study Denmark). PA was assessed with GT3X accelerometer (ActiGraph, Florida, USA) worn for 7 full consecutive days at the period August to October 2010: mean intensity was estimated as counts/min (CPM); and cut off-points for sedentary (SED...