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Sample records for high-risk childhood acute

  1. Intrinsic and chemo-sensitizing activity of SMAC-mimetics on high-risk childhood acute lymphoblastic leukemia

    PubMed Central

    Schirmer, M; Trentin, L; Queudeville, M; Seyfried, F; Demir, S; Tausch, E; Stilgenbauer, S; Eckhoff, S M; Meyer, L H; Debatin, K-M

    2016-01-01

    SMAC-mimetics represent a targeted therapy approach to overcome apoptosis resistance in many tumors. Here, we investigated the efficacy of the SMAC-mimetic BV6 in B-cell precursor acute lymphoblastic leukemia (BCP-ALL). In ALL cell lines, intrinsic apoptosis sensitivity was associated with rapid cIAP degradation, NF-κB activation, TNF-α secretion and induction of an autocrine TNF-α-dependent cell death loop. This pattern of responsiveness was also observed upon ex vivo analysis of 40 primograft BCP-ALL samples. Treatment with BV6 induced cell death in the majority of ALL primografts including leukemias with high-risk and poor-prognosis features. Inhibition of cell death by the TNF receptor fusion protein etanercept demonstrated that BV6 activity is dependent on TNF-α. In a preclinical NOD/SCID/huALL model of high-risk ALL, marked anti-leukemia effectivity and significantly prolonged survival were observed upon BV6 treatment. Interestingly, also in vivo, intrinsic SMAC-mimetic activity was mediated by TNF-α. Importantly, BV6 increased the effectivity of conventional induction therapy including vincristine, dexamethasone and asparaginase leading to prolonged remission induction. These data suggest SMAC-mimetics as an important addendum to efficient therapy of pediatric BCP-ALL. PMID:26775704

  2. Next-generation-sequencing of recurrent childhood high hyperdiploid acute lymphoblastic leukemia reveals mutations typically associated with high risk patients.

    PubMed

    Chen, Cai; Bartenhagen, Christoph; Gombert, Michael; Okpanyi, Vera; Binder, Vera; Röttgers, Silja; Bradtke, Jutta; Teigler-Schlegel, Andrea; Harbott, Jochen; Ginzel, Sebastian; Thiele, Ralf; Husemann, Peter; Krell, Pina F I; Borkhardt, Arndt; Dugas, Martin; Hu, Jianda; Fischer, Ute

    2015-09-01

    20% of children suffering from high hyperdiploid acute lymphoblastic leukemia develop recurrent disease. The molecular mechanisms are largely unknown. Here, we analyzed the genetic landscape of five patients at relapse, who developed recurrent disease without prior high-risk indication using whole-exome- and whole-genome-sequencing. Oncogenic mutations of RAS pathway genes (NRAS, KRAS, FLT3, n=4) and deactivating mutations of major epigenetic regulators (CREBBP, EP300, each n=2 and ARID4B, EZH2, MACROD2, MLL2, each n=1) were prominent in these cases and virtually absent in non-recurrent cases (n=6) or other pediatric acute lymphoblastic leukemia cases (n=18). In relapse nucleotide variations were detected in cell fate determining transcription factors (GLIS1, AKNA). Structural genomic alterations affected genes regulating B-cell development (IKZF1, PBX1, RUNX1). Eleven novel translocations involved the genes ART4, C12orf60, MACROD2, TBL1XR1, LRRN4, KIAA1467, and ELMO1/MIR1200. Typically, patients harbored only single structural variations, except for one patient who displayed massive rearrangements in the context of a germline tumor suppressor TP53 mutation and a Li-Fraumeni syndrome-like family history. Another patient harbored a germline mutation in the DNA repair factor ATM. In summary, the relapse patients of our cohort were characterized by somatic mutations affecting the RAS pathway, epigenetic and developmental programs and germline mutations in DNA repair pathways. PMID:26189108

  3. Gene Expression Signatures Predictive of Early Response and Outcome in High-Risk Childhood Acute Lymphoblastic Leukemia: A Children's Oncology Group Study

    PubMed Central

    Bhojwani, Deepa; Kang, Huining; Menezes, Renee X.; Yang, Wenjian; Sather, Harland; Moskowitz, Naomi P.; Min, Dong-Joon; Potter, Jeffrey W.; Harvey, Richard; Hunger, Stephen P.; Seibel, Nita; Raetz, Elizabeth A.; Pieters, Rob; Horstmann, Martin A.; Relling, Mary V.; den Boer, Monique L.; Willman, Cheryl L.; Carroll, William L.

    2008-01-01

    Purpose To identify children with acute lymphoblastic leukemia (ALL) at initial diagnosis who are at risk for inferior response to therapy by using molecular signatures. Patients and Methods Gene expression profiles were generated from bone marrow blasts at initial diagnosis from a cohort of 99 children with National Cancer Institute–defined high-risk ALL who were treated uniformly on the Children's Oncology Group (COG) 1961 study. For prediction of early response, genes that correlated to marrow status on day 7 were identified on a training set and were validated on a test set. An additional signature was correlated with long-term outcome, and the predictive models were validated on three large, independent patient cohorts. Results We identified a 24–probe set signature that was highly predictive of day 7 marrow status on the test set (P = .0061). Pathways were identified that may play a role in early blast regression. We have also identified a 47–probe set signature (which represents 41 unique genes) that was predictive of long-term outcome in our data set as well as three large independent data sets of patients with childhood ALL who were treated on different protocols. However, we did not find sufficient evidence for the added significance of these genes and the derived predictive models when other known prognostic features, such as age, WBC, and karyotype, were included in a multivariate analysis. Conclusion Genes and pathways that play a role in early blast regression may identify patients who may be at risk for inferior responses to treatment. A fully validated predictive gene expression signature was defined for high-risk ALL that provided insight into the biologic mechanisms of treatment failure. PMID:18802149

  4. Biomarkers in Bone Marrow Samples From Pediatric Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    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); Recurrent Childhood Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  5. 5T4 oncofetal antigen is expressed in high risk of relapse childhood pre-B acute lymphoblastic leukemia and is associated with a more invasive and chemotactic phenotype.

    PubMed

    Castro, F V; McGinn, O J; Krishnan, S; Marinov, G; Li, J; Rutkowski, A J; Elkord, E; Burt, D J; Holland, M; Vaghjiani, R; Gallego, A; Saha, V; Stern, P L

    2012-07-01

    Although the overall prognosis in childhood acute lymphoblastic leukemia (ALL) is good, outcome after relapse is poor. Recurrence is frequently characterized by the occurrence of disease at extramedullary sites, such as the central nervous system and testes. Subpopulations of blasts able to migrate to such areas may have a survival advantage and give rise to disease recurrence. Gene expression profiling of 85 diagnostic pre-B-ALL bone marrow samples revealed higher 5T4 oncofetal antigen transcript levels in cytogenetic high-risk subgroups of patients (P<0.001). Flow cytometric analysis determined that bone marrow from relapse patients have a significantly higher percentage of 5T4-positive leukemic blasts than healthy donors (P=0.005). The high-risk Sup-B15 pre-B-ALL line showed heterogeneity in 5T4 expression, and the derived, 5T4(+) (Sup5T4) and 5T4(-) (Sup) subline cells, displayed differential spread to the omentum and ovaries following intraperitoneal inoculation of immunocompromised mice. Consistent with this, Sup5T4 compared with Sup cells show increased invasion in vitro concordant with increased LFA-1 and VLA-4 integrin expression, adhesion to extracellular matrix and secretion of matrix metalloproteases (MMP-2/-9). We also show that 5T4-positive Sup-B15 cells are susceptible to 5T4-specific superantigen antibody-dependent cellular toxicity providing support for targeted immunotherapy in high-risk pre-B-ALL. PMID:22266911

  6. Donor Stem Cell Transplant in Treating Patients With High Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-29

    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(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 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); 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

  7. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-08-23

    B Acute Lymphoblastic Leukemia; Bone Necrosis; Central Nervous System Leukemia; Cognitive Side Effects of Cancer Therapy; Neurotoxicity Syndrome; Pain; Testicular Leukemia; Therapy-Related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  8. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  9. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  10. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... recovery) and treatment options. Childhood acute lymphoblastic leukemia (ALL) is a type of cancer in which the ... genetic conditions affect the risk of having childhood ALL. Anything that increases your risk of getting a ...

  11. General Information about Childhood Acute Lymphoblastic Leukemia

    MedlinePlus

    ... Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Childhood Acute Lymphoblastic Leukemia Go to Health ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  12. 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

    ClinicalTrials.gov

    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

  13. High risk cohort study for psychiatric disorders in childhood: rationale, design, methods and preliminary results.

    PubMed

    Salum, Giovanni Abrahão; Gadelha, Ary; Pan, Pedro Mario; Moriyama, Tais Silveira; Graeff-Martins, Ana Soledade; Tamanaha, Ana Carina; Alvarenga, Pedro; Valle Krieger, Fernanda; Fleitlich-Bilyk, Bacy; Jackowski, Andrea; Sato, João Ricardo; Brietzke, Elisa; Polanczyk, Guilherme Vanoni; Brentani, Helena; de Jesus Mari, Jair; Do Rosário, Maria Conceição; Manfro, Gisele Gus; Bressan, Rodrigo Affonseca; Mercadante, Marcos Tomanik; Miguel, Eurípedes Constantino; Rohde, Luis Augusto

    2015-03-01

    The objective of this study is to present the rationale, methods, design and preliminary results from the High Risk Cohort Study for the Development of Childhood Psychiatric Disorders. We describe the sample selection and the components of each phases of the study, its instruments, tasks and procedures. Preliminary results are limited to the baseline phase and encompass: (i) the efficacy of the oversampling procedure used to increase the frequency of both child and family psychopathology; (ii) interrater reliability and (iii) the role of differential participation rate. A total of 9937 children from 57 schools participated in the screening procedures. From those 2512 (random = 958; high risk = 1554) were further evaluated with diagnostic instruments. The prevalence of any child mental disorder in the random strata and high-risk strata was 19.9% and 29.7%. The oversampling procedure was successful in selecting a sample with higher family rates of any mental disorders according to diagnostic instruments. Interrater reliability (kappa) for the main diagnostic instrument range from 0.72 (hyperkinetic disorders) to 0.84 (emotional disorders). The screening instrument was successful in selecting a sub-sample with "high risk" for developing mental disorders. This study may help advance the field of child psychiatry and ultimately provide useful clinical information. PMID:25469819

  14. Global Characteristics of Childhood Acute Promyelocytic Leukemia

    PubMed Central

    Zhang, L; Samad, A; Pombo-de-Oliveira, MS; Scelo, G; Smith, MT; Feusner, J; Wiemels, JL; Metayer, C

    2014-01-01

    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. PMID:25445717

  15. Childhood abuse and neglect may induce deficits in cognitive precursors of psychosis in high-risk children

    PubMed Central

    Berthelot, Nicolas; Paccalet, Thomas; Gilbert, Elsa; Moreau, Isabel; Mérette, Chantal; Gingras, Nathalie; Rouleau, Nancie; Maziade, Michel

    2015-01-01

    Background Millions of children are born to parents affected by major psychoses. Cognitive dysfunctions seen in patients are already detectable in these children. In parallel, childhood maltreatment increases the risk of adult psychoses through unknown mechanisms. We investigated whether high-risk offspring exposed to abuse/neglect displayed more cognitive precursors of adult psychoses in childhood and adolescence than nonexposed offspring. Methods We used a stepwise selection strategy from a 25-year follow-up of 48 densely affected kindreds including 1500 adults (405 patients with schizophrenia or bipolar disorder) to select high-risk offspring aged 6–22 years for inclusion in our study. All offspring were assessed for childhood trauma from direct interviews with the offspring, parents and relatives and from the review of lifetime medical records of parents and children and administered a neuropsychological battery including IQ and 4 of the most impaired neuropsychological domains in psychoses. Results Our study included 66 high-risk offspring. Those who were exposed to abuse/neglect had significantly lower IQ (effect size [ES] = 0.61) than nonexposed offspring and displayed poorer cognitive performance in visual episodic memory (ES = 0.67) and in executive functions of initiation (ES = 1.01). Moreover, exposed offspring presented more combinations of cognitive deficits that were associated with lower Global Assessment of Functioning scores. Limitations Exposure to abuse/neglect was not assessed in the control group, thus the study could not test whether the effect of childhood maltreatment occured only in a high-risk setting and not in the general population. Conclusion In high-risk youths, maltreatment in childhood/adolescence may negatively impact cognitive domains known to be impaired in adults with psychoses, suggesting an early mediating effect in the association between abuse/neglect and adult psychoses. This finding provides a target for future

  16. Early childhood caries: analysis of psychosocial and biological factors in a high-risk population.

    PubMed

    Quiñonez, R B; Keels, M A; Vann, W F; McIver, F T; Heller, K; Whitt, J K

    2001-01-01

    The influences that link social factors and caries development are not well understood, although mediation by stress has been suggested. The association between caregiver stress and early childhood caries (ECC), in particular, remains unclear. The purpose of this study was to examine the relationships between parenting stress and ECC while controlling for behavioral and biological factors in a high-risk population. One hundred and fifty healthy children aged 18-36 months were examined in a cross-sectional study design. Parental interviews were conducted to obtain demographic, oral health behavior and parenting stress data. Clinical data included parent and child bacterial measures, fingernail fluoride analyses, caries prevalence and presence of child enamel hypoplasia. Bivariate analyses revealed that parenting stress predicted caries. Multivariate analyses demonstrated that a combination of psychosocial, behavioral, temporal and biological variables predicted ECC outcomes. Total parenting stress did not contribute independently to the best prediction model. Our findings suggest the need for the development of a multidimensional stress model that considers the parent-child dyad to elucidate further the link between psychosocial factors and ECC. PMID:11641574

  17. Acute diabetic abdomen in childhood.

    PubMed

    Valerio, D

    1976-01-10

    Three children presented as acute surgical emergencies due to undiagnosed diabetes mellitus. Where diabetic ketoacidosis mimicks the acute abdomen three clinical features are important in reaching the right diagnosis-namely, a history of polydipsia, polyuria, and anorexia preceding the abdominal pain, the deep sighing and rapid respirations, and severe dehydration. PMID:54584

  18. Pipazethate--acute childhood poisoning.

    PubMed

    da Silva, O A; Lopez, M

    1977-01-01

    A previously healthy child who who had accidentally ingested an unknown quantity of 20-mg tablets of pipazethate developed severe acute poisoning with neurologic, metabolic, and cardiovascular disturbances. She recovered with symptomatic and supportive therapy. PMID:589958

  19. High-Risk Populations Identified in Childhood Cancer Survivor Study Investigations: Implications for Risk-Based Surveillance

    PubMed Central

    Hudson, Melissa M.; Mulrooney, Daniel A.; Bowers, Daniel C.; Sklar, Charles A.; Green, Daniel M.; Donaldson, Sarah S.; Oeffinger, Kevin C.; Neglia, Joseph P.; Meadows, Anna T.; Robison, Leslie L.

    2009-01-01

    Childhood cancer survivors often experience complications related to cancer and its treatment that may adversely affect quality of life and increase the risk of premature death. The purpose of this manuscript is to review how data derived from Childhood Cancer Survivor Study (CCSS) investigations have facilitated identification of childhood cancer survivor populations at high risk for specific organ toxicity and secondary carcinogenesis and how this has informed clinical screening practices. Articles previously published that used the resource of the CCSS to identify risk factors for specific organ toxicity and subsequent cancers were reviewed and results summarized. CCSS investigations have characterized specific groups to be at highest risk of morbidity related to endocrine and reproductive dysfunction, pulmonary toxicity, cerebrovascular injury, neurologic and neurosensory sequelae, and subsequent neoplasms. Factors influencing risk for specific outcomes related to the individual survivor (eg, sex, race/ethnicity, age at diagnosis, attained age), sociodemographic status (eg, education, household income, health insurance) and cancer history (eg, diagnosis, treatment, time from diagnosis) have been consistently identified. These CCSS investigations that clarify risk for treatment complications related to specific treatment modalities, cumulative dose exposures, and sociodemographic factors identify profiles of survivors at high risk for cancer-related morbidity who deserve heightened surveillance to optimize outcomes after treatment for childhood cancer. PMID:19289611

  20. Acute Phase IL-10 Plasma Concentration Associates with the High Risk Sources of Cardiogenic Stroke

    PubMed Central

    Arponen, Otso; Muuronen, Antti; Taina, Mikko; Sipola, Petri; Hedman, Marja; Jäkälä, Pekka; Vanninen, Ritva; Pulkki, Kari; Mustonen, Pirjo

    2015-01-01

    Background Etiological assessment of stroke is essential for accurate treatment decisions and for secondary prevention of recurrence. There is evidence that interleukin-10 (IL-10) associates with ischemic stroke. The aim of this prospective study was to assess the levels of IL-10 in ischemic stroke with unknown or suspected cardiogenic etiology, and evaluate the correlation between IL-10 plasma concentration and the number of diagnosed high risk sources for cardioembolism. Methods A total of 141 patients (97 males; mean age 61±11 years) with acute ischemic stroke with unknown etiology or suspected cardiogenic etiology other than known atrial fibrillation (AF) underwent imaging investigations to assess high risk sources for cardioembolic stroke established by the European Association of Echocardiography (EAE). IL-10 was measured on admission to the hospital and on a three month follow-up visit. Results Acute phase IL-10 concentration was higher in patients with EAE high risk sources, and correlated with their number (p<0.01). In patients with no risk sources (n = 104), the mean IL-10 concentration was 2.7±3.1 ng/L (range 0.3–16.3 ng/L), with one risk source (n = 26) 3.7±5.5 ng/L (0.3–23.6 ng/L), with two risk sources (n = 10) 7.0±10.0 ng/L (1.29–34.8 ng/L) and with three risk sources (n = 1) 37.2 ng/L. IL-10 level was not significantly associated with cerebral infarct volume, presence of previous or recent myocardial infarction, carotid/vertebral artery atherosclerosis, paroxysmal AF registered on 24-hour ECG Holter monitoring or given intravenous thrombolytic treatment. Conclusion IL-10 plasma concentration correlates independently with the number of EAE cardioembolic risk sources in patients with acute stroke. IL-10 may have potential to improve differential diagnostics of stroke with unknown etiology. PMID:25923658

  1. Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia.

    PubMed

    Salina, Thais Ditolvo da Costa; Ferreira, Yvelise Antunes; Alves, Eliana Brasil; Ferreira, Cristina Motta; De Paula, Erich Vinícius; Mira, Marcelo Távora; Passos, Leny da Mota

    2016-01-01

    Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols. PMID:27526794

  2. Role of peripheral blood minimum residual disease at day 8 of induction therapy in high-risk pediatric patients with acute lymphocytic leukemia

    PubMed Central

    Salina, Thais Ditolvo da Costa; Ferreira, Yvelise Antunes; Alves, Eliana Brasil; Ferreira, Cristina Motta; De Paula, Erich Vinícius; Mira, Marcelo Távora; Passos, Leny da Mota

    2016-01-01

    Risk stratification and treatment intensification, based on minimal residual disease (MRD) mensurement, changed the prognosis of pediatric patients with acute lymphocytic leukemia (ALL). The main aim of this study was to investigate whether peripheral blood (PB) MRD measurement at day 8 (D8) could predict the risk stratification category determined by bone marrow (BM) MRD at day 15 (D15). The study was performed prospectively, in a cohort of 40 children with B-lineage ALL, adopting the protocol of the Brazilian Cooperative Group of the Treatment Childhood Leukemia (GBTLI-2009). MRD was detected by flow cytometry (FC) using a simplifed panel that can reliably identify MRD at early phases of induction therapy. Upon diagnosis, the proportion of low and high-risk patients, was 24:16 (60%:40%). The main result of our study demonstrated the potential of D8 MRD in anticipating of week the risk stratification of high-risk patients as determined by D15 BM MRD. In these patients D8 MRD level of 1% was able to segregate high risk fast responders from high risk slow responders (p = 0.0097). This result could represent an opportunity for early treatment intensification, as already performed in some protocols. PMID:27526794

  3. Childhood Adversity Among Institutionalized Male Juvenile Offenders and Other High-Risk Groups Without Offense Records in Portugal.

    PubMed

    Pinto, Ricardo José; Fernandes, Ana Isabel; Mesquita, Cristina; Maia, Ângela Costa

    2015-01-01

    The literature has shown that delinquent adolescents report high rates of childhood adversity and family dysfunction. However, it is important to know both the degree of adversity among delinquent adolescents in comparison with other high-risk samples and the contribution of each single form of adversity to this comparison. The purpose of this study was to evaluate childhood adversity, psychopathology, and risk behaviors among 4 high-risk groups, including incarcerated delinquent youths. The participants were 120 male youths between 13 and 19 years old (M = 16.18, SD = 1.26), including 30 youths who were arrested and held in detention centers as a consequence of violent crimes; 30 youths who were identified by Child Protective Services (CPS) and remained with their families; 30 youths who were identified by CPS, removed from their homes, and placed in child and youth residential care; and 30 youths who were randomly selected from schools. The incarcerated youths reported significantly more adversity, global psychopathology, and global index of risk behaviors. When considering each risk behavior, the incarcerated youths reported higher percentages of alcohol abuse, drug use, early smoking initiation, physical assault, carrying weapons, early initiation of sexual intercourse, sexual intercourse under the influence of drugs, and sexual intercourse without condom use. The logistic regression analyses showed that only emotional neglect was significantly associated with delinquency. This study suggests that delinquent youths are exposed to a great magnitude of adversities in childhood, with emotional neglect as an independent risk factor for delinquency. In addition, these youths have higher rates of psychopathology and risk behaviors compared to other high-risk samples. PMID:26159627

  4. Sexual Risk-Taking among High-Risk Urban Women with and without Histories of Childhood Sexual Abuse: Mediating Effects of Contextual Factors

    ERIC Educational Resources Information Center

    Mosack, Katie E.; Randolph, Mary E.; Dickson-Gomez, Julia; Abbott, Maryann; Smith, Ellen; Weeks, Margaret R.

    2010-01-01

    This study investigated the mechanisms of risk for urban women at high risk for HIV with and without childhood sexual abuse histories. Childhood sexual abuse survivors reported more unprotected intercourse and sexually transmitted infections (STIs). The association of STI locus of control with frequency of unprotected sex was fully mediated by…

  5. Epidemiology of childhood acute myelogenous leukemia.

    PubMed

    Bhatia, S; Neglia, J P

    1995-05-01

    Acute myelogenous leukemia (AML) is the second most common leukemia in children, with approximately 400 new cases occurring annually in the United States. Worldwide, the highest rates of childhood AML occur in Asia and the lowest rates are reported from India and South America. Numerous genetic risk factors for childhood AML have been defined, including Down syndrome, neurofibromatosis, and Fanconi anemia. Research into environmental risk factors has been limited by the rarity of this disease; however, studies of AML in adults have implicated ionizing radiation, solvents, and petroleum products as potential etiologic agents. The largest analytic study of childhood AML found that occupational exposures of either parent to pesticides, paternal exposure to petroleum products, and postnatal exposures to pesticides are increased in children with AML. In addition, maternal use of marijuana during pregnancy was associated with an increased risk of AML, especially the monocytic subtypes. Further study of childhood AML, including occurrence of the disease as a second malignancy, is needed in order to confirm these findings and to increase our understanding of this leukemia. PMID:7749772

  6. Childhood Onset Diagnoses in a Case Series of Teens at Clinical High Risk for Psychosis

    PubMed Central

    Mazzoni, Paola; Kimhy, David; Khan, Shamir; Posner, Kelly; Maayan, Lawrence; Eilenberg, Mara; Messinger, Julie; Kestenbaum, Clarice

    2009-01-01

    Abstract Reasons Schizophrenia is typically an adult neurodevelopmental disorder that has its antecedents in childhood and adolescence. Little is known about disorders “usually first diagnosed in infancy, childhood and adolescence” (e.g., childhood-onset disorders) in “prodromal” teens at heightened clinical risk for psychotic disorder. Main Findings Childhood-onset disorders were prevalent in putatively prodromal teens, including anxiety and disruptive disorders, attention-deficit/hyperactivity disorder (ADHD), and, surprisingly, elimination disorders. These may reflect developmental antecedents in psychotic disorders such as schizophrenia. Key Data and Statistics A case series of 9 teens (ages 13–17) identified as prodromal to psychosis were evaluated with the Kiddie Schedule for Affective Disorders and Schizophrenia–Present and Lifetime Version (K-SADS-PL). Childhood-onset diagnoses commonly endorsed (threshold or subthreshold) included ADHD (5/9), oppositional defiant disorder (5/9), enuresis or encopresis (4/9), conduct disorder (2/9), separation anxiety (3/9), and transient tic disorder (2/9). Enuresis was identified in 3 of the 4 older teens (ages 15–17). Major Conclusions An understanding of the childhood-onset disorders that occur in teens at risk for psychotic illnesses, such as schizophrenia, can shed light on the pathophysiology of schizophrenia and potentially inform early identification and intervention. PMID:20035596

  7. High-risk patients following hospitalisation for an acute exacerbation of COPD.

    PubMed

    Piquet, Jacques; Chavaillon, Jean-Michel; David, Philippe; Martin, Francis; Blanchon, François; Roche, Nicolas

    2013-10-01

    The aim of this study was to assess long-term mortality and predictive factors of death after hospital admission for acute exacerbation of chronic obstructive pulmonary disease (COPD). 1824 patients (23.2% female; mean age 70.3±11.3 years) consecutively admitted for acute exacerbation of COPD in the respiratory medicine departments of 68 general hospitals between October 2006 and June 2007 were prospectively enrolled in a follow-up cohort. Their vital status was documented between October 2010 and April 2011. Vital status was available for 1750 patients (95.9%), among whom 787 (45%) died during follow-up. Multivariate analysis found that age (60-80 years and ≥80 years versus <60 years, relative risk 2.99, 95% CI 2.31-3.89), lower body mass index (25-30 kg·m(-2) versus ≤20 kg·m(-2), relative risk 0.80, 95% CI 0.66-0.97), lung cancer (relative risk 2.08, 95% CI 1.43-3.01), cardiovascular comorbidity (relative risk 1.35, 95% CI 1.16-1.58), previous hospital admissions for acute exacerbation of COPD (four or more versus none, relative risk 1.91, 95% CI 1.44-2.53), use of accessory respiratory muscles (relative risk 1.19, 95% CI 1.01-1.40) or lower-limb oedema (relative risk 1.74, 95% CI (1.44-2.12)) at admission and treatment by long-term oxygen therapy at discharge (relative risk 2.09, 95% CI 1.79-2.45) were independent risk factors of death. Mortality rate during the 4 years following hospital admission for acute exacerbation of COPD was high (45%). Simple clinical information relating to respiratory and general status can help in identifying high-risk patients and targeting more intensive follow-up and care. Interestingly, cardiovascular comorbidities and past hospitalisations for acute exacerbation of COPD, but not forced expiratory volume in 1 s, independently predicted the risk of death. PMID:23349446

  8. Prognostic factors in acute promyelocytic leukemia: strategies to define high-risk patients.

    PubMed

    Testa, Ugo; Lo-Coco, Francesco

    2016-04-01

    All trans retinoic acid (ATRA) has revolutionized the therapy of acute promyelocytic leukemia (APL). Treatment of this leukemia with ATRA in combination with chemotherapy has resulted in complete remission rates >90 % and long-term remission rates above 80 %. Furthermore, the combination of ATRA and arsenic trioxide (ATO) was shown to be safe and effective in frontline treatment and, for patients with low and intermediate risk disease, possibly superior to the standard ATRA and anthracycline-based regimen. However, in spite of this tremendous progress, APL still remains associated with a high incidence of early death due to the frequent occurrence of an abrupt bleeding diathesis. This hemorrhagic syndrome more frequently develops in high-risk APL patients, currently defined as those exhibiting >10 × 10(9)/L WBC at presentation. In addition to high WBC count, other molecular and immunophenotypic features have been associated with high-risk APL. Among them, the expression in APL blasts of the stem/progenitor cell antigen CD34, the neural adhesion molecule (CD56), and the T cell antigen CD2 help to identify a subset of patients at higher risk of relapse and often the expression of these markers is associated with high WBC count. At the molecular level, the short PML/RARA isoform and FLT3-internal tandem duplication (ITD) mutations have been associated with increased relapse risk. These observations indicate that extended immunophenotypic and molecular characterization of APL at diagnosis including evaluation of CD2, CD56, and CD34 antigens and of FLT3 mutations may help to better design risk-adapted treatment in this disease. PMID:26920716

  9. Active surveillance for acute flaccid paralysis in poliomyelitis high-risk areas in southern China.

    PubMed Central

    Chiba, Y.; Hikita, K.; Matuba, T.; Chosa, T.; Kyogoku, S.; Yu, J.; Wang, Z.

    2001-01-01

    OBJECTIVE: On 29 October 2000 poliomyelitis was officially declared to have been eradicated from the Western Pacific Region. This article describes the results of surveillance for cases of acute flaccid paralysis (AFP) in China during the final phase of the eradication effort. METHODS: We conducted hospital-based active surveillance in high-risk areas for poliomyelitis in 5 provinces of southern-China (Sichuan, Yunnan, Guizhou, Guangxi and Jiangxi) between 1995 and 1997 to determine the adequacy of reporting and laboratory diagnosis of cases of AFP. FINDINGS: A total of 1069 AFP cases occurring since 1993 were identified in 311 hospital visits. Less than 50% of AFP cases occurring in 1993 and 1994 had been reported by AFP surveillance, and laboratory diagnosis had been carried out on only a small proportion of these. However, improved cooperation between hospital sectors increased the rate of case reporting and laboratory diagnosis to 85% and 78%, respectively, in 1997. Despite this overall improvement, these two indicators were approximately 10-20% lower in Yunnan Province. Epidemiological analysis revealed that cases of clinical poliomyelitis accounted for as much as one-third of all AFP in 1993 and that some of these cases were clustered. Clusters were rarely observed after 1994. Active surveillance in the China-Myanmar border areas of Yunnan over 1995-96 detected 9 cross-border cases of clinical poliomyelitis, including 2 of wild poliomyelitis. Import of poliomyelitis was thus considered to have occurred frequently until 1996 in this border area of Yunnan. These data were important for the outbreak response immunization carried out in 1996 in the border prefectures of Yunnan. CONCLUSION: Our investigation confirmed a high level of AFP surveillance in poliomyelitis high-risk areas of the five provinces and provided valuable information on the interruption of wild poliovirus circulation in southern China that will be of use to countries in other regions that have

  10. Genomic characterization of childhood acute lymphoblastic leukemia

    PubMed Central

    Mullighan, Charles G.

    2013-01-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and a leading case of childhood cancer death. The last decade has witnessed a transformation in our understanding of the genetic basis of ALL due to detailed integrative genomic profiling of large cohorts of childhood ALL. Initially using microarray based approaches, and more recently with next-generation sequencing, these studies have enabled more precise sub-classification of ALL, and have shown that each ALL entity is characterized by constellations of structural and sequence mutations that typically perturb key cellular pathways including lymphoid development, cell cycle regulation, tumor suppression, Ras- and tyrosine kinase driven signaling, and epigenetic regulation. Importantly, several of the newly identified genetic alterations have entered the clinic to improve diagnosis and risk stratification, and are being pursued as new targets for therapeutic intervention. Studies of ALL have also led the way in dissecting the subclonal heterogeneity of cancer, and have shown that individual patients commonly harbor multiple related but genetically distinct subclones, and that this genetically determined clonal heterogeneity is an important determinant of relapse. In addition, genome-wide profiling has identified inherited genetic variants that influence ALL risk. Ongoing studies are deploying detailed integrative genetic transcriptomic and epigenetic sequencing to comprehensively define the genomic landscape of ALL. This review describes the recent advances in our understanding of the genetics of ALL, with an emphasis on those alterations of key pathogenic or therapeutic importance. PMID:24246699

  11. Genomic characterization of childhood acute lymphoblastic leukemia.

    PubMed

    Mullighan, Charles G

    2013-10-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy and a leading case of childhood cancer death. The last decade has witnessed a transformation in our understanding of the genetic basis of ALL due to detailed integrative genomic profiling of large cohorts of childhood ALL. Initially using microarray based approaches, and more recently with next-generation sequencing, these studies have enabled more precise subclassification of ALL, and have shown that each ALL entity is characterized by constellations of structural and sequence mutations that typically perturb key cellular pathways including lymphoid development, cell cycle regulation, tumor suppression, Ras- and tyrosine kinase-driven signaling, and epigenetic regulation. Importantly, several of the newly identified genetic alterations have entered the clinic to improve diagnosis and risk stratification, and are being pursued as new targets for therapeutic intervention. Studies of ALL have also led the way in dissecting the subclonal heterogeneity of cancer, and have shown that individual patients commonly harbor multiple related but genetically distinct subclones, and that this genetically determined clonal heterogeneity is an important determinant of relapse. In addition, genome-wide profiling has identified inherited genetic variants that influence ALL risk. Ongoing studies are deploying detailed integrative genetic transcriptomic and epigenetic sequencing to comprehensively define the genomic landscape of ALL. This review describes the recent advances in our understanding of the genetics of ALL, with an emphasis on those alterations of key pathogenic or therapeutic importance. PMID:24246699

  12. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed High-Risk B Acute Lymphoblastic Leukemia and Ph-Like TKI Sensitive Mutations

    ClinicalTrials.gov

    2016-09-14

    B Acute Lymphoblastic Leukemia; Bone Necrosis; Central Nervous System Leukemia; Cognitive Side Effects of Cancer Therapy; Neurotoxicity Syndrome; Pain; Testicular Leukemia; Therapy-Related Toxicity; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

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

    PubMed Central

    2011-01-01

    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 classified as high

  14. CLAG-based induction therapy in previously untreated high risk acute myeloid leukemia patients.

    PubMed

    Seiter, Karen; Ahmed, Nasir; Shaikh, Azfar; Baskind, Paul; Liu, Delong

    2016-07-01

    The CLAG regimen is highly active in patients with relapsed and/or refractory acute myeloid leukemia (AML). We administered CLAG-based chemotherapy to 20 previously untreated AML patients who were poor candidates for standard induction therapy. Responding patients received further CLAG as post-remission therapy followed by additional therapy that was tailored to their AML subtype. Patients were considered poor candidates for standard therapy due to either cardiac disease, prior chemotherapy for another malignancy, prior myeloproliferative disease, or myelodysplastic syndrome that had progressed after hypomethylator therapy. Overall, thirteen patients had a complete response (CR) to the first cycle of therapy (65%), one patient had a CR without platelet recovery, and 3 patients had a partial response (PR). Two of the patients with PR converted to CR after further therapy. The median duration of response has not been reached; the mean duration of response is 36.8 months (95% CI 28.8-44.8 months). Median overall survival (including deaths from all causes) is 29.0 months (95% CI 18.0-46.0 months). Patients with de novo AML had a CR rate of 90.9% and a median overall survival of 38.5 months. CLAG-based therapy is a well-tolerated, efficacious induction strategy in previously-untreated patients with high risk AML. CLAG-based regimens should be studied in a broader group of newly diagnosed AML patients. PMID:27151544

  15. Psychosocial pathways to childhood obesity: a pilot study involving a high risk preschool sample.

    PubMed

    Braungart-Rieker, Julia M; Moore, Elizabeth S; Planalp, Elizabeth M; Lefever, Jennifer Burke

    2014-12-01

    This pilot study adopts a systems theory perspective to explore associations between parent and child factors and children's body mass index (BMI). Forty mothers and their preschool-aged children (3-6years) who were eligible for Head Start were recruited. Measures included demographic risk, maternal depression, negative parenting, children's impulsivity, children's approach to eating, and BMI. Structural Equation Modeling supported a mediating model such that mothers who reported greater demographic risk and more depressive symptoms showed higher rates of negative parenting. In turn, more negative parenting predicted higher child impulsivity ratings, which were related to higher food approach scores. Finally, children who scored higher in food approach had higher BMIs. Tests of sub-models excluding any of the mediating variables indicated a significantly worse fit to the data in each case. Results have implications for family-wide intervention strategies to help lower the risk for early-onset obesity in high-risk children. PMID:25098723

  16. Azacitidine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-01-06

    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(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); Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia

  17. Early Patterns of Self-Regulation as Risk and Promotive Factors in Development: A Longitudinal Study from Childhood to Adulthood in a High-Risk Sample

    ERIC Educational Resources Information Center

    Causadias, Jose M.; Salvatore, Jessica E.; Sroufe, L. Alan

    2012-01-01

    The present study examines two childhood markers of self-regulation, ego control and ego resiliency, as promotive factors for the development of global adjustment and as risk factors for the development of internalizing and externalizing behavior problems in a high-risk sample. Teachers and observers rated ego control and ego resiliency when…

  18. Lentivirus-Induced Dendritic Cells for Immunization Against High-Risk WT1+ Acute Myeloid Leukemia

    PubMed Central

    Sundarasetty, Bala Sai; Singh, Vijay Kumar; Salguero, Gustavo; Geffers, Robert; Rickmann, Mareike; Macke, Laura; Borchers, Sylvia; Figueiredo, Constanca; Schambach, Axel; Gullberg, Urban; Provasi, Elena; Bonini, Chiara; Ganser, Arnold; Woelfel, Thomas

    2013-01-01

    Abstract Wilms' tumor 1 antigen (WT1) is overexpressed in acute myeloid leukemia (AML), a high-risk neoplasm warranting development of novel immunotherapeutic approaches. Unfortunately, clinical immunotherapeutic use of WT1 peptides against AML has been inconclusive. With the rationale of stimulating multiantigenic responses against WT1, we genetically programmed long-lasting dendritic cells capable of producing and processing endogenous WT1 epitopes. A tricistronic lentiviral vector co-expressing a truncated form of WT1 (lacking the DNA-binding domain), granulocyte-macrophage colony-stimulating factor (GM-CSF), and interleukin-4 (IL-4) was used to transduce human monocytes ex vivo. Overnight transduction induced self-differentiation of monocytes into immunophenotypically stable “SmartDC/tWT1” (GM-CSF+, IL-4+, tWT1+, IL-6+, IL-8+, TNF-α+, MCP-1+, HLA-DR+, CD86+, CCR2+, CCR5+) that were viable for 3 weeks in vitro. SmartDC/tWT1 were produced with peripheral blood mononuclear cells (PBMC) obtained from an FLT3-ITD+ AML patient and surplus material from a donor lymphocyte infusion (DLI) and used to expand CD8+ T cells in vitro. Expanded cytotoxic T lymphocytes (CTLs) showed antigen-specific reactivity against WT1 and against WT1+ leukemia cells. SmartDC/tWT1 injected s.c. into Nod.Rag1−/−.IL2rγc−/− mice were viable in vivo for more than three weeks. Migration of human T cells (huCTLs) to the immunization site was demonstrated following adoptive transfer of huCTLs into mice immunized with SmartDC/tWT1. Furthermore, SmartDC/tWT1 immunization plus adoptive transfer of T cells reactive against WT1 into mice resulted in growth arrest of a WT1+ tumor. Gene array analyses of SmartDC/tWT1 demonstrated upregulation of several genes related to innate immunity. Thus, SmartDC/tWT1 can be produced in a single day of ex vivo gene transfer, are highly viable in vivo, and have great potential for use as immunotherapy against malignant transformation overexpressing WT1

  19. Sexual risk-taking among high-risk urban women with and without histories of childhood sexual abuse: mediating effects of contextual factors.

    PubMed

    Mosack, Katie E; Randolph, Mary E; Dickson-Gomez, Julia; Abbott, Maryann; Smith, Ellen; Weeks, Margaret R

    2010-01-01

    This study investigated the mechanisms of risk for urban women at high risk for HIV with and without childhood sexual abuse histories. Childhood sexual abuse survivors reported more unprotected intercourse and sexually transmitted infections (STIs). The association of STI locus of control with frequency of unprotected sex was fully mediated by being intoxicated during sex and engaging in sex work, whereas the association between relational control and unprotected sex was not mediated by contextual factors for the childhood sexual abuse group. The mechanisms of risk are different for those with divergent childhood sexual abuse histories and thus interventions should be developed to educate women with a history of childhood sexual abuse about ways to avoid revictimization, particularly within a context of poverty, prostitution, and drug use. PMID:20390778

  20. Whole-pelvic volumetric-modulated arc therapy for high-risk prostate cancer: treatment planning and acute toxicity

    PubMed Central

    Ishii, Kentaro; Ogino, Ryo; Hosokawa, Yukinari; Fujioka, Chiaki; Okada, Wataru; Nakahara, Ryota; Kawamorita, Ryu; Tada, Takuhito; Hayashi, Yoshiki; Nakajima, Toshifumi

    2015-01-01

    The objectives of this study were to evaluate dosimetric quality and acute toxicity of volumetric-modulated arc therapy (VMAT) and daily image guidance in high-risk prostate cancer patients. A total of 100 consecutive high-risk prostate cancer patients treated with definitive VMAT with prophylactic whole-pelvic radiotherapy (WPRT) were enrolled. All patients were treated with a double-arc VMAT plan delivering 52 Gy to the prostate planning target volume (PTV), while simultaneously delivering 46.8 Gy to the pelvic nodal PTV in 26 fractions, followed by a single-arc VMAT plan delivering 26 Gy to the prostate PTV in 13 fractions. Image-guided RT was performed with daily cone-beam computed tomography. Dose–volume parameters for the PTV and the organs at risk (OARs), total number of monitor units (MUs) and treatment time were evaluated. Acute toxicity was assessed using the Common Terminology Criteria for Adverse Events, version 4.0. All dosimetric parameters met the present plan acceptance criteria. Mean MU and treatment time were 471 and 146 s for double-arc VMAT, respectively, and were 520 and 76 s for single-arc VMAT, respectively. No Grade 3 or higher acute toxicity was reported. Acute Grade 2 proctitis, diarrhea, and genitourinary toxicity occurred in 12 patients (12%), 6 patients (6%) and 13 patients (13%), respectively. The present study demonstrated that VMAT for WPRT in prostate cancer results in favorable PTV coverage and OAR sparing with short treatment time and an acceptable rate of acute toxicity. These findings support the use of VMAT for delivering WPRT to high-risk prostate cancer patients. PMID:25304328

  1. Dipeptidyl Peptidase-4 Inhibitor Use Is Not Associated With Acute Pancreatitis in High-Risk Type 2 Diabetic Patients

    PubMed Central

    Chang, Chia-Hsuin; Lin, Jou-Wei; Chen, Shu-Ting; Lai, Mei-Shu; Chuang, Lee-Ming; Chang, Yi-Cheng

    2016-01-01

    Abstract To analyze the association between use of DPP-4 inhibitors and acute pancreatitis in high-risk type 2 diabetic patients. A retrospective nationwide cohort study was conducted using the Taiwan National Health Insurance claim database. The risk associated with sitagliptin was compared to that with acarbose, a second-line antidiabetic drug prescribed for patients with similar diabetes severity and with a known neutral effect on pancreatitis. Between January 1, 2009 and December 31, 2010, a total of 8526 sitagliptin initiators and 8055 acarbose initiators who had hypertriglyceridemia or prior hospitalization history for acute pancreatitis were analyzed for the risk of hospitalization due to acute pancreatitis stratified for baseline propensity score. In the crude analysis, sitagliptin was associated with a decreased risk of acute pancreatitis (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.62–0.88) compared to acarbose in diabetic patients with prior history of hospitalization for pancreatitis or hypertriglyceridemia. The association was abolished after stratification for propensity score quintiles (adjusted HR 0.95; 95% CI: 0.79–1.16). Similar results were found separately in both patients’ histories of prior hospitalization of acute pancreatitis (adjusted HR 0.97; 95% CI: 0.76–1.24) and those with hypertriglyceridemia (adjusted HR 0.86; 95% CI: 0.65–1.13). No significant association was found for different durations or accumulative doses of sitagliptin. In the stratified analysis, no significant effect modification was found in relation to patients’ characteristics. Use of sitagliptin was not associated with an increased risk of acute pancreatitis in high-risk diabetic patients with hypertriglyceridemia or with history of acute pancreatitis. PMID:26886601

  2. Fluoroscopy-Guided Percutaneous Gallstone Removal Using a 12-Fr Sheath in High-Risk Surgical Patients with Acute Cholecystitis

    PubMed Central

    Kim, Yong Joo; Shin, Tae Beom

    2011-01-01

    Objective To evaluate the technical feasibility and clinical efficacy of percutaneous transhepatic cholecystolithotomy under fluoroscopic guidance in high-risk surgical patients with acute cholecystitis. Materials and Methods Sixty-three consecutive patients of high surgical risk with acute calculous cholecystitis underwent percutaneous transhepatic gallstone removal under conscious sedation. The stones were extracted through the 12-Fr sheath using a Wittich nitinol stone basket under fluoroscopic guidance on three days after performing a percutaneous cholecystostomy. Large or hard stones were fragmented using either the snare guide wire technique or the metallic cannula technique. Results Gallstones were successfully removed from 59 of the 63 patients (94%). Reasons for stone removal failure included the inability to grasp a large stone in two patients, and the loss of tract during the procedure in two patients with a contracted gallbladder. The mean hospitalization duration was 7.3 days for acute cholecystitis patients and 9.4 days for gallbladder empyema patients. Bile peritonitis requiring percutaneous drainage developed in two patients. No symptomatic recurrence occurred during follow-up (mean, 608.3 days). Conclusion Fluoroscopy-guided percutaneous gallstone removal using a 12-Fr sheath is technically feasible and clinically effective in high-risk surgical patients with acute cholecystitis. PMID:21430938

  3. Dietary resveratrol does not delay engraftment, sensitize to vincristine, or inhibit growth of high-risk acute lymphoblastic leukemia cells in NOD/SCID mice

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute lymphoblastic leukemia (ALL) with translocation t(4;11) is a high-risk leukemia found in 60-85% of infants with ALL and is often refractory to conventional chemotherapeutics after relapse. Although resveratrol is able to kill high-risk leukemia in vitro, this agent has not been evaluated agai...

  4. Acute Toxicity in High-Risk Prostate Cancer Patients Treated With Androgen Suppression and Hypofractionated Intensity-Modulated Radiotherapy

    SciTech Connect

    Pervez, Nadeem; Small, Cormac; MacKenzie, Marc; Yee, Don; Parliament, Matthew; Ghosh, Sunita; Mihai, Alina; Amanie, John; Murtha, Albert; Field, Colin; Murray, David; Fallone, Gino; Pearcey, Robert

    2010-01-15

    Purpose: To report acute toxicity resulting from radiotherapy (RT) dose escalation and hypofractionation using intensity-modulated RT (IMRT) treatment combined with androgen suppression in high-risk prostate cancer patients. Methods and Materials: Sixty patients with a histological diagnosis of high-risk prostatic adenocarcinoma (having either a clinical Stage of >=T3a or an initial prostate-specific antigen [PSA] level of >=20 ng/ml or a Gleason score of 8 to 10 or a combination of a PSA concentration of >15 ng/ml and a Gleason score of 7) were enrolled. RT prescription was 68 Gy in 25 fractions (2.72 Gy/fraction) over 5 weeks to the prostate and proximal seminal vesicles. The pelvic lymph nodes and distal seminal vesicles concurrently received 45 Gy in 25 fractions. The patients were treated with helical TomoTherapy-based IMRT and underwent daily megavoltage CT image-guided verification prior to each treatment. Acute toxicity scores were recorded weekly during RT and at 3 months post-RT, using Radiation Therapy Oncology Group acute toxicity scales. Results: All patients completed RT and follow up for 3 months. The maximum acute toxicity scores were as follows: 21 (35%) patients had Grade 2 gastrointestinal (GI) toxicity; 4 (6.67%) patients had Grade 3 genitourinary (GU) toxicity; and 30 (33.33%) patients had Grade 2 GU toxicity. These toxicity scores were reduced after RT; there were only 8 (13.6%) patients with Grade 1 GI toxicity, 11 (18.97%) with Grade 1 GU toxicity, and 5 (8.62%) with Grade 2 GU toxicity at 3 months follow up. Only the V60 to the rectum correlated with the GI toxicity. Conclusion: Dose escalation using a hypofractionated schedule to the prostate with concurrent pelvic lymph node RT and long-term androgen suppression therapy is well tolerated acutely. Longer follow up for outcome and late toxicity is required.

  5. Identification of high-risk patients with acute coronary syndrome using point-of-care echocardiography in the ED.

    PubMed

    Frenkel, Oron; Riguzzi, Christine; Nagdev, Arun

    2014-06-01

    Stratifying risk of patients with acute coronary syndrome (ACS) in the emergency department (ED) remains a frequent challenge. When ST-elevation criteria are absent, current recommendations rely upon insensitive and time-intensive methods such as the electrocardiogram and cardiac enzyme testing. Here, we report on a series of cases, where emergency physicians used a simplified model for identifying regional wall motion abnormalities by point-of-care echocardiography in patients presenting with chest pain to the ED. With the use of a simplified model described herein, high-risk patients with ACS were identified rapidly in a cohort usually difficult to risk stratify. PMID:24745875

  6. Bone mineral density in survivors of childhood acute lymphoblastic leukemia.

    PubMed

    Athanassiadou, Fani; Tragiannidis, Athanassios; Rousso, Israel; Katsos, Georgios; Sidi, Vassiliki; Papageorgiou, Theodotis; Papastergiou, Christos; Tsituridis, Ioannis; Koliouskas, Dimitrios

    2006-01-01

    The aim of our study was to evaluate bone metabolism with measurement of bone mineral density (BMD) after management (chemo-, radiotherapy) for childhood acute lymphoblastic leukemia (ALL). Bone mineral density (g/cm2) of lumbar spine was measured by dual energy X-ray absorptiometry (Norland bone densitometer) in 18 children with ALL and a median of 34 months' post-diagnosis with no history of relapse, secondary malignancy, or transplantation. In addition, patients' BMDs were correlated with particular attention to age, sex and time (years) from completion of chemotherapy. The results were compared with healthy age- and sex-matched controls of the same population and expressed as standard deviation scores (SDS). Mean age of children was 9.8 +/- 3.7 years. Of 18 children (10 boys and 8 girls), 13 were grouped as standard and 5 as high-risk, respectively. Based on z-score values, 9 were classified as normal (z-score <1 SD), 7 as osteopenic (z-score 1-2.5 SD) and 2 as osteoporotic (z-score >2.5 SD). Children with ALL had reduced lumbar BMDs (z score -0.99) in comparison to healthy controls (z score -0.14) (p=0.011), which is indicative of relative osteopenia. Moreover, the reduced BMD was associated with patient age (z score -0.14 and -1.52 for ages <10 and >10 years, respectively, p=0.016). Reduced BMD was not correlated with time from completion of chemotherapy (p=0.33), risk group (p=0.9) and sex (p=0.3). We conclude that children's BMDs are reduced after completion of chemotherapy for ALL. The causes are multifactorial and mainly related to antineoplastic treatments, such as corticosteroids and methotrexate, physical inactivity and cranial irradiation. We suggest that further studies are needed to evaluate the long-term effect on BMD in these children and to prevent pathological fractures later in life. PMID:16848106

  7. Management of acute moderate and severe childhood malnutrition

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Acute childhood malnutrition affects about a tenth of the world's children under 5 years of age, particularly those living in circumstances of extreme poverty in the developing world. Malnutrition is typically the result of an inadequate diet and is one of the most common diagnoses in children in he...

  8. Pulmonary function after treatment for acute lymphoblastic leukaemia in childhood.

    PubMed Central

    Nysom, K.; Holm, K.; Olsen, J. H.; Hertz, H.; Hesse, B.

    1998-01-01

    The aim of this study was to examine pulmonary function after acute lymphoblastic leukaemia in childhood and identify risk factors for reduced pulmonary function. We studied a population-based cohort of 94 survivors of acute lymphoblastic leukaemia in childhood who were in first remission after treatment without spinal irradiation or bone marrow transplantation. Pulmonary function test results were compared with reference values for our laboratory, based on 348 healthy subjects who had never smoked from a local population study. A median of 8 years after cessation of therapy (range 1-18 years) the participants had a slight, subclinical, restrictive ventilatory insufficiency and reduced transfer factor and transfer coefficient. The changes in lung function were related to younger age at treatment and to more dose-intensive treatment protocols that specified more use of cranial irradiation and higher cumulative doses of anthracyclines, cytosine arabinoside and intravenous cyclophosphamide than previous protocols. We conclude that, 8 years after treatment without bone marrow transplantation or spinal irradiation, survivors of childhood acute lymphoblastic leukaemia in first remission were without pulmonary symptoms but had signs of slight restrictive pulmonary disease including reduced transfer factor. The increased dose intensity of many recent protocols for childhood acute lymphoblastic leukaemia may lead to increased late pulmonary toxicity. PMID:9662245

  9. Acute necrotizing encephalopathy of childhood: report of a Spanish case.

    PubMed

    San Millan, Beatriz; Teijeira, Susana; Penin, Carmen; Garcia, Jose L; Navarro, Carmen

    2007-12-01

    Acute necrotizing encephalopathy of childhood is a rare disease with a broad clinical, radiologic, and biochemical spectrum. In the few postmortem studies published to date, the neuropathologic findings involved symmetric, necrotic brain lesions as the hallmark. Here we report on the clinical and neuropathologic findings of a Spanish child with the most severe form of the disease. PMID:18021928

  10. Laboratory-Treated T Cells in Treating Patients With High-Risk Relapsed Acute Myeloid Leukemia, Myelodysplastic Syndrome, or Chronic Myelogenous Leukemia Previously Treated With Donor Stem Cell Transplant

    ClinicalTrials.gov

    2016-08-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Myelodysplastic Syndrome; Childhood Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Secondary Acute Myeloid Leukemia; Therapy-Related Acute Myeloid Leukemia

  11. Acute hemiplegia with lacunar infarct after varicella infection in childhood.

    PubMed

    Eda, I; Takashima, S; Takeshita, K

    1983-01-01

    We report 4 cases of acute hemiplegia and a small low-density lesion on computerized tomography (CT) after varicella infection. In 3 of them, CT in the acute hemiplegic stage, and later, reveals the development of lacunar infarct around the internal capsule. Focal low density may be caused by occlusive vascular lesions of the penetrating arteries. Varicella infection may play an important role as one of the causes of acute hemiplegia in childhood producing lacunar infarct, as well as delayed hemiplegia, reported previously in herpes zoster ophthalmicus. PMID:6660422

  12. History of family violence, childhood behavior problems, and adolescent high-risk behaviors as predictors of girls' repeated patterns of dating victimization in two developmental periods.

    PubMed

    Vézina, Johanne; Hébert, Martine; Poulin, François; Lavoie, Francine; Vitaro, Frank; Tremblay, Richard E

    2015-04-01

    This study aims to document the prevalence of repeated patterns of dating victimization and to examine, within the frameworks of an ecological model and lifestyle/routine activities theories, associations between such patterns and family, peer, and individual factors. Dating victimization in adolescence (age 15) and early adulthood (age 21) was evaluated in 443 female participants. Multinomial logistic regression analyses revealed that history of family violence, childhood behavior problems, and adolescent high-risk behaviors were associated with an increased risk for girls of being victimized (psychologically and/or physically/sexually) in their dating relationships, either in adolescence or early adulthood, or at both developmental periods. PMID:25736801

  13. Auxiliary partial liver transplantation for acute liver failure using "high risk" grafts: Case report

    PubMed Central

    Duan, Wei-Dong; Wang, Xi-Tao; Wang, Hong-Guang; Ji, Wen-Bin; Li, Hao; Dong, Jia-Hong

    2016-01-01

    Acute liver failure (ALF) is a reversible disorder that is associated with an abrupt loss of hepatic mass, rapidly progressive encephalopathy and devastating complications. Despite its high mortality, an emergency liver transplantation nowadays forms an integral part in ALF management and has substantially improved the outcomes of ALF. Here, we report the case of a 32-year-old female patient who was admitted with grade IV hepatic encephalopathy (coma) following drug-induced ALF. We performed an emergency auxiliary partial orthotopic liver transplantation with a “high risk” graft (liver macrovesicular steatosis approximately 40%) from a living donor. The patient was discharged on postoperative day 57 with normal liver function. Weaning from immunosuppression was achieved 9 mo after transplantation. A follow-up using CT scan showed a remarkable increase in native liver volume and gradual loss of the graft. More than 6 years after the transplantation, the female now has a 4-year-old child and has returned to work full-time without any neurological sequelae. PMID:26855552

  14. Can Saliva Proteins Be Used to Predict the Onset of Acute Myocardial Infarction among High-Risk Patients?

    PubMed Central

    Rahim, Mohd Aizat Abdul; Rahim, Zubaidah Haji Abdul; Ahmad, Wan Azman Wan; Hashim, Onn Haji

    2015-01-01

    Human saliva plays a pivotal role in digesting food and maintaining oral hygiene. The presence of electrolytes, mucus, glycoproteins, enzymes, antibacterial compounds, and gingival crevicular fluid in saliva ensures the optimum condition of oral cavity and general health condition. Saliva collection has been proven non-invasive, convenient, and inexpensive compared to conventional venipuncture procedure. These distinctive advantages provide a promising potential of saliva as a diagnostic fluid. Through comprehensive analysis, an array of salivary proteins and peptides may be beneficial as biomarkers in oral and systemic diseases. In this review, we discuss the utility of human salivary proteomes and tabulate the recent salivary biomarkers found in subjects with acute myocardial infarction as well as respective methods employed. In a clinical setting, since acute myocardial infarction contributes to large cases of mortality worldwide, an early intervention using these biomarkers will provide an effective solution to reduce global heart attack incidence particularly among its high-risk group of type-2 diabetes mellitus patients. The utility of salivary biomarkers will make the prediction of this cardiac event possible due to its reliability hence improve the quality of life of the patients. Current challenges in saliva collection are also addressed to improve the quality of saliva samples and produce robust biomarkers for future use in clinical applications. PMID:25897294

  15. Mechanisms of clonal evolution in childhood acute lymphoblastic leukemia

    PubMed Central

    Park, Eugene; Papaemmanuil, Elli; Ford, Anthony; Kweon, Soo-Mi; Trageser, Daniel; Hasselfeld, Brian; Henke, Nadine; Mooster, Jana; Geng, Huimin; Schwarz, Klaus; Kogan, Scott C.; Casellas, Rafael; Schatz, David G.; Lieber, Michael R; Greaves, Mel F.; Müschen, Markus

    2015-01-01

    Childhood acute lymphoblastic leukemia can often be retraced to a pre-leukemic clone carrying a prenatal genetic lesion. Postnatally acquired mutations then drive clonal evolution towards overt leukemia. RAG1-RAG2 and AID enzymes, the diversifiers of immunoglobulin genes, are strictly segregated to early and late stages of B-lymphopoiesis, respectively. Here, we identified small pre-BII cells as a natural subset of increased genetic vulnerability owing to concurrent activation of these enzymes. Consistent with epidemiological findings on childhood ALL etiology, susceptibility to genetic lesions during B-lymphopoiesis at the large to small pre-BII transition is exacerbated by abnormal cytokine signaling and repetitive inflammatory stimuli. We demonstrate that AID and RAG1-RAG2 drive leukemic clonal evolution with repeated exposure to inflammatory stimuli, paralleling chronic infections in childhood. PMID:25985233

  16. NSAID-Avoidance Education in Community Pharmacies for Patients at High Risk for Acute Kidney Injury, Upstate New York, 2011

    PubMed Central

    Jang, Soo Min; Cerulli, Jennifer; Grabe, Darren W.; Fox, Chester; Vassalotti, Joseph A.; Prokopienko, Alexander J.

    2014-01-01

    Introduction Nonsteroidal anti-inflammatory drugs (NSAIDs) are frequently associated with community-acquired acute kidney injury (AKI), a strong risk factor for development and progression of chronic kidney disease. Using access to prescription medication profiles, pharmacists can identify patients at high risk for NSAID-induced AKI. The primary objective of this analysis was to evaluate the effectiveness of a community pharmacy–based patient education program on patient knowledge of NSAID-associated renal safety concerns. Methods Patients receiving prescription medications for hypertension or diabetes mellitus were invited to participate in an educational program on the risks of NSAID use. A patient knowledge questionnaire (PKQ) consisting of 5 questions scored from 1 to 5 was completed before and after the intervention. Information was collected on age, race, sex, and frequency of NSAID use. Results A total of 152 participants (60% women) completed both the pre- and post-intervention questionnaire; average age was 54.6 (standard deviation [SD], 17.5). Mean pre-intervention PKQ score was 3.3 (SD, 1.4), and post-intervention score was 4.6 (SD, 0.9) (P = .002). Participants rated program usefulness (1 = not useful to 5 = extremely useful) as 4.2 (SD, 1.0). In addition, 48% reported current NSAID use and 67% reported that the program encouraged them to limit their use. Conclusion NSAID use was common among patients at high risk for AKI. A brief educational intervention in a community pharmacy improved patient knowledge on NSAID-associated risks. Pharmacists practicing in the community can partner with primary care providers in the medical home model to educate patients at risk for AKI. PMID:25523351

  17. [Imaging of acute abdomen in childhood and adolescence].

    PubMed

    Wunsch, R; Wunsch, C

    2014-09-01

    Acute abdominal pain in childhood is a frequent reason for a medical consultation. The main diseases that lead to the clinical situation of acute abdomen show a significant age dependency. It is reasonable to group such ailments into three age categories: (1) the neonatal and infant period, (2) toddlerhood to kindergarten and (3) school age children. The task of the pediatric radiological examination is the differential diagnostic correlation of symptoms to the respective diseases. In children ultrasound is the appropriate method of choice. PMID:25216571

  18. Acute pancreatitis as a complication of childhood cancer treatment.

    PubMed

    Stefanović, Milica; Jazbec, Janez; Lindgren, Fredrik; Bulajić, Milutin; Löhr, Matthias

    2016-05-01

    Acute pancreatitis (AP) is now well recognized as a possible complication of childhood cancer treatment, interrupting the chemotherapy regimen, and requiring prolonged hospitalization, possibly with intensive care and surgical intervention, thereby compromising the effect of chemotherapy and the remission of the underlying malignant disease. This review summarizes the current literature and presents the various etiological factors for AP during chemotherapy as well as modern trends in the diagnosis and therapy of AP in children. PMID:26872431

  19. Frequency and pattern of childhood symptom onset reported by first episode schizophrenia and clinical high risk youth

    PubMed Central

    Woodberry, Kristen A.; Serur, Rachael A.; Hallinan, Sean B.; Mesholam-Gately, Raquelle I.; Giuliano, Anthony J.; Wojcik, Joanne D.; Keshavan, Matcheri S.; Frazier, Jean A.; Goldstein, Jill M.; Shenton, Martha E.; McCarley, Robert W.; Seidman, Larry J.

    2014-01-01

    Background Psychosis prevention and early intervention efforts in schizophrenia have focused increasingly on sub-threshold psychotic symptoms in adolescents and young adults. Although many youth report symptom onset prior to adolescence, the childhood incidence of prodromal-level symptoms in those with schizophrenia or related psychoses is largely unknown. Methods This study reports on the retrospective recall of prodromal-level symptoms from 40 participants in a first-episode of schizophrenia (FES) and 40 participants at “clinical high risk” (CHR) for psychosis. Onset of positive and non-specific symptoms was captured using the Structured Interview for Prodromal Syndromes. Frequencies are reported according to onset during childhood (prior to age 13), adolescence (13–17), or adulthood (18 +). Results Childhood-onset of attenuated psychotic symptoms was not rare. At least 11% of FES and 23% of CHR reported specific recall of childhood-onset of unusual or delusional ideas, suspiciousness, or perceptual abnormalities. Most recalled experiencing non-specific symptoms prior to positive symptoms. CHR and FES did not differ significantly in the timing of positive and non-specific symptom onset. Other than being younger at assessment, those with childhood onset did not differ demographically from those with later onset. Conclusion Childhood-onset of initial psychotic-like symptoms may be more common than previous research has suggested. Improved characterization of these symptoms and a focus on their predictive value for subsequent schizophrenia and other major psychoses are needed to facilitate screening of children presenting with attenuated psychotic symptoms. Accurate detection of prodromal symptoms in children might facilitate even earlier intervention and the potential to alter pre-illness trajectories. PMID:24924404

  20. The Effects of Childhood Maltreatment on Violent Injuries and Premature Death During Young Adulthood Among Urban High-Risk Men

    PubMed Central

    Lee, Chioun; White, Helene R.

    2013-01-01

    Objective To assess childhood maltreatment as a risk factor for violent injuries and premature death in young adulthood and whether these associations are mediated by adolescent heavy drinking, hard drug use, hard drug selling, and violent offending. Design A prospective longitudinal study of boys followed from childhood into young adulthood. Setting Pittsburgh, Pennsylvania Participants A total 1,009 men of the Pittsburgh Youth Study Main Outcome Measures Premature deaths between ages 18 and 38 from the Social Security Death Index and self-reports of violent injuries inflicted by gunshot or knife between ages 18 and 28. Results Young men who experienced childhood maltreatment, compared to their counterparts who did not experience it, had a greater risk of violent injuries (relative risk [RR], 1.61; 95% confidence interval [CI], 1.01–2.35) and death (hazard ratio, [HR], 2.85; 95% CI, 1.37–5.93) during young adulthood. Adolescent violent offending and hard drug selling explained the association between childhood maltreatment and violent injuries, and violent offending partially accounted for the association between childhood maltreatment and premature death. Although adolescent violent offending predicted both outcomes, maltreated boys still had an increased risk of premature death (HR, 2.54; 95% CI, 1.21–5.34) after accounting for their adolescent violence. Conclusions Childhood maltreatment significantly predicts premature death and violent injuries during young adulthood. These associations are partially explained by adolescent involvement in violence and drug dealing. Targeted interventions for maltreated boys to reduce their involvement in adolescent deviant behaviors may help decrease their risks for later serious injuries and premature death. PMID:22566518

  1. Mediators of Childhood Sexual Abuse and High-Risk Sex among Men-Who-Have-Sex-with-Men

    ERIC Educational Resources Information Center

    Catania, Joseph A.; Paul, Jay; Osmond, Dennis; Folkman, Susan; Pollack, Lance; Canchola, Jesse; Chang, Jason; Neilands, Torsten

    2008-01-01

    Objective: Mediators of childhood sexual abuse (CSA) and HIV risk behavior were examined for men-who-have-sex-with-men (MSM). Method: Data from a dual frame survey of urban MSM (N = 1078) provided prevalence estimates of CSA, and a test of two latent variable models (defined by partner type) of CSA-risk behavior mediators. Results: A 20%…

  2. Early Childhood Gut Microbiomes Show Strong Geographic Differences Among Subjects at High Risk for Type 1 Diabetes

    PubMed Central

    Kemppainen, Kaisa M.; Ardissone, Alexandria N.; Davis-Richardson, Austin G.; Fagen, Jennie R.; Gano, Kelsey A.; León-Novelo, Luis G.; Vehik, Kendra; Casella, George; Simell, Olli; Ziegler, Anette G.; Rewers, Marian J.; Lernmark, Åke; Hagopian, William; She, Jin-Xiong; Krischer, Jeffrey P.; Akolkar, Beena; Schatz, Desmond A.; Atkinson, Mark A.

    2015-01-01

    OBJECTIVE Gut microbiome dysbiosis is associated with numerous diseases, including type 1 diabetes. This pilot study determines how geographical location affects the microbiome of infants at high risk for type 1 diabetes in a population of homogenous HLA class II genotypes. RESEARCH DESIGN AND METHODS High-throughput 16S rRNA sequencing was performed on stool samples collected from 90 high-risk, nonautoimmune infants participating in The Environmental Determinants of Diabetes in the Young (TEDDY) study in the U.S., Germany, Sweden, and Finland. RESULTS Study site–specific patterns of gut colonization share characteristics across continents. Finland and Colorado have a significantly lower bacterial diversity, while Sweden and Washington state are dominated by Bifidobacterium in early life. Bacterial community diversity over time is significantly different by geographical location. CONCLUSIONS The microbiome of high-risk infants is associated with geographical location. Future studies aiming to identify the microbiome disease phenotype need to carefully consider the geographical origin of subjects. PMID:25519450

  3. Is ketamine a lifesaving agent in childhood acute severe asthma?

    PubMed Central

    Hendaus, Mohamed A; Jomha, Fatima A; Alhammadi, Ahmed H

    2016-01-01

    Children with acute severe asthma exacerbation are at risk of developing respiratory failure. Moreover, conventional aggressive management might be futile in acute severe asthma requiring intubation and invasive ventilation. The aim of this review is to detail evidence on the use of ketamine in childhood asthma exacerbations. A search of the MEDLINE, EMBASE, and Cochrane databases was performed, using different combinations of the following terms: ketamine, asthma, use, exacerbation, and childhood. In addition, we searched the references of the identified articles for additional articles. We then reviewed titles and included studies that were relevant to the topic of interest. Finally, the search was limited to studies published in English and Spanish from 1918 to June 2015. Due to the scarcity in the literature, we included all published articles. The literature reports conflicting results of ketamine use for acute severe asthma in children. Taking into consideration the relatively good safety profile of the drug, ketamine might be a reasonable option in the management of acute severe asthma in children who fail to respond to standard therapy. Furthermore, pediatricians and pediatric emergency clinicians administering ketamine should be knowledgeable about the unique actions of this drug and its potential side effects. PMID:26955277

  4. Genetic susceptibility in childhood acute leukaemias: a systematic review

    PubMed Central

    Brisson, Gisele D; Alves, Liliane R; Pombo-de-Oliveira, Maria S

    2015-01-01

    Acute leukaemias (AL) correspond to 25–35% of all cancer cases in children. The aetiology is still sheltered, although several factors are implicated in causality of AL subtypes. Childhood acute leukaemias are associated with genetic syndromes (5%) and ionising radiation as risk factors. Somatic genomic alterations occur during fetal life and are initiating events to childhood leukaemia. Genetic susceptibility has been explored as a risk factor, since environmental exposure of the child to xenobiotics, direct or indirectly, can contribute to the accumulation of somatic mutations. Hence, a systematic review was conducted in order to understand the association between gene polymorphisms and childhood leukaemia risk. The search was performed in the electronic databases PubMed, Lilacs, and Scielo, selecting articles published between 1995 and 2013. This review included 90 case-control publications, which were classified into four groups: xenobiotic system (n = 50), DNA repair (n = 16), regulatory genes (n = 15), and genome wide association studies (GWAS) (n = 9). We observed that the most frequently investigated genes were: NQO1, GSTM1, GSTT1, GSTP1, CYP1A1, NAT2, CYP2D6, CYP2E1, MDR1 (ABCB1), XRCC1, ARID5B, and IKZF1. The collected evidence suggests that genetic polymorphisms in CYP2E1, GSTM1, NQO1, NAT2, MDR1, and XRCC1 are capable of modulating leukaemia risk, mainly when associated with environmental exposures, such as domestic pesticides and insecticides, smoking, trihalomethanes, alcohol consumption, and x-rays. More recently, genome wide association studies identified significant associations between genetic polymorphisms in ARID5B e IKZF1 and acute lymphoblastic leukaemia, but only a few studies have replicated these results until now. In conclusion, genetic susceptibility contributes to the risk of childhood leukaemia through the effects of gene–gene and gene–environment interactions. PMID:26045716

  5. Clinical outcomes of acute myocarditis in childhood

    PubMed Central

    Lee, K; McCrindle, B; Bohn, D; Wilson, G; Taylor, G; Freedom, R; Smallhorn, J; Benson, L

    1999-01-01

    OBJECTIVE—To describe clinical outcomes of a paediatric population with histologically confirmed lymphocytic myocarditis.
DESIGN—A retrospective review between November 1984 and February 1998.
SETTING—A major paediatric tertiary care hospital.
PATIENTS—36 patients with histologically confirmed lymphocytic myocarditis.
MAIN OUTCOME MEASURES—Survival, cardiac transplantation, recovery of ventricular function, and persistence of dysrhythmias.
RESULTS—Freedom from death or cardiac transplantation was 86% at one month and 79% after two years. Five deaths occurred within 72 hours of admission, and one late death at 1.9 years. Extracorporeal membrane oxygenation support was used in four patients, and three patients underwent heart replacement. 34 patients were treated with intravenous corticosteroids. In the survivor/non-cardiac transplantation group (n = 29), the median follow up was 19 months (range 1.2-131.6 months), and the median period for recovery of a left ventricular ejection fraction to > 55% was 2.8 months (range 0-28 months). The mean (SD) final left ventricular ejection and shortening fractions were 66 (9)% and 34 (8)%, respectively. Two patients had residual ventricular dysfunction. No patient required antiarrhythmic treatment. All survivors reported no cardiac symptoms or restrictions in physical activity.
CONCLUSIONS—Our experience documents good outcomes in paediatric patients presenting with acute heart failure secondary to acute lymphocytic myocarditis treated with immunosuppression. Excellent survival and recovery of ventricular function, with the absence of significant arrhythmias, continued cardiac medications, or restrictions in physical activity were the normal outcomes.


Keywords: myocarditis; paediatric cardiology; immunosuppression PMID:10409542

  6. Dasatinib in high-risk core binding factor acute myeloid leukemia in first complete remission: a French Acute Myeloid Leukemia Intergroup trial

    PubMed Central

    Boissel, Nicolas; Renneville, Aline; Leguay, Thibaut; Lefebvre, Pascale Cornillet; Recher, Christian; Lecerf, Thibaud; Delabesse, Eric; Berthon, Céline; Blanchet, Odile; Prebet, Thomas; Pautas, Cécile; Chevallier, Patrice; Leprêtre, Stéphane; Girault, Stéphane; Bonmati, Caroline; Guièze, Romain; Himberlin, Chantal; Randriamalala, Edouard; Preudhomme, Claude; Jourdan, Eric; Dombret, Hervé; Ifrah, Norbert

    2015-01-01

    Core-binding factor acute myeloid leukemia is a favorable acute myeloid leukemia subset cytogenetically defined by t(8;21) or inv(16)/t(16;16) rearrangements, disrupting RUNX1 (previously CBFA/AML1) or CBFB transcription factor functions. The receptor tyrosine kinase KIT is expressed in the vast majority of these acute myeloid leukemias and frequent activating KIT gene mutations have been associated with a higher risk of relapse. This phase II study aimed to evaluate dasatinib as maintenance therapy in patients with core-binding factor acute myeloid leukemia in first hematologic complete remission, but at higher risk of relapse due to molecular disease persistence or recurrence. A total of 26 patients aged 18–60 years old previously included in the CBF-2006 trial were eligible to receive dasatinib 140 mg daily if they had a poor initial molecular response (n=18) or a molecular recurrence (n=8). The tolerance of dasatinib as maintenance therapy was satisfactory. The 2-year disease-free survival in this high-risk population of patients was 25.7%. All but one patient with molecular recurrence presented subsequent hematologic relapse. Patients with slow initial molecular response had a similar disease-free survival when treated with dasatinib (40.2% at 2 years) or without any maintenance (50.0% at 2 years). The disappearance of KIT gene mutations at relapse suggests that clonal devolution may in part explain the absence of efficacy observed with single-agent dasatinib in these patients (n. EudraCT: 2006-006555-12). PMID:25715404

  7. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10−3 a 10−5), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  8. Current Strategies for the Detection of Minimal Residual Disease in Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Rocha, Juliana Maria Camargos; Xavier, Sandra Guerra; de Lima Souza, Marcelo Eduardo; Assumpção, Juliana Godoy; Murao, Mitiko; de Oliveira, Benigna Maria

    2016-01-01

    Acute lymphoblastic leukemia (ALL) is the most common cancer in children. Current treatment strategies for childhood ALL result in long-term remission for approximately 90% of patients. However, the therapeutic response is worse among those who relapse. Several risk stratification approaches based on clinical and biological aspects have been proposed to intensify treatment in patients with high risk of relapse and reduce toxicity on those with a greater probability of cure. The detection of residual leukemic cells (minimal residual disease, MRD) is the most important prognostic factor to identify high-risk patients, allowing redefinition of chemotherapy. In the last decades, several standardized research protocols evaluated MRD using immunophenotyping by flow cytometry and/or real-time quantitative polymerase chain reaction at different time points during treatment. Both methods are highly sensitive (10(-3) a 10(-5)), but expensive, complex, and, because of that, require qualified staff and frequently are restricted to reference centers. The aim of this article was to review technical aspects of immunophenotyping by flow cytometry and real-time quantitative polymerase chain reaction to evaluate MRD in ALL. PMID:27158437

  9. Early Patterns of Self-Regulation as Risk and Promotive Factors in Development: A Longitudinal Study from Childhood to Adulthood in a High-Risk Sample.

    PubMed

    Causadias, José M; Salvatore, Jessica E; Sroufe, L Alan

    2012-07-01

    The present study examines two childhood markers of self-regulation, ego-control and ego-resiliency, as promotive factors for the development of global adjustment and as risk factors for the development of internalizing and externalizing behavior problems in a high-risk sample. Teachers and observers rated ego-control and ego-resiliency when participants (n = 136) were in preschool and elementary school. Ratings showed evidence for convergent and discriminant validity and stability over time. Ego-resiliency, but not ego-control, emerged as powerful predictor of adaptive functioning at age 19 and 26, as well as internalizing and externalizing problems at 16, 23, 26, and 32 years. We interpret these findings as evidence that flexibility and adaptability -measured with ego-resiliency- may reduce risk and promote successful adaptation in low-SES environments. PMID:23155299

  10. Early Patterns of Self-Regulation as Risk and Promotive Factors in Development: A Longitudinal Study from Childhood to Adulthood in a High-Risk Sample

    PubMed Central

    Causadias, José M.; Salvatore, Jessica E.; Sroufe, L. Alan

    2012-01-01

    The present study examines two childhood markers of self-regulation, ego-control and ego-resiliency, as promotive factors for the development of global adjustment and as risk factors for the development of internalizing and externalizing behavior problems in a high-risk sample. Teachers and observers rated ego-control and ego-resiliency when participants (n = 136) were in preschool and elementary school. Ratings showed evidence for convergent and discriminant validity and stability over time. Ego-resiliency, but not ego-control, emerged as powerful predictor of adaptive functioning at age 19 and 26, as well as internalizing and externalizing problems at 16, 23, 26, and 32 years. We interpret these findings as evidence that flexibility and adaptability -measured with ego-resiliency- may reduce risk and promote successful adaptation in low-SES environments. PMID:23155299

  11. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    NASA Astrophysics Data System (ADS)

    Satake, Noriko; Lee, Joyce; Xiao, Kai; Luo, Juntao; Sarangi, Susmita; Chang, Astra; McLaughlin, Bridget; Zhou, Ping; Kenney, Elaina; Kraynov, Liliya; Arnott, Sarah; McGee, Jeannine; Nolta, Jan; Lam, Kit

    2011-06-01

    The goal of our project is to develop a unique ligand-conjugated nanoparticle (NP) therapy against childhood acute lymphoblastic leukemia (ALL). LLP2A, discovered by Dr. Kit Lam, is a high-affinity and high-specificity peptidomimetic ligand against an activated α4β1 integrin. Our study using 11 fresh primary ALL samples (10 precursor B ALL and 1 T ALL) showed that childhood ALL cells expressed activated α4β1 integrin and bound to LLP2A. Normal hematopoietic cells such as activated lymphocytes and monocytes expressed activated α4β1 integrin; however, normal hematopoietic stem cells showed low expression of α4β1 integrin. Therefore, we believe that LLP2A can be used as a targeted therapy for childhood ALL. The Lam lab has developed novel telodendrimer-based nanoparticles (NPs) which can carry drugs efficiently. We have also developed a human leukemia mouse model using immunodeficient NOD/SCID/IL2Rγ null mice engrafted with primary childhood ALL cells from our patients. LLP2A-conjugated NPs will be evaluated both in vitro and in vivo using primary leukemia cells and this mouse model. NPs will be loaded first with DiD near infra-red dye, and then with the chemotherapeutic agents daunorubicin or vincristine. Both drugs are mainstays of current chemotherapy for childhood ALL. Targeting properties of LLP2A-conjugated NPs will be evaluated by fluorescent microscopy, flow cytometry, MTS assay, and mouse survival after treatment. We expect that LLP2A-conjugated NPs will be preferentially delivered and endocytosed to leukemia cells as an effective targeted therapy.

  12. [Access to high-risk families through selected actors of the health care system. Results of an explorative questioning of early childhood intervention pilot projects].

    PubMed

    Renner, I

    2010-10-01

    A requirement for preventive child protection is an early and systematic access to high-risk families. Actors of the health care system, in particular doctors in private practice and midwives, are highly accepted within the population and therefore offer perfect requirements to provide this access. For this reason the aim in the context of early childhood intervention is a close cooperation of the Child and Youth Services with doctors and midwives. To what extent can these service providers of the health care system fulfill these expectations? The National Centre on Early Prevention tried to find an answer to this question with the support of 10 pilot projects which were set up within the framework of the action program "Early Prevention and Intervention for Parents and Children and Social Warning Systems". The comprehensive project presentation of selected results, insights and experiences concerning cooperation between agents of the Child and Youth Services and doctors in private practice and midwives is based on explorative written questioning of the 10 projects. The study shows from the point of view of the pilot projects that the cooperation with freelance midwives is promising. In contrast, the cooperation with doctors in private practice does not yet meet the hopes and expectations. To achieve an improvement of this situation, conditions have to be supported which promote a stronger commitment of the medical profession to early childhood intervention. PMID:20936448

  13. Ipilimumab in Treating Patients With Relapsed or Refractory High-Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-06-27

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome

  14. Cediranib Maleate in Treating Patients With Relapsed, Refractory, or Untreated Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-09-18

    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); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

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

    PubMed Central

    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

  16. Acute-onset nontraumatic paraplegia in childhood: fibrocartilaginous embolism or acute myelitis?

    PubMed

    Davis, G A; Klug, G L

    2000-09-01

    Fibrocartilaginous embolus causing acute spinal cord infarction is a rare cause of acute-onset paraplegia or quadriplegia. Few cases of survivors have been reported in the neurosurgical literature, with most reports involving postmortem or biopsy findings. There is little information on MRI findings in such patients. We present the youngest patient ever reported, and discuss the important differences between fibrocartilaginous embolus and acute myelitis of childhood. A 6-year-old girl with a history of back pain presented with sudden-onset nontraumatic paraplegia, with a clinical anterior spinal artery syndrome. Initial MRI scan revealed intervertebral disc disease at L1-2 and an incidental thoracic syrinx, but no cause for her acute-onset paraplegia was identified. Cerebrospinal fluid and other investigations were all negative. Sequential MRI scans revealed development of spinal cord expansion from T10 to the conus medullaris, with increased cord signal in the anterior aspect of the spinal cord. The intervertebral disc disease was unchanged. The imaging and clinical findings were caused by fibrocartilaginous embolus, which meant there was no need for spinal cord biopsy. The report describes the clinical and imaging criteria for diagnosis of fibrocartilaginous embolus, highlighting the case for avoiding an unnecessary biopsy. The clinical pattern in the paediatric group is discussed, with features differentiating it from acute myelitis of childhood. PMID:11048627

  17. Human leukocyte antigen-DRB1 polymorphism in childhood acute lymphoblastic leukemia

    PubMed Central

    EL ANSARY, MERVAT M.; MOHAMMED, LAMIAA A.; HASSAN, TAMER H.; BARAKA, AHMED; AHMED, ALSHYMAA A.

    2015-01-01

    Similar to autoimmune diseases, there are clear associations between resistance or susceptibility to cancer and the classic human leukocyte antigen (HLA) profile of an individual. HLA-associated susceptibility to childhood acute lymphoblastic leukemia (ALL) may provide clues to leukemogenesis in general and to the role of other risk factors. The present study aimed to determine the association between the HLA-DRB1 genotype and susceptibility to ALL in children and to assess the prognostic value of HLA-DRB1 alleles in these patients. This study included 50 ALL patients who were consecutively admitted to the Pediatric Oncology Unit of Zagazig University Hospital and 50 gender-matched healthy volunteers as a control group. The patients were subjected to full clinical history, thorough clinical examination and routine laboratory investigations. Molecular HLA-DRB1 typing for patients and controls using the reverse sequence-specific oligonucleotide probe technique was performed. HLA-DRB1*04 allele frequency was significantly higher in female patients compared to that in female controls (P=0.03) and in patients aged <10 years compared to those aged ≥10 years at the time of diagnosis (P=0.01). HLA-DRB1*11 allele frequency was significantly higher in high-risk compared to standard-risk patients (P=0.01) and in refractory patients compared to those who achieved remission (P=0.02). In conclusion, the HLA-DRB1*04 allele appears to be a female-specific susceptibility factor for the acquisition of childhood ALL and it may affect the age of onset of ALL. In addition, the HLA-DRB1*11 allele may be of prognostic significance in childhood ALL. However, further larger studies are required to support the conclusions drawn from this study. PMID:25798280

  18. Dosimetric correlation of acute and late toxicities in high-risk prostate cancer patients treated with three-dimensional conformal radiotherapy followed by intensity modulated radiotherapy boost

    PubMed Central

    Kapoor, Rakesh; Bansal, Anshuma; Kumar, Narendra; Oinam, Arun S.

    2016-01-01

    Introduction: In prostate cancer, higher radiation doses are often related to higher local control rates. However, the clinical effect of these higher doses on normal tissue toxicities is generally overlooked. We dosimetrically analyze sequential intensity modulated radiotherapy (IMRT) plans in high-risk prostate cancer patients and correlate them with acute and late normal tissue toxicities. Materials and Methods: Twenty-five high-risk prostate cancer patients were planned with three-dimensional conformal radiotherapy to a dose of 50 Gy delivered in 25 fractions in 5 weeks, followed by seven-field IMRT boost, to a dose of 24 Gy delivered in 12 fractions in 2.5 weeks, along with hormonal therapy. Acute and late toxicities were analyzed using Radiation Therapy Oncology Group toxicity criteria. Student's t-test was used for correlating doses received by normal tissues with toxicity grade. Five-year disease-free survival (DFS) and biochemical relapse-free survival (RFS) were evaluated using Kaplan–Meier analysis. Results: Median follow-up of patients was 65 months. Of 25 patients, two developed acute Grade 2 rectal toxicity. Only 1 patient developed acute Grade 2 bladder toxicity. Late Grade 2 and 3 rectal toxicity was seen in 2 and 1 patient, respectively. Late Grade 2 and 3 bladder toxicity was seen in 1 patient each. Grade 2 or more acute rectal toxicity correlated significantly with rectal volume receiving >70 Gy (P = 0.04). The 5-year DFS and biochemical RFS was 70.2% and 79.2%, respectively. One patient failed locally and seven failed at distant sites. Conclusion: Sequential IMRT with a dose of 74 Gy and maximum androgen blockade is well tolerated in high-risk patients in Indian setup with adequate control rates. PMID:27555679

  19. Dipeptidyl Peptidase-4 Inhibitor Use Is Not Associated With Acute Pancreatitis in High-Risk Type 2 Diabetic Patients: A Nationwide Cohort Study.

    PubMed

    Chang, Chia-Hsuin; Lin, Jou-Wei; Chen, Shu-Ting; Lai, Mei-Shu; Chuang, Lee-Ming; Chang, Yi-Cheng

    2016-02-01

    To analyze the association between use of DPP-4 inhibitors and acute pancreatitis in high-risk type 2 diabetic patients. A retrospective nationwide cohort study was conducted using the Taiwan National Health Insurance claim database. The risk associated with sitagliptin was compared to that with acarbose, a second-line antidiabetic drug prescribed for patients with similar diabetes severity and with a known neutral effect on pancreatitis. Between January 1, 2009 and December 31, 2010, a total of 8526 sitagliptin initiators and 8055 acarbose initiators who had hypertriglyceridemia or prior hospitalization history for acute pancreatitis were analyzed for the risk of hospitalization due to acute pancreatitis stratified for baseline propensity score. In the crude analysis, sitagliptin was associated with a decreased risk of acute pancreatitis (hazard ratio [HR] 0.74; 95% confidence interval [CI]: 0.62-0.88) compared to acarbose in diabetic patients with prior history of hospitalization for pancreatitis or hypertriglyceridemia. The association was abolished after stratification for propensity score quintiles (adjusted HR 0.95; 95% CI: 0.79-1.16). Similar results were found separately in both patients' histories of prior hospitalization of acute pancreatitis (adjusted HR 0.97; 95% CI: 0.76-1.24) and those with hypertriglyceridemia (adjusted HR 0.86; 95% CI: 0.65-1.13). No significant association was found for different durations or accumulative doses of sitagliptin. In the stratified analysis, no significant effect modification was found in relation to patients' characteristics. Use of sitagliptin was not associated with an increased risk of acute pancreatitis in high-risk diabetic patients with hypertriglyceridemia or with history of acute pancreatitis. PMID:26886601

  20. Patients treated in a coronary care unit without acute myocardial infarction: identification of high risk subgroup for subsequent myocardial infarction and/or cardiovascular death.

    PubMed Central

    Nordlander, R; Nyquist, O

    1979-01-01

    Consecutive patients admitted to a coronary care unit (CCU) during one year were studied. The diagnosis of acute myocardial infarction was not substantiated by our criteria in 206 of the patients discharged from the CCU. Of these, 193 were retrospectively followed up during one year. Seventeen of the patients (9%) died from cardiovascular causes during the 1-year period. Another 14 patients (7%) had a subsequent non-fatal acute myocardial infarction during the same period. The majority of the patients had coronary artery disease. Only 32 (17%) could be classified as non-coronary cases, and these had an excellent prognosis without any subsequent acute myocardial infarctions or deaths. The occurrence of transient ST-T shifts in serial electrocardiograms obtained during the first 3 days in hospital selected a subgroup of patients who had a high risk for subsequent non-fatal acute myocardial infarction and/or cardiovascular death. This high risk subgroup provides a basis for more aggressive diagnostic and therapeutic intervention. Images PMID:465239

  1. Therapeutic benefit of decitabine, a hypomethylating agent, in patients with high-risk primary myelofibrosis and myeloproliferative neoplasm in accelerated or blastic/acute myeloid leukemia phase.

    PubMed

    Badar, Talha; Kantarjian, Hagop M; Ravandi, Farhad; Jabbour, Elias; Borthakur, Gautam; Cortes, Jorge E; Pemmaraju, Naveen; Pierce, Sherry R; Newberry, Kate J; Daver, Naval; Verstovsek, Srdan

    2015-09-01

    Myeloproliferative neoplasm (MPN) transformed to acute myeloid leukemia (MPN-AML), MPN in accelerated phase (MPN-AP), and high-risk primary myelofibrosis (PMF) are associated with a poor response to therapy and very short survival. Several reports have suggested clinical activity of hypomethylating agents in these patients. We conducted a retrospective study of 21 patients with MPN-AML, 13 with MPN-AP and 11 with DIPSS-plus high-risk PMF treated with decitabine at our institution over the last 7 years and evaluated their clinical outcomes. Six patients (29%) with MPN-AML responded to decitabine (3 CR, 2 CRi, and 1 PR); median response duration was 7 months. The median overall survival (OS) was significantly higher in those who responded (10.5 vs 4 months). Among patients with MPN-AP, 8 patients (62%) benefited; the median response duration was 6.5 months. The median OS was 11.8 months in responders vs 4.7 months in non-responders. Among patients with DIPSS-plus high-risk PMF, 9 (82%) benefited; the median response duration was 9 months. The median OS was 32 months in responders vs 16.3 months in non-responders. Decitabine is a viable therapeutic option for patients with MPN-AML, MP-AP and high-risk PMF. Prospective clinical studies combining decitabine with other clinically active agents are needed to improve overall outcome. PMID:26183878

  2. Eight different viral agents in childhood acute gastroenteritis.

    PubMed

    Bozkurt, Derya; Selimoğlu, Mukadder Ayşe; Otlu, Barış; Sandıkkaya, Ayşe

    2015-01-01

    Viral gastroenteritis is the most frequent cause of acute gastroenteritis (AGE) of childhood. The aim of this study was to determine the prevalence of viral agents including astrovirus, rotavirus, adenovirus, enterovirus, norovirus, parechovirus, Aichivirus and sapovirus in children with AGE in a pediatric Turkish population. Fecal specimens of 240 children with AGE were investigated by polymerase chain reaction, and viral agents were identified in 131 (54.6%) samples. The distribution of viral agents was as follows: 56 (42.8%) norovirus, 44 (33.6%) rotavirus, 29 (22.1%) enterovirus, 21 (16.0%) adenovirus, 21 (16.0%) parechovirus, 5 (3.8%) sapovirus and 1 (0.8%) Aichivirus. Single and multiple viral agents were detected in 38.8% and 15.8% of patients, respectively. The duration of hospitalization was longer in children with multiple viral agents than in those infected with a single viral agent (p<0.001). While the highest rate of rotavirus infection was detected in winter, the highest rate of norovirus was found in the summer. In conclusion, norovirus and rotavirus are the most frequent causes of childhood AGE in our country. PMID:26613223

  3. The Ecology of Early Childhood Risk: A Canonical Correlation Analysis of Children’s Adjustment, Family, and Community Context in a High-Risk Sample

    PubMed Central

    Aiyer, Sophie M.; Wilson, Melvin N.; Shaw, Daniel S.; Dishion, Thomas J.

    2013-01-01

    The ecology of the emergence of psycho-pathology in early childhood is often approached by the analysis of a limited number of contextual risk factors. In the present study, we provide a comprehensive analysis of ecological risk by conducting a canonical correlation analysis of 13 risk factors at child age 2 and seven narrow-band scales of internalizing and externalizing problem behaviors at child age 4, using a sample of 364 geographically and ethnically diverse, disadvantaged primary caregivers, alternative caregivers, and preschool-age children. Participants were recruited from Special Supplemental Nutrition Program for Women, Infants, and Children sites and were screened for family risk. Canonical correlation analysis revealed that (1) a first latent combination of family and individual risks of caregivers predicted combinations of child emotional and behavioral problems, and that (2) a second latent combination of contextual and structural risks predicted child somatic complaints. Specifically, (1) the combination of chaotic home, conflict with child, parental depression, and parenting hassles predicted a co-occurrence of internalizing and externalizing behaviors, and (2) the combination of father absence, perceived discrimination, neighborhood danger, and fewer children living in the home predicted child somatic complaints. The research findings are discussed in terms of the development of psychopathology, as well as the potential prevention needs of families in high-risk contexts. PMID:23700232

  4. Pediatric Acute Q Fever Mimics Other Common Childhood Illnesses

    PubMed Central

    Bart, Ingeborg Y.; Schabos, Yvonne; van Hout, Roeland W. N. M.; Leenders, Alexander C. A. P.; de Vries, Esther

    2014-01-01

    Knowledge of Q fever has increased over the last decades, but research has mainly focused on adults. Data in children are scarce, and current knowledge is mostly based on case reports. The aim of this study was to determine predictors for acute Q fever in children in the general population. We retrospectively studied all children tested for Coxiella burnetii by serology and/or PCR upon request of their general practitioner in the regional laboratory for Medical Microbiology of the Jeroen Bosch during the Q fever outbreak in the Netherlands between 2007 and 2011. A total of 1061 patients was analyzed. Influenza-like illness and respiratory tract infection were the most common presentations of acute Q fever, mimicking other common childhood illnesses. None of the reported symptoms was significantly related to a positive test outcome and therefore presenting signs or symptoms have no predictive value in diagnosing Q-fever in children. Only diagnostic tests are reliable. As the infection generally follows a mild and uncomplicated course, we question if the difficulty of recognizing pediatric Q fever is a problem worth solving. PMID:24520412

  5. Pediatric acute Q fever mimics other common childhood illnesses.

    PubMed

    Bart, Ingeborg Y; Schabos, Yvonne; van Hout, Roeland W N M; Leenders, Alexander C A P; de Vries, Esther

    2014-01-01

    Knowledge of Q fever has increased over the last decades, but research has mainly focused on adults. Data in children are scarce, and current knowledge is mostly based on case reports. The aim of this study was to determine predictors for acute Q fever in children in the general population. We retrospectively studied all children tested for Coxiella burnetii by serology and/or PCR upon request of their general practitioner in the regional laboratory for Medical Microbiology of the Jeroen Bosch during the Q fever outbreak in the Netherlands between 2007 and 2011. A total of 1061 patients was analyzed. Influenza-like illness and respiratory tract infection were the most common presentations of acute Q fever, mimicking other common childhood illnesses. None of the reported symptoms was significantly related to a positive test outcome and therefore presenting signs or symptoms have no predictive value in diagnosing Q-fever in children. Only diagnostic tests are reliable. As the infection generally follows a mild and uncomplicated course, we question if the difficulty of recognizing pediatric Q fever is a problem worth solving. PMID:24520412

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

    ClinicalTrials.gov

    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

  7. Childhood Acute Lymphoblastic Leukemia and Indicators of Early Immune Stimulation: A Childhood Leukemia International Consortium Study

    PubMed Central

    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

    2015-01-01

    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. PMID:25731888

  8. General Information about Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

    MedlinePlus

    ... Other Myeloid Malignancies Treatment (PDQ®)–Patient Version General Information About Childhood Acute Myeloid Leukemia and Other Myeloid ... the PDQ Pediatric Treatment Editorial Board . Clinical Trial Information A clinical trial is a study to answer ...

  9. Impact of catheter fragmentation followed by local intrapulmonary thrombolysis in acute high risk pulmonary embolism as primary therapy

    PubMed Central

    Mohan, Bishav; Aslam, Naved; Kumar Mehra, Anil; Takkar Chhabra, Shibba; Wander, Praneet; Tandon, Rohit; Singh Wander, Gurpreet

    2014-01-01

    Background Pulmonary embolism (PE) with more than 50% compromise of pulmonary circulation results significant right ventricular (RV) afterload leading to progressive RV failure, systemic hypotension and shock. Prompt restoration of thrombolysis, surgical embolectomy, or percutaneous mechanical thrombectomy (PMT) prevents progressive hemodynamic decline. We report our single center experience in high risk PE patients treated with standard pigtail catheter mechanical fragmentation followed by intrapulmonary thrombolysis as a primary therapy. Methods 50 consecutive patients with diagnosis of high risk PE defined as having shock index >1 with angiographic evidence of >50% pulmonary arterial occlusion are included in the present study. All patients underwent emergent cardiac catheterization. After ensuring flow across pulmonary artery with mechanical breakdown of embolus by rotating 5F pigtail catheter; bolus dose of urokinase (4400 IU/kg) followed by infusion for 24 h was given in the thrombus. Hemodynamic parameters were recorded and follow up pulmonary angiogram was done. Clinical and echo follow up was done for one year. Results Pigtail rotational mechanical thrombectomy restored antegrade flow in all patients. The mean pulmonary artery pressure, Miller score, Shock index decreased significantly from 41 ± 8 mmHg, 20 ± 5, 1.32 ± 0.3 to 24.52 ± 6.89, 5.35 ± 2.16, 0.79 ± 0.21 respectively (p < 0.0001). In-hospital major complications were seen in 4 patients. There was a statistically significant reduction of PA pressures from 62 ± 11 mmHg to 23±6 mmHg on follow up. Conclusions Rapid reperfusion of pulmonary arteries with mechanical fragmentation by pigtail catheter followed by intrapulmonary thrombolysis results in excellent immediate and intermediate term outcomes in patients presenting with high risk pulmonary embolism. PMID:24973834

  10. Hypofractionated Accelerated Radiotherapy Using Concomitant Intensity-Modulated Radiotherapy Boost Technique for Localized High-Risk Prostate Cancer: Acute Toxicity Results

    SciTech Connect

    Lim, Tee S.; Cheung, Patrick Loblaw, D. Andrew; Morton, Gerard; Sixel, Katharina E.; Pang, Geordi; Basran, Parminder; Zhang Liying; Tirona, Romeo; Szumacher, Ewa; Danjoux, Cyril; Choo, Richard; Thomas, Gillian

    2008-09-01

    Purpose: To evaluate the acute toxicities of hypofractionated accelerated radiotherapy (RT) using a concomitant intensity-modulated RT boost in conjunction with elective pelvic nodal irradiation for high-risk prostate cancer. Methods and Materials: This report focused on 66 patients entered into this prospective Phase I study. The eligible patients had clinically localized prostate cancer with at least one of the following high-risk features (Stage T3, Gleason score {>=}8, or prostate-specific antigen level >20 ng/mL). Patients were treated with 45 Gy in 25 fractions to the pelvic lymph nodes using a conventional four-field technique. A concomitant intensity-modulated radiotherapy boost of 22.5 Gy in 25 fractions was delivered to the prostate. Thus, the prostate received 67.5 Gy in 25 fractions within 5 weeks. Next, the patients underwent 3 years of adjuvant androgen ablative therapy. Acute toxicities were assessed using the Common Terminology Criteria for Adverse Events, version 3.0, weekly during treatment and at 3 months after RT. Results: The median patient age was 71 years. The median pretreatment prostate-specific antigen level and Gleason score was 18.7 ng/L and 8, respectively. Grade 1-2 genitourinary and gastrointestinal toxicities were common during RT but most had settled at 3 months after treatment. Only 5 patients had acute Grade 3 genitourinary toxicity, in the form of urinary incontinence (n = 1), urinary frequency/urgency (n = 3), and urinary retention (n = 1). None of the patients developed Grade 3 or greater gastrointestinal or Grade 4 or greater genitourinary toxicity. Conclusion: The results of the present study have indicated that hypofractionated accelerated RT with a concomitant intensity-modulated RT boost and pelvic nodal irradiation is feasible with acceptable acute toxicity.

  11. CXXC5 (Retinoid-Inducible Nuclear Factor, RINF) is a Potential Therapeutic Target in High-Risk Human Acute Myeloid Leukemia

    PubMed Central

    Astori, Audrey; Fredly, Hanne; Aloysius, Thomas Aquinas; Bullinger, Lars; Mas, Véronique Mansat-De; de la Grange, Pierre; Delhommeau, François; Hagen, Karen Marie; Récher, Christian; Dusanter-Fourt, Isabelle; Knappskog, Stian; Lillehaug, Johan Richard

    2013-01-01

    The retinoid-responsive gene CXXC5 localizes to the 5q31.2 chromosomal region and encodes a retinoid-inducible nuclear factor (RINF) that seems important during normal myelopoiesis. We investigated CXXC5/RINF expression in primary human acute myeloid leukemia (AML) cells derived from 594 patients, and a wide variation in CXXC5/RINF mRNA levels was observed both in the immature leukemic myeloblasts and in immature acute lymphoblastic leukemia cells. Furthermore, patients with low-risk cytogenetic abnormalities showed significantly lower levels compared to patients with high-risk abnormalities, and high RINF/CXXC5/ mRNA levels were associated with decreased overall survival for patients receiving intensive chemotherapy for newly diagnosed AML. This association with prognosis was seen both when investigating (i) an unselected patient population as well as for patients with (ii) normal cytogenetic and (iii) core-binding factor AML. CXXC5/RINF knockdown in AML cell lines caused increased susceptibility to chemotherapy-induced apoptosis, and regulation of apoptosis also seemed to differ between primary human AML cells with high and low RINF expression. The association with adverse prognosis together with the antiapoptotic effect of CXXC5/RINF suggests that targeting of CXXC5/RINF should be considered as a possible therapeutic strategy, especially in high-risk patients who show increased expression in AML cells compared with normal hematopoietic cells. PMID:23988457

  12. Economic evaluation of treatment for acute lymphoblastic leukaemia in childhood.

    PubMed

    Rae, C; Furlong, W; Jankovic, M; Moghrabi, Albert; Naqvi, A; Sala, A; Samson, Y; DePauw, S; Feeny, D; Barr, R

    2014-11-01

    Berlin-Frankfurt-Munster (BFM) and Dana-Farber Cancer Institute (DFCI) consortia's treatment strategies for acute lymphoblastic leukaemia (ALL) in children are widely used. We compared the health effects and monetary costs of hospital treatments for these two strategies. Parents of children treated at seven centres in Canada, Italy and the USA completed health-related quality of life (HRQL) assessments during four active treatment phases and at 2 years after treatment. Mean HRQL scores were used to calculate quality-adjusted life years (QALYs) for a period of 5 years following diagnosis. Total costs of treatment were determined from variables in administrative databases in a universally accessible and publicly funded healthcare system. Valid HRQL assessments (n = 1200) were collected for 307 BFM and 317 DFCI patients, with costs measured for 66 BFM and 28 DFCI patients. QALYs per patient were <1.0% greater for BFM than DFCI. Median HRQL scores revealed no difference in QALYs. The difference in mean total costs for BFM (US$88 480) and DFCI (US$93 026) was not significant (P = 0.600). This study provides no evidence of superiority for one treatment strategy over the other. Current BFM or DFCI strategies should represent conventional management for the next economic evaluation of treatments for ALL in childhood. PMID:24393150

  13. Personalization of dexamethasone therapy in childhood acute lymphoblastic leukaemia.

    PubMed

    Jackson, Rosanna K; Irving, Julie A E; Veal, Gareth J

    2016-04-01

    Dexamethasone is a key component in the treatment of childhood acute lymphoblastic leukaemia (ALL). Despite playing a key role in the improved survival of ALL over several decades, intensification of dexamethasone therapy has also contributed to the increased toxicity associated with treatment, which is now seen to be at unacceptable levels given the favourable disease prognosis. Therefore the focus for treatment is now shifting towards reducing toxicity whilst maintaining current survival rates. As approximately 50% of patients were successfully treated on less intensive protocols of the 1980s, it has been questioned whether therapy intensification is necessary in all patients. Furthermore, there remains a subset of children who are still not cured of their disease. New strategies are therefore needed to identify patients who could benefit from dose reduction or intensification. However, adjusting a potentially life threatening therapy is a challenging task, particularly given the heterogeneous nature of ALL. This review focuses on the potential for patient stratification based on our current knowledge of dexamethasone pharmacokinetics, pharmacogenetics and the action of dexamethasone at the cellular level. A carefully designed, combined approach is needed if we are to achieve the aim of improved personalization of dexamethasone therapy for future patients. PMID:26729065

  14. The HAS-BLED Score Identifies Patients with Acute Venous Thromboembolism at High Risk of Major Bleeding Complications during the First Six Months of Anticoagulant Treatment

    PubMed Central

    Kooiman, Judith; van Hagen, Nadja; Iglesias del Sol, Antonio; Planken, Erwin V.; Lip, Gregory Y. H.; van der Meer, Felix J. M.; Cannegieter, Suzanne C.; Klok, Frederikus A.; Huisman, Menno V.

    2015-01-01

    Objective The HAS-BLED score enables a risk estimate of major bleeds in patients with atrial fibrillation on vitamin K-antagonists (VKA) treatment, but has not been validated for patients with venous thromboembolism (VTE). We analyzed whether the HAS-BLED score accurately identifies patients at high risk of major bleeds during VKA treatment for acute VTE. Methods Medical records of 537 patients with acute VTE (primary diagnosis pulmonary embolism in 223, deep vein thrombosis in 314) starting VKA treatment between 2006-2007 were searched for items on the HAS-BLED score and the occurrence of major bleeds during the first 180 days of follow-up. The hazard ratio (HR) for the occurrence of major bleeds comparing non-high with high-risk patients as defined by a HAS-BLED score ≥ 3 points was calculated using Cox-regression analysis. Results Major bleeds occurred in 11/537 patients (2.0%, 5.2/100 person years, 95% CI 2.8-9.2). Cumulative incidences of major bleeds were 1.3% (95% CI 0.1-2.5) in the non-high (HAS-BLED < 3) and 9.6% (95%CI 2.2-17.0) in the high-risk group (HAS-BLED ≥ 3), (p <0.0001 by Log-Rank test), with a HR of 8.7 (95% CI 2.7-28.4). Of the items in the HAS-BLED score, abnormal renal function (HR 10.8, 95% CI 1.9-61.7) and a history of bleeding events (HR 10.4, 95% CI 2.5-42.5) were independent predictors of major bleeds during follow-up. Conclusion Acute VTE patients with a HAS-BLED score ≥ 3 points are at increased risk of major bleeding. These results warrant for correction of the potentially reversible risk factors for major bleeding and careful International Normalized Ratio monitoring in acute VTE patients with a high HAS-BLED score. PMID:25905638

  15. Donor Peripheral Blood Stem Cell Transplant and Pretargeted Radioimmunotherapy in Treating Patients With High-Risk Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-03-01

    Chronic Myelomonocytic Leukemia; Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ringed Sideroblasts; Secondary Acute Myeloid Leukemia

  16. Severe Hypertriglyceridemia During Therapy For Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Bhojwani, Deepa; Darbandi, Rashid; Pei, Deqing; Ramsey, Laura B.; Chemaitilly, Wassim; Sandlund, John T.; Cheng, Cheng; Pui, Ching-Hon; Relling, Mary V.; Jeha, Sima; Metzger, Monika L.

    2014-01-01

    Background Asparaginase and steroids can cause hypertriglyceridemia in children with acute lymphoblastic leukemia (ALL). There are no guidelines for screening or management of patients with severe hypertriglyceridemia (>1000 mg/dL) during ALL therapy. Patients and Methods Fasting lipid profiles were obtained prospectively at 4 time-points for 257 children consecutively enrolled on a frontline ALL study. Risk factors were evaluated by the exact chi-square test. Details of adverse events and management of hypertriglyceridemia were extracted retrospectively. Results Eighteen of 257 (7%) patients developed severe hypertriglyceridemia. Older age and treatment with higher doses of asparaginase and steroids on the standard/high-risk arm were significant risk factors. Severe hypertriglyceridemia was not associated with pancreatitis after adjustment for age and treatment arm or with osteonecrosis after adjustment for age. However, patients with severe hypertriglyceridemia had a 2.5 to 3 times higher risk of thrombosis compared to patients without, albeit the difference was not statistical significant. Of the 30 episodes of severe hypertriglyceridemia in 18 patients, 7 were managed conservatively while the others with pharmacotherapy. Seventeen of 18 patients continued to receive asparaginase and steroids. Triglyceride levels normalized after completion of ALL therapy in all 12 patients with available measurements. Conclusion Asparaginase- and steroid-induced transient hypertriglyceridemia can be adequately managed with dietary modifications and close monitoring without altering chemotherapy. Patients with severe hypertriglyceridemia were not at increased risk of adverse events, with a possible exception of thrombosis. The benefit of pharmacotherapy in decreasing symptoms and potential complications requires further investigation. PMID:25087182

  17. Comparison of outcomes after umbilical cord blood and unmanipulated haploidentical hematopoietic stem cell transplantation in children with high-risk acute lymphoblastic leukemia.

    PubMed

    Mo, Xiao-Dong; Tang, Bao-Lin; Zhang, Xiao-Hui; Zheng, Chang-Cheng; Xu, Lan-Ping; Zhu, Xiao-Yu; Wang, Yu; Liu, Hui-Lan; Yan, Chen-Hua; Chu, Xian-Deng; Chen, Huan; Geng, Liang-Quan; Liu, Kai-Yan; Sun, Zi-Min; Huang, Xiao-Jun

    2016-11-01

    Allogeneic hematopoietic stem cell transplantation (HSCT) is an effective therapy for children with high-risk acute lymphoblastic leukemia (ALL). Human leukocyte antigen (HLA)-haploidentical HSCT (haplo-HSCT) or umbilical cord blood transplantation (UCBT) are both important alternative sources of stem cells for those without an HLA-identical sibling donor or unrelated matched donor. We aimed to compare the therapeutic effects of single UCBT and unmanipulated haplo-HSCT in high-risk ALL children (n = 129). Hematopoietic recovery was significantly faster in haplo-HSCT recipients than in UCBT recipients. The 2-year cumulative incidences of relapse in the haplo-HSCT and UCBT groups were 16.1% and 24.1%, respectively (p = 0.169). The 2-year cumulative incidences of non-relapse mortality in the haplo-HSCT and UCBT groups were 12.8% and 18.8%, respectively (p = 0.277). The 2-year probabilities of overall survival in the haplo-HSCT and UCBT groups were 82.0% and 69.6%, respectively (p = 0.071), and the 2-year probability of disease-free survival in the haplo-HSCT group was higher than in the UCBT group (71.0% vs. 57.2%, p = 0.040). However, several variables (such as leukocyte count and cytogenetics at diagnosis) were different between the groups, and a possible center effect should also be considered. In addition, only mild and moderate chronic graft-versus-host disease (GVHD) was associated with significantly improved survival compared to those without chronic GVHD in multivariate analysis. Thus, our results show that both unmanipulated haplo-HSCT and UCBT are valid for high-risk ALL children lacking a HLA matched donor, and both strategies expand the donor pool for children in need. PMID:27356906

  18. [Treatment of acute coronary syndrome in older adults and high-risk patients."When the going gets tough…"].

    PubMed

    Bassanelli, Giorgio; Morici, Nuccia; De Luca, Leonardo; De Servi, Stefano; Savonitto, Stefano

    2015-10-01

    The increasing life expectancy in older adults and the better survival of patients with multiple pathologies require the capability to treat complex clinical conditions with an increased risk of iatrogenic complications. Nevertheless, recent improvements in the pharmacological and interventional treatment of acute coronary syndrome (ACS) have promoted a shift from therapeutic nihilism to a more active management of complex ACS cases. Despite the paucity of specific randomized clinical trials, observational studies seem to show benefit of an early invasive treatment in these patients. This approach requires close cooperation of clinical intensivists, interventional cardiologists and cardiovascular surgeons either in a specialized heart center or in a network of hospitals. PMID:26442976

  19. A revised definition for cure of childhood acute lymphoblastic leukemia.

    PubMed

    Pui, C H; Pei, D; Campana, D; Cheng, C; Sandlund, J T; Bowman, W P; Hudson, M M; Ribeiro, R C; Raimondi, S C; Jeha, S; Howard, S C; Bhojwani, D; Inaba, H; Rubnitz, J E; Metzger, M L; Gruber, T A; Coustan-Smith, E; Downing, J R; Leung, W H; Relling, M V; Evans, W E

    2014-12-01

    With improved contemporary therapy, we reassess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia (ALL) to determine when cure can be declared with a high degree of confidence. In six successive clinical trials between 1984 and 2007, 1291 (84.5%) patients completed all therapies in continuous complete remission. The post-therapy cumulative risk of relapse or development of a second neoplasm and the event-free survival rate and overall survival were analyzed according to the presenting features and the three treatment periods defined by relative outcome. Over the three treatment periods, there has been progressive increase in the rate of event-free survival (65.2% vs 74.8% vs 85.1% (P<0.001)) and overall survival (76.5% vs 81.1% vs 91.7% (P<0.001)) at 10 years. The most important predictor of outcome after completion of therapy was the type of treatment. In the most recent treatment period, which omitted the use of prophylactic cranial irradiation, the post-treatment cumulative risk of relapse was 6.4%, death in remission 1.5% and development of a second neoplasm 2.3% at 10 years, with all relapses except one occurring within 4 years of therapy. None of the 106 patients with the t(9;22)/BCR-ABL1, t(1;19)/TCF3-PBX1 or t(4;11)/MLL-AFF1 had relapsed after 2 years from completion of therapy. These findings demonstrate that with contemporary effective therapy that excludes cranial irradiation, approximately 6% of children with ALL may relapse after completion of treatment, and those who remain in remission at 4 years post treatment may be considered cured (that is, less than 1% chance of relapse). PMID:24781017

  20. Rationale for an international consortium to study inherited genetic susceptibility to childhood acute lymphoblastic leukemia

    PubMed Central

    Sherborne, Amy L.; Hemminki, Kari; Kumar, Rajiv; Bartram, Claus R.; Stanulla, Martin; Schrappe, Martin; Petridou, Eleni; Semsei, Ágnes F.; Szalai, Csaba; Sinnett, Daniel; Krajinovic, Maja; Healy, Jasmine; Lanciotti, Marina; Dufour, Carlo; Indaco, Stefania; El-Ghouroury, Eman A; Sawangpanich, Ruchchadol; Hongeng, Suradej; Pakakasama, Samart; Gonzalez-Neira, Anna; Ugarte, Evelia L.; Leal, Valeria P.; Espinoza, Juan P.M.; Kamel, Azza M.; Ebid, Gamal T.A.; Radwan, Eman R.; Yalin, Serap; Yalin, Erdinc; Berkoz, Mehmet; Simpson, Jill; Roman, Eve; Lightfoot, Tracy; Hosking, Fay J.; Vijayakrishnan, Jayaram; Greaves, Mel; Houlston, Richard S.

    2011-01-01

    Acute lymphoblastic leukemia is the major pediatric cancer in developed countries. To date most association studies of acute lymphoblastic leukemia have been based on the candidate gene approach and have evaluated a restricted number of polymorphisms. Such studies have served to highlight difficulties in conducting statistically and methodologically rigorous investigations into acute lymphoblastic leukemia risk. Recent genome-wide association studies of childhood acute lymphoblastic leukemia have provided robust evidence that common variation at four genetic loci confers a modest increase in risk. The accumulated experience to date and relative lack of success of initial efforts to identify novel acute lymphoblastic leukemia predisposition loci emphasize the need for alternative study designs and methods. The International Childhood Acute Lymphoblastic Leukaemia Genetics Consortium includes 12 research groups in Europe, Asia, the Middle East and the Americas engaged in studying the genetics of acute lymphoblastic leukemia. The initial goal of this consortium is to identify and characterize low-penetrance susceptibility variants for acute lymphoblastic leukemia through association-based analyses. Efforts to develop genome-wide association studies of acute lymphoblastic leukemia, in terms of both sample size and single nucleotide polymorphism coverage, and to increase the number of single nucleotide polymorphisms taken forward to large-scale replication should lead to the identification of additional novel risk variants for acute lymphoblastic leukemia. Ethnic differences in the risk of acute lymphoblastic leukemia are well recognized and thus in assessing the interplay between inherited and non-genetic risk factors, analyses using different population cohorts with different incidence rates are likely to be highly informative. Given that the frequency of many acute lymphoblastic leukemia subgroups is small, identifying differential effects will realistically only be

  1. Phase 2 clinical trial of 5-azacitidine, valproic acid, and all-trans retinoic acid in patients with high-risk acute myeloid leukemia or myelodysplastic syndrome

    PubMed Central

    Raffoux, Emmanuel; Cras, Audrey; Recher, Christian; Boëlle, Pierre-Yves; de Labarthe, Adrienne; Turlure, Pascal; Marolleau, Jean-Pierre; Reman, Oumedaly; Gardin, Claude; Victor, Maud; Maury, Sébastien; Rousselot, Philippe; Malfuson, Jean-Valère; Maarek, Odile; Daniel, Marie-Thérèse; Fenaux, Pierre; Degos, Laurent; Chomienne, Christine; Chevret, Sylvie; Dombret, Hervé

    2010-01-01

    In this Phase 2 study, we evaluated the efficacy of combination of 5-azacitidine (AZA), valproic acid (VPA), and all-trans retinoic acid (ATRA) in patients with high-risk acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). Treatment consisted of six cycles of AZA and VPA for 7 days, followed by ATRA for 21 days. Sixty-five patients were enrolled (median age, 72 years; 55 AML including 13 relapsed/refractory patients, 10 MDS; 30 unfavorable karyotypes). Best responses included 14 CR and 3 PR (26%), 75% of the responders and 36% of the non-responders achieving an erythroid response. Median overall survival (OS) was 12.4 months. Untreated patients had a longer OS than relapsed/refractory patients. In patients who fulfilled the 6 planned cycles, OS did not appear to depend on CR/PR achievement, suggesting that stable disease while on-treatment would be a surrogate for survival with this approach. During therapy, early platelet response and demethylation of the FZD9, ALOX12, HPN, and CALCA genes were associated with clinical response. Finally, there was no evidence for the restoration of an ATRA-induced differentiation during therapy. Epigenetic modulation deserves prospective comparisons to conventional care in patients with high-risk AML, at least in those presenting previously untreated disease and low blast count. PMID:21293051

  2. Transcatheter Mitral Valve Repair in Surgical High-Risk Patients: Gender-Specific Acute and Long-Term Outcomes

    PubMed Central

    Tigges, Eike; Kalbacher, Daniel; Thomas, Christina; Appelbaum, Sebastian; Deuschl, Florian; Schofer, Niklas; Schlüter, Michael; Conradi, Lenard; Schirmer, Johannes; Treede, Hendrik; Reichenspurner, Hermann; Blankenberg, Stefan; Schäfer, Ulrich; Lubos, Edith

    2016-01-01

    Background. Analyses emphasizing gender-related differences in acute and long-term outcomes following MitraClip therapy for significant mitral regurgitation (MR) are rare. Methods. 592 consecutive patients (75 ± 8.7 years, 362 men, 230 women) underwent clinical and echocardiographic follow-up for a median of 2.13 (0.99–4.02) years. Results. Significantly higher prevalence of cardiovascular comorbidities, renal failure, and adverse echocardiographic parameters in men resulted in longer device time (p = 0.007) and higher numbers of implanted clips (p = 0.0075), with equal procedural success (p = 1.0). Rehospitalization for heart failure did not differ (p[logrank] = 0.288) while survival was higher in women (p[logrank] = 0.0317). Logarithmic increase of NT-proBNP was a common independent predictor of death. Hypercholesterolemia and peripheral artery disease were predictors of death only in men while ischemic and dilative cardiomyopathy (CM) and age were predictors in women. Independent predictors of rehospitalization for heart failure were severely reduced ejection fraction and success in men while both ischemic and dilative CM, logistic EuroSCORE, and MR severity were predictive in women. Conclusions. Higher numbers of implanted clips and longer device time are likely related to more comorbidities in men. Procedural success and acute and mid-term clinical outcomes were equal. Superior survival for women in long-term analysis is presumably attributable to a comparatively better preprocedural health. PMID:27042662

  3. A phase II study of AZD2171 (cediranib) in the treatment of patients with acute myeloid leukemia or high-risk myelodysplastic syndrome

    PubMed Central

    Mattison, Ryan; Jumonville, Alcee; Flynn, Patrick James; Moreno-Aspitia, Alvaro; Erlichman, Charles; Laplant, Betsy; Juckett, Mark B.

    2015-01-01

    Patients with acute myeloid leukemia (AML) and myelodysplastic syndrome (MDS) not fit for intensive treatment need novel therapy options. Vascular endothelial growth factor (VEGF) receptor inhibition is one potential mechanism by which AML and MDS could be treated. The receptor tyrosine kinase inhibitor AZD2171 (cediranib) has activity against VEGF receptors KDR and FLT-1. This multicenter phase II study was designed to test cediranib's activity in patients with AML or high-risk MDS. The primary endpoint was confirmed disease response defined as a composite of complete remission, partial remission or hematologic improvement. The study enrolled 23 subjects in the AML cohort and 16 subjects in the MDS cohort. There were no confirmed responses in either group. Since the study met the stopping rule after the first stage of enrollment, the trial was closed to further accrual. Common adverse events in both cohorts included thrombocytopenia, neutropenia, anemia, fatigue, dyspnea, diarrhea, nausea and dehydration. PMID:25329007

  4. The kSORT Assay to Detect Renal Transplant Patients at High Risk for Acute Rejection: Results of the Multicenter AART Study

    PubMed Central

    Hsieh, Sue; Dai, Hong; Bestard, Oriol; Metes, Diana; Zeevi, Andrea; Gritsch, Albin; Cheeseman, Jennifer; Macedo, Camila; Peddy, Ram; Medeiros, Mara; Vincenti, Flavio; Asher, Nancy; Salvatierra, Oscar; Shapiro, Ron; Kirk, Allan; Reed, Elaine; Sarwal, Minnie M.

    2014-01-01

    Background Development of noninvasive molecular assays to improve disease diagnosis and patient monitoring is a critical need. In renal transplantation, acute rejection (AR) increases the risk for chronic graft injury and failure. Noninvasive diagnostic assays to improve current late and nonspecific diagnosis of rejection are needed. We sought to develop a test using a simple blood gene expression assay to detect patients at high risk for AR. Methods and Findings We developed a novel correlation-based algorithm by step-wise analysis of gene expression data in 558 blood samples from 436 renal transplant patients collected across eight transplant centers in the US, Mexico, and Spain between 5 February 2005 and 15 December 2012 in the Assessment of Acute Rejection in Renal Transplantation (AART) study. Gene expression was assessed by quantitative real-time PCR (QPCR) in one center. A 17-gene set—the Kidney Solid Organ Response Test (kSORT)—was selected in 143 samples for AR classification using discriminant analysis (area under the receiver operating characteristic curve [AUC] = 0.94; 95% CI 0.91–0.98), validated in 124 independent samples (AUC = 0.95; 95% CI 0.88–1.0) and evaluated for AR prediction in 191 serial samples, where it predicted AR up to 3 mo prior to detection by the current gold standard (biopsy). A novel reference-based algorithm (using 13 12-gene models) was developed in 100 independent samples to provide a numerical AR risk score, to classify patients as high risk versus low risk for AR. kSORT was able to detect AR in blood independent of age, time post-transplantation, and sample source without additional data normalization; AUC = 0.93 (95% CI 0.86–0.99). Further validation of kSORT is planned in prospective clinical observational and interventional trials. Conclusions The kSORT blood QPCR assay is a noninvasive tool to detect high risk of AR of renal transplants. Please see later in the article for the Editors' Summary PMID

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

    Technology Transfer Automated Retrieval System (TEKTRAN)

    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...

  6. Study to Improve Cardiovascular Outcomes in high-risk older patieNts (ICON1) with acute coronary syndrome: study design and protocol of a prospective observational study

    PubMed Central

    Kunadian, Vijay; Neely, R Dermot G; Sinclair, Hannah; Batty, Jonathan A; Veerasamy, Murugapathy; Ford, Gary A; Qiu, Weiliang

    2016-01-01

    Introduction The ICON1 study (a study to Improve Cardiovascular Outcomes in high-risk older patieNts with acute coronary syndrome) is a prospective observational study of older patients (≥75 years old) with non-ST-elevation acute coronary syndrome managed by contemporary treatment (pharmacological and invasive). The aim of the study was to determine the predictors of poor cardiovascular outcomes in this age group and to generate a risk prediction tool. Methods and analysis Participants are recruited from 2 tertiary hospitals in the UK. Baseline evaluation includes frailty, comorbidity, cognition and quality-of-life measures, inflammatory status assessed by a biomarker panel, including microRNAs, senescence assessed by telomere length and telomerase activity, cardiovascular status assessed by arterial stiffness, endothelial function, carotid intima media thickness and left ventricular systolic and diastolic function, and coronary plaque assessed by virtual histology intravascular ultrasound and optical coherence tomography. The patients are followed-up at 30 days and at 1 year for primary outcome measures of death, myocardial infarction, stroke, unplanned revascularisation, bleeding and rehospitalisation. Ethics and dissemination The study has been approved by the regional ethics committee (REC 12/NE/016). Findings of the study will be presented in scientific sessions and will be published in peer-reviewed journals. Trial registration number NCT01933581: Pre-results. PMID:27554105

  7. Radioimmunotherapy with [188Re]-labelled anti-CD66 antibody in the conditioning for allogeneic stem cell transplantation for high-risk acute myeloid leukemia.

    PubMed

    Koenecke, Christian; Hofmann, Michael; Bolte, Oliver; Gielow, Peter; Dammann, Elke; Stadler, Michael; Franzke, Anke; Boerner, Anne Rose; Eder, Matthias; Ganser, Arnold; Knapp, Wolfram; Hertenstein, Bernd

    2008-05-01

    Between July 2000 and June 2003 a total of 21 patients with high-risk acute myeloid leukemia (AML; n = 14), AML after myelodysplastic syndrome (MDS; n = 6) or advanced MDS (n = 1) were treated with an 188-Re labelled anti-CD66 antibody in the conditioning regimen for allogeneic stem cell transplantation. Radioimmunotherapy (RIT) was followed by standard full-dose conditioning with busulfan and high-dose cyclophosphamide in 11 patients and reduced intensity conditioning regimen in 10 patients. All patients received an unmanipulated allogeneic graft from alternative donors (n = 15) or a HLA-identical familiy donor (n = 6). With a median follow up of 42 months (23-60) disease free survival for all patients was 43%. Nine patients are still alive and in ongoing complete hematological remission. The treatment related mortality was 28.6% (n = 6) and an equal number of patients died of relapsing disease within 30-385 days after transplantation. Late organ toxicity, monitored for more than 1 year, was mild and not clinically relevant. The combination of RIT with chemotherapeutic conditioning seems to be a therapy with an acceptable risk of treatment related morbidity and mortality as well as occurrence of severe acute GvHD. PMID:18415659

  8. The Efficacy of Percutaneous Transhepatic Gallbladder Drainage on Acute Cholecystitis in High-Risk Elderly Patients Based on the Tokyo Guidelines

    PubMed Central

    Ni, Qingqiang; Chen, Dongbo; Xu, Rui; Shang, Dong

    2015-01-01

    Abstract To evaluate the efficacy of percutaneous transhepatic gallbladder drainage (PTGD) for high-risk elderly patients with acute cholecystitis. Retrospective analysis of 159 acute cholecystitis patients who were admitted to General Surgery Division III of the First Affiliated Hospital of Dalian Medical University between January 2005 and November 2012. A total of 123 patients underwent laparoscopic cholecystectomy (LC), and 36 received only PTGD treatment. The LC patients were divided into 3 groups based on their preoperative treatment: group A, emergency patients (33 patients); group B (26 patients), patients who were treated with PTGD prior to LC; and group C (64 patients), patients who received nonsurgical treatment prior to LC. General conditions, LC surgery duration, intraoperative blood loss, rate of conversion to open surgery, incidence of postoperative complications, total fasting time, and total hospitalization time were analyzed and compared among the 3 groups. The remission rates of patients in the PTGD treatment groups (including group B and PTGD treatment only group) were significantly higher within 24 and 48 hours than those of patients who received nonsurgical treatment prior to LC (P < 0.05). Among the patients in the 3 surgery groups, the operation conversion rate (19.2%) of group B was significantly higher than that of group A (3.0%) and group C (1.6%) (P < 0.05). The total hospitalization time of the patients in group B (18.5 ± 4.5 days) was longer than that of the patients in group A (8.2 ± 3.9 days) and group C (10.5 ± 6.4 days). The total fasting time of the patients in group A (2.4 ± 1.2 days) was significantly shorter than that of those in group B (4.1 ± 1.7 days) and group C (3.4 ± 2.7 days) (P < 0.05). For high-risk elderly patients, if there is any emergency surgery contraindication, PTGD therapy may be safe and effective and can relieve the symptoms within a short time. For acute

  9. The Efficacy of Percutaneous Transhepatic Gallbladder Drainage on Acute Cholecystitis in High-Risk Elderly Patients Based on the Tokyo Guidelines: A Retrospective Case-Control Study.

    PubMed

    Ni, Qingqiang; Chen, Dongbo; Xu, Rui; Shang, Dong

    2015-08-01

    To evaluate the efficacy of percutaneous transhepatic gallbladder drainage (PTGD) for high-risk elderly patients with acute cholecystitis.Retrospective analysis of 159 acute cholecystitis patients who were admitted to General Surgery Division III of the First Affiliated Hospital of Dalian Medical University between January 2005 and November 2012. A total of 123 patients underwent laparoscopic cholecystectomy (LC), and 36 received only PTGD treatment. The LC patients were divided into 3 groups based on their preoperative treatment: group A, emergency patients (33 patients); group B (26 patients), patients who were treated with PTGD prior to LC; and group C (64 patients), patients who received nonsurgical treatment prior to LC. General conditions, LC surgery duration, intraoperative blood loss, rate of conversion to open surgery, incidence of postoperative complications, total fasting time, and total hospitalization time were analyzed and compared among the 3 groups.The remission rates of patients in the PTGD treatment groups (including group B and PTGD treatment only group) were significantly higher within 24 and 48 hours than those of patients who received nonsurgical treatment prior to LC (P < 0.05). Among the patients in the 3 surgery groups, the operation conversion rate (19.2%) of group B was significantly higher than that of group A (3.0%) and group C (1.6%) (P < 0.05). The total hospitalization time of the patients in group B (18.5 ± 4.5 days) was longer than that of the patients in group A (8.2 ± 3.9 days) and group C (10.5 ± 6.4 days). The total fasting time of the patients in group A (2.4 ± 1.2 days) was significantly shorter than that of those in group B (4.1 ± 1.7 days) and group C (3.4 ± 2.7 days) (P < 0.05).For high-risk elderly patients, if there is any emergency surgery contraindication, PTGD therapy may be safe and effective and can relieve the symptoms within a short time. For acute cholecystitis patients

  10. High-Risk Enteric Pathogens Associated with HIV-Infection and HIV-Exposure in Kenyan Children with Acute Diarrhea

    PubMed Central

    PAVLINAC, PB; JOHN-STEWART, GC; NAULIKHA, JM; ONCHIRI, FM; DENNO, DM; ODUNDO, EA; SINGA, BO; RICHARDSON, BA; WALSON, JL

    2015-01-01

    Objective HIV-infection is an established risk for diarrheal severity, less is known about specific enteric pathogens associated with HIV status. We determined associations of selected enteric pathogens with HIV-infection and HIV-exposure among Kenyan children. Design Cross-sectional study among 6 months to 15 year olds presenting to two Western Kenya District hospitals with acute diarrhea between 2011–2013. Methods Stool was tested using standard bacterial culture and microscopy for ova and parasites. HIV testing was obtained on children and mothers. Enteric pathogen prevalence was compared between HIV-infected and HIV-uninfected children and between HIV-exposed uninfected (HEU) and HIV-unexposed. Unadjusted and adjusted prevalence ratios (PR) for selected pathogens by HIV-status were estimated using relative risk (RR) regression and P-values. Age, site, income, household crowding, water source/treatment, anthropometrics, cotrimoxazole use, and breastfeeding history were accounted for in multivariable models. Results Among 1,076 children, median age was 22 months (interquartile range: 11–42), 56 (5.2%) were HIV-infected, and 10.3%(105/1020) of HIV-uninfected children were HIV-exposed. The following organisms were most frequently isolated from stool: enteroaggregative Escherichia coli (13.3%), Giardia spp. (11.1%) Campylobacter (6.3%), enteropathogenic Escherichia coli (EPEC) (6.1%) and Cryptosporidium spp. (3.7%). Accounting for age, HIV-infection was associated with EPEC infection (PR: 3.70, P=0.002) while HIV-exposure was associated with Cryptosporidium among HIV-uninfected children (PR: 2.81, P=0.005). Conclusion EPEC and Cryptosporidium infections were more common in HIV-infected and HIV-exposed children, respectively. This could explain the increased mortality attributed to these pathogens in other studies. Interventions targeting EPEC and Cryptosporidium may reduce morbidity and mortality in high HIV-prevalence settings. PMID:25028987

  11. TIMP2•IGFBP7 biomarker panel accurately predicts acute kidney injury in high-risk surgical patients

    PubMed Central

    Gunnerson, Kyle J.; Shaw, Andrew D.; Chawla, Lakhmir S.; Bihorac, Azra; Al-Khafaji, Ali; Kashani, Kianoush; Lissauer, Matthew; Shi, Jing; Walker, Michael G.; Kellum, John A.

    2016-01-01

    BACKGROUND Acute kidney injury (AKI) is an important complication in surgical patients. Existing biomarkers and clinical prediction models underestimate the risk for developing AKI. We recently reported data from two trials of 728 and 408 critically ill adult patients in whom urinary TIMP2•IGFBP7 (NephroCheck, Astute Medical) was used to identify patients at risk of developing AKI. Here we report a preplanned analysis of surgical patients from both trials to assess whether urinary tissue inhibitor of metalloproteinase 2 (TIMP-2) and insulin-like growth factor–binding protein 7 (IGFBP7) accurately identify surgical patients at risk of developing AKI. STUDY DESIGN We enrolled adult surgical patients at risk for AKI who were admitted to one of 39 intensive care units across Europe and North America. The primary end point was moderate-severe AKI (equivalent to KDIGO [Kidney Disease Improving Global Outcomes] stages 2–3) within 12 hours of enrollment. Biomarker performance was assessed using the area under the receiver operating characteristic curve, integrated discrimination improvement, and category-free net reclassification improvement. RESULTS A total of 375 patients were included in the final analysis of whom 35 (9%) developed moderate-severe AKI within 12 hours. The area under the receiver operating characteristic curve for [TIMP-2]•[IGFBP7] alone was 0.84 (95% confidence interval, 0.76–0.90; p < 0.0001). Biomarker performance was robust in sensitivity analysis across predefined subgroups (urgency and type of surgery). CONCLUSION For postoperative surgical intensive care unit patients, a single urinary TIMP2•IGFBP7 test accurately identified patients at risk for developing AKI within the ensuing 12 hours and its inclusion in clinical risk prediction models significantly enhances their performance. LEVEL OF EVIDENCE Prognostic study, level I. PMID:26816218

  12. Filgrastim, Cladribine, Cytarabine, and Mitoxantrone Hydrochloride in Treating Patients With Newly Diagnosed or Relapsed/Refractory Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2016-03-30

    Acute Biphenotypic Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

  13. Dose-enhanced combined priming regimens for refractory acute myeloid leukemia and middle-and-high-risk myelodysplastic syndrome: a single-center, retrospective cohort study

    PubMed Central

    Ma, Xiaorong; Wang, Jin; Xu, Yan; Zhang, Wanggang; Liu, Jie; Cao, Xingmei; He, Aili; Wang, Fangxia; Gu, Liufang; Lei, Bo; Wang, Jianli

    2016-01-01

    Objective To assess chemotherapeutic regimens for refractory acute myeloid leukemia (AML) and middle-and-high-risk myelodysplastic syndrome (MDS). Methods Between 2004 and 2014, 44 patients with refractory AML and 36 patients with MDS were treated with new priming regimens (CHAG, CHTG, CHMG, or CTMG), and 77 patients with refractory AML and 52 patients with MDS were treated with conventional priming regimens (CHG or CAG). This was a single-center retrospective analysis of remission, adverse event, mortality, and survival. The capacity of clinical features (including the expression of co-stimulatory molecule B7.1 on tumor cells) to influence survival was assessed by multivariate Cox regression. Results Complete and partial remission rates (RRs) were significantly higher in AML patients treated with new regimens compared to conventional ones (68.2% vs 13.6%, P<0.05). Complete and partial remission were also significantly higher in patients with MDS treated with new regimens (55.6% vs 19.4%, P<0.05). However, although survival advantages were observed in the first year, the new regimens did not significantly improve 3-year overall survival (P>0.05). Patients administered the new regimens experienced more severe and sustained myelosuppression (P<0.05), but no severe adverse events or treatment-related deaths were observed. The rate of non-hematological side effects did not differ significantly between treatment regimens (P>0.05). Both RR and B7.1 expression were significantly higher in patients with AML-M2 and M5 (P<0.05). Conclusion The new priming regimens improved the RR, lowered the recurrence rate, and improved survival in AML and middle-and-high-risk MDS, without significantly increasing adverse events. PMID:27382304

  14. High hyperdiploid childhood acute lymphoblastic leukemia: Chromosomal gains as the main driver event.

    PubMed

    Paulsson, Kajsa

    2016-01-01

    High hyperdiploid childhood acute lymphoblastic leukemia is characterized by multiple chromosomal gains. Recent results show that this subtype harbors relatively few genetic abnormalities besides the extra chromosomes, which appear to arise early and are likely the main driver event. Secondary hits primarily target genes in the rat sarcoma (RAS) signaling pathway and histone modifiers. PMID:27308574

  15. High hyperdiploid childhood acute lymphoblastic leukemia: Chromosomal gains as the main driver event

    PubMed Central

    Paulsson, Kajsa

    2016-01-01

    ABSTRACT High hyperdiploid childhood acute lymphoblastic leukemia is characterized by multiple chromosomal gains. Recent results show that this subtype harbors relatively few genetic abnormalities besides the extra chromosomes, which appear to arise early and are likely the main driver event. Secondary hits primarily target genes in the rat sarcoma (RAS) signaling pathway and histone modifiers. PMID:27308574

  16. Predictors of Developmental Outcomes of High-Risk and Developmentally Delayed Infants and Children Enrolled in a State Early Childhood Intervention Program

    ERIC Educational Resources Information Center

    Giannoni, Peggy P.; Kass, Philip H.

    2012-01-01

    A retrospective cohort study was conducted to identify child, maternal, family, and community factors associated with rate of developmental disability among children enrolled in the California Early Start Program. The cohort included 8,987 children considered at high risk for developmental disability due to medical risks and/or developmental…

  17. Idarubicin-intensified BUCY2 conditioning regimen improved survival in high-risk acute myeloid, but not lymphocytic leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: A retrospective comparative study.

    PubMed

    Fang, Jun; Zhang, Ran; Wang, Huafang; Hong, Mei; Wu, Qiuling; Nie, Dimin; You, Yong; Zhong, Zhaodong; Li, Weiming; Hu, Yu; Xia, Linghui

    2016-07-01

    The intensity of conditioning regimen is highly correlated with outcomes of allogeneic hematopoietic stem cell transplantation (allo-HSCT). We have previously reported that idarubicin (IDA) intensified BUCY2 regimen could reduce relapse and improve survival for high-risk hematological malignancies undergoing allo-HSCT. However, there is no published study comparing the efficacy of IDA-BUCY2 regimen for high-risk acute myeloid leukemia (AML) versus acute lymphocytic leukemia (ALL). We further retrospectively compared therapeutic outcomes of intensified conditioning regimen on 140 high-risk AML and ALL patients in the data analyses. IDA 15mg/m(2)/d was administered by continuous infusion from day -11 to -9, followed by intravenous injection of busulfan (BU) (3.2mg/kg/d) from day -6 to -4, and intravenous injection of cyclophosphamide (CY) (1.8g/m(2)/d) from day -3 to -2 in IDA-BUCY2 regimen. For high-risk AML, cumulative probabilities of 3-year relapse rates in IDA-BUCY2 and traditional BUCY2 regimens were 16.9%, 43.3% (P=0.016). Cumulative probabilities of 3-year overall survival (OS) and disease-free survival (DFS) were 69.2% vs 44.0% (P=0.024), and 66.9% vs 38.2% (P=0.01). However, two regimens showed no significant differences for high-risk ALL. Multivariate analysis also indicated that IDA intensified BUCY2 conditioning was the favorable variable to reduce relapse and elevate survival for high-risk AML patients. In conclusion, IDA-BUCY2 regimen reduces relapse and improves survival for high-risk AML undergoing allo-HSCT, but not presenting uniform therapeutic effects for high-risk ALL. PMID:27131062

  18. Comparison of allogeneic stem cell transplantation from familial-mismatched/haploidentical donors and from unrelated donors in adults with high-risk acute myelogenous leukemia.

    PubMed

    Cho, Byung-Sik; Yoon, Jae-Ho; Shin, Seung-Hwan; Yahng, Seung-Ah; Lee, Sung-Eun; Eom, Ki-Seong; Kim, Yoo-Jin; Lee, Seok; Min, Chang-Ki; Cho, Seok-Goo; Kim, Dong-Wook; Lee, Jong-Wook; Min, Woo-Sung; Park, Chong-Won; Kim, Hee-Je

    2012-10-01

    To weigh the pros and cons of familial-mismatched/haploidentical transplantation (FMT) in patients with high-risk acute myelogenous leukemia, we assessed outcomes of 23 patients who underwent FMT, using reduced-intensity conditioning with total body irradiation 800 cGy/busulfan/fludarabine/antithymocyte globulin without ex vivo T cell depletion, compared to 33 patients who underwent well-matched unrelated donor transplantation (WM-UDT) and 13 who underwent partially matched unrelated donor transplantation (PM-UDT) during the same period. The FMT patients had not only a similar pattern of engraftment and immune reconstitution as the WM-UDT and PM-UDT patients but also comparable incidences and severity of acute and chronic graft-versus-host disease. The FMT patients did not experience any form of engraftment failure. However, the cumulative incidence of cytomegalovirus DNAemia was significantly higher in the FMT group compared with the other groups (P = .036). After a median follow-up of 28 months, overall survival, disease-free survival, relapse, and nonrelapse mortality were 83%, 74%, 20%, and 7%, respectively, for WM-UDT; 51%, 51%, 31%, and 18% for PM-UDT; and 66%, 64%, 26%, and 10% for FMT. This demonstrates a trend for favorable survival outcomes of WM-UDT over FMT and of FMT over PM-UDT. However, we found no significant statistical differences in survival according to donor type. These data need to be interpreted cautiously because of limited power calculations due to the small number of each donor group. This pilot study suggests the feasibility of FMT using our novel regimen with careful evaluation of CMV DNAemia compared with WM-UDT and PM-UDT. Further trials with larger numbers of patients, comparing FMT directly with transplantation with other donor types, are needed. PMID:22516055

  19. Evaluation of early interventional treatment opportunity of the elderly & high-risk patients with non-ST segment elevation acute myocardial infarction

    PubMed Central

    Liu, Zhiqiang; Zhao, Lipei; Li, Yibo; Wang, Zhifang; Liu, Lingling; Zhang, Fucheng

    2015-01-01

    Objective: To investigate the effect of treatment on prognosis of patients with different timing of early interventional treatment for non-ST segment elevation acute myocardial infarction (NSTEMI). Methods: Forty two cases above 75 years old, diagnosed with high-risk on NSTEMI, were selected in cardiology department of Xinxiang central hospital. They were randomly divided into two groups: 22 in group A and 20 in group B. Group A was performed PCI surgery within 12 hours after the onset while group B from 12 to 24 hour after the onset. Major adverse cardiovascular events (including death, heart failure readmission rates after ischemia, malignant arrhythmias, again target vessel revascularization) and bleeding data were recorded at the three terms of hospitalization, one month after the onset and six months after the onset. Results: Angina, malignant arrhythmia and heart failure during hospitalization can be reduced after interventional treatment carried out within 12 hours after the onset. Readmission rates after ischemia, heart failure and the incidence of death can be significantly reduced after interventional treatment carried out during 1-6 month after the onset with no significant increase in bleeding rate. Conclusion: In the treatment of elderly patients with NSTEMI, early interventional treatment is safe and effective. PMID:26648985

  20. The impact of dose escalation and resistance modulation in older patients with acute myeloid leukaemia and high risk myelodysplastic syndrome: the results of the LRF AML14 trial.

    PubMed

    Burnett, Alan K; Milligan, Donald; Goldstone, Anthony; Prentice, Archibald; McMullin, Mary-Frances; Dennis, Michael; Sellwood, Elizabeth; Pallis, Monica; Russell, Nigel; Hills, Robert K; Wheatley, Keith

    2009-05-01

    The acute myeloid leukaemia (AML)14 trial addressed four therapeutic questions in patients predominantly aged over 60 years with AML and High Risk Myelodysplastic Syndrome: (i) Daunorubicin 50 mg/m(2) vs. 35 mg/m(2); (ii) Cytarabine 200 mg/m(2) vs. 400 mg/m(2) in two courses of DA induction; (iii) for part of the trial, patients allocated Daunorubicin 35 mg/m(2) were also randomized to receive, or not, the multidrug resistance modulator PSC-833 in a 1:1:1 randomization; and (iv) a total of three versus four courses of treatment. A total of 1273 patients were recruited. The response rate was 62% (complete remission 54%, complete remission without platelet/neutrophil recovery 8%); 5-year survival was 12%. No benefits were observed in either dose escalation randomization, or from a fourth course of treatment. There was a trend for inferior response in the PSC-833 arm due to deaths in induction. Multivariable analysis identified cytogenetics, presenting white blood count, age and secondary disease as the main predictors of outcome. Although patients with high Pgp expression and function had worse response and survival, this was not an independent prognostic factor, and was not modified by PSC-833. In conclusion, these four interventions have not improved outcomes in older patients. New agents need to be explored and novel trial designs are required to maximise prospects of achieving timely progress. PMID:19291085

  1. Resveratrol given intraperitoneally does not inhibit the growth of high-risk t(4;11) acute lymphoblastic leukemia cells in a NOD/SCID mouse model

    PubMed Central

    ZUNINO, SUSAN J.; STORMS, DAVID H.; NEWMAN, JOHN W.; PEDERSEN, THERESA L.; KEEN, CARL L.; DUCORE, JONATHAN M.

    2012-01-01

    The efficacy of resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL SEM cell line. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, mice were injected intraperitoneally with resveratrol (10 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). Comparisons of the percent of human leukemia cells in blood and survival curves showed resveratrol did not inhibit progression of the disease. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed resveratrol was rapidly metabolized to glucuronidated and sulfated forms 1 h post-injection, with low to no resveratrol or metabolites observed in sera by 24–48 h. These data indicate that in contrast to findings in in vitro models, parenterally administered resveratrol does not have potential as a preventive agent against high risk t(4;11) ALL. PMID:22200740

  2. GTI-2040 in Treating Patients With Relapsed, Refractory, or High-Risk Acute Leukemia, High-Grade Myelodysplastic Syndromes, or Refractory or Blastic Phase Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2015-12-03

    Acute Undifferentiated Leukemia; 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); Blastic Phase Chronic Myelogenous Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  3. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Lymphocytic or Myelogenous Leukemia

    ClinicalTrials.gov

    2016-09-07

    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 Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia

  4. Mutations in LPIN1 cause recurrent acute myoglobinuria in childhood.

    PubMed

    Zeharia, Avraham; Shaag, Avraham; Houtkooper, Riekelt H; Hindi, Tareq; de Lonlay, Pascale; Erez, Gilli; Hubert, Laurence; Saada, Ann; de Keyzer, Yves; Eshel, Gideon; Vaz, Frédéric M; Pines, Ophry; Elpeleg, Orly

    2008-10-01

    Recurrent episodes of life-threatening myoglobinuria in childhood are caused by inborn errors of glycogenolysis, mitochondrial fatty acid beta-oxidation, and oxidative phosphorylation. Nonetheless, approximately half of the patients do not suffer from a defect in any of these pathways. Using homozygosity mapping, we identified six deleterious mutations in the LPIN1 gene in patients who presented at 2-7 years of age with recurrent, massive rhabdomyolysis. The LPIN1 gene encodes the muscle-specific phosphatidic acid phosphatase, a key enzyme in triglyceride and membrane phospholipid biosynthesis. Of six individuals who developed statin-induced myopathy, one was a carrier for Glu769Gly, a pathogenic mutation in the LPIN1 gene. Analysis of phospholipid content disclosed accumulation of phosphatidic acid and lysophospholipids in muscle tissue of the more severe genotype. Mutations in the LPIN1 gene cause recurrent rhabdomyolysis in childhood, and a carrier state may predispose for statin-induced myopathy. PMID:18817903

  5. Uptake of childhood influenza vaccine from 2012–2013 to 2014–2015 in the UK and the implications for high-risk children: a retrospective observational cohort study

    PubMed Central

    Rajaram, Sankarasubramanian; Steffey, Amy; Blak, Betina; Hickman, Matthew; Christensen, Hannah; Caspard, Herve

    2016-01-01

    Objectives To evaluate changes in influenza vaccination rates in healthy and at-risk children following the implementation of the UK's childhood influenza immunisation programme. Design Observational cohort study before and after initiation of the UK's childhood influenza immunisation programme over three influenza seasons (2012–2013, 2013–2014 and 2014–2015) using data from the Clinical Practice Research Datalink (CPRD). Setting More than 500 primary care practices in the UK. Population All individuals aged 2–17 years on 1 September, with at least 12 months of medical history documented in CPRD were retained in the analysis. Intervention Starting in 2013–2014, all children aged 2 and 3 years were offered influenza vaccination through general practice, and primary school-aged children were offered influenza vaccination in selected counties in England (described as pilot regions). The vaccination programme was extended to all children aged 4 years in England in 2014–2015. Main outcome measure Cumulative vaccination rate from 1 September to 28 February of the next calendar year as assessed by a time-to-event statistical model (vaccination uptake). Age group, sex, region and type of high-risk medical condition were assessed as predictors. Results Vaccination uptake increased considerably from 2012–2013 to 2013–2014 in targeted children aged 2–3 years, both in children with a high-risk medical condition (from 40.7% to 61.1%) and those without (from 1.0% to 43.0%). Vaccination rates increased also, though less markedly, in older children. In 2014–2015, vaccination rates remained higher than 40% in healthy children aged 2–3 years, although they decreased slightly from 2013–2014 (from 43.0% to 41.8%). Vaccination rates in older healthy children continued to increase, driven primarily by an increase in children aged 4 years to 31.3% in 2014–2015. Conclusions The introduction of a universal childhood vaccination policy in the UK

  6. Acute and late toxicity following adjuvant high-dose chemotherapy for high-risk primary operable breast cancer--a quality assessment study.

    PubMed

    Svane, Inge M; Homburg, Keld M; Kamby, Claus; Nielsen, Dorte L; Roer, Ole; Sliffsgaard, Dorte; Johnsen, Hans E; Hansen, Steen W

    2002-01-01

    From 1996 to 2000, high-dose chemotherapy with haematopoietic stem-cell support was used as an adjuvant treatment strategy for management of primary high-risk breast cancer patients with more than five positive nodes. This single institution study included 52 women aged < or = 56 years with primary operable breast cancer and > or = 6 tumour-positive axillary lymph nodes. The treatment regimen consisted of at least three initial courses of FEC (5-fluorouracil, epirubicin, cyclophosphamide) followed by high-dose chemotherapy (cyclophosphamide, thiotepa, carboplatin) supported by autologous peripheral blood stem-cell reinfusion. This study focuses on quality control including evaluation of toxicity, supportive therapy and assessment of the stem-cell products. Cytokeratin 19 positive cells were found in the stem-cell product from 3/37 patients. Data regarding organ toxicity were used for evaluation of short- and long-term side effects. Substantial acute toxicity and frequent catheter-related infections were found. Long-term toxicities included reduced lung diffusion capacity (n = 36), fatigue (n = 14), arthralgia/myalgia (n = 10), neurotoxicity (n = 9) and memory loss (n = 4). However, most toxicities were grade 1-2 and reversible within two years. No treatment-related death occurred. Within a median follow-up of 30 months (range, 11-57), 25% of the patients had relapsed. Recurrence-free survival was 75% and overall survival was 88% three years after the start of treatment. Overall, high-dose chemotherapy was relatively well tolerated, with manageable toxicity and an acceptable requirement of supportive therapy. Until now, high-dose chemotherapy has not proven superior to conventional-dose adjuvant chemotherapy, therefore it is necessary in the future to focus on well-designed randomized studies. PMID:14651213

  7. Phase II study of tosedostat with cytarabine or decitabine in newly diagnosed older patients with acute myeloid leukaemia or high-risk MDS.

    PubMed

    Mawad, Raya; Becker, Pamela S; Hendrie, Paul; Scott, Bart; Wood, Brent L; Dean, Carol; Sandhu, Vicky; Deeg, Hans Joachim; Walter, Roland; Wang, Lixia; Myint, Han; Singer, Jack W; Estey, Elihu; Pagel, John M

    2016-01-01

    Tosedostat, an oral aminopeptidase inhibitor, has synergy with cytarabine and hypomethylating agents. We performed a Phase II trial to determine rates of complete remission (CR) and survival using tosedostat with cytarabine or decitabine in older patients with untreated acute myeloid leukaemia (AML) or high-risk myelodysplastic syndrome (MDS). Thirty-four patients ≥60 years old (median age 70 years; range, 60-83) were randomized to receive tosedostat (120 mg on days 1-21 or 180 mg continuously) with 5 d of either cytarabine (1 g/m2 /d) or decitabine (20 mg/m2 /d) every 35 d. Twenty-nine patients (85%) had AML, including 15 (44%) with secondary AML/MDS, and 5 (15%) had MDS-refractory anaemia with excess blasts type 2. The CR/CR with incomplete count recovery (CRi) rate was 53% [9 in each arm; 14 CR (41%) and 4 CRi (12%)], attained in 6 of 14 patients with adverse cytogenetics and 4 of 7 with FLT3-internal tandem duplication mutations. Median follow-up was 11.2 months (range, 0.5-22.3), and median survival was 11.5 months (95% confidence interval, 5.2-16.7). Twenty-three patients (67.6%) were treated as outpatients and 10 of these patients required hospitalization for febrile neutropenia. No Grade 3-4 non-haematological toxicities required withdrawal from study. Tosedostat with cytarabine or decitabine is tolerated in older patients with untreated AML/MDS, results in a CR/CRi rate of >50%, and warrants further study in larger trials. PMID:26568032

  8. Inherited GATA3 variants are associated with Ph-like childhood acute lymphoblastic leukemia and risk of relapse

    PubMed Central

    Perez-Andreu, Virginia; Roberts, Kathryn G.; Harvey, Richard C.; Yang, Wenjian; Cheng, Cheng; Pei, Deqing; Xu, Heng; Gastier-Foster, Julie; Shuyu, E; Yew-Suang Lim, Joshua; Chen, I-Ming; Fan, Yiping; Devidsa, Meenakshi; Borowitz, Michael J.; Smith, Colton; Neale, Geoffrey; Burchard, Esteban G.; Torgerson, Dara G.; Klussmann, Federico Antillon; Villagran, Cesar Rolando Najera; Winick, Naomi J.; Camitta, Bruce M.; Raetz, Elizabeth; Wood, Brent; Yue, Feng; Carroll, William L.; Larsen, Eric; Bowman, W. Paul; Loh, Mignon L.; Dean, Michael; Bhojwani, Deepa; Pui, Ching-Hon; Evans, William E.; Relling, Mary V.; Hunger, Stephen P.; Willman, Cheryl L.; Mullighan, Charles G.; Yang, Jun J.

    2014-01-01

    Recent genomic profiling of childhood acute lymphoblastic leukemia (ALL) identified a novel high-risk subtype with a gene expression signature resembling Philadelphia chromosome-positive ALL and a poor prognosis (Ph-like ALL). However, the role of inherited genetic variation in Ph-like ALL pathogenesis remains unknown. In a genome-wide association study (GWAS) of 511 ALL cases and 6,661 non-ALL controls, we identified a single susceptibility locus for Ph-like ALL (GATA3, rs3824662, P=2.17×10−14, odds ratio [OR]=3.85, for Ph-like ALL vs. non-ALL; P=1.05×10−8, OR=3.25, for Ph-like ALL vs. non-Ph-like ALL) that was independently validated. The rs3824662 risk allele was associated with somatic lesions underlying Ph-like ALL (i.e., CRLF2 rearrangement, JAK mutation, and IKZF1 deletion) and directly influenced GATA3 transcription. Finally, GATA3 SNP genotype was also associated with early treatment response and the risk of ALL relapse. Our results provide insights into interactions between host and tumor genomes and their importance in ALL pathogenesis and prognosis. PMID:24141364

  9. Veliparib and Topotecan With or Without Carboplatin in Treating Patients With Relapsed or Refractory Acute Leukemia, High-Risk Myelodysplasia, or Aggressive Myeloproliferative Disorders

    ClinicalTrials.gov

    2016-04-05

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; 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 Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndrome; Essential Thrombocythemia; Hematopoietic and Lymphoid Cell Neoplasm; Philadelphia Chromosome Negative, BCR-ABL1 Positive Chronic Myelogenous Leukemia; Polycythemia Vera; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Disease; Secondary Myelodysplastic Syndrome

  10. Development of secondary skull sarcoma after treatment for childhood acute myeloid leukemia.

    PubMed

    Ohno, Makoto; Narita, Yoshitaka; Miyakita, Yasuji; Okita, Yoshiko; Kayama, Takamasa; Shibui, Soichiro

    2012-12-01

    Secondary cancer is a serious late complication in childhood leukemia survivors. Here, we report a case of secondary skull sarcoma developing after treatment for childhood acute myeloid leukemia, including bone marrow transplantation (BMT). This patient had breast cancer 1 year before treatment for the skull sarcoma. The patient underwent macroscopic total removal of the skull tumor with bone margin with postoperative radiation therapy and did not develop tumor recurrence for 25 months. Our patient's experience suggests that survivors of childhood leukemia are at risk of developing skull sarcoma and that multi-agent chemotherapy, including anthracycline, TBI used as conditioning for BMT, and development of GVHD, are possible risk factors. Considering the possibility of multiple secondary malignancies in such patients, careful long-term follow up is mandatory. PMID:22897987

  11. Does childhood misfortune raise the risk of acute myocardial infarction in adulthood?

    PubMed Central

    Morton, Patricia M.; Mustillo, Sarah A.; Ferraro, Kenneth F.

    2014-01-01

    Whereas most research on acute myocardial infarction (AMI) has focused on more proximal influences, such as adult health behaviors, the present study examines the early origins of AMI. Longitudinal data were drawn from the National Survey of Midlife Development in the United States (N=3,032), a nationally representative survey of men and women aged 25–74, which spans from 1995 to 2005. A series of event history analyses modeling age of first AMI investigated the direct effects of accumulated and separate domains of childhood misfortune as well as the mediating effects of adult health lifestyle and psychosocial factors. Findings reveal that accumulated childhood misfortune and child maltreatment increased AMI risk, net of several adult covariates, including family history of AMI. Smoking fully mediated the effects of both accumulated childhood misfortune and child maltreatment. These findings reveal the importance of the early origins of AMI and health behaviors as mediating factors. PMID:24581071

  12. Does childhood misfortune raise the risk of acute myocardial infarction in adulthood?

    PubMed

    Morton, Patricia M; Mustillo, Sarah A; Ferraro, Kenneth F

    2014-03-01

    Whereas most research on acute myocardial infarction (AMI) has focused on more proximal influences, such as adult health behaviors, the present study examines the early origins of AMI. Longitudinal data were drawn from the National Survey of Midlife Development in the United States (N = 3032), a nationally representative survey of men and women aged 25-74, which spans from 1995 to 2005. A series of event history analyses modeling age of first AMI investigated the direct effects of accumulated and separate domains of childhood misfortune as well as the mediating effects of adult health lifestyle and psychosocial factors. Findings reveal that accumulated childhood misfortune and child maltreatment increased AMI risk, net of several adult covariates, including family history of AMI. Smoking fully mediated the effects of both accumulated childhood misfortune and child maltreatment. These findings reveal the importance of the early origins of AMI and health behaviors as mediating factors. PMID:24581071

  13. 7-Hydroxystaurosporine and Perifosine in Treating Patients With Relapsed or Refractory Acute Leukemia, Chronic Myelogenous Leukemia or High Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2013-09-27

    Accelerated Phase Chronic Myelogenous Leukemia; 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 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); Adult Acute Myelomonocytic Leukemia (M4); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Blastic Phase Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Neoplasms; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia; T-cell Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Myeloid Leukemia

  14. The effect of sodium tetraborate and alum in the management of acute childhood diarrhoea.

    PubMed

    Aung, M M; U, P P

    1986-03-01

    The effect of oral rehydration (OR) has been well established in the management of dehydration in acute childhood diarrhoea. Many authors have been trying to find additives of all types which would be effective in retaining oral fluids and promoting their active absorption into the circulation. Any agent which will effectively reduce oral rehydration requirements should be considered for prospective studies. Amongst the traditional medicines, it was noticed that sodium tetraborate (borax) and alum reduced appreciably the fluid requirement in many cases of acute childhood diarrhoea. This traditional usage of these chemicals without any noticeable side effects has been described for centuries. During preliminary observations on 26 of our children given these salts no side effects were detected. PMID:2428288

  15. Acute Ataxia in Childhood: 11-Year Experience at a Major Pediatric Neurology Referral Center.

    PubMed

    Thakkar, Kavita; Maricich, Stephen M; Alper, Gulay

    2016-08-01

    We categorized the causes of acute ataxia in the pediatric population-referred to the Division of Neurology-at a large, urban pediatric medical center. Of the 120 cases identified over the past 11 years, post-infectious cerebellar ataxia was the most commonly diagnosed (59%), followed by drug intoxication, opsoclonus-myoclonus ataxia syndrome, episodic ataxia, acute cerebellitis, cerebellar stroke, ADEM, meningitis, cerebral vein thrombosis, Leigh's disease, Miller-Fisher syndrome, and concussion. Among the patients with post-infectious cerebellar ataxia, 85% were 1-6 years old and all had a history of antecedent viral illness. CSF pleocytosis was present in 40% of patients; all had normal brain MRIs. The majority (91%) recovered within 30 days. We conclude that post-infectious cerebellar ataxia remains the most common cause of acute ataxia in childhood and that it carries a good prognosis. We also differentiate acute post-infectious cerebellar ataxia from other causes with similar presentations. PMID:27071467

  16. Clofarabine and Cytarabine in Treating Older Patients With Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes That Have Relapsed or Not Responded to Treatment

    ClinicalTrials.gov

    2013-08-06

    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); Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  17. Minimal residual disease analysis by eight-color flow cytometry in relapsed childhood acute lymphoblastic leukemia

    PubMed Central

    Karawajew, Leonid; Dworzak, Michael; Ratei, Richard; Rhein, Peter; Gaipa, Giuseppe; Buldini, Barbara; Basso, Giuseppe; Hrusak, Ondrej; Ludwig, Wolf-Dieter; Henze, Günter; Seeger, Karl; von Stackelberg, Arend; Mejstrikova, Ester; Eckert, Cornelia

    2015-01-01

    Multiparametric flow cytometry is an alternative approach to the polymerase chain reaction method for evaluating minimal residual disease in treatment protocols for primary acute lymphoblastic leukemia. Given considerable differences between primary and relapsed acute lymphoblastic leukemia treatment regimens, flow cytometric assessment of minimal residual disease in relapsed leukemia requires an independent comprehensive investigation. In the present study we addressed evaluation of minimal residual disease by flow cytometry in the clinical trial for childhood relapsed acute lymphoblastic leukemia using eight-color flow cytometry. The major challenge of the study was to reliably identify low amounts of residual leukemic cells against the complex background of regeneration, characteristic of follow-up samples during relapse treatment. In a prospective study of 263 follow-up bone marrow samples from 122 patients with B-cell precursor acute lymphoblastic leukemia, we tested various B-cell markers, adapted the antibody panel to the treatment protocol, and evaluated its performance by a blinded parallel comparison with the polymerase chain reaction data. The resulting eight-color single-tube panel showed a consistently high overall concordance (P<0.001) and, under optimal conditions, sensitivity similar to that of the reference polymerase chain reaction method. Overall, evaluation of minimal residual disease by flow cytometry can be successfully integrated into the clinical management of relapsed childhood acute lymphoblastic leukemia either as complementary to the polymerase chain reaction or as an independent risk stratification tool. ALL-REZ BFM 2002 clinical trial information: NCT00114348 PMID:26001791

  18. Parents' help-seeking behaviours during acute childhood illness at home: A contribution to explanatory theory.

    PubMed

    Neill, Sarah J; Jones, Caroline H D; Lakhanpaul, Monica; Roland, Damian T; Thompson, Matthew J

    2016-03-01

    Uncertainty and anxiety surround parents' decisions to seek medical help for an acutely ill child. Consultation rates for children are rising, yet little is known about factors that influence parents' help-seeking behaviours. We used focus groups and interviews to examine how 27 parents of children under five years, from a range of socioeconomic groups in the East Midlands of England, use information to make decisions during acute childhood illness at home. This article reports findings elucidating factors that influence help-seeking behaviours. Parents reported that decision-making during acute childhood illness was influenced by a range of personal, social and health service factors. Principal among these was parents' concern to do the right thing for their child. Their ability to assess the severity of the illness was influenced by knowledge and experience of childhood illness. When parents were unable to access their general practitioner (GP), feared criticism from or had lost trust in their GP, some parents reported using services elsewhere such as Accident and Emergency. These findings contribute to explanatory theory concerning parents' help-seeking behaviours. Professional and political solutions have not reduced demand; therefore, collaborative approaches involving the public and professionals are now needed to improve parents' access to information. PMID:25296933

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

    PubMed Central

    Liu, Ruiling; Zhang, Luoping; McHale, Cliona M.; Hammond, S. Katharine

    2011-01-01

    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. PMID:21765828

  20. Sirolimus and Azacitidine in Treating Patients With High Risk Myelodysplastic Syndrome or Acute Myeloid Leukemia That is Recurrent or Not Eligible for Intensive Chemotherapy

    ClinicalTrials.gov

    2016-06-03

    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); de Novo Myelodysplastic Syndromes; Myelodysplastic Syndrome With Isolated Del(5q); Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia

  1. Bone marrow fibrosis in childhood acute lymphoblastic leukaemia.

    PubMed Central

    Wallis, J P; Reid, M M

    1989-01-01

    Bone marrow trephine biopsy specimens were obtained at diagnosis from 63 of 76 consecutively presenting children with acute lymphoblastic leukaemia (ALL). The association between marrow fibrosis and presenting features, including immunophenotype, was analysed. Reticulin was increased in 45 of 56 cases in which blasts expressed B lineage markers, but in only one of seven with T-ALL. A weak association was also found between marrow fibrosis and splenomegaly in those with common ALL. Marrow fibrosis is apparently associated with some examples of ALL of B cell lineage, but precisely which subtypes and whether the phenomenon is clinically important remain to be determined. PMID:2613918

  2. Cranial radiation in childhood acute lymphocytic leukemia. Neuropsychologic sequelae

    SciTech Connect

    Whitt, J.K.; Wells, R.J.; Lauria, M.M.; Wilhelm, C.L.; McMillan, C.W.

    1984-08-01

    A battery of neuropsychologic tests was administered ''blindly'' to 18 children with acute lymphocytic leukemia (ALL) who had been randomly assigned to treatment regimens with or without cranial radiation. These children were all in complete continuous remission for more than 3 1/2 years and were no longer receiving therapy. The results indicated no substantial differences between groups as a function of radiation therapy. However, decreased neuropsychologic performance was found when the entire sample was compared with population norms. These data do not support the hypothesis that cranial radiation therapy is responsible for the neuropsychologic sequelae seen in these survivors of ALL. Post hoc multiple regression analysis indicated that parental education levels accounted for more of the neuropsychologic variability seen in these children than other factors such as age at diagnosis, type of therapy, or sex of child.

  3. Metabolic syndrome in the survivors of childhood acute lymphoblastic leukaemia.

    PubMed

    Abu-Ouf, Noran M; Jan, Mohammed M

    2015-01-01

    Metabolic syndrome is a common complication encountered in children surviving acute lymphoblastic leukaemia (ALL). Affected patients develop obesity, insulin resistance, hypertension, and hyperlipidemia. Metabolic syndrome is a consequence of multiple factors, particularly hormonal imbalance induced by various ALL treatments. This review aims to evaluate the risk factors and mechanisms leading to the development of metabolic syndrome. Further research is needed to improve our understanding of the mechanisms leading to insulin resistance and the associated endothelial and adipose tissue dysfunction. Future studies should also examine other possible contributing factors, such as environmental and genetic factors. Understanding these factors will help in guiding modifications of the current ALL treatment protocols in order to prevent the development of this syndrome and hence improve the quality of life of ALL survivors. Until this is achieved, clinicians should continue to identify patients at risk early and use a therapeutic approach that combines dietary restrictions and enhanced physical activity. PMID:25081809

  4. The high risks of ventriculoperitoneal shunt procedures for hydrocephalus associated with vein of Galen malformations in childhood: case report and literature review.

    PubMed

    Jea, Andrew; Bradshaw, Tina J; Whitehead, William E; Curry, Daniel J; Dauser, Robert C; Luerssen, Thomas G

    2010-08-01

    Little to no pediatric or neurosurgical literature has been published about the complications of ventriculoperitoneal shunt procedures for hydrocephalus associated with vein of Galen malformations in childhood. The interventional neuroradiology literature, however, suggests that ventriculoperitoneal shunting as first-line treatment for hydrocephalus in children with vein of Galen malformations is fraught with short- and long-term dangers, including status epilepticus, intraventricular hemorrhage, subdural hematoma and hygroma, venous infarction, malignant dystrophic calcification, and worsening developmental delay. We present a single pediatric case where a ventriculoperitoneal shunt procedure for symptomatic hydrocephalus seemed to be the major contributing factor to the rapid neurological deterioration and eventual death of an infant with a vein of Galen malformation. Based on this experience and our review of the literature, we suggest the use of endovascular embolization of the vein of Galen malformation to reestablish a balance in hydrovenous dynamics as first-line treatment rather than directly addressing hydrocephalus with CSF diversion. The ventriculoperitoneal shunt procedure should be reserved for cases with symptomatic hydrocephalus in which the patient is a poor candidate for embolization, or for cases where endovascular therapy has already been maximized. The role of endoscopy in the treatment of hydrocephalus associated with vein of Galen malformations is not clear. PMID:20664304

  5. Household pesticide exposure and the risk of childhood acute leukemia in Shanghai, China.

    PubMed

    Zhang, Yan; Gao, Yu; Shi, Rong; Chen, Didi; Wang, Xiaojin; Kamijima, Michihiro; Sakai, Kiyoshi; Nakajima, Tamie; Khalequzzaman, Md; Zhou, Yijun; Zheng, Ying; Bao, Pingping; Tian, Ying

    2015-08-01

    Childhood acute leukemia (AL) is the most common malignant tumor in children, but its etiology remains largely unknown. We investigated the relationship between household exposure to pesticides and childhood AL. Between 2009 and 2010 in Shanghai, a total of 248 newly diagnosed cases of AL and 111 gender-, age-, and hospital-matched controls were included. Five nonspecific dialkyl phosphate (DAP) metabolites of organophosphate pesticides (OPPs) [including dimethyl phosphate (DMP), diethyl phosphate (DEP), dimethyl thiophosphate (DMTP), diethyl thiophosphate (DETP), and diethyl dithiophosphate (DEDTP)] in the urine were analyzed by gas chromatography. The results showed that the median DMP, DEP, DMTP, DETP, and DEDEP levels adjusted for creatinine (Cr) in cases (13.2, 10.0, 31.3, 8.5, and 6.1 μg g(-1), respectively) were all significantly elevated compared with those in controls (3.6, 3.6, 13.3, 2.7, and 1.7 μg g(-1), respectively) (P < 0.05). The household use of mosquito repellent was significantly associated with an increased risk of childhood AL (odds ratio (OR) = 1.9; 95% confidence interval (CI) 1.2-3.1). Moreover, higher exposures were significantly associated with an elevated risk of childhood AL for DMs, DEs, and DAPs. Our findings support the notion that the household use of pesticides may play a role in the etiology of childhood AL and provide some evidence to warrant further investigation of the link between household pesticide exposures and childhood AL in Shanghai. PMID:25854207

  6. Genetic markers in a multi-ethnic sample for childhood acute lymphoblastic leukemia risk.

    PubMed

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

    2015-01-01

    Genome-wide association studies have identified multiple risk loci for childhood acute lymphoblastic leukemia (ALL), but mostly in European/White populations, despite Hispanics having a greater risk. We re-examined single nucleotide polymorphisms (SNPs) of known associations with childhood ALL and known human leukocyte antigen (HLA) region lymphoma risk markers in a multi-ethnic population. Significant associations were found in two ARID5B variants (rs7089424 and rs10821936). We replicated a strong risk association in non-Hispanic White males with rs2395185, a protective marker for lymphoma. Another HLA region marker, rs2647012, showed a risk association among Hispanics only, while a strong protective association was found with rs1048456, a follicular lymphoma risk marker. Our study validated this new case-control sample by confirming genetic markers associated with childhood ALL, and yielded new associations with lymphoma markers. Despite positive results, our study did not provide any clues as to why Hispanics have a higher susceptibility to childhood leukemia, suggesting that environmental factors may have a strong contribution. PMID:24707947

  7. Outcome following late marrow relapse in childhood acute lymphoblastic leukemia

    SciTech Connect

    Chessells, J.; Leiper, A.; Rogers, D.

    1984-10-01

    Thirty-four children with acute lymphoblastic leukemia, who developed bone marrow relapse after treatment was electively stopped, received reinduction, consolidation, continuing therapy, and intrathecal (IT) methotrexate (MTX). Sixteen children who relapsed within six months of stopping treatment had a median second-remission duration of 26 weeks; all next relapses occurred in the bone marrow. In 18 children who relapsed later, the median duration of second remission was in excess of two years, but after a minimum of four years follow-up, 16 patients have so far relapsed again (six in the CNS). CNS relapse occurred as a next event in four of 17 children who received five IT MTX injections only and in two of 14 children who received additional regular IT MTX. Although children with late marrow relapses may achieve long second remissions, their long-term out-look is poor, and regular IT MTX does not afford adequate CNS prophylaxis. It remains to be seen whether more intensive chemotherapy, including high-dose chemoradiotherapy and bone marrow transplantation, will improve the prognosis in this group of patients.

  8. Deletion analysis of p16(INKa) and p15(INKb) in relapsed childhood acute lymphoblastic leukemia.

    PubMed

    Graf Einsiedel, Hagen; Taube, Tillmann; Hartmann, Reinhard; Wellmann, Sven; Seifert, Georg; Henze, Günter; Seeger, Karl

    2002-06-15

    This study aimed at determining the prevalence of INK4 deletions and their impact on outcome in 125 children with acute lymphoblastic leukemia (ALL) at first relapse using real-time quantitative polymerase chain reaction. Patients were enrolled into relapse trials ALL-REZ BFM (ALL-Relapse Berlin-Frankfurt-Münster) 90 and 96. The prevalence of p16(INK4a) and p15(INK4b) homozygous deletions was 35% (44 of 125) and 30% (38 of 125), respectively. A highly significant association of both gene deletions was found with the 2 major adverse prognostic factors known for relapsed childhood ALL: T-cell immunophenotype and first remission duration. There was no correlation between INK4 deletions and probability of event-free survival. These findings argue against an independent prognostic role of INK4 deletions in relapsed childhood ALL. PMID:12036898

  9. No involvement of bovine leukemia virus in childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma

    SciTech Connect

    Bender, A.P.; Robison, L.L.; Kashmiri, S.V.; McClain, K.L.; Woods, W.G.; Smithson, W.A.; Heyn, R.; Finlay, J.; Schuman, L.M.; Renier, C.

    1988-05-15

    Bovine leukemia virus (BLV) is the causative agent of enzootic bovine lymphosarcoma. Much speculation continues to be directed at the role of BLV in human leukemia. To test this hypothesis rigorously, a case-control study of childhood acute lymphoblastic leukemia and non-Hodgkin's lymphoma was conducted between December 1983 and February 1986. Cases (less than or equal to 16 years at diagnosis) derived from patients diagnosed at the primary institutions and affiliated hospitals were matched (age, sex, and race) with regional population controls. DNA samples from bone marrow or peripheral blood from 157 cases (131 acute lymphoblastic leukemia, 26 non-Hodgkin's lymphoma) and peripheral blood from 136 controls were analyzed by Southern blot technique, under highly stringent conditions, using cloned BLV DNA as a probe. None of the 157 case or 136 control DNA samples hybridized with the probe. The high statistical power and specificity of this study provide the best evidence to date that genomic integration of BLV is not a factor in childhood acute lymphoblastic leukemia/non-Hodgkin's lymphoma.

  10. Peritoneal Dialysis in Childhood Acute Kidney Injury: Experience in Southwest Nigeria

    PubMed Central

    Ademola, Adebowale Dele; Asinobi, Adanze Onyenonachi; Ogunkunle, Oluwatoyin Olufunmilayo; Yusuf, Bamidele Nurudeen; Ojo, Olalekan Ezekiel

    2012-01-01

    ♦ Background: The choices for renal replacement therapy (RRT) in childhood acute kidney injury (AKI) are limited in low-resource settings. Peritoneal dialysis (PD) appears to be the most practical modality for RRT in young children with AKI in such settings. Data from sub-Saharan Africa on the use of PD in childhood AKI are few. ♦ Methods: We performed a retrospective study of children who underwent PD for AKI at a tertiary-care hospital in southwest Nigeria from February 2004 to March 2011 (85 months). ♦ Results: The study included 27 children (55.6% female). Mean age was 3.1 ± 2.6 years, with the youngest being 7 days, and the oldest, 9 years. The causes of AKI were intravascular hemolysis (n = 11), septicemia (n = 8), acute glomerulonephritis (n = 3), gastroenteritis (n = 3), and hemolytic uremic syndrome (n = 2). Peritoneal dialysis was performed manually using percutaneous or adapted catheters. Duration of PD ranged from 6 hours to 12 days (mean: 5.0 ± 3.3 days). The main complications were peritonitis (n = 10), pericatheter leakage (n = 9), and catheter outflow obstruction (n = 5). Of the 27 patients, 19 (70%) survived till discharge. ♦ Conclusions: In low-resource settings, PD can be successfully performed for the management of childhood AKI. In our hospital, the use of adapted catheters may have contributed to the high complication rates. Peritoneal dialysis should be promoted for the management of childhood AKI in low-resource settings, and access to percutaneous or Tenckhoff catheters, dialysis fluid, and automated PD should be increased. PMID:22550119

  11. Developmental emergence of alcohol use disorder symptoms and their potential as early indicators for progression to alcohol dependence in a high risk sample: a longitudinal study from childhood to early adulthood.

    PubMed

    Buu, Anne; Wang, Wei; Schroder, Stephanie A; Kalaida, Natalia L; Puttler, Leon I; Zucker, Robert A

    2012-11-01

    This study characterized developmental emergence of individual alcohol use disorder (AUD) symptoms, and evaluated their ability as early indicators of progression into alcohol dependence (AD), conditional upon gender, parental alcohol dependence, early onset of drinking, and level of delinquent behavior at onset. The two parameters of interest were (a) likelihood of specific AUD symptom appearance once drinking has begun, and (b) primacy of symptom appearance as an indicator of likelihood for eventual move into diagnosis. We analyzed prospective data from a community sample of high risk youth from childhood to early adulthood. Symptoms that were at higher probability of being experienced at drinking onset and that could serve as good indicators for the early stage of disease progression were: persistent desire or unsuccessful efforts to control alcohol use (AD4), and continued use despite having persistent or recurrent interpersonal problems (AA4). Tolerance (AD1) may serve as an indicator for the intermediate stage of progression. Young people tended to be at an elevated risk for developing AD6 (activities given up), AD7 (physical/psychological problems), and AA3 (legal problems) in later years so these symptoms may be good indicators for later stages of progression. In addition to being male, an early onset drinker, or high in delinquent behavior, drinkers who experienced AA4 or AD1 as first symptoms were at higher risk for progression to AD. We also identified two high risk clusters: late onset drinkers with AA4 as first symptom, and children of alcoholics with AD1 as first symptom. PMID:21842966

  12. RUNX1 amplification in lineage conversion of childhood B-cell acute lymphoblastic leukemia to acute myelogenous leukemia.

    PubMed

    Podgornik, Helena; Debeljak, Marusa; Zontar, Darja; Cernelc, Peter; Prestor, Veronika Velensek; Jazbec, Janez

    2007-10-01

    Amplification of RUNX1 (alias AML1) is a recurrent karyotypic abnormality in childhood acute lymphoblastic leukemia (ALL) that is generally associated with a poor outcome. It does not occur with other primary chromosomal abnormalities in acute ALL. AML1 amplification in acute myelogenous leukemia (AML) is a rare secondary event described mainly in therapy-related cases. AML1 amplification was found in a 13-year-old patient with AML M4/M5 leukemia that occurred 5 years after she had been diagnosed with common B-cell ALL. Conventional cytogenetic, fluorescent in situ hybridization (FISH), and polymerase chain reaction methods revealed no other chromosomal change expected to occur in a disease that we assumed to be a secondary leukemia. Due to the lack of cytogenetic data from the diagnostic sample, we developed a new approach to analyze the archived bone marrow smear, which had been stained previously with May-Grünwald-Geimsa by the FISH method. This analysis confirmed that in addition to t(12;21), AML1 amplification and overexpression existed already at the time the diagnosis was made. The chromosomal changes, however, were found in different clones of bone marrow cells. While the first course of chemotherapy successfully eradicated the cell line with the t(12;21), the second cell line with AML1 amplification remained latent during the time of complete remission and reappeared with a different immunophenotype. PMID:17889714

  13. Terminal Deoxynucleotidyl Transferase in a Case of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    McCaffrey, Ronald; Smoler, Donna F.; Baltimore, David

    1973-01-01

    Cells from a patient with childhood acute lymphoblastic leukemia contain an apparent DNA polymerase activity that was not found in any other cells except thymus cells. The enzyme has the properties of terminal transferase, an enzyme known to be found in thymocytes. The cells also contain the three major DNA polymerases found in growing cells. The results suggest that these tumor cells arose from a block in the differentiation of thymocytes. Terminal transferase may be a marker for the origin of leukemic cells. PMID:4346893

  14. Childhood acute lymphoblastic leukemia presenting as ''cold'' lesions on bone scan: a report of two cases

    SciTech Connect

    Caudle, R.J.; Crawford, A.H.; Gelfand, M.J.; Gruppo, R.A.

    1987-01-01

    ''Cold'' lesions on bone scan have been reported in a variety of disease processes, including infection, avascular necrosis, and cysts. We present two cases of children who presented with large ''cold'' areas on technetium bone scans and were treated initially for septic processes. Acute childhood leukemia frequently presents with bone or joint pain, fever, and elevation of the erythrocyte sedimentation rate. Although the diagnosis may be difficult if the characteristic clinical signs and laboratory findings are absent, the presence of anemia should alert the physician to the possibility of malignancy. Bone scanning provides a sensitive method of localizing pathology, but diagnosis requires biopsy or marrow aspiration.

  15. Cardiac Failure 30 Years after Treatment Containing Anthracycline for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Goldberg, John M.; Scully, Rebecca E.; Sallan, Stephen E.; Lipshultz, Steven E.

    2012-01-01

    In 1977, a 5-year-old girl diagnosed with acute lymphoblastic leukemia (ALL) was treated on DFCI Childhood ALL Protocol 77-01, receiving a cumulative doxorubicin dose of 465 mg/m2, cranial radiation, and other drugs. After being in continuous complete remission for 34 months, she developed heart failure (HF) and was treated with digoxin and furosemide. At 16, she was diagnosed and treated for dilated cardiomyopathy. Over the years she continued to have bouts of HF, which became less responsive to treatment. At 36, she received a heart transplant. Six months later, she stopped taking her medications and suffered a sudden cardiac death. PMID:22584777

  16. Reducing time to angiography and hospital stay for patients with high-risk non-ST-elevation acute coronary syndrome: retrospective analysis of a paramedic-activated direct access pathway

    PubMed Central

    Koganti, S; Patel, N; Seraphim, A; Kotecha, T; Whitbread, M; Rakhit, R D

    2016-01-01

    Objective To assess whether a novel ‘direct access pathway’ (DAP) for the management of high-risk non-ST-elevation acute coronary syndromes (NSTEACS) is safe, results in ‘shorter time to intervention and shorter admission times’. This pathway was developed locally to enable London Ambulance Service to rapidly transfer suspected high-risk NSTEACS from the community to our regional heart attack centre for consideration of early angiography. Methods This is a retrospective case–control analysis of 289 patients comparing patients with high-risk NSTEACS admitted via DAP with age-matched controls from the standard pan-London high-risk ACS pathway (PLP) and the conventional pathway (CP). The primary end point of the study was time from admission to coronary angiography/intervention. Secondary end point was total length of hospital stay. Results Over a period of 43 months, 101 patients were admitted by DAP, 109 matched patients by PLP and 79 matched patients through CP. Median times from admission to coronary angiography for DAP, PLP and CP were 2.8 (1.5–9), 16.6 (6–50) and 60 (33–116) hours, respectively (p<0.001). Median length of hospital stay for DAP and PLP was similar at 3.0 (2.0–5.0) days in comparison to 5 (3–7) days for CP (p<0.001). Conclusions DAP resulted in a significant reduction in time to angiography for patients with high-risk NSTEACS when compared to existing pathways. PMID:27324709

  17. Yttrium Y 90 Anti-CD45 Monoclonal Antibody BC8 Followed by Donor Stem Cell Transplant in Treating Patients With High-Risk Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-08-08

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Acute Myeloid Leukemia

  18. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment: a Delphi consensus.

    PubMed

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit; Escherich, Gabriele; Frandsen, Thomas Leth; Halsey, Christina; Hough, Rachael; Jeha, Sima; Kato, Motohiro; Liang, Der-Cherng; Mikkelsen, Torben Stamm; Möricke, Anja; Niinimäki, Riitta; Piette, Caroline; Putti, Maria Caterina; Raetz, Elizabeth; Silverman, Lewis B; Skinner, Roderick; Tuckuviene, Ruta; van der Sluis, Inge; Zapotocka, Ester

    2016-06-01

    Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis, asparaginase-associated pancreatitis, arterial hypertension, posterior reversible encephalopathy syndrome, seizures, depressed level of consciousness, methotrexate-related stroke-like syndrome, peripheral neuropathy, high-dose methotrexate-related nephrotoxicity, sinusoidal obstructive syndrome, thromboembolism, and Pneumocystis jirovecii pneumonia) that are serious but too rare to be addressed comprehensively within any single group, or are deemed to need consensus definitions for reliable incidence comparisons, were selected for assessment. Our results showed that none of the protocols addressed all 14 toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall assessment of outcome of acute lymphoblastic leukaemia treatment, these expert opinion-based definitions will allow reliable comparisons of frequencies and severities of acute toxic effects across treatment protocols, and facilitate international research on cause, guidelines for treatment adaptation, preventive strategies, and development of consensus algorithms for reporting on acute lymphoblastic leukaemia treatment. PMID:27299279

  19. A Pilot Study of Intensified PEG-Asparaginase in High-risk Acute Lymphoblastic Leukemia: Children's Oncology Group Study AALL08P1.

    PubMed

    Rodriguez, Vilmarie; Kairalla, John; Salzer, Wanda L; Raetz, Elizabeth A; Loh, Mignon Lc; Carroll, Andrew J; Heerema, Nyla A; Wood, Brent L; Borowitz, Michael J; Burke, Michael J; Asselin, Barbara L; Devidas, Meenakshi; Winick, Naomi J; Carroll, William L; Hunger, Stephen P; Dreyer, ZoAnn E

    2016-08-01

    AALL08P1 was designed to determine whether biweekly intensified pegaspargase (I-PEG) was feasible and safe in pediatric patients with newly diagnosed high-risk B-precursor lymphoblastic leukemia when given with Children's Oncology Group hemiaugmented BFM therapy. High-risk average (HR-Avg) patients received standard pegaspargase dosing (6 doses), whereas high-risk high (HR-High) patients received I-PEG biweekly from the start of Consolidation until day 1 of Maintenance. Feasibility and safety were defined in advance as ≥65% of patients tolerating at least 8 doses of I-PEG and 90% requiring ≤49 weeks from day 1 of Consolidation to the initiation of Maintenance. Targeted toxicities included allergic reactions, anaphylaxis, pancreatitis, thrombosis, bleeding, central nervous system events, and sepsis. AALL08P1 enrolled 104 patients; 54 were classified as HR-Avg and 30 as HR-High after completion of induction therapy. Only 53% (16/30) of the HR-High patients received ≥8 total doses of I-PEG and 50% (15/30) took ≤49 weeks from start of Consolidation to the initiation of Maintenance. I-PEG did not significantly increase grade 2 to 5 targeted toxicities. I-PEG was not feasible or safe as defined in AALL08P1. Complete assessment of this regimen was limited due to removal of patients from I-PEG regimen and early closure of the study. PMID:27299599

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

    PubMed

    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. PMID:27492895

  1. Residential Proximity to Agricultural Pesticide Applications and Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Rull, Rudolph P.; Gunier, Robert; Von Behren, Julie; Hertz, Andrew; Crouse, Vonda; Buffler, Patricia A.; Reynolds, Peggy

    2009-01-01

    Ambient exposure from residential proximity to applications of agricultural pesticides may contribute to the risk of childhood acute lymphoblastic leukemia (ALL). Using residential histories collected from the families of 213 ALL cases and 268 matched controls enrolled in the Northern California Childhood Leukemia Study, the authors assessed residential proximity within a half-mile (804.5 meters) of pesticide applications by linking address histories with reports of agricultural pesticide use. Proximity was ascertained during different time windows of exposure, including the first year of life and the child’s lifetime through the date of diagnosis for cases or reference for controls. Agricultural pesticides were categorized a priori into groups based on similarities in toxicological effects, physicochemical properties, and target pests or uses. The effects of moderate and high exposure for each group of pesticides were estimated using conditional logistic regression. Elevated ALL risk was associated with lifetime moderate exposure, but not high exposure, to certain physicochemical categories of pesticides, including organophosphates, cholorinated phenols, and triazines, and with pesticides classified as insecticides or fumigants. A similar pattern was also observed for several toxicological groups of pesticides. These findings suggest future directions for the identification of specific pesticides that may play a role in the etiology of childhood leukemia. PMID:19700145

  2. Patterns of Acute Poisoning in Childhood in Zagazig, Egypt: An Epidemiological Study

    PubMed Central

    Hassan, Basheir A.; Siam, Mohamed G.

    2014-01-01

    Background. Acute poisoning represents one of the most common medical emergencies in childhood. In view of paucity of literature on accidental poisoning among children in Egypt, this study was designed to describe the pattern of childhood poisoning in Zagazig University Hospitals. Patients and Methods. This retrospective study included 300 children up to 12 years with acute poisoning admitted to the Pediatric Department and Poisoning Treatment Unit, Zagazig University Hospitals, from January 2011 to August 2012. Complete epidemiological and clinical data were recorded and analyzed. Results. Three hundred of poisoned children were enrolled in this study. Children from 1 to 6 years were more liable to poisoning (81%). More boys than girls were poisoned at all age groups. The majority of all cases (99%) were due to accidental poisoning. Overall, 32% of the poisoned cases were living in Zagazig city while 68% were living in the rural areas. The presenting symptoms were classic in 60% of the cases. Pesticides, therapeutic drugs, and cleaning and disinfectant agents were the most frequent poisoning agents (28.7%, 22.7%, and 17.0%, resp.). In 86.0% of cases, observation with or without supportive measures together with decontamination and specific antidote therapy whenever needed was sufficient. Conclusion. Most of the poisonings were due to accidental ingestions by infants and young children. Pesticides and medications were the most commonly involved agents. PMID:27351009

  3. Childhood Sjögren syndrome presenting as acute brainstem encephalitis.

    PubMed

    Matsui, Yoriko; Takenouchi, Toshiki; Narabayashi, Atsushi; Ohara, Kentaro; Nakahara, Tadaki; Takahashi, Takao

    2016-01-01

    Sjögren syndrome is an autoimmune disease characterized by dry mouth and eyes, known as sicca symptoms. The exact spectrum of neurological involvement, especially of the central nervous system, in childhood Sjögren syndrome has not been well defined. We report a girl who presented with acute febrile brainstem encephalitis. In retrospect, she had exhibited a preceding history of recurrent conjunctivitis and strong halitosis that could be considered as sicca symptoms. The histopathology results of a minor salivary biopsy, the presence of anti-SSA/Ro antibody, and keratoconjunctivitis confirmed the diagnosis of Sjögren syndrome. Commonly observed features in previously reported patients with childhood Sjögren syndrome and central nervous system complications have included fever at the time of neurologic presentation, cerebrospinal fluid pleocytosis, abnormal neuroimaging, and positivity for several specific antibodies. In children presenting with unknown acute febrile encephalopathy, Sjögren syndrome should be included in the differential diagnosis, especially when sicca symptoms are present. PMID:26006751

  4. High incidence of obesity in young adults after treatment of acute lymphoblastic leukemia in childhood.

    PubMed

    Didi, M; Didcock, E; Davies, H A; Ogilvy-Stuart, A L; Wales, J K; Shalet, S M

    1995-07-01

    To determine whether obesity complicated the treatment of childhood acute lymphoblastic leukemia, we studied the body mass index (BMI) of 63 female when and 51 male patients from the time of diagnosis of acute lymphoblastic leukemia to the time when final height was attained. The BMI z score was calculated for each patient at diagnosis, at end of treatment, and at attainment of final height. Obesity at attainment of final height was defined as a BMI greater than the 85th percentile of the normal reference population. At final height 23 of 51 male (45%) and 30 of 63 female patients (47%) were obese. Girls became obese between diagnosis and the end of chemotherapy (p = 0.02), after which they had no further increase, indicating that chemotherapy may have played a role in their obesity. Boys had a progressive and gradual increase in BMI z score through to attainment of final height. Obesity did not appear to be associated with growth hormone insufficiency, disproportionate growth, or abnormal timing of puberty. We conclude that approximately half the survivors of leukemia in childhood become obese young adults. Many of those treated with the more recent regimens studied are still only in their mid or preteen years and should be advised regarding a more active lifestyle and a healthy diet in an attempt to reduce the incidence of obesity. PMID:7608813

  5. Gastroesophageal Reflux Disease Increases Infant Acute Respiratory Illness Severity, but not Childhood Asthma.

    PubMed

    Valet, Robert S; Carroll, Kecia N; Gebretsadik, Tebeb; Minton, Patricia A; Woodward, Kimberly B; Liu, Zhouwen; Hartert, Tina V

    2014-03-01

    It is unknown whether gastroesophageal reflux disease (GERD) during infancy affects infant bronchiolitis severity or childhood asthma inception. Four hundred thirty-two infants presenting with acute respiratory illness due to bronchiolitis or upper respiratory infection were studied. The primary exposure was the parental report of a previous GERD diagnosis. Outcomes included bronchiolitis severity at initial presentation and childhood asthma diagnosis at age 4. Infants with parentally reported GERD had a higher bronchiolitis severity score (range=0-12, clinically significant difference=0.5), indicating more severe disease, than infants without reported GERD (median 5.5 [interquartile range 3.5-9.0] among those with reported GERD versus 4.0 [1.0-7.0] among those without, P=0.005). This association persisted after adjusting for infant age, race, gender, and secondhand smoke exposure by a propensity score (adjusted odds ratio [OR] 1.99, 95% confidence interval [CI] 1.14-3.46, P=0.02). The parental report of GERD during infancy was not associated with the parental report of asthma diagnosis at age 4. GERD during infancy may contribute to acute respiratory illness severity, but is not associated with asthma diagnosis at age 4. Future prospective studies are needed to confirm these findings. PMID:24669353

  6. Combined venoarterial extracorporeal membrane oxygenation and transcatheter aortic valve implantation for the treatment of acute aortic prosthesis dysfunction in a high-risk patient.

    PubMed

    Pergolini, Amedeo; Zampi, Giordano; Tinti, Maria Denitza; Polizzi, Vincenzo; Pino, Paolo Giuseppe; Pontillo, Daniele; Musumeci, Francesco; Luzi, Giampaolo

    2016-01-01

    We describe the case of a patient with acute bioprosthesis dysfunction in cardiogenic shock, in whom hemodynamic support was provided by venoarterial extracorporeal membrane oxygenation, and successfully treated by transcatheter aortic valve implantation. PMID:27402446

  7. Combination Chemotherapy and Imatinib Mesylate in Treating Children With Relapsed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-07

    L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; Non-T, Non-B Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  8. Studying Biomarkers in Samples From Younger Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-17

    Childhood Acute Monoblastic Leukemia (M5a); Childhood Acute Monocytic Leukemia (M5b); Childhood Acute Myeloblastic Leukemia Without Maturation (M1); Childhood Acute Myeloid Leukemia/Other Myeloid Malignancies; Childhood Acute Myelomonocytic Leukemia (M4)

  9. Corrigendum: The Associations Between Maternal Factors During Pregnancy and the Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis.

    PubMed

    Yan, Kangkang; Xu, Xuejing; Liu, Xiaodong; Wang, Xikui; Hua, Shucheng; Wang, Chunpeng; Liu, Xin

    2016-05-01

    Because of the erroneous application of multiple publications, the conclusions of our recent paper (Pediatr Blood Cancer 2015;62:1162-70) were not reliable. The corrected results show that coffee drinking during pregnancy was risk factor for childhood acute lymphoblastic leukemia (OR = 1.44, 95% confidence interval = 1.07-1.92). PMID:26999072

  10. Resveratrol given intraperitoneally does not inhibit growth of high-risk t(4;11) acute lymphoblastic leukemia cells in NOD/SCID mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of the phytochemical resveratrol as a preventive agent against the growth of t(4;11) acute lymphoblastic leukemia (ALL) was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) ALL line SEM. SEM cells were injected into the tail vein and engraftment was monitored by ...

  11. Dust-metal Loadings and the Risk of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

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

    2015-01-01

    We evaluated the relationship between the risk of childhood acute lymphoblastic leukemia (ALL) and 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 less than 15% of homes. Relationships between dust-metal loadings (μg metal per m2 carpet) and ALL risk were modeled using multivariable logistic regression, adjusting for the child’s age, sex, and race/ethnicity and confounders, including household annual income. A doubling of dust-metal loadings was not associated with significant changes in ALL risk [odds ratio (95% confidence interval): arsenic: 0.94 (0.83, 1.05), cadmium: 0.91 (0.80, 1.04), chromium: 0.99 (0.87, 1.12), copper: 0.96 (0.90, 1.03), lead: 1.01 (0.93, 1.10), nickel: 0.92 (0.80, 1.07), tin: 0.93 (0.82, 1.05), and zinc: 0.91 (0.81, 1.02)]. Our findings do not support the hypothesis that metals in carpet dust are risk factors for childhood ALL. PMID:25736162

  12. TESTIN Induces Rapid Death and Suppresses Proliferation in Childhood B Acute Lymphoblastic Leukaemia Cells

    PubMed Central

    Weeks, Robert J.; Ludgate, Jackie L.; LeMée, Gwenn; Morison, Ian M.

    2016-01-01

    Background Childhood acute lymphoblastic leukaemia (ALL) is the most common malignancy in children. Despite high cure rates, side effects and late consequences of the intensive treatments are common. Unquestionably, the identification of new therapeutic targets will lead to safer, more effective treatments. We identified TES promoter methylation and transcriptional silencing as a very common molecular abnormality in childhood ALL, irrespective of molecular subtype. The aims of the present study were to demonstrate that TES promoter methylation is aberrant, to determine the effects of TES re-expression in ALL, and to determine if those effects are mediated via TP53 activity. Methods Normal fetal and adult tissue DNA was isolated and TES promoter methylation determined by Sequenom MassARRAY. Quantitative RT-PCR and immunoblot were used to confirm re-expression of TES in ALL cell lines after 5’-aza-2’-deoxycytidine (decitabine) exposure or transfection with TES expression plasmids. The effects of TES re-expression on ALL cells were investigated using standard cell proliferation, cell death and cell cycle assays. Results In this study, we confirm that the TES promoter is unmethylated in normal adult and fetal tissues. We report that decitabine treatment of ALL cell lines results in demethylation of the TES promoter and attendant expression of TES mRNA. Re-expression of TESTIN protein in ALL cells using expression plasmid transfection results in rapid cell death or cell cycle arrest independent of TP53 activity. Conclusions These results suggest that TES is aberrantly methylated in ALL and that re-expression of TESTIN has anti-leukaemia effects which point to novel therapeutic opportunities for childhood ALL. PMID:26985820

  13. Molecular Analysis of Central Nervous System Disease Spectrum in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Hicks, Chindo; Sitthi-Amorn, Jitsuda; Douglas, Jessica; Ramani, Ritika; Miele, Lucio; Vijayakumar, Vani; Karlson, Cynthia; Chipeta, James; Megason, Gail

    2016-01-01

    Treatment of the central nervous system (CNS) is an essential therapeutic component in childhood acute lymphoblastic leukemia (ALL). The goal of this study was to identify molecular signatures distinguishing patients with CNS disease from those without the disease in pediatric patients with ALL. We analyzed gene expression data from 207 pediatric patients with ALL. Patients without CNS were classified as CNS1, while those with mild and advanced CNS disease were classified as CNS2 and CNS3, respectively. We compared gene expression levels among the three disease classes. We identified gene signatures distinguishing the three disease classes. Pathway analysis revealed molecular networks and biological pathways dysregulated in response to CNS disease involvement. The identified pathways included the ILK, WNT, B-cell receptor, AMPK, ERK5, and JAK signaling pathways. The results demonstrate that transcription profiling could be used to stratify patients to guide therapeutic decision-making in pediatric ALL. PMID:26997880

  14. Brain sarcoma of meningeal origin after cranial irradiation in childhood acute lymphocytic leukemia. Case report

    SciTech Connect

    Tiberin, P.; Maor, E.; Zaizov, R.; Cohen, I.J.; Hirsch, M.; Yosefovich, T.; Ronen, J.; Goldstein, J.

    1984-10-01

    The authors report their experience with an unusual case of intracerebral sarcoma of meningeal cell origin in an 8 1/2-year-old girl. This tumor occurred 6 1/2 years after cranial irradiation at relatively low dosage (2200 rads) had been delivered to the head in the course of a multimodality treatment for acute lymphocytic leukemia. The tumor recurred approximately 10 months after the first surgical intervention. Macroscopic total excision of the recurrent growth followed by whole-brain irradiation (4500 rads) failed to eradicate it completely and local recurrence prompted reoperation 18 months later. This complication of treatment in long-term childhood leukemia survivors is briefly discussed, as well as the pathology of meningeal sarcomas.

  15. Significance of CD66c expression in childhood acute lymphoblastic leukemia.

    PubMed

    Kiyokawa, Nobutaka; Iijima, Kazutoshi; Tomita, Osamu; Miharu, Masashi; Hasegawa, Daisuke; Kobayashi, Kenichiro; Okita, Hajime; Kajiwara, Michiko; Shimada, Hiroyuki; Inukai, Takeshi; Makimoto, Atsushi; Fukushima, Takashi; Nanmoku, Toru; Koh, Katsuyoshi; Manabe, Atsushi; Kikuchi, Akira; Sugita, Kanji; Fujimoto, Junichiro; Hayashi, Yasuhide; Ohara, Akira

    2014-01-01

    Upon analyzing 696 childhood B-cell precursor acute lymphoblastic leukemia (BCP-ALL) cases, we identified the characteristics of CD66c expression. In addition to the confirmation of strong correlation with BCR-ABL positivity and hyperdiploid, we further observed that CD66c is frequently expressed in CRLF2-positive (11/15, p<0.01 against chimeric gene-negative) as well as hypodiploid cases (3/4), whereas it is never expressed in ETV6-RUNX1, MLL-AF4, MLL-AF9, MLL-ENL, and E2A-PBX1-positive cases. Although the expression of CD66c itself is not directly linked to the prognosis, the accompanying genetic abnormalities are important prognostic factors for BCP-ALL, indicating the importance of CD66c expression in the initial diagnosis of BCP-ALL. PMID:24231528

  16. Genetic Aberrations in Childhood Acute Lymphoblastic Leukaemia: Application of High-Density Single Nucleotide Polymorphism Array

    PubMed Central

    Sulong, Sarina

    2010-01-01

    Screening of the entire human genome using high-density single nucleotide polymorphism array (SNPA) has become a powerful technique used in cancer genetics and population genetics studies. The GeneChip® Mapping Array, introduced by Affymetrix, is one SNPA platform utilised for genotyping studies. This GeneChip system allows researchers to gain a comprehensive view of cancer biology on a single platform for the quantification of chromosomal amplifications, deletions, and loss of heterozygosity or for allelic imbalance studies. Importantly, this array analysis has the potential to reveal novel genetic findings involved in the multistep development of cancer. Given the importance of genetic factors in leukaemogenesis and the usefulness of screening the whole genome, SNPA analysis has been utilised in many studies to characterise genetic aberrations in childhood acute lymphoblastic leukaemia. PMID:22135543

  17. Early childhood attention deficit hyperactivity disorder predicts poorer response to acute lithium therapy in adolescent mania.

    PubMed

    Strober, M; DeAntonio, M; Schmidt-Lackner, S; Freeman, R; Lampert, C; Diamond, J

    1998-11-01

    We compared the response to acute lithium therapy in 30 adolescents, 13-17 years of age, with mania and a prior history of early childhood attention deficit hyperactivity disorder (ADHD) to a sex- and age-matched control group of adolescent manics without premorbid psychiatric illness. Response to treatment was assessed daily over the course of 28 days using measures of global clinical improvement and severity ratings on the Bech-Rafaelsen Mania Scale (BRMS). BRMS scores decreased by a mean of 24.3 in the subgroup without prior ADHD compared to 16.7 in patients with ADHD (P = 0.0005). The average percent drop in BRMS scores over the study period in these two subgroups was 80.6% and 57.7%, respectively (P = 0.0005). Time to onset of sustained global clinical improvement was also assessed using Kaplan-Meier survival methods and possible covariates of time to improvement were tested in a Cox proportional hazards model. Median time to onset of sustained improvement was lengthened significantly in patients with early ADHD (23 days) compared to those without it (17 days; log rank chi2 = 7.2, P = 0.007). The results suggest that early childhood ADHD defines an important source of heterogeneity in bipolar illness with developmental, clinical, and neuropharmacogenetic implications. PMID:10743847

  18. Polymorphisms of the vincristine pathway and response to treatment in children with childhood acute lymphoblastic leukemia

    PubMed Central

    Ceppi, Francesco; Langlois-Pelletier, Chloé; Gagné, Vincent; Rousseau, Julie; Ciolino, Claire; Lorenzo, Samanta De; Kevin, Kojok M; Cijov, Diana; Sallan, Stephen E; Silverman, Lewis B; Neuberg, Donna; Kutok, Jeffery L; Sinnett, Daniel; Laverdière, Caroline; Krajinovic, Maja

    2015-01-01

    Background Vincristine (VCR) is a standard component in the treatment of childhood acute lymphoblastic leukemia (ALL). VCR cytotoxicity is primarily due to its ability to disrupt the formation of microtubules of the mitotic spindle. Patients & methods A total of 17 polymorphisms in regulatory and coding regions of genes controlling VCR targets (TUBB1, MAP4, ACTG1 and CAPG) or potentially influencing VCR levels (ABCB1 and CYP3A5) were investigated for an association with peripheral neuropathy and outcome in childhood ALL patients. Results High-grade neurotoxicity was more frequent in carriers of the A allele of synonymous (Ala310) G to A (rs1135989) variation in the ACTG1 gene. Substitution (rs4728709) in the promoter of the ABCB1 gene had a protective effect against lower grade neurotoxicity and C to A variation (rs3770102) located 17 nucleotides upstream from the transcription start site had a protective effect against high-grade neurotoxicity. Patients with the ABCB1 3435TT genotype had lower event-free survival; the association with event-free survival was not supported by the analysis in the replication patient set. Conclusion The polymorphisms in the ACTG1, CAPG and ABCB1 genes may modulate VCR-related neurotoxicity, whereas the risk of relapse seems not to be affected by the genes of the VCR pathway. PMID:25084203

  19. Intracellular Signaling Pathways Involved in Childhood Acute Lymphoblastic Leukemia; Molecular Targets.

    PubMed

    Layton Tovar, Cristian Fabián; Mendieta Zerón, Hugo

    2016-06-01

    Acute lymphoblastic leukemia (ALL) is a malignant disease characterized by an uncontrolled proliferation of immature lymphoid cells. ALL is the most common hematologic malignancy in early childhood, and it reaches peak incidence between the ages of 2 and 3 years. The prognosis of ALL is associated with aberrant gene expression, in addition to the presence of numerical or structural chromosomal alterations, age, race, and immunophenotype. The Relapse rate with regard to pharmacological treatment rises in childhood; thus, the expression of biomarkers associated with the activation of cell signaling pathways is crucial to establish the disease prognosis. Intracellular pathways involved in ALL are diverse, including Janus kinase/Signal transducers and transcription activators (JAK-STAT), Phosphoinositide-3-kinase-protein kinase B (PI3K-AKT), Ras mitogen-activated protein kinase (Ras-MAPK), Glycogen synthase kinase-3β (GSK-3β), Nuclear factor-kappa beta (NF-κB), and Hypoxia-inducible transcription factor 1α (HIF-1α), among others. In this review, we present several therapeutic targets, intracellular pathways, and molecular markers that are being studied extensively at present. PMID:27065575

  20. Pre-hospital care seeking behaviour for childhood acute respiratory infections in south-western Nigeria.

    PubMed

    Ukwaja, Kingsley N; Talabi, Ademola A; Aina, Olufemi B

    2012-12-01

    WHO/UNICEF currently recommend that childhood malaria and pneumonia be managed together in the community; most African countries are in the process of developing this policy. We conducted a cross-sectional study to determine maternal awareness of general danger signs of childhood illnesses and the prevalence, determinants and sources of pre-hospital treatment by mothers during their child's acute respiratory illness in a poor urban community in south-western Nigeria. A total of 226 mothers were interviewed. Only 4.9% of the mothers were aware of the two pneumonia symptoms: difficult breathing and fast breathing. About 75% of the children were given pre-hospital medication at home and only 16.5% of them received the drugs within 24 hour of symptom recognition. Drug shops/patent medicine vendors (PMVs; 70.6%) were the most common source of care. Wishing to try home management first (46.6%); waiting for the child to improve (14.4%) and lack of money (31.6%) delayed care-seeking. Older maternal age (aOR 2.3; 95% CI 1.2-4.4) and having a child with cough and difficult and/or fast breathing (aOR 2.3; 95% CI 1.1-5.2) were positive predictors of pre-hospital treatment. Maternal education and adequately equipping PMVs could improve prompt access to integrated community-based child health services in Nigeria. PMID:24029675

  1. Acute myocardial ischemia in adults secondary to missed Kawasaki disease in childhood.

    PubMed

    Rizk, Sherif R Y; El Said, Galal; Daniels, Lori B; Burns, Jane C; El Said, Howaida; Sorour, Khaled A; Gharib, Soliman; Gordon, John B

    2015-02-15

    Coronary artery aneurysms that occur in 25% of untreated Kawasaki disease (KD) patients may remain clinically silent for decades and then thrombose resulting in myocardial infarction. Although KD is now the most common cause of acquired heart disease in children in Asia, the United States, and Western Europe, the incidence of KD in Egypt is unknown. We tested the hypothesis that young adults in Egypt presenting with acute myocardial ischemia may have coronary artery lesions because of KD in childhood. We reviewed a total of 580 angiograms of patients ≤40 years presenting with symptoms of myocardial ischemia. Coronary artery aneurysms were noted in 46 patients (7.9%), of whom 9 presented with myocardial infarction. The likelihood of antecedent KD as the cause of the aneurysms was classified as definite (n = 10), probable (n = 29), or equivocal (n = 7). Compared with the definite and probable groups, the equivocal group had more traditional cardiovascular risk factors, smaller sized aneurysms, and fewer coronary arteries affected. In conclusion, in a major metropolitan center in Egypt, 6.7% of adults aged ≤40 years who underwent angiography for evaluation of possible myocardial ischemia had lesions consistent with antecedent KD. Because of the unique therapeutic challenges associated with these lesions, adult cardiologists should be aware that coronary artery aneurysms in young adults may be because of missed KD in childhood. PMID:25555655

  2. HLA-A11 is associated with poor prognosis in childhood acute lymphoblastic leukemia (ALL).

    PubMed

    Orgad, S; Cohen, I J; Neumann, Y; Vogel, R; Kende, G; Ramot, B; Zaizov, R; Gazit, E

    1988-12-01

    A possible association between HLA antigens, susceptibility or resistance to leukemia, and responsiveness to treatment has been studied in 144 patients with childhood acute lymphoblastic leukemia (ALL) and compared to other prognostic factors, i.e. white blood cell (WBC) counts, age at onset, sex, ethnic origin, and cell surface markers. All sequentially newly diagnosed children (97) comprised the group for the prospective study (PSG) and were followed for 6 years. The group included 37 patients classified as T-ALL, 41 as CALLA+, 27 as NULL, 12 as B and pre-B, and 27 unclassified patients, who were diagnosed before 1980. During the follow-up period, 45 patients of the PSG died. Forty-seven patients designated long-term survivors (LTS) have been followed 6-20 years after diagnosis, having completed a 3-5 year course of anti-leukemia therapy, and having remained disease free thereafter. High WBC counts at diagnosis and T-cell-surface markers were associated with poor prognosis, as were enthnic origin and specific HLA antigens. Thus, there was one (1) a significant increase in HLA-A30 and a decrease in HLA B-14 in the PSG Jewish patients; and (2) a complete absence of HLA-ALL in LTS while, in the PSG, 8 of 9 HLA-All-positive patients died during the follow-up period. This suggests that HLA-All is associated with poor prognosis in childhood ALL. PMID:3199882

  3. Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study.

    PubMed

    Oudin, Claire; Auquier, Pascal; Bertrand, Yves; Chastagner, Philippe; Kanold, Justyna; Poirée, Maryline; Thouvenin, Sandrine; Ducassou, Stephane; Plantaz, Dominique; Tabone, Marie-Dominique; Dalle, Jean-Hugues; Gandemer, Virginie; Lutz, Patrick; Sirvent, Anne; Villes, Virginie; Barlogis, Vincent; Baruchel, André; Leverger, Guy; Berbis, Julie; Michel, Gérard

    2016-06-01

    Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1-21.1) and 24.6% (95% CI: 20.4-29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0-15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients. Clinicaltrials.gov identifier: NCT 01756599. PMID:26969082

  4. Late thyroid complications in survivors of childhood acute leukemia. An L.E.A. study

    PubMed Central

    Oudin, Claire; Auquier, Pascal; Bertrand, Yves; Chastagner, Philippe; Kanold, Justyna; Poirée, Maryline; Thouvenin, Sandrine; Ducassou, Stephane; Plantaz, Dominique; Tabone, Marie-Dominique; Dalle, Jean-Hugues; Gandemer, Virginie; Lutz, Patrick; Sirvent, Anne; Villes, Virginie; Barlogis, Vincent; Baruchel, André; Leverger, Guy; Berbis, Julie; Michel, Gérard

    2016-01-01

    Thyroid complications are known side effects of irradiation. However, the risk of such complications in childhood acute leukemia survivors who received either central nervous system irradiation or hematopoietic stem cell transplantation is less described. We prospectively evaluated the incidence and risk factors for thyroid dysfunction and tumors in survivors of childhood acute myeloid or lymphoid leukemia. A total of 588 patients were evaluated for thyroid function, and 502 individuals were assessed for thyroid tumors (median follow-up duration: 12.6 and 12.5 years, respectively). The cumulative incidence of hypothyroidism was 17.3% (95% CI: 14.1–21.1) and 24.6% (95% CI: 20.4–29.6) at 10 and 20 years from leukemia diagnosis, respectively. Patients who received total body irradiation (with or without prior central nervous system irradiation) were at higher risk of hypothyroidism (adjusted HR: 2.87; P=0.04 and 2.79, P=0.01, respectively) as compared with transplanted patients who never received any irradiation. Patients transplanted without total body irradiation who received central nervous system irradiation were also at higher risk (adjusted HR: 3.39; P=0.02). Patients irradiated or transplanted at older than 10 years of age had a lower risk (adjusted HR: 0.61; P=0.02). Thyroid malignancy was found in 26 patients (5.2%). Among them, two patients had never received any type of irradiation: alkylating agents could also promote thyroid cancer. The cumulative incidence of thyroid malignancy was 9.6% (95% CI: 6.0–15.0) at 20 years. Women were at higher risk than men (adjusted HR: 4.74; P=0.002). In conclusion, thyroid complications are frequent among patients who undergo transplantation after total body irradiation and those who received prior central nervous system irradiation. Close monitoring is thus warranted for these patients. Clinicaltrials.gov identifier: NCT 01756599. PMID:26969082

  5. [Markers of metabolic syndrome and peptides regulating metabolism in survivors of childhood acute lymphoblastic leukemia].

    PubMed

    Skoczeń, Szymon; Tomasik, Przemysław; Balwierz, Walentyna; Surmiak, Marcin; Sztefko, Krystyna; Galicka-Latała, Danuta

    2011-01-01

    Along with the growing epidemic of overweight the risk of atherosclerosis, cardiovascular disease morbidity and mortality are increasing markedly. Metabolic syndrome (MS) is a condition clustering together several risk factors of those complications such as visceral obesity, glucose intolerance, arterial hypertension and dislipidemia. The risk of obesity in acute lymphoblastic leukemia (ALL) survivors is higher than in general population. We aimed to assess (1) the relationships between chosen adipokines and neuropeptides, chemotherapy, CRT, and body fatness and (2) evaluate adipokines and neuropeptides concentrations as a new markers of MS in children. We conducted cross-sectional evaluation of 82 ALL survivors (median age: 13.2 years; range: 4,8-26,2; median time from treatment: 3.2 years), including fasting laboratory testing: peptides (leptin, GLP-1, orexin, PYY, apelin), total cholesterol and its fractions, triglycerides; anthropometric measurements (weight, height), systolic and diastolic blood pressure. We estimated percentiles of body mass index and percentiles of blood pressure. Between 82 survivors overweight and diastolic hypertension was diagnosed in 31% of patients (35% in CRT group) and 15% respectively. At least one abnormality in lipids concentrations was found in 43%. Girls were more affected than boys. Statistically significant increased in leptin and apelin concentrations and decreased in soluble leptin receptor concentrations in the overweight group were observed compared to the non overweight subjects. Significant increase in orexin levels in females who had received CRT compared to those who had not received CRT was found. CRT is the main risk factor of elevated of body mass among survivors of childhood leukemia. Dyslipidemia and hypertension, along with increased adiposity indicate higher risk of MS development. Girls are more affected than boys. Leptin, orexin and apelin seem to be good markers of increased adiposity especially after CRT

  6. Growth hormone deficiency predicts cardiovascular risk in young adults treated for acute lymphoblastic leukemia in childhood.

    PubMed

    Link, Katarina; Moëll, Christian; Garwicz, Stanislaw; Cavallin-Ståhl, Eva; Björk, Jonas; Thilén, Ulf; Ahrén, Bo; Erfurth, Eva Marie

    2004-10-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, and until recently prophylactic cranial radiotherapy (CRT) was important for achieving long-term survival. Hypothalamic-pituitary hormone insufficiency is a well-recognized consequence of CRT for childhood cancer. Another problem is increased cardiovascular risk, which has been shown in long-term survivors of other childhood cancers. In the only previously reported study on cardiovascular risk after childhood ALL, obesity and dyslipidemia were recorded in a small subgroup treated with CRT, compared with patients treated with chemotherapy. The mechanisms behind the increase in cardiovascular risk in survivors of childhood cancer are not clarified. The aim of the present study was to elucidate mechanisms of increased cardiovascular risk in former childhood ALL patients. A group of 44 ALL survivors (23 males, median age 25 yr, range 19-32 yr at the time of study) treated with CRT (median 24 Gy, 18-30 Gy) at a median age of 5 yr (1-18 yr) and chemotherapy were investigated for prevalence of GH deficiency and cardiovascular risk factors. Comparison was made with controls randomly selected from the general population and individually matched for sex, age, smoking habits, and residence. All patients and controls underwent a GHRH-arginine test, and patients with a peak GH 3.9 microg/liter or greater were further investigated with an additional insulin tolerance test. Significantly higher plasma levels of insulin (P = 0.002), blood glucose (P = 0.01), and serum levels of low-density lipoprotein cholesterol, apolipoprotein (Apo) B, triglycerides, fibrinogen, and leptin (all P

  7. Allogeneic hematopoietic cell transplantation after conditioning with I-131-anti-CD45 antibody plus fludarabine and low-dose total body irradiation for elderly patients with advanced acute myeloid leukemia or high-risk myelodysplastic syndrome.

    SciTech Connect

    Pagel, John M.; Gooley, T. A.; Rajendran, Joseph G.; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, B. M.; Matthews, D. C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, P. J.; Storb, R.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-12-24

    We conducted a study to estimate the maximum tolerated dose (MTD) of I-131-anti-CD45 antibody (Ab; BC8) that can be combined with a standard reduced-intensity conditioning regimen before allogeneic hematopoietic cell transplantation. Fifty-eight patients older than 50 years with advanced acute myeloid leukemia (AML) or high-risk myelodysplastic syndrome (MDS) were treated with (131)I-BC8 Ab and fludarabine plus 2 Gy total body irradiation. Eighty-six percent of patients had AML or MDS with greater than 5% marrow blasts at the time of transplantation. Treatment produced a complete remission in all patients, and all had 100% donor-derived CD3(+) and CD33(+) cells in the blood by day 28 after the transplantation. The MTD of I-131-BC8 Ab delivered to liver was estimated to be 24 Gy. Seven patients (12%) died of nonrelapse causes by day 100. The estimated probability of recurrent malignancy at 1 year is 40%, and the 1-year survival estimate is 41%. These results show that CD45-targeted radiotherapy can be safely combined with a reduced-intensity conditioning regimen to yield encouraging overall survival for older, high-risk patients with AML or MDS. This study was registered at www.clinicaltrials.gov as #NCT00008177.

  8. Iodine I 131 Monoclonal Antibody BC8, Fludarabine Phosphate, Cyclophosphamide, Total-Body Irradiation and Donor Bone Marrow Transplant in Treating Patients With Advanced Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2016-07-18

    Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Chronic Myelomonocytic Leukemia; Previously Treated Myelodysplastic Syndrome; Refractory Anemia With Excess Blasts; Refractory Anemia With Ring Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Refractory Cytopenia With Multilineage Dysplasia and Ring Sideroblasts

  9. Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years.

    PubMed

    Yildiz, Inci; Ozdemir, Nihal; Celkan, Tiraje; Soylu, Selen; Karaman, Serap; Canbolat, Aylin; Dogru, Omer; Erginoz, Ethem; Apak, Hilmi

    2015-01-01

    Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids. PMID:26154620

  10. Experience with four consecutive BFM-based protocols for treatment of childhood with non-promyelocytic acute myeloblastic leukemia in Argentina.

    PubMed

    Felice, Maria S; Rossi, Jorge G; Alonso, Cristina N; Gallego, Marta S; Eberle, Silvia Eandi; Alfaro, Elizabeth M; Guitter, Myriam R; Bernasconi, Andrea R; Rubio, Patricia L; Coccé, Mariela C; Zubizarreta, Pedro A

    2016-09-01

    Childhood acute myeloid leukemia (AML) achieves event-free-survival (EFS) rates of ∼50%. Double induction phase has been introduced for improving these results. Four consecutive protocols for AML treatment were evaluated to assess the impact of the addition of a second induction course in our setting. From January 1990 to January 2014, 307 evaluable AML patients were accrued. They were classified into low-risk (LR) and high-risk (HR) according to cytogenetic/molecular findings and response on day 15. The first two studies administered one induction cycle while the latter two protocols administered double induction. Relapse was the most frequent event and early-deaths were reduced by 50% in the last protocol. Statistically significant differences were observed when comparing EFS in LR and HR groups. Patients from both risk-groups who received double induction achieved significantly better outcome. EFS improved in protocols with double induction and early-deaths rate was decreased. Cytogenetic/molecular features and early-response were confirmed as prognostic factors. PMID:26734812

  11. Mutational analysis of the candidate tumor suppressor genes TEL and KIP1 in childhood acute lymphoblastic leukemia.

    PubMed

    Stegmaier, K; Takeuchi, S; Golub, T R; Bohlander, S K; Bartram, C R; Koeffler, H P

    1996-03-15

    We have shown previously that loss of heterozygosity at chromosome band 12p13 is among the most frequent genetic abnormalities identified in acute lymphoblastic leukemia (ALL) of childhood. Two known genes map within the critically deleted region of 12p: TEL, the gene encoding a new member of the ETS family of transcription factors, which is rearranged in a variety of hematological malignancies; and KIP1, the gene encoding the cyclin-dependent kinase inhibitor p27. Both genes are, therefore, excellent candidate tumor suppressor genes. In this report, we determined the exon organization of the TEL gene and performed mutational analysis of TEL and KIP1 in 33 childhood ALL patients known to have loss of heterozygosity at this locus. No mutations in either TEL or KIP1 were found; this suggest that neither TEL nor KIP1 is the critical 12p tumor suppressor gene in childhood ALL. PMID:8640833

  12. Tobacco Smoke Exposure and the Risk of Childhood Acute Lymphoblastic and Myeloid Leukemias by Cytogenetic Subtype

    PubMed Central

    Metayer, Catherine; Zhang, Luoping; Wiemels, Joseph L.; Bartley, Karen; Schiffman, Joshua; Ma, Xiaomei; Aldrich, Melinda C.; Chang, Jeffrey S.; Selvin, Steve; Fu, Cecilia H.; Ducore, Jonathan; Smith, Martyn T.; Buffler, Patricia A.

    2013-01-01

    Background Tobacco smoke contains carcinogens known to damage somatic and germ cells. We investigated the effect tobacco smoke on the risk of childhood acute lymphoblastic leukemia (ALL) and myeloid leukemia (AML), especially subtypes of pre-natal origin like ALL with translocation t(12;21) or high-hyperdiploidy (51–67 chromosomes). Methods We collected information on exposures to tobacco smoking before conception, during pregnancy, and after birth in 767 ALL cases, 135 AML cases, and 1,139 controls (1996–2008). Among cases, chromosome translocations, deletions, or aneuploidy were identified by conventional karyotype and fluorescence in-situ hybridization. Results Multivariable regression analyses for ALL and AML overall showed no definite evidence of associations with self-reported (yes/no) parental prenatal active smoking and child's passive smoking. However, children with history of paternal prenatal smoking combined with postnatal passive smoking had a 1.5-fold increased risk of ALL (95% CI: 1.01–2.23), compared to those without smoking history (ORs for pre- or postnatal smoking only were close to one). This joint effect was seen for B-cell precursor ALL with t(12;21) (OR=2.08; 95% CI: 1.04–4.16), but not high hyperdiploid B-cell ALL. Similarly, child's passive smoking was associated with an elevated risk of AML with chromosome structural changes (OR=2.76; 95% CI: 1.01–7.58), but not aneuploidy. Conclusions our data suggest that exposure to tobacco smoking before were associated with increased risks of childhood ALL and AML; and risks varied by timing of exposure (before and/or after birth) and cytogenetic subtype, based on imprecise estimates. Impact Parents should limit exposures to tobacco smoke before and after the child's birth. PMID:23853208

  13. Identification and validation of the dopamine agonist bromocriptine as a novel therapy for high-risk myelodysplastic syndromes and secondary acute myeloid leukemia

    PubMed Central

    Liberante, Fabio Giuseppe; Pouryahya, Tara; McMullin, Mary-Frances

    2016-01-01

    Myelodysplastic syndromes (MDS) represent a broad spectrum of diseases characterized by their clinical manifestation as one or more cytopenias, or a reduction in circulating blood cells. MDS is predominantly a disease of the elderly, with a median age in the UK of around 75. Approximately one third of MDS patients will develop secondary acute myeloid leukemia (sAML) that has a very poor prognosis. Unfortunately, most standard cytotoxic agents are often too toxic for older patients. This means there is a pressing unmet need for novel therapies that have fewer side effects to assist this vulnerable group. This challenge was tackled using bioinformatic analysis of available transcriptomic data to establish a gene-based signature of the development and progression of MDS. This signature was then used to identify novel therapeutic compounds via statistically-significant connectivity mapping. This approach suggested re-purposing an existing and widely-prescribed drug, bromocriptine as a novel potential therapy in these disease settings. This drug has shown selectivity for leukemic cells as well as synergy with current therapies. PMID:26735888

  14. Spontaneous remission of acute myeloid leukemia relapse after hematopoietic cell transplantation in a high-risk patient with 11q23/MLL abnormality.

    PubMed

    Hudecek, Michael; Bartsch, Kristina; Jäkel, Nadja; Heyn, Simone; Pfannes, Roald; Al-Ali, Haifa Kathrin; Cross, Michael; Pönisch, Wolfram; Gerecke, Ulrich; Edelmann, Jeanett; Ittel, Thomas; Niederwieser, Dietger

    2008-01-01

    A 35-year-old female patient was diagnosed with acute myeloid leukemia with multiple genetic aberrations [48 XX, del(3)(q21), +6, t(11;15)(q23;q15), +21] including an 11q23/MLL abnormality. The patient achieved a complete remission after one induction chemotherapy cycle. After three courses of consolidation, a matched unrelated hematopoietic cell transplantation (HCT) was performed. Following an upper respiratory tract infection 7 years after transplant, her blood counts declined to leukocytes of 1 x 10(9)/l, platelets of 51 x 10(9)/l and hemoglobin of 7.5 g/dl. A bone marrow aspirate revealed 55% leukemic blasts carrying the unfavorable genetic aberrations seen at initial diagnosis (11q23/MLL). In the absence of any disease-specific treatment, the leukemic blasts cleared from the bone marrow within 6 days after diagnosis of relapse and peripheral blood counts returned to normal. Molecular analysis of the 11q23/MLL rearrangement was used to evaluate minimal residual disease, which became undetectable in repetitive FISH analyses. This is the first report of spontaneous remission in a patient with initially a multiaberrant leukemic cell clone and a proven 11q23/MLL abnormality at relapse after HCT. PMID:18367831

  15. Minimal Residual Disease Evaluation in Childhood Acute Lymphoblastic Leukemia: A Clinical Evidence Review

    PubMed Central

    2016-01-01

    Background Leukemia accounts for nearly a third of childhood cancers in Canada, with acute lymphoblastic leukemia (ALL) comprising nearly 80% of cases. Identification of prognostic factors that allow risk stratification and tailored treatment have improved overall survival. However, nearly a quarter of patients considered standard risk on the basis of conventional prognostic factors still relapse, and relapse is associated with increased morbidity and mortality. Relapse is thought to result from extremely low levels of leukemic cells left over once complete remission is reached, termed minimal residual disease (MRD). Poor event-free survival (EFS) as well as overall survival for those who are classified as MRD-positive have been substantiated in seminal studies demonstrating the prognostic value of MRD for EFS in the past few decades. This review sought to further elucidate the relationship between MRD and EFS by looking at relapse, the primary determinant of EFS and the biological mechanism through which MRD is thought to act. This evidence review aimed to ascertain whether MRD is an independent prognostic factor for relapse and to assess the effect of MRD-directed treatment on patient-important outcomes in childhood ALL. Methods Large prospective cohort studies with a priori multivariable analysis that includes potential confounders are required to draw confirmatory conclusions about the independence of a prognostic factor. Data on the prognostic value of MRD for relapse measured by molecular methods (polymerase chain reaction [PCR] of immunoglobulin or T-cell receptor rearrangements) or flow cytometry for leukemia-associated immunophenotypes or difference-from-normal approach were abstracted from included studies. Relevant data on relapse, EFS, and overall survival were abstracted from randomized controlled trials (RCTs) evaluating the effect of MRD-directed treatment. Results A total of 2,832 citations were reviewed, of which 12 studies were included in this

  16. FLT3 and NPM1 gene mutations in childhood acute myeloblastic leukemia.

    PubMed

    Mukda, Ekchol; Pintaraks, Katsarin; Sawangpanich, Rachchadol; Wiangnon, Surapon; Pakakasama, Samart

    2011-01-01

    Mutations of receptor tyrosine kinases are implicated in the constitutive activation and development of human hematologic malignancies. Mutations in fms-like tyrosine kinase 3 (FLT3) gene including internal tandem duplication (ITD) and point mutation in the tyrosine kinase domain (TKD) as well as in nucleoplasmin (NPM1) gene are associated with pathogenesis of acute myeloblastic leukemia (AML). Several reports have demonstrated high incidences of the FLT3 and NPM1 mutations in adult AML patients. Since the pathogenesis of pediatric AML is different from that of adult and the FLT3 and NPM1 mutations have not been well characterized in childhood AML. Therefore, the objective of this study was to determine the frequencies of FLT3 and NPM1 mutations in 64 newly diagnosed childhood AML patients. All blood and bone marrow samples were previously diagnosed with AML by using flow cytometry and/or cytochemistry. FLT3-ITD and FLT3-TKD were detected by PCR and PCR-RFLP methods, respectively. The NPM1 mutation was analyzed by PCR and direct DNA sequencing. The FLT3 mutations were detected in 7 of 64 (11.1%), including FLT3-ITD in 4 of 64 (6.3%) and FLT-TKD in 3 of 62 (4.8%). The NPM1 mutation was not detected in this cohort. By multivariate analysis, white blood cell counts, peripheral blood and bone marrow blast cell counts at diagnosis were significantly higher in children with FLT3-ITD (P<0.05). In addition, the median percentage of CD117 was significantly higher in leukemic blast cells with FLT3-ITD than those with wild type (P=0.01). We did not find any FLT3 mutations in children aged less than 5 years. The AML M3 cell type was most frequently associated with FLT3 gene mutations (50%). In conclusion, the FLT3 mutations was found in 11.1% but none of NPM1 mutation was detected in Thai children with AML. These data support the hypothesis of different biology and pathogenesis between adult and childhood AML. PMID:22126574

  17. Residential Levels of Polybrominated Diphenyl Ethers and Risk of Childhood Acute Lymphoblastic Leukemia in California

    PubMed Central

    Colt, Joanne S.; Deziel, Nicole C.; Whitehead, Todd P.; Reynolds, Peggy; Gunier, Robert B.; Nishioka, Marcia; Dahl, Gary V.; Rappaport, Stephen M.; Buffler, Patricia A.; Metayer, Catherine

    2014-01-01

    Background: House dust is a major source of exposure to polybrominated diphenyl ethers (PBDEs), which are found at high levels in U.S. homes. Methods: We studied 167 acute lymphoblastic leukemia (ALL) cases 0–7 years of age and 214 birth certificate controls matched on date of birth, sex, and race/ethnicity from the Northern California Childhood Leukemia Study. In 2001–2007, we sampled carpets in the room where the child spent the most time while awake; we used a high-volume small-surface sampler or we took dust from the home vacuum. We measured concentrations of 14 PBDE congeners including penta (28, 47, 99, 100, 153, 154), octa (183, 196, 197, 203), and decaBDEs (206–209). Odds ratios (ORs) were calculated using logistic regression, adjusting for demographics, income, year of dust collection, and sampling method. Results: BDE-47, BDE-99, and BDE-209 were found at the highest concentrations (medians, 1,173, 1,579, and 938 ng/g, respectively). Comparing the highest to lowest quartile, we found no association with ALL for summed pentaBDEs (OR = 0.7; 95% CI: 0.4, 1.3), octaBDEs (OR = 1.3; 95% CI: 0.7, 2.3), or decaBDEs (OR = 1.0; 95% CI: 0.6, 1.8). Comparing homes in the highest concentration (nanograms per gram) tertile to those with no detections, we observed significantly increased ALL risk for BDE-196 (OR = 2.1; 95% CI: 1.1, 3.8), BDE-203 (OR = 2.0; 95% CI: 1.1, 3.6), BDE-206 (OR = 2.1; 95% CI: 1.1, 3.9), and BDE-207 (OR = 2.0; 95% CI: 1.03, 3.8). Conclusion: We found no association with ALL for common PBDEs, but we observed positive associations for specific octa and nonaBDEs. Additional studies with repeated sampling and biological measures would be informative. Citation: Ward MH, Colt JS, Deziel NC, Whitehead TP, Reynolds P, Gunier RB, Nishioka M, Dahl GV, Rappaport SM, Buffler PA, Metayer C. 2014. Residential levels of polybrominated diphenyl ethers and risk of childhood acute lymphoblastic leukemia in California. Environ Health Perspect 122:1110–1116

  18. Pilot Study of Nelarabine in Combination With Intensive Chemotherapy in High-Risk T-Cell Acute Lymphoblastic Leukemia: A Report From the Children's Oncology Group

    PubMed Central

    Dunsmore, Kimberly P.; Devidas, Meenakshi; Linda, Stephen B.; Borowitz, Michael J.; Winick, Naomi; Hunger, Stephen P.; Carroll, William L.; Camitta, Bruce M.

    2012-01-01

    Purpose Children's Oncology Group study AALL00P2 was designed to assess the feasibility and safety of adding nelarabine to a BFM 86–based chemotherapy regimen in children with newly diagnosed T-cell acute lymphoblastic leukemia (T-ALL). Patients and Methods In stage one of the study, eight patients with a slow early response (SER) by prednisone poor response (PPR; ≥ 1,000 peripheral blood blasts on day 8 of prednisone prephase) received chemotherapy plus six courses of nelarabine 400 mg/m2 once per day; four patients with SER by high minimal residual disease (MRD; ≥ 1% at day 36 of induction) received chemotherapy plus five courses of nelarabine; 16 patients with a rapid early response (RER) received chemotherapy without nelarabine. In stage two, all patients received six 5-day courses of nelarabine at 650 mg/m2 once per day (10 SER patients [one by MRD, nine by PPR]) or 400 mg/m2 once per day (38 RER patients; 12 SER patients [three by MRD, nine by PPR]). Results The only significant difference in toxicities was decreased neutropenic infections in patients treated with nelarabine (42% with v 81% without nelarabine). Five-year event-free survival (EFS) rates were 73% for 11 stage one SER patients and 67% for 22 stage two SER patients treated with nelarabine versus 69% for 16 stage one RER patients treated without nelarabine and 74% for 38 stage two RER patients treated with nelarabine. Five-year EFS for all patients receiving nelarabine (n = 70) was 73% versus 69% for those treated without nelarabine (n = 16). Conclusion Addition of nelarabine to a BFM 86–based chemotherapy regimen was well tolerated and produced encouraging results in pediatric patients with T-ALL, particularly those with a SER, who have historically fared poorly. PMID:22734022

  19. Cost-effectiveness of zinc as adjunct therapy for acute childhood diarrhoea in developing countries.

    PubMed Central

    Robberstad, Bjarne; Strand, Tor; Black, Robert E.; Sommerfelt, Halvor

    2004-01-01

    OBJECTIVE: To analyse the incremental costs, effects and cost-effectiveness of zinc used as adjunct therapy to standard treatment of acute childhood diarrhoea, including dysentery, and to reassess the cost-effectiveness of standard case management with oral rehydration salt (ORS). METHODS: A decision tree was used to model expected clinical outcomes and expected costs under four alternative treatment strategies. The best available epidemiological, clinical and economic evidence was used in the calculations, and the United Republic of Tanzania was the reference setting. Probabilistic cost-effectiveness analysis was performed using a Monte-Carlo simulation technique and the potential impacts of uncertainty in single parameters were explored in one-way sensitivity analyses. FINDINGS: ORS was found to be less cost-effective than previously thought. The use of zinc as adjunct therapy significantly improved the cost-effectiveness of standard management of diarrhoea for dysenteric as well as non-dysenteric illness. The results were particularly sensitive to mortality rates in non-dysenteric diarrhoea, but the alternative interventions can be defined as highly cost-effective even in pessimistic scenarios. CONCLUSION: There is sufficient evidence to recommend the inclusion of zinc into standard case management of both dysenteric and non-dysenteric acute diarrhoea.A direct transfer of our findings from the United Republic of Tanzania to other settings is not justified, but there are no indications of large geographical differences in the efficacy of zinc. It is therefore plausible that our findings are also applicable to other developing countries. PMID:15500284

  20. Prelabor cesarean delivery and early-onset acute childhood leukemia risk.

    PubMed

    Thomopoulos, Thomas P; Skalkidou, Alkistis; Dessypris, Nick; Chrousos, George; Karalexi, Maria A; Karavasilis, Theodoros G; Baka, Margarita; Hatzipantelis, Emmanuel; Kourti, Maria; Polychronopoulou, Sophia; Sidi, Vasiliki; Stiakaki, Eftichia; Moschovi, Maria; Loutradis, Dimitrios; Petridou, Eleni Th

    2016-03-01

    The long-term impact of cesarean delivery (CD) on the health of the offspring is being explored methodically. We sought to investigate the effect of birth by (a) prelabor and (b) during-labor CD on the risk of early-onset (≤3 years) acute lymphoblastic leukemia (ALL), specifically of its prevailing precursor B (B-ALL) subtype. A total of 1099 incident cases of ALL (957 B-ALL), 131 of acute myeloid leukemia (AML), and their 1 : 1 age-matched and sex-matched controls, derived from the Nationwide Registry for Childhood Hematological Malignancies (1996-2013), were analyzed using multivariate regression models. A null association was found between prelabor and/or during labor CD and either ALL (B-ALL) or AML in the 0-14 age range. By contrast, birth by CD increased significantly the risk of early-onset ALL [odds ratioCD (ORCD)=1.57, 95% confidence interval (CI): 1.10-2.24] mainly on account of prelabor CD (ORprelaborCD=1.66, 95% CI: 1.13-2.43). The respective figures were even higher for the early-onset precursor B-ALL (ORCD=1.66, 95% CI: 1.15-2.40 and ORprelaborCD=1.79, 95% CI: 1.21-2.66), whereas no association emerged for early-onset AML. Prelabor CD, which deprives exposure of the fetus/infant to the presumably beneficial effect of stress hormones released in both vaginal labor and during labor CD, was associated exclusively with an increased risk of early-onset ALL, particularly the precursor B-ALL subtype. If confirmed, these adverse long-term outcomes of CD may point to re-evaluation of prelabor CD practices and prompt scientific discussion on the best ways to simulate the effects of vaginal delivery, such as a precesarean induction of labor. PMID:25793919

  1. Magnetic resonance imaging of the brain in survivors of childhood acute lymphoblastic leukemia

    PubMed Central

    BADR, MOHAMED AHMED; HASSAN, TAMER HASAN; EL-GERBY, KHALED MOHAMED; LAMEY, MOHAMED EL-SAYED

    2013-01-01

    The issue of delayed neurological damage as a result of treatment is becoming increasingly important now that an increased number of children survive treatment for acute lymphoblastic leukemia (ALL). Following modification of the treatment protocols, severe symptomatic late effects are rare, and most adverse effects are detected by sensitive imaging methods such as magnetic resonance imaging (MRI) or by neuropsychological testing. In this study we aimed to determine the prevalence and characteristics of late central nervous system (CNS) damage by MRI and clinical examination in children treated for ALL. A cross-sectional study was carried out at the pediatric oncology unit of Zagazig University, Egypt, and included 25 patients who were consecutively enrolled and treated according to the modified Children’s Cancer Group (CCG) 1991 protocol for standard risk ALL and the modified CCG 1961 protocol for high-risk ALL and who had survived more than 5 years from the diagnosis. All relevant data were collected from patients’ medical records; particularly the data concerning the initial clinical presentation and initial brain imaging. All patients were subjected to thorough history and full physical examination with special emphasis on the neurological system. MRI of the brain was performed for all patients. The mean age of patients was 6.9±3.04 years at diagnosis and was 12.9±3.2 years at the time of study. The patients comprised 14 boys and 11 girls. Abnormal MRI findings were detected in six patients (24%). They were in the form of leukoencephalopathy in two patients (8%), brain atrophy in two patients (8%), old infarct in one patient (4%) and old hemorrhage in one patient (4%). The number of abnormal MRI findings was significantly higher in high-risk patients, patients who had CNS manifestations at diagnosis and patients who had received cranial irradiation. We concluded that cranial irradiation is associated with higher incidence of MRI changes in children

  2. Stromal cell-mediated mitochondrial redox adaptation regulates drug resistance in childhood acute lymphoblastic leukemia

    PubMed Central

    Liu, Jizhong; Masurekar, Ashish; Johnson, Suzanne; Chakraborty, Sohini; Griffiths, John; Smith, Duncan; Alexander, Seema; Dempsey, Clare; Parker, Catriona; Harrison, Stephanie; Li, Yaoyong; Miller, Crispin; Di, Yujun; Ghosh, Zhumur; Krishnan, Shekhar; Saha, Vaskar

    2015-01-01

    Despite the high cure rates in childhood acute lymphoblastic leukemia (ALL), relapsed ALL remains a significant clinical problem. Genetic heterogeneity does not adequately explain variations in response to therapy. The chemoprotective tumor microenvironment may additionally contribute to disease recurrence. This study identifies metabolic reprogramming of leukemic cells by bone marrow stromal cells (BMSC) as a putative mechanism of drug resistance. In a BMSC-extracellular matrix culture model, BMSC produced chemoprotective soluble factors and facilitated the emergence of a reversible multidrug resistant phenotype in ALL cells. BMSC environment induced a mitochondrial calcium influx leading to increased reactive oxygen species (ROS) levels in ALL cells. In response to this oxidative stress, drug resistant cells underwent a redox adaptation process, characterized by a decrease in ROS levels and mitochondrial membrane potential with an upregulation of antioxidant production and MCL-1 expression. Similar expanded subpopulations of low ROS expressing and drug resistant cells were identified in pre-treatment bone marrow samples from ALL patients with slower response to therapy. This suggests that the bone marrow microenvironment induces a redox adaptation in ALL subclones that protects against cytotoxic stress and potentially gives rise to minimal residual disease. Targeting metabolic remodeling by inhibiting antioxidant production and antiapoptosis was able to overcome drug resistance. Thus metabolic plasticity in leukemic cell response to environmental factors contributes to chemoresistance and disease recurrence. Adjunctive strategies targeting such processes have the potential to overcome therapeutic failure in ALL. PMID:26474278

  3. Dissecting the clonal origins of childhood acute lymphoblastic leukemia by single-cell genomics

    PubMed Central

    Gawad, Charles; Koh, Winston; Quake, Stephen R.

    2014-01-01

    Many cancers have substantial genomic heterogeneity within a given tumor, and to fully understand that diversity requires the ability to perform single cell analysis. We performed targeted sequencing of a panel of single nucleotide variants (SNVs), deletions, and IgH sequences in 1,479 single tumor cells from six acute lymphoblastic leukemia (ALL) patients. By accurately segregating groups of cooccurring mutations into distinct clonal populations, we identified codominant clones in the majority of patients. Evaluation of intraclonal mutation patterns identified clone-specific punctuated cytosine mutagenesis events, showed that most structural variants are acquired before SNVs, determined that KRAS mutations occur late in disease development but are not sufficient for clonal dominance, and identified clones within the same patient that are arrested at varied stages in B-cell development. Taken together, these data order the sequence of genetic events that underlie childhood ALL and provide a framework for understanding the development of the disease at single-cell resolution. PMID:25425670

  4. Endothelial Health in Childhood Acute Lymphoid Leukemia Survivors: Pilot Evaluation with Peripheral Artery Tonometry

    PubMed Central

    Ruble, Kathy; Davis, Catherine L; Han, Hae-Ra

    2014-01-01

    Background Childhood cancer survivors are a growing population at risk for poor cardiac outcomes. Acute lymphoid leukemia (ALL) survivors are among those at increased risk of cardiovascular complications. Early identification of impaired vascular health may allow for interventions to improve these outcomes. The purpose of this study is to evaluate vascular health using peripheral artery tonometry in ALL survivors and compare results to healthy siblings. Procedure Sixteen ALL survivor, healthy sibling pairs, ages 8-20, were evaluated for vascular health and cardiovascular risk factors (body mass index, central adiposity, blood pressure and fitness). One tailed paired T-test was used to compare the groups. Results Survivors were similar to siblings in cardiovascular risk measures but had poorer vascular health as measured by reactive hyperemia index (survivor RHI 1.54 vs sibling 1.77, p=0.0474). Conclusion This study reveals that even among survivors who are comparable to their healthy siblings in other traditional cardiovascular risks there is evidence of poorer vascular health. PMID:24577544

  5. Stromal cell-mediated mitochondrial redox adaptation regulates drug resistance in childhood acute lymphoblastic leukemia.

    PubMed

    Liu, Jizhong; Masurekar, Ashish; Johnson, Suzanne; Chakraborty, Sohini; Griffiths, John; Smith, Duncan; Alexander, Seema; Dempsey, Clare; Parker, Catriona; Harrison, Stephanie; Li, Yaoyong; Miller, Crispin; Di, Yujun; Ghosh, Zhumur; Krishnan, Shekhar; Saha, Vaskar

    2015-12-15

    Despite the high cure rates in childhood acute lymphoblastic leukemia (ALL), relapsed ALL remains a significant clinical problem. Genetic heterogeneity does not adequately explain variations in response to therapy. The chemoprotective tumor microenvironment may additionally contribute to disease recurrence. This study identifies metabolic reprogramming of leukemic cells by bone marrow stromal cells (BMSC) as a putative mechanism of drug resistance. In a BMSC-extracellular matrix culture model, BMSC produced chemoprotective soluble factors and facilitated the emergence of a reversible multidrug resistant phenotype in ALL cells. BMSC environment induced a mitochondrial calcium influx leading to increased reactive oxygen species (ROS) levels in ALL cells. In response to this oxidative stress, drug resistant cells underwent a redox adaptation process, characterized by a decrease in ROS levels and mitochondrial membrane potential with an upregulation of antioxidant production and MCL-1 expression. Similar expanded subpopulations of low ROS expressing and drug resistant cells were identified in pre-treatment bone marrow samples from ALL patients with slower response to therapy. This suggests that the bone marrow microenvironment induces a redox adaptation in ALL subclones that protects against cytotoxic stress and potentially gives rise to minimal residual disease. Targeting metabolic remodeling by inhibiting antioxidant production and antiapoptosis was able to overcome drug resistance. Thus metabolic plasticity in leukemic cell response to environmental factors contributes to chemoresistance and disease recurrence. Adjunctive strategies targeting such processes have the potential to overcome therapeutic failure in ALL. PMID:26474278

  6. The Progression of Bone Mineral Density Abnormalities After Chemotherapy for Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Vitanza, Nicholas A; Hogan, Laura E; Zhang, Guangxiang; Parker, Robert I

    2015-07-01

    Although reduced bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL) is well documented, the degree of demineralization and relation to age are not well described. This is a retrospective chart analysis of 58 patients consecutively treated for ALL without relapse, cranial irradiation, or transplantation. Bone mineral densities were measured by dual-energy x-ray absorptiometry and patients were divided by sex and age (≤5, 6 to 10, and >10 y) at diagnosis. Serial scans for 6 years after therapy were analyzed as Z-scores. Over 6 years after therapy, 93.1% of patients exhibited a decreased Z-score in at least 1 anatomic site. The difference in Z-score among the age cohorts was significant at both the lumbar spine and femoral neck. Patients older than 10 years at diagnosis had the lowest Z-scores: -2.78 and -2.87 for boys and -2.39 and -2.91 for girls at the lumbar spine and femoral neck, respectively. Children after ALL therapy exhibit a significant bone mineral deficit shortly after completion of therapy that persists for at least 6 years. The degree of bone demineralization can be followed up by a dual-energy x-ray absorptiometry scan and is most severe in patients older than 10 years at the initiation of therapy. PMID:25222061

  7. Absence of Association between CCR5 rs333 Polymorphism and Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    de Oliveira, Carlos Eduardo Coral; Perim, Aparecida de Lourdes; Ozawa, Patricia Midori Murobushi; Freire Vitiello, Glauco Akelinghton; Losi Guembarovski, Roberta; Watanabe, Maria Angelica Ehara

    2014-01-01

    Acute lymphoblastic leukemia (ALL) is a malignant disorder that originates from one single hematopoietic precursor committed to B- or T-cell lineage. Ordinarily, these cells express CCR5 chemokine receptor, which directs the immune response to a cellular pattern and is involved in cancer pathobiology. The genetic rs333 polymorphism of CCR5 (Δ32), results in a diminished receptor expression, thus leading to impaired cell trafficking. The objective of the present study was to investigate the effect of CCR5 chemokine receptor rs333 polymorphism in the pathogenesis of ALL. The genotype distribution was studied in 79 patients and compared with 80 control subjects, in a childhood population of Southern Brazil. Genotyping was performed using DNA samples amplified by polymerase chain reaction with sequence-specific primers (PCR-SSP). The homozygous (Δ32/Δ32) deletion was not observed in any subject involved in the study. Heterozygous genotype was not associated with ALL risk (OR 0.7%; 95% CI 0.21–2.32; P > 0.05), nor recurrence status of ALL (OR 0.86; 95% CI 0.13–5.48; P > 0.05). This work demonstrated, for the first time, no significant differences in the frequency of the CCR5/Δ32 genotype between ALL and control groups, indicating no effect of this genetic variant on the ALL susceptibility and recurrence risk. PMID:24822066

  8. Childhood acute lymphoblastic leukaemia and indicators of early immune stimulation: the Estelle study (SFCE)

    PubMed Central

    Ajrouche, R; Rudant, J; Orsi, L; Petit, A; Baruchel, A; Lambilliotte, A; Gambart, M; Michel, G; Bertrand, Y; Ducassou, S; Gandemer, V; Paillard, C; Saumet, L; Blin, N; Hémon, D; Clavel, J

    2015-01-01

    Background: Factors related to early stimulation of the immune system (breastfeeding, proxies for exposure to infectious agents, normal delivery, and exposure to animals in early life) have been suggested to decrease the risk of childhood acute lymphoblastic leukaemia (ALL). Methods: The national registry-based case–control study, ESTELLE, was carried out in France in 2010–2011. Population controls were frequency matched with cases on age and gender. The participation rates were 93% for cases and 86% for controls. Data were obtained from structured telephone questionnaires administered to mothers. Odds ratios (OR) were estimated using unconditional regression models adjusted for age, gender, and potential confounders. Results: In all, 617 ALL and 1225 controls aged ⩾1 year were included. Inverse associations between ALL and early common infections (OR=0.8, 95% confidence interval (CI): 0.6, 1.0), non-first born (⩾3 vs 1; OR=0.7, 95% CI: 0.5, 1.0), attendance of a day-care centre before age 1 year (OR=0.7, 95% CI: 0.5, 1.0), breastfeeding (OR=0.8, 95% CI: 0.7, 1.0), and regular contact with pets (OR=0.8, 95% CI: 0.7, 1.0) in infancy were observed. Conclusions: The results support the hypothesis that conditions promoting the maturation of the immune system in infancy have a protective role with respect to ALL. PMID:25675150

  9. A computer-aided method to expedite the evaluation of prognosis for childhood acute lymphoblastic leukemia.

    PubMed

    Wang, Xingwei; Li, Shibo; Liu, Hong; Mulvihill, John J; Chen, Wei; Zheng, Bin

    2006-08-01

    This study presented a fully-automated computer-aided method (scheme) to detect metaphase chromosomes depicted on microscopic digital images, count the total number of chromosomes in each metaphase cell, compute the DNA index, and correlate the results to the prognosis of childhood acute lymphoblastic leukemia (ALL). The computer scheme first uses image filtering, threshold, and labeling algorithms to segment and count the number of the suspicious "chromosome," and then computes a feature vector for each "detected chromosome." Based on these features, a knowledge-based classifier is used to eliminate those "non-chromosome" objects (i.e., inter-phase cells, stain debris, and other kinds of background noises). Due to the possible overlap of the chromosomes, a classification criterion was used to identify the overlapped chromosomes and adjust the initially counted number of the total chromosomes in each image. In this preliminary study with 60 testing images (depicting metaphase chromosome cells) acquired from three pediatric patients, the computer scheme generated results matched with the diagnostic results provided by the clinical cytogeneticists. The results demonstrated the feasibility or potential of using a computerized method to replace the tedious and the reader-dependent diagnostic methods commonly used in genetic laboratories to date. PMID:16866573

  10. The methylenetetrahydrofolate reductase C677T gene polymorphism decreases the risk of childhood acute lymphocytic leukaemia.

    PubMed

    Franco, R F; Simões, B P; Tone, L G; Gabellini, S M; Zago, M A; Falcão, R P

    2001-12-01

    We have determined the prevalence of methylenetetrahydrofolate reductase (MTHFR) mutations C677T and A1298C in 71 children (< or = 15 years) with acute lymphoblastic leukaemia (ALL) and in 71 control subjects. Odds ratio (OR) for ALL linked to MTHFR C677T was 0.4 (95% CI 0.2-0.8); for heterozygotes it was 0.5 (95% CI 0.2-0.9) and for homozygotes it was 0.3 (95%CI 0.09-0.8). MTHFR A1298C yielded an overall OR for ALL of 1.3 (95% CI: 0.7-2.6); for heterozygotes it was 1.3 (95% CI: 0.7-7.6) and for homozygotes it was 2.8 (95% CI 0.5-15.6). In conclusion, MTHFR C677T was linked to a significant 2.4-fold decreased risk of developing childhood ALL, whereas MTHFR A1298C did not significantly affect the risk of ALL in our population. PMID:11736945

  11. The outcomes and treatment burden of childhood acute myeloid leukaemia in Australia, 1997-2008: A report from the Australian Paediatric Cancer Registry.

    PubMed

    Foresto, Steven A; Youlden, Danny R; Baade, Peter D; Hallahan, Andrew R; Aitken, Joanne F; Moore, Andrew S

    2015-09-01

    Childhood acute myeloid leukaemia (AML) requires intensive therapy and is associated with survival rates that are substantially inferior to many other childhood malignancies. We undertook a retrospective analysis of Australian Paediatric Cancer Registry data from 1997 to 2008 together with a single-centre audit during the same period assessing burden on service delivery at a tertiary children's hospital (Royal Children's Hospital, Brisbane). Although survival improved from 54.3% (1997-2002) to 69.2% (2003-2008), childhood AML caused a disproportionate number of childhood cancer deaths, accounting for 5.5% of all childhood cancer diagnoses yet 7.9% of all childhood cancer mortality. Furthermore, treatment was associated with significant toxicity requiring intensive use of local health resources. Novel therapeutic strategies aimed at improving survival and reducing toxicity are urgently required. PMID:25855531

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

    ClinicalTrials.gov

    2016-03-16

    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

  13. Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

    PubMed Central

    ZUNINO, SUSAN J.; STORMS, DAVID H.; NEWMAN, JOHN W.; PEDERSEN, THERESA L.; KEEN, CARL L.; DUCORE, JONATHAN M.

    2013-01-01

    In this study, the efficacy of orally and parenter-ally administered curcumin was evaluated in non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice (NOD.CB17-Prkdcscid/J mice) engrafted with the human t(4;11) acute lymphoblastic leukemia line, SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed, the chemotherapeutic potential was examined by injecting mice intraperitoneally with curcumin (5 mg/kg body weight) dissolved in dimethylsulfoxide (DMSO) or DMSO alone (control) every other day, or vincristine (0.5 mg/kg body weight) 3 times per week for 4 weeks (n=16 per group). The intraperitoneal administration of curcumin did not inhibit the growth of the leukemia cells. To determine the efficacy of oral curcumin, mice were fed a control diet or a diet containing 0.5% w/w curcumin 3 weeks prior to the injection of the leukemia cells and throughout the experimental period (n=16 per group). To determine whether dietary curcumin can enhance the efficacy of a conventional chemotherapeutic agent, vincristine was injected intraperitoneally into leukemic mice fed the different diets. Dietary curcumin did not delay the engraftment or growth of leukemia cells, or sensitize the cells to vincristine. Liquid chromatography-tandem mass spectrometry analyses of mouse sera showed that curcumin rapidly metabolized to glucuronidated and sulfated forms within 1 h post-injection and these were the major curcumin metabolites found in the sera of the mice fed the curcumin diet. In contrast to the findings in previous in vitro models, the current data indicate that orally or parenterally administered curcumin is not a potent preventive agent against high-risk t(4;11) acute lymphoblastic leukemia. PMID:23232667

  14. Association of SHMT1 gene polymorphisms with the risk of childhood acute lymphoblastic leukemia in a sample of Iranian population.

    PubMed

    Bahari, G; Hashemi, M; Naderi, M; Sadeghi-Bojd, S; Taheri, M

    2016-01-01

    The enzymes serine hydroxymethyltransferase 1 (SHMT1) regulate key reaction in folate-mediated one-carbon metabolism. In the current study we aimed to examine the possible association between SHMT1 gene polymorphisms and childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. The rs9901160, rs2273027, rs9909104, rs1979277, and rs11868708 gene polymorphisms of SHMT1 were genotyped in 120 children diagnosed with ALL and 120 healthy children by the polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). The results showed that rs9901160, rs2273027 as well as rs1979277 polymorphism significantly increased the risk of childhood ALL (P<0.05). While, rs9909104 polymorphism significantly decreased the ALL risk (P<0.05). The rs11868708 variant was not associated with risk/protection of childhood ALL (P>0.05). In conclusion, our results suggest that the polymorphisms of SHMT1 gene are associated with childhood ALL risk in a sample of Iranian population. Further studies with larger sample sizes and different ethnicities are necessary to verify our findings. PMID:26950450

  15. Clinical impact of circulating microRNAs as blood-based marker in childhood acute lymphoblastic leukemia.

    PubMed

    Swellam, Menha; El-Khazragy, Nashwa

    2016-08-01

    Aberrant microRNA (miRNA) expression participates in childhood acute lymphoblastic leukemia (ALL). This study aimed to investigate the expression of miRNA-100, miRNA-196a, and miRNA-146a among childhood ALL and study their correlation with other hematological parameters and different phenotypes. Peripheral blood mononuclear cells (PMNCs) were obtained from 85 childhood ALL and 25 healthy children for the detection of miRNA expression using quantitative real-time PCR. Significant higher median levels were reported for ALL compared to control children. The diagnostic efficacy for miRNA-146a was superior as both sensitivity and specificity were absolute. A significant correlation was observed between higher expression of miRNA-100 and lower platelet and lymphocyte counts; high expression of miRNA-146a showed significant correlation with low total leukocyte count (TLC) and lymphocyte counts. Significant relation was reported between studied miRNAs and different phenotyping. miRNA-100, miRNA-196a, and miRNA-146a have significant role in childhood ALL leukemogenesis, and they may be useful as biological diagnostic molecular markers. PMID:26857279

  16. A phase I/II study of oral clofarabine plus low-dose cytarabine in previously treated acute myeloid leukaemia and high-risk myelodysplastic syndrome patients at least 60 years of age.

    PubMed

    Buckley, Sarah A; Mawad, Raya; Gooley, Ted A; Becker, Pamela S; Sandhu, Vicky; Hendrie, Paul; Scott, Bart L; Wood, Brent L; Walter, Roland B; Smith, Kelly; Dean, Carol; Estey, Elihu H; Pagel, John M

    2015-08-01

    Outcomes for older adults with acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) are generally poor, and new effective therapies are needed. We investigated oral clofarabine combined with low-dose cytarabine (LDAC) in patients aged 60 years and above with relapsed or refractory AML or high-risk MDS in a phase I/II trial. A 3 + 3 dose escalation of oral clofarabine was followed by a phase II expansion with the aim of obtaining a complete response (CR) rate ≥30%. We identified 20 mg/d for 5 d as the maximum tolerated dose (MTD) of oral clofarabine. A total of 35 patients, with a median age of 72 years, were treated. Of 26 patients enrolled at the MTD, 4 had treatment-related grade 3-4 non-haematological toxicities, but none died within 28 d. The observed CR rate and median survival were 34% [95% confidence interval (CI), 18-50%] and 6.8 months overall and 38% [95% CI, 19-57%] and 7.2 months at the MTD. The median disease-free survival was 7.4 months. Fifty-two percent (23/44) of cycles administered at the MTD were done without hospital admission. This combination of oral clofarabine and LDAC demonstrated efficacy with a CR rate of >30% and acceptable toxicity in older patients. PMID:25854284

  17. [High risk acute lymphoblastic leukaemia in children. Preliminary report after introducing a new version of New York (1997) protocol adjusted to the age of the patients. Report of the Polish Paediatric Leukaemia/Lymphoma Study Group].

    PubMed

    Skoczen, S; Klus, K; Armata, J; Kowalczyk, J; Wisniewska-Slusarz, H; Kolecki, P; Derwich, K; Matysiak, M; Krauze, A; Rokicka-Milewska, R; Pawelec, K; Boguslawska-Jaworska, J; Juszczak, K; Pisarek, J; Sońta-Jakimczyk, D; Tomaszewska, R; Łuszczynska, A; Wysocki, M; Styczyński, J

    2000-01-01

    The paper presents the experience of the Polish Paediatric Leukaemia/Lymphoma Study Group in the treatment of high-risk acute lymphoblastic leukaemia in children using a new version of the New York (1997-1999). Protocol with treatment intensity adjusted according to the age of the patients. From April 1997 to December 1999 a group of 49 children with leukocytosis ranging from 50 900/mm3 to 580 000/mm3 (median 122 000/mm3) and 6 children with leukocytosis below 50 000/mm3 and poor response to steroids were treated with this protocol. Children below 10 years (43 patients) were treated according to the previous protocol, children above 10 years (12 patients) were treated with intensified protocol (high doses of ARA-C in consolidation and intermediate doses of Mtx in maintenance). Induction was identical for all patients. Complete remission was achieved in 92.6% patients. There were 2 relapses. Six children died - 3 without remission, 2 due to a relapse, 1 due to treatment complications. The current opinions concerning classification of HRG-ALL and treatment possibilities in this group of children are discussed. PMID:12021459

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

    PubMed Central

    Karakaya, Pakize; Yılmaz, Şebnem; Tüfekçi, Özlem; Kır, Mustafa; Böber, Ece; İrken, Gülersu; Ören, Hale

    2013-01-01

    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 one adverse

  19. Tobacco Smoke and Risk of Childhood Acute Non-Lymphocytic Leukemia: Findings from the SETIL Study

    PubMed Central

    Mattioli, Stefano; Farioli, Andrea; Legittimo, Patrizia; Miligi, Lucia; Benvenuti, Alessandra; Ranucci, Alessandra; Salvan, Alberto; Rondelli, Roberto; Magnani, Corrado

    2014-01-01

    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. PMID:25401754

  20. The combination effects of bendamustine with antimetabolites against childhood acute lymphoblastic leukemia cells.

    PubMed

    Goto, Shoko; Goto, Hiroaki; Yokosuka, Tomoko

    2016-05-01

    Bendamustine combined with other drugs is clinically efficacious for some adult lymphoid malignancies, but to date there are no reports of the use of such combinatorial approaches in pediatric patients. We investigated the in vitro activity of bendamustine combined with other antimetabolite drugs on B cell precursor acute lymphoblastic leukemia (BCP-ALL) cell lines established from pediatric patients with refractory or relapsed ALL. We also developed a mathematically drown improved isobologram method to assess the data objectively. Three BCP-ALL cell lines; YCUB-2, YCUB-5, and YCUB-6, were simultaneously exposed to various concentrations of bendamustine and cladribine, cytarabine, fludarabine, or clofarabine. Cell growth inhibition was determined using the WST-8 assay. Combinatorial effects were estimated using our improved isobologram method with IC80 (drug concentration corresponding to 80 % of maximum inhibition). Bendamustine alone inhibited ALL cell growth with mean IC80 values of 11.30-18.90 μg/ml. Combinations of bendamustine with other drugs produced the following effects: (1) cladribine; synergistic-to-additive on all cell lines; (2) cytarabine; synergistic-to-additive on YCUB-5 and YCUB-6, and synergistic-to-antagonistic on YCUB-2; (3) fludarabine; additive-to-antagonistic on YCUB-5, and synergistic-to-antagonistic on YCUB-2 and YCUB-6; (4) clofarabine; additive-to-antagonistic on all cell lines. Flow cytometric analysis also showed the combination effects of bendamustine and cladribine. Bendamustine/cladribine or bendamustine/cytarabine may thus represent a promising combination for salvage treatment in childhood ALL. PMID:26886449

  1. Different molecular mechanisms causing 9p21 deletions in acute lymphoblastic leukemia of childhood.

    PubMed

    Novara, Francesca; Beri, Silvana; Bernardo, Maria Ester; Bellazzi, Riccardo; Malovini, Alberto; Ciccone, Roberto; Cometa, Angela Maria; Locatelli, Franco; Giorda, Roberto; Zuffardi, Orsetta

    2009-10-01

    Deletion of chromosome 9p21 is a crucial event for the development of several cancers including acute lymphoblastic leukemia (ALL). Double strand breaks (DSBs) triggering 9p21 deletions in ALL have been reported to occur at a few defined sites by illegitimate action of the V(D)J recombination activating protein complex. We have cloned 23 breakpoint junctions for a total of 46 breakpoints in 17 childhood ALL (9 B- and 8 T-lineages) showing different size deletions at one or both homologous chromosomes 9 to investigate which particular sequences make the region susceptible to interstitial deletion. We found that half of 9p21 deletion breakpoints were mediated by ectopic V(D)J recombination mechanisms whereas the remaining half were associated to repeated sequences, including some with potential for non-B DNA structure formation. Other mechanisms, such as microhomology-mediated repair, that are common in other cancers, play only a very minor role in ALL. Nucleotide insertions at breakpoint junctions and microinversions flanking the breakpoints have been detected at 20/23 and 2/23 breakpoint junctions, respectively, both in the presence of recombination signal sequence (RSS)-like sequences and of other unspecific sequences. The majority of breakpoints were unique except for two cases, both T-ALL, showing identical deletions. Four of the 46 breakpoints coincide with those reported in other cases, thus confirming the presence of recurrent deletion hotspots. Among the six cases with heterozygous 9p deletions, we found that the remaining CDKN2A and CDKN2B alleles were hypermethylated at CpG islands. PMID:19484265

  2. Energy balance and fitness in adult survivors of childhood acute lymphoblastic leukemia

    PubMed Central

    DeLany, James P.; Kaste, Sue C.; Mulrooney, Daniel A.; Pui, Ching-Hon; Chemaitilly, Wassim; Karlage, Robyn E.; Lanctot, Jennifer Q.; Howell, Carrie R.; Lu, Lu; Srivastava, Deo Kumar; Robison, Leslie L.; Hudson, Melissa M.

    2015-01-01

    There is limited information on body composition, energy balance, and fitness among survivors of childhood acute lymphoblastic leukemia (ALL), especially those treated without cranial radiation therapy (CRT). This analysis compares these metrics among 365 ALL survivors with a mean age of 28.6 ± 5.9 years (149 treated with and 216 without CRT) and 365 age-, sex-, and race-matched peers. We also report risk factors for outcomes among survivors treated without CRT. Male survivors not exposed to CRT had abnormal body composition when compared with peers (% body fat, 26.2 ± 8.2 vs 22.7 ± 7.1). Survivors without CRT had similar energy balance but had significantly impaired quadriceps strength (−21.9 ± 6.0 Newton-meters [Nm]/kg, 60°/s) and endurance (−11.4 ± 4.6 Nm/kg, 300°/s), exercise capacity (−2.0 ± 2.1 ml/kg per minute), low-back and hamstring flexibility (−4.7 ± 1.6 cm), and dorsiflexion range of motion (−3.1 ± 0.9°) and higher modified total neuropathy scores (+1.6 ± 1.1) than peers. Cumulative asparaginase dose ≥120 000 IU/m2 was associated with impaired flexibility, vincristine dose ≥39 mg/m2 with peripheral neuropathy, glucocorticoid (prednisone equivalent) dose ≥8000 mg/m2 with hand weakness, and intrathecal methotrexate dose ≥225 mg with dorsiflexion weakness. Physical inactivity was associated with hand weakness and decreased exercise capacity. Smoking was associated with peripheral neuropathy. Elimination of CRT from ALL therapy has improved, but not eliminated, body-composition outcomes. Survivors remain at risk for impaired fitness. PMID:25814529

  3. Tacrolimus and Methotrexate With or Without Sirolimus in Preventing Graft-Versus-Host Disease in Young Patients Undergoing Donor Stem Cell Transplant for Acute Lymphoblastic Leukemia in Complete Remission

    ClinicalTrials.gov

    2014-01-23

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Graft Versus Host Disease; L1 Childhood Acute Lymphoblastic Leukemia; L2 Childhood Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

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

    ClinicalTrials.gov

    2016-05-19

    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

  5. Maternal Benzene Exposure during Pregnancy and Risk of Childhood Acute Lymphoblastic Leukemia: A Meta-Analysis of Epidemiologic Studies

    PubMed Central

    Li, Zhen; Zhu, Jie; Bi, Yongyi; Bai, YuE; Wang, Hong

    2014-01-01

    Background 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. Methods 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. Results 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. Conclusions 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. PMID:25333868

  6. Childhood Leukemia

    MedlinePlus

    ... acute types. Symptoms include Infections Fever Loss of appetite Tiredness Easy bruising or bleeding Swollen lymph nodes Night sweats Shortness of breath Pain in the bones or joints Risk factors for childhood leukemia include having a brother ...

  7. Residual disease detected by flow cytometry is an independent predictor of survival in childhood acute myeloid leukaemia; results of the NOPHO-AML 2004 study.

    PubMed

    Tierens, Anne; Bjørklund, Elizabeth; Siitonen, Sanna; Marquart, Hanne Vibeke; Wulff-Juergensen, Gitte; Pelliniemi, Tarja-Terttu; Forestier, Erik; Hasle, Henrik; Jahnukainen, Kirsi; Lausen, Birgitte; Jonsson, Olafur G; Palle, Josefine; Zeller, Bem; Fogelstrand, Linda; Abrahamsson, Jonas

    2016-08-01

    Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively (P < 0·001) and an OS of 77 ± 6% (P = 0·025) and 51 ± 8%. RD-negative and -positive patients at start of consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively (P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) (P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio (HR):5·0; 95% confidence interval (CI):1·9-13·3] and OS (HR:7·0; 95%CI:2·0-24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials. PMID:27072379

  8. Busulfan, Fludarabine Phosphate, and Anti-Thymocyte Globulin Followed By Donor Stem Cell Transplant and Azacitidine in Treating Patients With High-Risk Myelodysplastic Syndrome and Older Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-07-20

    Adult Acute Megakaryoblastic Leukemia; Adult Acute Monoblastic Leukemia; Adult Acute Monocytic Leukemia; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Myeloid Leukemia With Maturation; Adult Acute Myeloid Leukemia With Minimal Differentiation; 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 Myeloid Leukemia Without Maturation; Adult Acute Myelomonocytic Leukemia; Adult Erythroleukemia; Adult Pure Erythroid Leukemia; Alkylating Agent-Related Acute Myeloid Leukemia; de Novo Myelodysplastic Syndrome; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Secondary Myelodysplastic Syndrome; Untreated Adult Acute Myeloid Leukemia

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

    ClinicalTrials.gov

    2016-04-07

    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

  10. Cumulative Experiences of Violence among High-Risk Urban Youth

    ERIC Educational Resources Information Center

    Taylor, Catherine A.; Boris, Neil W.; Heller, Sherryl Scott; Clum, Gretchen A.; Rice, Janet C.; Zeanah, Charles H.

    2008-01-01

    This study examines type-specific and cumulative experiences of violence among a vulnerable population of youth. Sixty high-risk, shelter-dwelling, urban youth were interviewed regarding their history of childhood maltreatment, exposure to community violence (ECV), and experience with intimate partner violence (IPV). Results show a high prevalence…

  11. Sociocultural determinants of anticipated vaccine acceptance for acute watery diarrhea in early childhood in Katanga Province, Democratic Republic of Congo.

    PubMed

    Merten, Sonja; Schaetti, Christian; Manianga, Cele; Lapika, Bruno; Hutubessy, Raymond; Chaignat, Claire-Lise; Weiss, Mitchell

    2013-09-01

    Rotavirus and oral cholera vaccines have the potential to reduce diarrhea-related child mortality in low-income settings and are recommended by the World Health Organization. Uptake of vaccination depends on community support, and is based on local priorities. This study investigates local perceptions of acute watery diarrhea in childhood and anticipated vaccine acceptance in two sites in the Democratic Republic of Congo. In 2010, 360 randomly selected non-affected adults were interviewed by using a semi-structured questionnaire. Witchcraft and breastfeeding were perceived as potential cause of acute watery diarrhea by 51% and 48% of respondents. Despite misperceptions, anticipated vaccine acceptance at no cost was 99%. The strongest predictor of anticipated vaccine acceptance if costs were assumed was the educational level of the respondents. Results suggest that the introduction of vaccines is a local priority and local (mis)perceptions of illness do not compromise vaccine acceptability if the vaccine is affordable. PMID:23878187

  12. Sociocultural Determinants of Anticipated Vaccine Acceptance for Acute Watery Diarrhea in Early Childhood in Katanga Province, Democratic Republic of Congo

    PubMed Central

    Merten, Sonja; Schaetti, Christian; Manianga, Cele; Lapika, Bruno; Hutubessy, Raymond; Chaignat, Claire-Lise; Weiss, Mitchell

    2013-01-01

    Rotavirus and oral cholera vaccines have the potential to reduce diarrhea-related child mortality in low-income settings and are recommended by the World Health Organization. Uptake of vaccination depends on community support, and is based on local priorities. This study investigates local perceptions of acute watery diarrhea in childhood and anticipated vaccine acceptance in two sites in the Democratic Republic of Congo. In 2010, 360 randomly selected non-affected adults were interviewed by using a semi-structured questionnaire. Witchcraft and breastfeeding were perceived as potential cause of acute watery diarrhea by 51% and 48% of respondents. Despite misperceptions, anticipated vaccine acceptance at no cost was 99%. The strongest predictor of anticipated vaccine acceptance if costs were assumed was the educational level of the respondents. Results suggest that the introduction of vaccines is a local priority and local (mis)perceptions of illness do not compromise vaccine acceptability if the vaccine is affordable. PMID:23878187

  13. Molecular Cytogenetics in Childhood Acute Lymphoblastic Leukemia: A Hospital-Based Observational Study

    PubMed Central

    Pandita, Aakash; Harish, Rekha; Digra, Sanjeev K; Raina, Alok; Sharma, Annie Arvind; Koul, Ashwani

    2015-01-01

    OBJECTIVE This study was conducted to determine the frequency of chromosomal aberrations in children aged <19 years with newly diagnosed acute lymphoblastic leukemia (ALL), attending/admitted in the Department of Pediatrics and Radiotherapy, Government Medical College, Jammu. Furthermore, we aimed to study the correlation between the cytogenetic molecular abnormalities and the immediate clinical outcome (induction of remission). MATERIALS AND METHODS This was a prospective study conducted over a period of 2 years (May 2011 to May 2013) in a tertiary care hospital in India. Forty pediatric (1–19 years) patients (18 males, 22 females; M: F = 0.8 : 1) with newly diagnosed ALL were studied for molecular cytogenetic analysis. Written consent was obtained from the parents of the patients. Bone marrow aspiration was done for making the diagnosis of ALL. Children lost to follow-up and who failed to give consent were excluded from the survey. Host factors and clinical parameters were obtained from patients. RESULTS Bone marrow aspirate samples of 40 diagnosed cases of ALL were subjected to routine cytogenetic analysis, and reverse transcription-polymerase chain reaction (RT-PCR) technique was used for molecular analysis. Well-spread metaphase plates were obtained in 18/40 (45%) cases for analysis. RT-PCR revealed abnormal genes in 20/40 (50%) patients. The results of molecular cytogenetic analysis were correlated with patients’ clinical and hematological parameters for risk stratification and immediate outcome (induction of remission). Eighteen out of 40 (45%) cases revealed no abnormality. Among the remaining 22 cases, 8 had TEL–AML1 (20%), 6 had BCR–ABL (15%), 4 had MLL–AF4 (10%), 2 had E2A–PBX1 (5%) fusion genes, and 2 had hyperdiploidy. To conclude, a higher proportion of cases in this study showed adverse translocations such as t (9;22), t (4;11), and t (1;19) compared to that reported in literature. CONCLUSION RT-PCR assay was useful in detecting the

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

    PubMed Central

    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. Association between CEBPE Variant and Childhood Acute Leukemia Risk: Evidence from a Meta-Analysis of 22 Studies

    PubMed Central

    Tang, Linjun; Healy, Jasmine; Sinnett, Daniel; Dai, Yue-e

    2015-01-01

    The CCAAT/enhancer binding proteins (CEBPs) have been involved in the etiology of acute leukemia (AL) and investigated in numerous genetic association studies, however, the results were inconclusive. The current meta-analysis was conducted to clarify the effect of CEBPE rs2239633 variant on childhood AL risk. Electronic literature search was performed on August 15, 2014, from databases of Medline, PubMed, Embase, and Web of Science. A total of 22 case-control studies were eligible for the pooled analysis. The results demonstrated that rs2239633 A allele was significantly associated with a decreased risk of childhood AL (A vs G: OR=0.87, 95%CI = 0.80, 0.94, p<0.001), especially in B-cell ALL subgroup (A vs G: OR = 0.79, 95%CI = 0.74, 0.83, p<0.001), but not among T-cell ALL or AML subgroups. In the stratified analysis by ethnicity, the association was observed in Europeans (A vs G: OR = 0.80, 95%CI = 0.76, 0.84, p<0.001) but not in Asian and mixed populations. Moreover, the results of sensitivity and cumulative meta-analysis indicated the robustness of our results. Also, Begg’s and Egger’s tests did not indicate any evidence of obvious asymmetry. In summary, our study provided evidence that CEBPE rs2239633 variant is associated with decreased risk of childhood B-cell ALL in Europeans. PMID:25938438

  16. Methotrexate consolidation treatment according to pharmacogenetics of MTHFR ameliorates event-free survival in childhood acute lymphoblastic leukaemia.

    PubMed

    Salazar, J; Altés, A; del Río, E; Estella, J; Rives, S; Tasso, M; Navajas, A; Molina, J; Villa, M; Vivanco, J L; Torrent, M; Baiget, M; Badell, I

    2012-10-01

    Recent advances in treatment for childhood acute lymphoblastic leukaemia (ALL) have significantly increased outcome. High-dose methotrexate (MTX) is the most commonly used regimen during the consolidation period, but the optimal dose remains to be defined. We investigated the usefulness of the MTHFR genotype to increase the MTX dosage in the consolidation phase in 141 childhood ALL patients enrolled in the ALL/SHOP-2005 protocol. We also investigated the pharmacogenetic role of polymorphisms in genes involved in MTX metabolism on therapy-related toxicity and survival. Patients with a favourable MTHFR genotype (normal enzymatic activity) treated with MTX doses of 5 g m⁻² had a significantly lower risk of suffering an event than patients with an unfavourable MTHFR genotype (reduced enzymatic activity) that were treated with the classical MTX dose of 3 g m⁻² (P=0.012). Our results indicate that analysis of the MTHFR genotype is a useful tool to optimise MTX therapy in childhood patients with ALL. PMID:21747412

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

    PubMed Central

    Ripert, Mahaut; Menegaux, Florence; Perel, Yves; Méchinaud, Françoise; Plouvier, Emmanuel; Gandemer, Virginie; Lutz, Patrick; Vannier, Jean-Pierre; Lamagnére, Jean-Pierre; Margueritte, Geneviève; Boutard, Patrick; Robert, Alain; Armari-Alla, Corinne; Munzer, Martine; Millot, Frédéric; de Lumley, Lionel; Berthou, Christian; Rialland, Xavier; Pautard, Brigitte; Clavel, Jacqueline

    2007-01-01

    Objective A case-control study was conducted to investigate the role of a familial history of cancer in the etiology of childhood acute leukemia (AL). Methods The history of cancer in the relatives of 472 cases was compared to that of 567 population-based controls. Recruitment was frequency matched on age, gender and region. The familial history of cancer in each child’s relatives was reported by the mother in response to a standardized self-administered questionnaire. Results A familial history of solid tumor in first- or second-degree relatives was associated with an increased risk of ALL (OR=1.6 [1.2–2.1]), while a familial history of hematopoietic malignancies in first- or second-degree relatives was associated with an increased risk of AML (OR=4.3 [1.4–13]). The ORs for the histories of cancer increased with the number of relatives with cancer (OR=1.5 [1.1–2.0] for one relative and OR=2.3 [1.3–3.8] for two relatives or more; ptrend<0.0001). Significant associations between childhood AL and familial history of genital cancers and brain tumor were also observed (OR=2.7 [1.2–5.8], OR=10.7 [1.3–86], respectively). Conclusion This study supports the hypothesis that a familial history of cancer may play a role in the etiology of childhood acute leukemia. It also evidences some specific associations that require further investigation. PMID:17923819

  18. Individual, family and offence characteristics of high risk childhood offenders: comparing non-offending, one-time offending and re-offending Dutch-Moroccan migrant children in the Netherlands

    PubMed Central

    2011-01-01

    Background Childhood offenders are at an increased risk for developing mental health, social and educational problems later in life. An early onset of offending is a strong predictor for future persistent offending. Childhood offenders from ethnic minority groups are a vulnerable at-risk group. However, up until now, no studies have focused on them. Aims To investigate which risk factors are associated with (re-)offending of childhood offenders from an ethnic minority. Method Dutch-Moroccan boys, who were registered by the police in the year 2006-2007, and their parents as well as a control group (n = 40) were interviewed regarding their individual and family characteristics. Two years later a follow-up analysis of police data was conducted to identify one-time offenders (n = 65) and re-offenders (n = 35). Results All groups, including the controls, showed substantial problems. Single parenthood (OR 6.0) and financial problems (OR 3.9) distinguished one-time offenders from controls. Reading problems (OR 3.8), having an older brother (OR 5.5) and a parent having Dutch friends (OR 4.3) distinguished re-offenders from one-time offenders. First offence characteristics were not predictive for re-offending. The control group reported high levels of emotional problems (33.3%). Parents reported not needing help for their children but half of the re-offender's families were known to the Child Welfare Agency, mostly in a juridical framework. Conclusion The Moroccan subgroup of childhood offenders has substantial problems that might hamper healthy development. Interventions should focus on reaching these families tailored to their needs and expectations using a multi-system approach. PMID:22014276

  19. Confirmation of Childhood Acute Lymphoblastic Leukemia Variants, ARID5B and IKZF1, and Interaction with Parental Environmental Exposures

    PubMed Central

    Evans, Tiffany-Jane; Milne, Elizabeth; Anderson, Denise; de Klerk, Nicholas H.; Jamieson, Sarra E.; Talseth-Palmer, Bente A.; Bowden, Nikola A.; Holliday, Elizabeth G.; Rudant, Jérémie; Orsi, Laurent; Richardson, Ebony; Lavis, Laura; Catchpoole, Daniel; Attia, John R.; Armstrong, Bruce K.; Clavel, Jacqueline; Scott, Rodney J.

    2014-01-01

    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. PMID:25310577

  20. High concordance of subtypes of childhood acute lymphoblastic leukemia within families: lessons from sibships with multiple cases of leukemia.

    PubMed

    Schmiegelow, K; Lausten Thomsen, U; Baruchel, A; Pacheco, C E; Pieters, Rob; Pombo-de-Oliveira, M S; Andersen, E W; Rostgaard, K; Hjalgrim, H; Pui, C-H

    2012-04-01

    Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk of developing ALL. This international collaboration identified 54 sibships with two (N = 51) or more (N = 3) cases of childhood ALL (ages <18 years). The 5-year event-free survival for 61 patients diagnosed after 1 January 1990 was 0.83 ± 0.05. Ages at diagnosis (Spearman correlation coefficient, r(S) = 0.41, P = 0.002) were significantly correlated, but not WBCs (r(S) = 0.23, P = 0.11). In 18 sibships with successful karyotyping in both cases, six were concordant for high-hyperdiploidy (N = 3), t(12;21) [ETV6/RUNX1] (N = 1), MLL rearrangement (N = 1) or t(1;19)(q23/p13) (N = 1). Eleven sibships were ALL-subtype concordant, being T-cell ALL (T-ALL) (N = 5, of a total of six sibships, where the first-born had T-ALL) or B-lineage ALL belonging to the same cytogenetic subset (N = 6), a finding that differs significantly from the expected chance distribution (κ: 0.58; P < 0.0001). These data indicate strong genetic and/or environmental risk factors for childhood ALL that are restricted to specific ALL subtypes, which must be taken into account, when performing epidemiological studies to reveal etiological factors. PMID:22005784

  1. Monitoring mixed lineage leukemia expression may help identify patients with mixed lineage leukemia--rearranged acute leukemia who are at high risk of relapse after allogeneic hematopoietic stem cell transplantation.

    PubMed

    Liu, Jing; Wang, Yu; Xu, Lan-Ping; Liu, Dai-Hong; Qin, Ya-Zhen; Chang, Ying-Jun; Liu, Kai-Yan; Huang, Xiao-Jun

    2014-07-01

    To evaluate the prognostic value of the expression of the mixed lineage leukemia (MLL) gene for predicting the relapse of patients with MLL-rearranged acute leukemia (AL) after allogeneic hematopoietic stem cell transplantation (allo-HSCT), the levels of MLL transcripts in bone marrow (BM) specimens were monitored serially by real-time quantitative polymerase chain reaction (RQ-PCR) at predetermined time points in 40 patients with MLL-rearranged AL who were treated with allo-HSCT. These patients were followed for a median of 24.5 months (range, 8 to 60 months). A total of 236 BM samples were collected and analyzed. Of these, 230 were monitored concurrently for minimal residual disease (MRD) by flow cytometry (FCM) for leukemia-associated aberrant immune phenotypes and by RQ-PCR for the expression of the Wilms tumor (WT1) gene. The 3-year cumulative incidence of relapse in patients who experienced MLL-positive patients (MLL > .0000%) (n = 9) after HSCT was 93.5% (95% confidence interval [CI], 87% to 100%) compared with 12.5% (95% CI, 5.6% to 19.4%) for MLL-negative patients (n = 31) (P < .001). For these 2 patient groups, the 3-year overall survival (OS) was 12.5% (95% CI, .8% to 24.2%) and 77.8% (95% CI, 68.4% to 87.2%) (P < .001), respectively, and the 3-year leukemia-free survival (LFS) was 0% and 72.2% (95% CI, 61.1% to 83.3%), respectively (P < .001). MLL positivity was associated with a higher rate of relapse (hazard ratio [HR], 18.643; 95% CI, 3.449 to 57.025; P = .001), lower LFS (HR, 7.267; 95% CI, 2.038 to 25.916; P = .002), and lower OS (HR, 8.259; 95% CI, 2.109 to 32.336; P = .002), as determined by Cox multivariate analysis. The expression of the MLL gene had a higher specificity and sensitivity than WT1 or MRD monitored by FCM for predicting the relapse of the patients with MLL + AL. Our results suggest that monitoring the expression of the MLL gene may help to identify patients with MLL + AL who are at high risk of relapse after allo-HSCT and may

  2. Bortezomib and Combination Chemotherapy in Treating Younger Patients With Recurrent, Refractory, or Secondary Acute Myeloid Leukemia

    ClinicalTrials.gov

    2014-05-13

    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 With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Acute Myeloid Leukemia With t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Myelomonocytic Leukemia (M4); 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); Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia

  3. Radiolabeled Monoclonal Antibody Therapy, Fludarabine Phosphate, and Low-Dose Total-Body Irradiation Followed by Donor Stem Cell Transplant and Immunosuppression Therapy in Treating Older Patients With Advanced Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndromes

    ClinicalTrials.gov

    2015-11-16

    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); Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Refractory Anemia With Ringed Sideroblasts; Refractory Cytopenia With Multilineage Dysplasia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

  4. Detection of High-Risk Atherosclerotic Plaque

    PubMed Central

    Fleg, Jerome L.; Stone, Gregg W.; Fayad, Zahi A.; Granada, Juan F.; Hatsukami, Thomas S.; Kolodgie, Frank D.; Ohayon, Jacques; Pettigrew, Roderic; Sabatine, Marc S.; Tearney, Guillermo; Waxman, Sergio; Domanski, Michael J.; Srinivas, Pothur R.; Narula, Jagat

    2013-01-01

    The leading cause of major morbidity and mortality in most countries around the world is atherosclerotic cardiovascular disease, most commonly caused by thrombotic occlusion of a high-risk coronary plaque resulting in myocardial infarction or cardiac death, or embolization from a high-risk carotid plaque resulting in stroke. The lesions prone to result in such clinical events are termed vulnerable or high-risk plaques, and their identification may lead to the development of pharmacological and mechanical intervention strategies to prevent such events. Autopsy studies from patients dying of acute myocardial infarction or sudden death have shown that such events typically arise from specific types of atherosclerotic plaques, most commonly the thin-cap fibroatheroma. However, the search in human beings for vulnerable plaques before their becoming symptomatic has been elusive. Recently, the PROSPECT (Providing Regional Observations to Study Predictors of Events in the Coronary Tree) study demonstrated that coronary plaques that are likely to cause future cardiac events, regardless of angiographic severity, are characterized by large plaque burden and small lumen area and/or are thin-cap fibroatheromas verified by radiofrequency intravascular ultrasound imaging. This study opened the door to identifying additional invasive and noninvasive imaging modalities that may improve detection of high-risk atherosclerotic lesions and patients. Beyond classic risk factors, novel biomarkers and genetic profiling may identify those patients in whom noninvasive imaging for vulnerable plaque screening, followed by invasive imaging for risk confirmation is warranted, and in whom future pharmacological and/or device-based focal or regional therapies may be applied to improve long-term prognosis. PMID:22974808

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

    PubMed Central

    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

  6. Induction of autophagy-dependent necroptosis is required for childhood acute lymphoblastic leukemia cells to overcome glucocorticoid resistance

    PubMed Central

    Bonapace, Laura; Bornhauser, Beat C.; Schmitz, Maike; Cario, Gunnar; Ziegler, Urs; Niggli, Felix K.; Schäfer, Beat W.; Schrappe, Martin; Stanulla, Martin; Bourquin, Jean-Pierre

    2010-01-01

    In vivo resistance to first-line chemotherapy, including to glucocorticoids, is a strong predictor of poor outcome in children with acute lymphoblastic leukemia (ALL). Modulation of cell death regulators represents an attractive strategy for subverting such drug resistance. Here we report complete resensitization of multidrug-resistant childhood ALL cells to glucocorticoids and other cytotoxic agents with subcytotoxic concentrations of obatoclax, a putative antagonist of BCL-2 family members. The reversal of glucocorticoid resistance occurred through rapid activation of autophagy-dependent necroptosis, which bypassed the block in mitochondrial apoptosis. This effect was associated with dissociation of the autophagy inducer beclin-1 from the antiapoptotic BCL-2 family member myeloid cell leukemia sequence 1 (MCL-1) and with a marked decrease in mammalian target of rapamycin (mTOR) activity. Consistent with a protective role for mTOR in glucocorticoid resistance in childhood ALL, combination of rapamycin with the glucocorticoid dexamethasone triggered autophagy-dependent cell death, with characteristic features of necroptosis. Execution of cell death, but not induction of autophagy, was strictly dependent on expression of receptor-interacting protein (RIP-1) kinase and cylindromatosis (turban tumor syndrome) (CYLD), two key regulators of necroptosis. Accordingly, both inhibition of RIP-1 and interference with CYLD restored glucocorticoid resistance completely. Together with evidence for a chemosensitizing activity of obatoclax in vivo, our data provide a compelling rationale for clinical translation of this pharmacological approach into treatments for patients with refractory ALL. PMID:20200450

  7. CCND1 G870A polymorphism is associated with toxicity of methotrexate in childhood acute lymphoblastic leukemia

    PubMed Central

    Xue, Yao; Rong, Liucheng; Tong, Na; Wang, Meilin; Zhang, Zhengdong; Fang, Yongjun

    2015-01-01

    CCND1 plays a key role in cell cycle progression and may cause methotrexate (MTX) resistance, as well as its cytotoxicity. CCND1 870A variant allele is associated with altered transcripts of this gene. We hypothesized that this polymorphism may contribute to the elimination rate and hepatotoxicity of MTX in childhood acute lymphoblastic leukemia (ALL). We genotyped the CCND1 G870A polymorphism in 125 childhood ALL patients treated with HDMTX. We found no notable associations between G870A polymorphism and the risk of delayed MTX elimination. However, this polymorphism was significantly associated with an increased risk of MTX hepatotoxicity [adjusted odds ratio (OR) = 4.44, 95% confidence interval (CI) = 1.35-14.63 for AG versus GG and adjusted OR = 6.39, 95% CI = 1.82-22.43 for AA versus GG]. Our results indicated that the CCND1 G870A polymorphism may be involved in the hepatotoxicity of MTX and act as a biological marker. PMID:26617896

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

    PubMed Central

    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

  9. Epidemiology, aetiology and management of childhood acute community-acquired pneumonia in developing countries--a review.

    PubMed

    Falade, A G; Ayede, A I

    2011-12-01

    Childhood acute community-acquired pneumonia is one of the leading causes of morbidity and mortality in developing countries. In children who have not received prior antibiotic therapy, the main bacterial causes of clinical pneumonia in developing countries are Streptococcus pneumoniae and Haemophilus influenzae type b (Hib), and the main viral cause is respiratory syncytial virus (RSV), but estimates of their relative importance vary in different settings. The only vaccines for the prevention of bacterial pneumonia (excluding vaccines for pertussis and measles) are Hib and pneumococcal conjugate vaccines (PCV). In children with human immunodeficiency virus (HIV) infection, bacterial infection remains a major cause of pneumonia mortality; however, Pneumocystis jirovecii and Mycobacterium tuberculosis are important causes of pneumonia in them. Studies of bacterial aetiology of acute pneumonia in severely malnourished children have implicated Klebsiella pneumoniae, Staphylococcus aureus, S. pneumoniae, Escherichia coli, and H. influenzae, with very few data on the role of respiratory viruses and tuberculosis. Studies of neonatal sepsis suggest that Gram-negative enteric organisms, particularly Klebsiella spp., and Gram-positive organisms, mainly pneumococcus, group b Streptococcus and S. aureus are causes of neonatal pneumonia. Many of the developing countries that ranked high in pneumonia mortality are preparing to introduce new pneumonia vaccines with support from Global Alliance for Vaccine and Immunization (GAVI Alliance), plan for the expansion of community-based case management and have ambitious plans for strengthening health systems. Assurance that these plans are implemented will require funding and continued public attention to pneumonia, which will help contribute to a substantial decline in childhood pneumonia deaths. PMID:22783679

  10. Combination Chemotherapy and Rituximab in Treating Young Patients With Recurrent or Refractory Non-Hodgkin's Lymphoma or Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2013-10-07

    B-cell Childhood Acute Lymphoblastic Leukemia; Childhood Burkitt Lymphoma; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; L3 Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma

  11. Vitamin A supplementation and increased prevalence of childhood diarrhoea and acute respiratory infections.

    PubMed

    Stansfield, S K; Pierre-Louis, M; Lerebours, G; Augustin, A

    1993-09-01

    There is uncertainty over whether vitamin A supplementation reduces morbidity among children with subclinical deficiency of the vitamin. Hence a double-blind, placebo-controlled trial of the effect of vitamin A supplementation on childhood morbidity was conducted among 11,124 children aged 6-83 months in the northwest of Haiti. After a random start, children were sequentially assigned by household units to receive either megadose vitamin A or placebo in three distribution cycles 4 months apart. 2 to 8 weeks after each administration of the vitamin A and placebo capsules, indicators of childhood morbidity were reassessed through interviews conducted in the homes of participating families. The vitamin A group was found to have an increased 2-week prevalence of all symptoms and signs of childhood morbidity assessed, including diarrhoea (rate ratio [RR] = 1.09, 95% confidence interval 1.05-1.14), rhinitis (RR = 1.02, 95% confidence interval 1.00-1.04), cold/flu symptoms (RR = 1.04, 95% confidence interval 1.01-1.06), cough (RR = 1.07, 95% confidence interval 1.03-1.11), and rapid breathing (RR = 1.18, 95% confidence interval 1.09-1.27). The study shows an increased 2-week prevalence of diarrhoea and the symptoms of respiratory infections after vitamin A supplementation. PMID:8102720

  12. Decrease in cerebral metabolic rate of glucose after high-dose methotrexate in childhood acute lymphocytic leukemia

    SciTech Connect

    Komatsu, K.; Takada, G.; Uemura, K.; Shishido, F.; Kanno, I. )

    1990-09-01

    We measured changes in the regional cerebral metabolic rate of glucose (rCMRGlu) using {sup 18}F-fluorodeoxyglucose and positron emission tomography for the assessment of neurotoxicity in childhood acute lymphocytic leukemia treated with high-dose methotrexate (HD-MTX) therapy. We studied 8 children with acute lymphocytic leukemia (mean age: 9.6 years) treated with HD-MTX (200 mg/kg or 2,000 mg/M2) therapy. CMRGlu after HD-MTX therapy was most reduced (40%) in the patient who had central nervous system leukemia and was treated with the largest total doses of both intrathecal MTX (IT-MTX) and HD-MTX. CMRGlu in the whole brain after HD-MTX therapy was reduced by an average of 21% (P less than 0.05). The reductions of CMRGlu in 8 patients were correlated with total doses of both IT-MTX (r = 0.717; P less than 0.05) and systemic HD-MTX (r = 0.784; P less than 0.05). CMRGlu of the cerebral cortex, especially the frontal and occipital cortex, was reduced more noticeably than that of the basal ganglia and white matter. We suggest that the measurement of changes in rCMRGlu after HD-MTX therapy is useful for detecting accumulated MTX neurotoxicity.

  13. Idarubicin and Cytarabine With or Without Bevacizumab in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2013-01-23

    Adult Acute Basophilic Leukemia; Adult Acute Eosinophilic Leukemia; 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 With 11q23 (MLL) Abnormalities; 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 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); Secondary Acute Myeloid Leukemia; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  14. The impact of ADHD symptoms and global impairment in childhood on working disability in mid-adulthood: a 28-year follow-up study using official disability pension records in a high-risk in-patient population

    PubMed Central

    2012-01-01

    Background Individuals with ADHD have been associated with more employment difficulties in early adulthood than healthy community controls. To examine whether this association is attributable specifically to disturbance of activity and attention (ADHD) or to psychopathology in general, we wanted to extend existing research by comparing the rate of mid-adulthood working disabilities for individuals diagnosed with ADHD as children with the rate for clinical controls diagnosed with either conduct disorder, emotional disorder or mixed disorder of conduct and emotions. Methods Former Norwegian child-psychiatric in-patients (n = 257) were followed up 17–39 years after hospitalization by record linkage to the Norwegian national registry of disability pension (DP) awards. Based on the hospital records, the patients were re-diagnosed according to ICD-10. Associations between the diagnoses, other baseline factors and subsequent DP were investigated using Kaplan–Meier survival analyses and logrank testing. Results At follow-up, 19% of the participants had received a DP award. In the logrank testing, ADHD was the only disorder associated with a subsequent DP, with 30% being disabled at follow-up (p = 0.01). Low psychosocial functioning (assessed by the Children’s Global Assessment Scale) at admission uniquely predicted future DP (p = 0.04). Conclusions ADHD in childhood was highly associated with later receiving a DP. Our finding of worse prognosis in ADHD compared with other internalizing and externalizing disorders in mid-adulthood supports the assumption of ADHD being specifically linked to working disability. Assessment of psychosocial functioning in addition to diagnostic features could enhance prediction of children who are most at risk of future disability. PMID:23083209

  15. Fatal adenovirus hepatitis during standard chemotherapy for childhood acute lymphoblastic leukemia.

    PubMed

    Hough, Rachael; Chetwood, Andrew; Sinfield, Rebecca; Welch, Jenny; Vora, Ajay

    2005-02-01

    Fulminant hepatitis is a rare complication of adenoviral infection that has not previously been reported in children receiving standard chemotherapy for acute leukemia. The authors have observed fatal adenovirus hepatitis in three children receiving first-line chemotherapy for acute lymphoblastic leukemia (ALL). The patients presented 10, 17, and 8 months into therapy according to the UKALL XI (third intensification), UKALL 97/99 (maintenance), and pilot UKALL 2003 (delayed intensification II) protocols, respectively. All patients received aggressive supportive care and intravenous immunoglobulins. The second and third patients were also treated with intravenous cidofovir. Despite these measures, all three children deteriorated rapidly and died of fulminant liver failure. Although rare, adenovirus infection should be considered in the differential diagnosis of acute hepatitis in children receiving standard chemotherapy for ALL. PMID:15701979

  16. Controversies in the diagnosis and management of childhood acute immune thrombocytopenic purpura.

    PubMed

    Segel, George B; Feig, Stephen A

    2009-09-01

    Acute immune thrombocytopenic purpura (ITP) occurs most commonly in young children who present with severe isolated thrombocytopenia and purpura. A marrow examination is not required unless glucocorticoids are used, lest treatment mask incipient acute lymphoblastic leukemia, but controversy exists here. The recommendations for evaluation and management remain controversial, since prospective controlled trials have not been done. There is some consensus based on experience and empiric data. Almost all children with acute ITP will recover completely without therapy. Although the various treatments may increase the platelet count, they do not influence the outcome of the illness, may increase cost, and cause significant side effects. Therefore, careful observation may be the best management option for the patient with ITP, in the absence of severe bleeding. The data available relevant to these issues are discussed. PMID:19165890

  17. Epidemiological, clinical and prognostic profile of childhood acute bacterial meningitis in a resource poor setting

    PubMed Central

    Kuti, Bankole Peter; Bello, Emmanuel Olasehinde; Jegede, Tolulope Opeoluwa; Olubosede, Omolayo

    2015-01-01

    Background: Childhood bacterial meningitis is a neurologic emergency that continues to kill and maims children particularly in developing countries with poor immunization coverage. Objective: This study set out to assess the hospital incidence, pattern of presentation, etiologic agents, outcome and determinants of mortality among the children admitted with bacterial meningitis at the Wesley Guild Hospital (WGH), Ilesa. Patients and Methods: We carried out a retrospective review of admitted cases of bacterial meningitis in children aged one month to 15 years at the WGH, Ilesa over a three year period by looking at the hospital records. Factors in the history and examinations were compared among survivors and those that died to determine factors significantly associated with mortality in these children. Results: Eighty-one (5.5%) of the 1470 childhood admissions during the study period had bacterial meningitis. Male preponderance was observed and two-thirds of the children were infants. More cases were admitted during the wet rainy season than during the dry harmattan season. Haemophilus influenzae type B and Streptococcus pneumoniae were the leading etiologic agents and ciprofloxacin and ceftriaxone adequately cover for these organisms. Twenty-two (27.2%) of the 81 children died, while 34 (42.0%) survived with neurologic deficits. Children with multiple seizures, coma, neck retraction, hyponatremia, hypoglycorrhachia, turbid CSF as well as Gram positive meningitis at presentation were found to more likely to die (P < 0.05). None of these factors however independently predict mortality. Conclusion: Childhood bacterial meningitis often results in death and neurologic deficit among infants and young children admitted at the WGH, Ilesa. Children diagnosed with meningitis who in addition had multiple seizures, neck retraction and coma at presentation are at increased risk of dying. PMID:26752902

  18. Acute nonparaneoplastic limbic encephalitis in childhood: a case series in Japan.

    PubMed

    Sakuma, Hiroshi; Sugai, Kenji; Sasaki, Masayuki

    2010-09-01

    Limbic encephalitis not associated with malignancy was investigated in Japanese children, with particular focus on clinical features distinct from adult cases. Clinical, laboratory, and radiographic findings were studied in pediatric nonparaneoplastic limbic encephalitis, based on a literature review and questionnaire-based analyses. Analysis of 14 cases revealed the predominance of seizure occurrence, disturbance in consciousness, and frequent extralimbic signs. The majority manifested antecedent febrile illnesses, suggesting the involvement of infection-induced autoimmunity targeted to neuronal antigens. These clinical observations indicate a child-specific phenotype of limbic encephalitis. Further studies on its immunopathogenesis are needed to determine whether childhood limbic encephalitis is a distinct subcategory. PMID:20691937

  19. Levofloxacin in Preventing Infection in Young Patients With Acute Leukemia Receiving Chemotherapy or Undergoing Stem Cell Transplantation

    ClinicalTrials.gov

    2016-04-08

    Acute Leukemias of Ambiguous Lineage; Bacterial Infection; Diarrhea; Fungal Infection; Musculoskeletal Complications; Neutropenia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

  20. Symptom Differences in Acute and Chronic Presentation of Childhood Post-Traumatic Stress Disorder.

    ERIC Educational Resources Information Center

    Famularo, Richard; And Others

    1990-01-01

    Twenty-four child abuse victims, age 5-13, were diagnosed with posttraumatic stress disorder (PTSD). Children with the acute form of PTSD exhibited such symptoms as difficulty falling asleep, hypervigilance, nightmares, and generalized anxiety. Children exhibiting chronic PTSD exhibited increased detachment, restricted range of affect,…

  1. Is there an increased risk of metabolic syndrome among childhood acute lymphoblastic leukemia survivors? A developing country experience.

    PubMed

    Mohapatra, Sonali; Bansal, Deepak; Bhalla, A K; Verma Attri, Savita; Sachdeva, Naresh; Trehan, Amita; Marwaha, R K

    2016-03-01

    Data on metabolic syndrome (MS) in survivors of childhood acute lymphoblastic leukemia (ALL) from developing countries are lacking. The purpose of this single-center, uncontrolled, observational study was to assess the frequency of MS in our survivors. The survivors of ALL ≤15 years at diagnosis, who had completed therapy ≥2 years earlier, were enrolled. Anthropometric measurements (weight, height, waist circumference), biochemistry (glucose, insulin, triglycerides, high-density lipoprotein [HDL], thyroid function tests, C-reactive protein [CRP], magnesium), measurement of blood pressure, and Tanner staging were performed. MS was defined by International Diabetes Federation (IDF) and the National Cholesterol Education Program Third Adult Treatment Panel guidelines (NCEP ATP III) criteria, modified by Cook et al. (Arch Pediatr Adolesc Med. 2003;157:821-827) and Ford et al. (Diabetes Care. 2005;28:878-881). The median age of 76 survivors was 11.9 years (interquartile range [IQR]: 9.6-13.5). Twenty-four (32%) survivors were obese or overweight. The prevalence of insulin resistance (17%), hypertension (7%), hypertriglyceridemia (20%), and low HDL (37%) was comparable to the prevalence in children/adolescents in historical population-based studies from India. The prevalence of MS ranged from 1.3% to 5.2%, as per different defining criteria. Cranial radiotherapy, age at diagnosis, sex, or socioeconomic status were not risk factors for MS. The prevalence of MS in survivors of childhood ALL, at a median duration of 3 years from completion of chemotherapy, was comparable to the reference population. The prevalence of being obese or overweight was, however, greater than historical controls. PMID:26984439

  2. Severe Acute Malnutrition in Childhood: Hormonal and Metabolic Status at Presentation, Response to Treatment, and Predictors of Mortality

    PubMed Central

    Bartz, Sarah; Mody, Aaloke; Hornik, Christoph; Bain, James; Muehlbauer, Michael; Kiyimba, Tonny; Kiboneka, Elizabeth; Stevens, Robert; Bartlett, John; St Peter, John V.; Newgard, Christopher B.

    2014-01-01

    Objective: Malnutrition is a major cause of childhood morbidity and mortality. To identify and target those at highest risk, there is a critical need to characterize biomarkers that predict complications prior to and during treatment. Methods: We used targeted and nontargeted metabolomic analysis to characterize changes in a broad array of hormones, cytokines, growth factors, and metabolites during treatment of severe childhood malnutrition. Children aged 6 months to 5 years were studied at presentation to Mulago Hospital and during inpatient therapy with milk-based formulas and outpatient supplementation with ready-to-use food. We assessed the relationship between baseline hormone and metabolite levels and subsequent mortality. Results: Seventy-seven patients were enrolled in the study; a subset was followed up from inpatient treatment to the outpatient clinic. Inpatient and outpatient therapies increased weight/height z scores and induced striking changes in the levels of fatty acids, amino acids, acylcarnitines, inflammatory cytokines, and various hormones including leptin, insulin, GH, ghrelin, cortisol, IGF-I, glucagon-like peptide-1, and peptide YY. A total of 12.2% of the patients died during hospitalization; the major biochemical factor predicting mortality was a low level of leptin (P = .0002), a marker of adipose tissue reserve and a critical modulator of immune function. Conclusions: We have used metabolomic analysis to provide a comprehensive hormonal and metabolic profile of severely malnourished children at presentation and during nutritional rehabilitation. Our findings suggest that fatty acid metabolism plays a central role in the adaptation to acute malnutrition and that low levels of the adipose tissue hormone leptin associate with, and may predict, mortality prior to and during treatment. PMID:24606092

  3. Identification of de Novo Fanconi Anemia in Younger Patients With Newly Diagnosed Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-05-13

    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; Chronic Myelomonocytic Leukemia; de Novo Myelodysplastic Syndromes; Fanconi Anemia; 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

  4. Averting the legacy of kidney disease - Focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:26997373

  5. Averting the legacy of kidney disease-focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and chronic kidney disease in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of chronic kidney disease later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced chronic kidney disease in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplant, whereas only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:26880442

  6. Averting the legacy of kidney disease – focus on childhood

    PubMed Central

    Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group amongst children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help to detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, whilst only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policymakers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:27247150

  7. Averting the legacy of kidney disease - focus on childhood

    PubMed Central

    Ingelfinger, J.R.; Kalantar-Zadeh, K.; Schaefer, F.

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, in that the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease as a consequence of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that the World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:27096201

  8. Averting the Legacy of Kidney Disease - Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-04-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults, if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:27536691

  9. Methylenetetrahydrofolate reductase (MTHFR) polymorphisms and risk of molecularly defined subtypes of childhood acute leukemia.

    PubMed

    Wiemels, J L; Smith, R N; Taylor, G M; Eden, O B; Alexander, F E; Greaves, M F

    2001-03-27

    Low folate intake as well as alterations in folate metabolism as a result of polymorphisms in the enzyme methylenetetrahydrofolate reductase (MTHFR) have been associated with an increased incidence of neural tube defects, vascular disease, and some cancers. Polymorphic variants of MTHFR lead to enhanced thymidine pools and better quality DNA synthesis that could afford some protection from the development of leukemias, particularly those with translocations. We now report associations of MTHFR polymorphisms in three subgroups of pediatric leukemias: infant lymphoblastic or myeloblastic leukemias with MLL rearrangements and childhood lymphoblastic leukemias with either TEL-AML1 fusions or hyperdiploid karyotypes. Pediatric leukemia patients (n = 253 total) and healthy newborn controls (n = 200) were genotyped for MTHFR polymorphisms at nucleotides 677 (C-->T) and 1,298 (A-->C). A significant association for carriers of C677T was demonstrated for leukemias with MLL translocations (MLL+, n = 37) when compared with controls [adjusted odd ratios (OR) = 0.36 with a 95% confidence interval (CI) of 0.15-0.85; P = 0.017]. This protective effect was not evident for A1298C alleles (OR = 1.14). In contrast, associations for A1298C homozygotes (CC; OR = 0.26 with a 95% CI of 0.07--0.81) and C677T homozygotes (TT; OR = 0.49 with a 95% CI of 0.20--1.17) were observed for hyperdiploid leukemias (n = 138). No significant associations were evident for either polymorphism with TEL-AML1+ leukemias (n = 78). These differences in allelic associations may point to discrete attributes of the two alleles in their ability to alter folate and one-carbon metabolite pools and impact after DNA synthesis and methylation pathways, but should be viewed cautiously pending larger follow-up studies. The data provide evidence that molecularly defined subgroups of pediatric leukemias have different etiologies and also suggest a role of folate in the development of childhood leukemia. PMID:11274424

  10. Childhood Acute Respiratory Infections and Household Environment in an Eastern Indonesian Urban Setting

    PubMed Central

    Shibata, Tomoyuki; Wilson, James L.; Watson, Lindsey M.; LeDuc, Alyse; Meng, Can; Ansariadi; La Ane, Ruslan; Manyullei, Syamsuar; Maidin, Alimin

    2014-01-01

    This pilot study evaluated the potential effect of household environmental factors such as income, maternal characteristics, and indoor air pollution on children’s respiratory status in an Eastern Indonesian community. Household data were collected from cross-sectional (n = 461 participants) and preliminary childhood case-control surveys (pneumonia cases = 31 diagnosed within three months at a local health clinic; controls = 30). Particulate matter (PM2.5 and PM10) was measured in living rooms, kitchens, children’s bedrooms, and outside areas in close proximity once during the case-control household interviews (55 homes) and once per hour from 6 a.m. to midnight in 11 homes. The household survey showed that children were 1.98 times (p = 0.02) more likely to have coughing symptoms indicating respiratory infection, if mothers were not the primary caregivers. More children exhibited coughing if they were not exclusively breastfed (OR = 2.18; p = 0.06) or there was a possibility that their mothers were exposed to environmental tobacco smoke during pregnancy (OR = 2.05; p = 0.08). This study suggests that household incomes and mother’s education have an indirect effect on childhood pneumonia and respiratory illness. The concentrations of PM2.5 and PM10 ranged from 0.5 to 35.7 µg/m3 and 7.7 to 575.7 µg/m3, respectively, based on grab samples. PM was significantly different between the case and control groups (p < 0.01). The study also suggests that ambient air may dilute indoor pollution, but also introduces pollution into the home from the community environment. Effective intervention programs need to be developed that consider multiple direct and indirect risk factors to protect children. PMID:25429685

  11. Childhood acute respiratory infections and household environment in an Eastern Indonesian urban setting.

    PubMed

    Shibata, Tomoyuki; Wilson, James L; Watson, Lindsey M; LeDuc, Alyse; Meng, Can; Ansariadi; La Ane, Ruslan; Manyullei, Syamsuar; Maidin, Alimin

    2014-12-01

    This pilot study evaluated the potential effect of household environmental factors such as income, maternal characteristics, and indoor air pollution on children's respiratory status in an Eastern Indonesian community. Household data were collected from cross-sectional (n = 461 participants) and preliminary childhood case-control surveys (pneumonia cases = 31 diagnosed within three months at a local health clinic; controls = 30). Particulate matter (PM2.5 and PM10) was measured in living rooms, kitchens, children's bedrooms, and outside areas in close proximity once during the case-control household interviews (55 homes) and once per hour from 6 a.m. to midnight in 11 homes. The household survey showed that children were 1.98 times (p = 0.02) more likely to have coughing symptoms indicating respiratory infection, if mothers were not the primary caregivers. More children exhibited coughing if they were not exclusively breastfed (OR = 2.18; p = 0.06) or there was a possibility that their mothers were exposed to environmental tobacco smoke during pregnancy (OR = 2.05; p = 0.08). This study suggests that household incomes and mother's education have an indirect effect on childhood pneumonia and respiratory illness. The concentrations of PM2.5 and PM10 ranged from 0.5 to 35.7 µg/m3 and 7.7 to 575.7 µg/m3, respectively, based on grab samples. PM was significantly different between the case and control groups (p < 0.01). The study also suggests that ambient air may dilute indoor pollution, but also introduces pollution into the home from the community environment. Effective intervention programs need to be developed that consider multiple direct and indirect risk factors to protect children. PMID:25429685

  12. Role of glutathione S-transferase M1, T1 and P1 gene polymorphisms in childhood acute lymphoblastic leukemia susceptibility in a Turkish population.

    PubMed

    Guven, Mehmet; Unal, Selin; Erhan, Duygu; Ozdemir, Nihal; Baris, Safa; Celkan, Tiraje; Bostancı, Merve; Batar, Bahadir

    2015-09-01

    The variations between different individuals in the xenobiotic metabolizing enzymes' activity were shown to modify susceptibility to childhood acute lymphoblastic leukemia (ALL). Polymorphisms associated with genes coding for the glutathione S-transferase (GST) enzyme were known to affect the metabolism of different carcinogens. The aim of this study was to evaluate the influence of the GSTM1 and GSTT1 deletion polymorphisms, and the GSTP1 Ile105Val single nucleotide polymorphism (SNP) on the susceptibility to childhood ALL. The study was conducted in 95 children with ALL and 190 healthy control subjects from the Turkish population. The data revealed no difference in the prevalence of the GSTM1 and GSTT1 null genotypes between the childhood ALL patients and the controls. No association was found between GSTP1 Ile105Val variants and the susceptibility to childhood ALL, separately or in combination. Our findings suggested that the status of heritable GST polymorphism might not influence the risk of developing childhood ALL. Studies with a larger sample size are needed to evaluate and confirm the validity of our results. PMID:26137447

  13. Early and treatment-related deaths in childhood acute myeloid leukaemia in the Nordic countries: 1984-2003.

    PubMed

    Molgaard-Hansen, Lene; Möttönen, Merja; Glosli, Heidi; Jónmundsson, Guðmundur K; Abrahamsson, Jonas; Hasle, Henrik

    2010-12-01

    Despite major improvements in the cure rate of childhood acute myeloid leukaemia (AML), 5-15% of patients still die from treatment-related complications. In a historical prospective cohort study, we analysed the frequency, clinical features and risk factors for early deaths (ED) and treatment-related deaths (TRD) in 525 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-84, -88 and -93 trials. Seventy patients (13%) died before starting treatment or from treatment-related complications. The death rate rose from 11% in NOPHO-AML-84 to 29% in -88, but then fell to 8% in -93. Sixteen patients (3%) died within the first 2 weeks, mainly from bleeding or leucostasis. Hyperleucocytosis, age <2 or ≥10 years were risk factors. After day 15, 10% of patients died from treatment-related complications with infection as the main cause of death. Risk factors were age <2 or ≥10 years and treatment according to the NOPHO-AML-88 protocol. The number of EDs and TRDs in AML is high. Therefore optimal antifungal prophylaxis is essential, and studies on the benefit of antibacterial prophylaxis and individual risk factors for ED and TRD are needed. PMID:20955398

  14. Health and Risk Behaviors in Survivors of Childhood Acute Myeloid Leukemia: A Report From the Children’s Oncology Group

    PubMed Central

    Schultz, Kris Ann P.; Chen, Lu; Chen, Zhengjia; Zeltzer, Lonnie K.; Nicholson, H. Stacy; Neglia, Joseph P.

    2011-01-01

    Background Survivors of childhood acute myeloid leukemia (AML) face increased risks of chronic disease and secondary malignancies. Substance exposure may compound these risks. Procedures Participants were diagnosed with AML at <21 years of age and survived ≥5 years following diagnosis. All underwent chemotherapy alone or followed by autologous BMT (chemo ± autoBMT) or underwent allogeneic BMT (alloBMT) if an HLA-matched related donor was available. Survivors completed a health questionnaire and a Youth Risk Behavior Survey (YRBS). Results Of eligible survivors, 117 were ≥18 years of age and completed a YRBS. Survivors were a mean age of 10 years at diagnosis and 24 years at interview. Of the substance exposures assessed by YRBS, tobacco, alcohol, and marijuana were most common. Twenty-two percent (22%) had smoked cigarettes in the last 30 days. One-quarter (25%) reported binge drinking in the last month. None of these exposures varied by treatment group. Less than 10% of survivors reported cocaine, heroin, or methamphetamine use. Men were more likely to report high substance exposure (P = 0.004). Sadness/suicidality score was associated with cancer-related anxiety (P = 0.006) and multiple health conditions (P = 0.006). Conclusions This analysis reveals exposure to tobacco, alcohol, and marijuana in young adults with few differences based on treatment received. Survivors with cancer-related anxiety or multiple health conditions were more likely to report sadness/hopelessness. PMID:20232426

  15. Silencing of TESTIN by dense biallelic promoter methylation is the most common molecular event in childhood acute lymphoblastic leukaemia

    PubMed Central

    2010-01-01

    Background Aberrant promoter DNA methylation has been reported in childhood acute lymphoblastic leukaemia (ALL) and has the potential to contribute to its onset and outcome. However, few reports demonstrate consistent, prevalent and dense promoter methylation, associated with tumour-specific gene silencing. By screening candidate genes, we have detected frequent and dense methylation of the TESTIN (TES) promoter. Results Bisulfite sequencing showed that 100% of the ALL samples (n = 20) were methylated at the TES promoter, whereas the matched remission (n = 5), normal bone marrow (n = 6) and normal PBL (n = 5) samples were unmethylated. Expression of TES in hyperdiploid, TEL-AML+, BCR-ABL+, and E2A-PBX+ subtypes of B lineage ALL was markedly reduced compared to that in normal bone marrow progenitor cells and in B cells. In addition TES methylation and silencing was demonstrated in nine out of ten independent B ALL propagated as xenografts in NOD/SCID mice. Conclusion In total, 93% of B ALL samples (93 of 100) demonstrated methylation with silencing or reduced expression of the TES gene. Thus, TES is the most frequently methylated and silenced gene yet reported in ALL. TES, a LIM domain-containing tumour suppressor gene and component of the focal adhesion complex, is involved in adhesion, motility, cell-to-cell interactions and cell signalling. Our data implicate TES methylation in ALL and provide additional evidence for the involvement of LIM domain proteins in leukaemogenesis. PMID:20573277

  16. KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia

    PubMed Central

    Malinowska-Ozdowy, K; Frech, C; Schönegger, A; Eckert, C; Cazzaniga, G; Stanulla, M; zur Stadt, U; Mecklenbräuker, A; Schuster, M; Kneidinger, D; von Stackelberg, A; Locatelli, F; Schrappe, M; Horstmann, M A; Attarbaschi, A; Bock, C; Mann, G; Haas, O A; Panzer-Grümayer, R

    2015-01-01

    High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18–30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone. PMID:25917266

  17. KRAS and CREBBP mutations: a relapse-linked malicious liaison in childhood high hyperdiploid acute lymphoblastic leukemia.

    PubMed

    Malinowska-Ozdowy, K; Frech, C; Schönegger, A; Eckert, C; Cazzaniga, G; Stanulla, M; zur Stadt, U; Mecklenbräuker, A; Schuster, M; Kneidinger, D; von Stackelberg, A; Locatelli, F; Schrappe, M; Horstmann, M A; Attarbaschi, A; Bock, C; Mann, G; Haas, O A; Panzer-Grümayer, R

    2015-08-01

    High hyperdiploidy defines the largest genetic entity of childhood acute lymphoblastic leukemia (ALL). Despite its relatively low recurrence risk, this subgroup generates a high proportion of relapses. The cause and origin of these relapses remains obscure. We therefore explored the mutational landscape in high hyperdiploid (HD) ALL with whole-exome (n=19) and subsequent targeted deep sequencing of 60 genes in 100 relapsing and 51 non-relapsing cases. We identified multiple clones at diagnosis that were primarily defined by a variety of mutations in receptor tyrosine kinase (RTK)/Ras pathway and chromatin-modifying genes. The relapse clones consisted of reappearing as well as new mutations, and overall contained more mutations. Although RTK/Ras pathway mutations were similarly frequent between diagnosis and relapse, both intergenic and intragenic heterogeneity was essentially lost at relapse. CREBBP mutations, however, increased from initially 18-30% at relapse, then commonly co-occurred with KRAS mutations (P<0.001) and these relapses appeared primarily early (P=0.012). Our results confirm the exceptional susceptibility of HD ALL to RTK/Ras pathway and CREBBP mutations, but, more importantly, suggest that mutant KRAS and CREBBP might cooperate and equip cells with the necessary capacity to evolve into a relapse-generating clone. PMID:25917266

  18. Treatment-related deaths in second complete remission in childhood acute myeloid leukaemia.

    PubMed

    Molgaard-Hansen, Lene; Möttönen, Merja; Glosli, Heidi; Jónmundsson, Guðmundur K; Abrahamsson, Jonas; Hasle, Henrik

    2011-03-01

    The frequency and causes of treatment-related deaths (TRD) in second complete remission (CR2) in acute myeloid leukaemia (AML) were investigated in a historical, prospective cohort study of 429 children included in the Nordic Society of Paediatric Haematology and Oncology (NOPHO)-AML-88 and -93 trials. Relapse occurred in 158 children (39%). Seventeen (18%) of the 96 patients entering CR2 suffered TRD. The main causes were infection (59%) and complications from graft-versus-host disease (22%). Fourteen (82%) of 17 TRDs occurred in children undergoing haematopoietic stem cell transplantations (HSCT). Optimal supportive care after HSCT is essential, and studies on risk factors for TRD are needed. PMID:21241281

  19. Gonadal function after 12-Gy testicular irradiation in childhood acute lymphoblastic leukemia

    SciTech Connect

    Castillo, L.A.; Craft, A.W.; Kernahan, J.; Evans, R.G.; Aynsley-Green, A. )

    1990-01-01

    Gonadal function was assessed in 15 boys with acute lymphoblastic leukemia (ALL) who had received testicular irradiation. The dose to the testes was 12 Gy in 12, 15 Gy in 1, and 24 Gy in 2 cases. All of those who had received 12 or 15 Gy had normal Leydig cell function, although high levels of gonadotropins suggest subclinical Leydig cell damage. The 2 who had 24 Gy had Leydig cell failure. All who were old enough to produce a semen specimen were azoospermic.

  20. Clofarabine-based combination chemotherapy for relapse and refractory childhood acute lymphoblastic leukemia.

    PubMed

    Arakawa, Yuki; Koh, Katsuyoshi; Aoki, Takahiro; Kubota, Yasuo; Oyama, Ryo; Mori, Makiko; Hayashi, Mayumi; Hanada, Ryoji

    2014-11-01

    Clofarabine, one of the key treatment agents for refractory and relapsed acute lymphoblastic leukemia (ALL), achieves a remission rate of approximately 30% with single-agent clofarabine induction chemotherapy. However, a remission rate of approximately 50% was reported with a combination chemotherapy regimen consisting of clofarabine, etoposide, and cyclophosphamide. We treated two cases with refractory and relapsed ALL with combination chemotherapy including clofarabine; one was an induction failure but the other achieved remission. Both cases developed an infectious complication (NCI-CTCAE grade 3) and body pain with infusion. Prophylactic antibiotic and opioid infusions facilitated avoiding septic shock and pain. Further investigation of such cases is required. PMID:25501414

  1. Childhood Sexual Abuse and Acute Alcohol Effects on Men’s Sexual Aggression Intentions

    PubMed Central

    Davis, Kelly Cue; Schraufnagel, Trevor J.; Jacques-Tiura, Angela J.; Norris, Jeanette; George, William H.; Kiekel, Preston A.

    2012-01-01

    Objective Although research has established childhood sexual abuse (CSA) as a risk factor for men’s perpetration of sexual aggression, there has been little investigation of the factors undergirding this association. This study represents one of the first to use a laboratory-based sexual aggression analogue coupled with an alcohol administration protocol to investigate the pathways through which CSA and alcohol influence men’s self-reported sexual aggression intentions. Method After completing background questionnaires, male social drinkers (N = 220) were randomly assigned to a control, placebo, low alcohol dose or high alcohol dose condition. Following beverage consumption, participants read a sexual scenario in which the female partner refused to have unprotected sexual intercourse, after which they completed dependent measures. Results Path analysis indicated that men with a CSA history and intoxicated men perceived the female character as more sexually aroused and reported stronger sexual entitlement cognitions, both of which were in turn associated with greater condom use resistance and higher sexual aggression intentions. Exploratory analyses revealed that intoxication moderated the effects of CSA history on sexual entitlement cognitions, such that sexual entitlement cognitions were highest for men who had a CSA history and consumed alcohol. Conclusions Findings suggest that CSA history may facilitate sexual assault perpetration through its effects on in-the-moment cognitions, and that these effects may be exacerbated by alcohol intoxication. PMID:22754720

  2. Vitamin D Supplementation for the Treatment of Acute Childhood Pneumonia: A Systematic Review

    PubMed Central

    Das, Rashmi Ranjan; Singh, Meenu; Panigrahi, Inusha; Naik, Sushree Samiksha

    2013-01-01

    Background. Studies have found an increased incidence of vitamin D deficiency in children with pneumonia; however, there is no conclusive data regarding the direct effect of vitamin D supplementation in acute pneumonia. Methods. A comprehensive search was performed of the major electronic databases till September 2013. Randomized controlled trials (RCTs) comparing treatment with vitamin D3 versus placebo in children ≤5 years old with pneumonia were included. Results. Out of 32 full text articles, 2 RCTs including 653 children were eligible for inclusion. One trial used a single 100,000 unit of oral vitamin D3 at the onset of pneumonia. There was no significant difference in the mean (±SD) number of days to recovery between the vitamin D3 and placebo arms (P = 0.17). Another trial used oral vitamin D3 (1000 IU for <1 year and 2000 IU for >1 year) for 5 days in children with severe pneumonia. Median duration of resolution of severe pneumonia was similar in the two groups (intervention, 72 hours; placebo, 64 hours). Duration of hospitalization and time to resolution of tachypnea, chest retractions, and inability to feed were also comparable between the two groups. Conclusions. Oral vitamin D supplementation does not help children under-five with acute pneumonia. PMID:24455293

  3. Acute Motor Axonal Neuropathy (Aman) With Motor Conduction Blocks In Childhood; Case Report

    PubMed Central

    Yildirim, Serhan; Adviye, Rahşan; Gül, Hakan Levent; Türk Börü, Ülkü

    2016-01-01

    Objective Acute motor axonal neuropathy (AMAN), characterized with decreased compound muscle action potentials (CMAP) and absence of demyelinating findings in electrophysiological studies, is a subtype of Guillain-Barre Syndrome (GBS). A 4 yr-old male patient presented with ascending weakness, dysarthria and dysphagia to İstanbul Dr. Lütfi Kırdar Kartal Training and Research Hospital Neurology outpatient for three days to in 2012. Dysphonia, restricted eye movements, flaccid tetraplegia and areflexia were found in neurological examination. There were motor conduction blocks in all peripheral nerves in electrophysiological studies.According to these findings the patient was diagnosed as Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP). Reduction of CMAP amplitudes in posterior tibial nerve, absence of CMAPs in median, ulnar and peroneal nerves and loss of motor conduction blocks were found in following electrophysiological studies. According to these findings, patient was diagnosed as AMAN. Motor conduction blocks may appear in early stage of AMAN and they disappear in later examinations. That’s why electrophysiological studies must be repeated in patients with GBS. PMID:27057191

  4. Diapers in War Zones: Ethnomedical Factors in Acute Childhood Gastroenteritis in Peshawar, Pakistan

    PubMed Central

    Zaidi, Saira H.; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services’ admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient’s parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts. PMID:25768117

  5. Diapers in war zones: ethnomedical factors in acute childhood gastroenteritis in Peshawar, Pakistan.

    PubMed

    Zaidi, Saira H; Smith-Morris, Carolyn

    2015-01-01

    This article considers ethnomedical knowledge and practices among parents related to contraction of acute gastroenteritis among children in Peshawar, Pakistan. Research methods included analysis of the Emergency Pediatric Services' admission register, a structured interview administered to 47 parents of patients seen in the Khyber Medical College Teaching Hospital, semi-structured interviews of 12 staff, and four home visits among families with children treated at the hospital. The use of native research assistants and participant observation contributed to the reliability of the findings, though the ethnographic, home-visit sample is small. Our research indicated that infection rates are exacerbated in homes through two culturally salient practices and one socioeconomic condition. Various misconceptions propagate the recurrence or perserverance of acute gastroenteritis including assumptions about teething leading to poor knowledge of disease etiology, rehydration solutions leading to increased severity of disease, and diaper usage leading to the spread of disease. In our Discussion, we suggest how hospital structures of authority and gender hierarchy may impact hospital interactions, the flow of information, and its respective importance to the patient's parents leading to possible propagation of disease. These ethnographic data offer a relatively brief but targeted course of action to improve the effectiveness of prevention and treatment efforts. PMID:25768117

  6. Acute Motor Axonal Neuropathy (Aman) With Motor Conduction Blocks In Childhood; Case Report.

    PubMed

    Yildirim, Serhan; Adviye, Rahşan; Gül, Hakan Levent; Türk Börü, Ülkü

    2016-01-01

    Objective Acute motor axonal neuropathy (AMAN), characterized with decreased compound muscle action potentials (CMAP) and absence of demyelinating findings in electrophysiological studies, is a subtype of Guillain-Barre Syndrome (GBS). A 4 yr-old male patient presented with ascending weakness, dysarthria and dysphagia to İstanbul Dr. Lütfi Kırdar Kartal Training and Research Hospital Neurology outpatient for three days to in 2012. Dysphonia, restricted eye movements, flaccid tetraplegia and areflexia were found in neurological examination. There were motor conduction blocks in all peripheral nerves in electrophysiological studies.According to these findings the patient was diagnosed as Acute Inflammatory Demyelinating Polyradiculoneuropathy (AIDP). Reduction of CMAP amplitudes in posterior tibial nerve, absence of CMAPs in median, ulnar and peroneal nerves and loss of motor conduction blocks were found in following electrophysiological studies. According to these findings, patient was diagnosed as AMAN. Motor conduction blocks may appear in early stage of AMAN and they disappear in later examinations. That's why electrophysiological studies must be repeated in patients with GBS. PMID:27057191

  7. Effects of Race/Ethnicity and Socioeconomic Status on Outcome in Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Acharya, Sahaja; Hsieh, Samantha; Shinohara, Eric T; DeWees, Todd; Frangoul, Haydar; Perkins, Stephanie M

    2016-07-01

    With modern therapy, overall survival (OS) for children with acute lymphoblastic leukemia approaches 90%. However, inferior outcomes for minority children have been reported. Data on the effects of ethnicity/race as it relates to socioeconomic status are limited. Using state cancer registry data from Texas and Florida, we evaluated the impact of neighborhood-level poverty rate and race/ethnicity on OS for 4719 children with acute lymphoblastic leukemia. On multivariable analysis, patients residing in neighborhoods with the highest poverty rate had a 1.8-fold increase in mortality compared with patients residing in neighborhoods with the lowest poverty rate (hazard ratio [HR], 1.8; 95% confidence interval [CI], 1.41-2.30). Hispanic and non-Hispanic black patients also had increased risk of mortality compared with non-Hispanic white patients (Hispanic: HR, 1.18; 95% CI, 1.01-1.39; non-Hispanic black: HR, 1.31; 95% CI, 1.03-1.66). On subgroup analysis, there was a 21.7% difference in 5-year OS when comparing non-Hispanic white children living in the lowest poverty neighborhoods (5-year OS, 91.2%; 95% CI, 88.6-93.2) to non-Hispanic black children living in the highest poverty neighborhoods (5-year OS, 69.5%; 95% CI, 61.5-76.1). To address such disparities in survival, further work is needed to identify barriers to cancer care in this pediatric population. PMID:27177145

  8. Good News About Childhood Cancer

    MedlinePlus

    ... Home Current Issue Past Issues Good News About Childhood Cancer Past Issues / Spring 2008 Table of Contents ... 85 percent for the most common form of childhood cancer (acute lymphoblastic leukemia or ALL). During the ...

  9. Therapeutic Autologous Lymphocytes and Aldesleukin in Treating Patients With High-Risk or Recurrent Myeloid Leukemia After Undergoing Donor Stem Cell Transplant

    ClinicalTrials.gov

    2011-07-12

    Accelerated Phase Chronic Myelogenous Leukemia; Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; 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 Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Relapsing Chronic Myelogenous Leukemia; Secondary Acute Myeloid Leukemia

  10. Community health worker competency in managing acute respiratory infections of childhood in Bolivia.

    PubMed

    Zeitz, P S; Harrison, L H; López, M; Cornale, G

    1993-01-01

    A competency-based training and evaluation method was developed to improve and assess the management of acute respiratory infections (ARI) in young children by community health workers (CHWs) in Bolivia. This method was used to evaluate three groups of Bolivian CHWs, provide them with a one-day refresher course in ARI management, and assess the effects of the course. The results showed the CHWs capable of acquiring the skills needed to effectively manage ARI cases in accordance with the World Health Organization's ARI case management strategy. It was found important, however, that their training emphasize how to count the respirations of children with tachypnea and how to identify chest indrawing. In general, the competency-based methods appeared to be effective in training and evaluating CHWs in the area of ARI case management; it is expected that these methods will prove useful in other community-based health interventions. PMID:8339109

  11. Non-tumour bone marrow lymphocytes correlate with improved overall survival in childhood acute lymphoblastic leukaemia.

    PubMed

    Edwin, Claire; Dean, Joanne; Bonnett, Laura; Phillips, Kate; Keenan, Russell

    2016-10-01

    Composition of tumour immune cell infiltrates correlates with response to treatment and overall survival (OS) in several cancer settings. We retrospectively examined immune cells present in diagnostic bone marrow aspirates from paediatric patients with B-cell acute lymphoblastic leukaemia. Our analysis identified a sub-group (∼30% of patients) with >2.37% CD20 and >6.05% CD7 expression, which had 100% OS, and a sub-group (∼30% of patients) with ≤2.37% CD20 and ≤6.05% CD7 expression at increased risk of treatment failure (66.7% OS, P < 0.05). Immune cell infiltrate at diagnosis may predict treatment response and could provide a means to enhance immediate treatment risk stratification. PMID:27348401

  12. Knowledge, attitude and practice factors in childhood acute respiratory infections in a peninsular Malaysia health district.

    PubMed

    Vasanthamala, A; Arokiasamy, J T

    1989-01-01

    This study compares the knowledge, attitudes and practice of mothers in two ethnic groups with regard to acute respiratory infections (ARI) in their child. Most had traditional beliefs as to the cause of ARI with only a minority knowing the causes. Most mothers were aware of the effect of frequent attacks of ARI on the health status of their child and of the importance of early treatment. Reasons for their becoming worried during an episode of ARI in their child indicated that problems of distance, transportation and arrangements for care of their other children predominate. A large proportion of the respondents felt that their present knowledge of ARI was inadequate and were thus interested in obtaining more information. PMID:2620023

  13. Psychosocial Functioning in Youths at High Risk to Develop Major Depressive Disorder.

    ERIC Educational Resources Information Center

    Birmaher, Boris; Bridge, Jeffrey A.; Williamson, Douglas E.; Brent, David A.; Dahl, Ronald E.; Axelson, David A.; Dorn, Lorah D.; Ryan, Neal D.

    2004-01-01

    Objective: To compare the psychosocial functioning of children and adolescents at high risk of major depressive disorder with youths with acute major depressive disorder and healthy controls. Method: High-risk (n = 57), major depressive disorder (n = 71), and healthy control (n = 48) youths and their families were recruited from 1987 to 1996 and…

  14. Oral or parenteral administration of curcumin does not prevent the growth of high-risk t(4;11) acute lymphoblastic leukemia cells engrafted into a NOD/SCID mouse model

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The efficacy of orally and parenterally administered curcumin was evaluated in NOD.CB17-Prkdcscid/J mice engrafted with the human t(4;11) acute lymphoblastic leukemia line SEM. SEM cells were injected into the tail vein and engraftment was monitored by flow cytometry. Once engraftment was observed...

  15. Improving antenatal risk assessment in women exposed to high risks.

    PubMed

    Perry, Natasha; Newman, Louise K; Hunter, Mick; Dunlop, Adrian

    2015-01-01

    Antenatal substance use and related psychosocial risk factors are known to increase the likelihood of child protection involvement; less is known about the predictive nature of maternal reflective functioning (RF) in this population. This preliminary study assessed psychosocial and psychological risk factors for a group of substance dependent women exposed to high risks in pregnancy, and their impact on child protection involvement. Pregnant women on opiate substitution treatment (n = 11) and a comparison group (n = 15) were recruited during their third trimester to complete measures of RF (Pregnancy Interview), childhood trauma, mental health and psychosocial assessments. At postnatal follow-up, RF was reassessed (Parent Development Interview - Revised Short Version) and mother-infant dyads were videotaped to assess emotional availability (EA). Child protection services were contacted to determine if any concerns had been raised for infant safety. Significant between-group differences were observed for demographics, psychosocial factors, trauma and mental health symptoms. Unexpectedly, no significant differences were found for RF or EA between groups. Eight women in the 'exposed to high risks' group became involved with child protection services. Reflective functioning was not significantly associated with psychosocial risk factors, and therefore did not mediate the outcome of child protection involvement. Women 'exposed to high risks' were equally able to generate a model of their own and their infants' mental states and should not be seen within a deficit perspective. Further research is required to better understand the range of risk factors that predict child protection involvement in high risk groups. PMID:23982989

  16. Increased risk of childhood acute lymphoblastic leukemia (ALL) by prenatal and postnatal exposure to high voltage power lines: a case control study in Isfahan, Iran.

    PubMed

    Tabrizi, Maral Mazloomi; Bidgoli, Sepideh Arbabi

    2015-01-01

    Childhood acute lymphoblastic leukemia (ALL) is one of the most common hematologic malignancies, accounting 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 evaluted the role of prenatal and postnatal exposure to high voltage power lines on the incidence of childhood ALL.This cross-sectional case control study was carried out on 22 cases and 100 controls who were born and lived in low socioeconomic families in Isfahan and hospitalized for therapeutic purposes in different hospitals from 2013-2014.With regard to the underlying risk factors, familial history and parental factors were noted but in this age, socioeonomic and zonal matched case control study, prenatal and childhood exposure to high voltage power lines was considered as the most important environmental risk factors of ALL (p=0.006, OR=3.651, CI 95%, 1.692-7.878). As the population was of low socioeconomic background, use of mobiles, computers and microwave was negligible. Moreover prenatal and postnatal exposure to indoor electrically charged objects was not determined to be a significant environmental factor. Thus, pre and post natal exposure to high voltage power lines and living in pollutant regions as well as familial influence could be described as risk factors of ALL for the first time in a low socioeconomic status Iranian population. PMID:25824762

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

    ClinicalTrials.gov

    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

  18. Antibiotic Treatment and Surgery for Acute Hematogenous Calcaneal Osteomyelitis of Childhood.

    PubMed

    Pääkkönen, Markus; Kallio, Markku J T; Peltola, Heikki; Kallio, Pentti E

    2015-01-01

    Acute hematogenous calcaneal osteomyelitis characteristically affects children. A recent trend has emerged toward shorter courses of antibiotics. In our randomized, prospective treatment trial of children aged 3 months to 15 years, the intravenous antibiotic (clindamycin or a first-generation cephalosporin) was given only for the first 2 to 4 days and the remainder of the 20- to 30-day course was completed orally. A bone sample for culture was to be taken routinely, but all additional surgery was performed on special demand. We performed a retrospective subanalysis of cases affecting the calcaneus. The follow-up period was 1 year. Of the 14 participants enrolled, 11 completed the 1-year follow-up period, and their data were analyzed. Staphylococcus aureus was the cause of 10 cases; all strains were methicillin sensitive. The median intravenous treatment duration was 3 days. Four patients required open incisional trepanation (trephination). All participants attending the 1-year follow-up examination had fully recovered. The outcome of calcaneal osteomyelitis caused by methicillin-sensitive S. aureus in a child will be good, if the patient seeks treatment early and antibiotic therapy is started promptly. A bone biopsy is needed to obtain a representative sample for bacteriology. PMID:25912854

  19. Glucocorticoid-induced alterations in mitochondrial membrane properties and respiration in childhood acute lymphoblastic leukemia.

    PubMed

    Eberhart, Karin; Rainer, Johannes; Bindreither, Daniel; Ritter, Ireen; Gnaiger, Erich; Kofler, Reinhard; Oefner, Peter J; Renner, Kathrin

    2011-06-01

    Mitochondria are signal-integrating organelles involved in cell death induction. Mitochondrial alterations and reduction in energy metabolism have been previously reported in the context of glucocorticoid (GC)-triggered apoptosis, although the mechanism is not yet clarified. We analyzed mitochondrial function in a GC-sensitive precursor B-cell acute lymphoblastic leukemia (ALL) model as well as in GC-sensitive and GC-resistant T-ALL model systems. Respiratory activity was preserved in intact GC-sensitive cells up to 24h under treatment with 100 nM dexamethasone before depression of mitochondrial respiration occurred. Severe repression of mitochondrial respiratory function was observed after permeabilization of the cell membrane and provision of exogenous substrates. Several mitochondrial metabolite and protein transporters and two subunits of the ATP synthase were downregulated in the T-ALL and in the precursor B-ALL model at the gene expression level under dexamethasone treatment. These data could partly be confirmed in ALL lymphoblasts from patients, dependent on the molecular abnormality in the ALL cells. GC-resistant cell lines did not show any of these defects after dexamethasone treatment. In conclusion, in GC-sensitive ALL cells, dexamethasone induces changes in membrane properties that together with the reduced expression of mitochondrial transporters of substrates and proteins may lead to repressed mitochondrial respiratory activity and lower ATP levels that contribute to GC-induced apoptosis. PMID:21237131

  20. Meningosis prophylaxis with intrathecal /sup 198/Au-colloid and methotrexate in childhood acute lymphocytic leukemia

    SciTech Connect

    Metz, O.; Stoll, W.; Plenert, W.

    1982-01-15

    Since 1972, telecobalt irradiation plus intrathecal methotrexate (ITMTX) has been successfully replaced in Jena by intrathecal colloidal radioactive gold (/sup 198/Au) plus ITMTX for meningosis prophylaxis in leukemia. Seventy-three children with acute lymphocytic leukemia (ALL) were given 1.24-4.89 mCi (45.8-181 MBq) of colloidal 198Au IT after successful initiation of remission. During cytostatic therapy, the following relapses occurred: meningosis leucaemica, five patients (6.8%); bone-marrow relapse and the meningosis leucaemica, one patient; and bone-marrow relapse, 20 patients (27.4%). In 18 children, combination chemotherapy was terminated after two and a half or three years of treatment. After that time, one meningeal relapse and six bone-marrow relapses occurred. Within the first 24 hours after application of radioactive gold, headaches, vomiting, and fever occurred in less than 10% of the children. An apathy syndrome, leukecephalopathy, or severe infections, were not observed in a single case. Radioactive gold spreads in the subarachnoid space and is phagocytized by the arachnoidea. The tumoricide effect extends selectively over the space of distribution of the latent meningosis leucaemia. The cerebral parenchyma remains unaffected by radiation. Thus, radioactive gold may be preferable to telecobalt irradiation in preventing central nervous system leukemia.

  1. Reentry of nondividing leukemic cells into a proliferative phase in acute childhood leukemia

    PubMed Central

    Saunders, E. F.; Mauer, A. M.

    1969-01-01

    Reentry of small leukemic blast cells into a proliferative phase was demonstrated in a 3 yr old girl with untreated acute lymphoblastic leukemia. Since the proliferating leukemic cell compartment in this disease is not self-maintaining, continual entry of cells into this compartment is necessary to prevent depletion of proliferating cells. In order to identify the source of replacement cells, the rate of change of tritiated thymidine-labeled cells in the proliferating compartment was observed by means of serial bone marrow samples under two conditions. In the first study period only 10% of small leukemic blast cells were labeled, and in the second study period 72% of this population had become lebeled. During the first period the proliferating blast cells were rapidly replaced by unlabeled cells, while during the second period the replacement cells were coming largely from a labeled cell source. The only identifiable source of cells for maintenance of the proliferating population which was virtually unlabeled during the first period and largely labeled during the second period was the population of small leukemic blast cells. The finding that the small blast cells are only temporarily nonproliferative could account for effectiveness of therapy directed primarily against a dividing cell population. Persistence of some cells with longer resting times into remission could provide a focus for subsequent relapse. PMID:5256065

  2. Ethnicity and survival in childhood acute myeloid leukemia: a report from the Children's Oncology Group

    PubMed Central

    Aplenc, Richard; Alonzo, Todd A.; Gerbing, Robert B.; Smith, Franklin O.; Meshinchi, Soheil; Ross, Julie A.; Perentesis, John; Woods, William G.; Lange, Beverly J.; Davies, Stella M.

    2006-01-01

    We evaluated differences in outcome by ethnicity among children with acute myeloid leukemia (AML). We analyzed 791 children in the CCG 2891 trial and confirmed positive findings in 850 children in the CCG 2961 trial. Hispanic and black children treated with chemotherapy in CCG 2891 had significantly inferior overall survival (OS) from study entry compared with white children (37%± 9% vs 48%± 4% [P = .016] and 34% ± 10% vs 48% ± 4%, [P = .007], respectively). Significantly fewer black children had related donors. Analyses of CCG 2961 confirmed that black children had significantly decreased OS rates compared with white children (45% ± 12% vs 60% ± 4%; P = .007) The difference in OS rates between Hispanic and white children approached statistical significance (51% ± 8% vs 60% ± 4%; P = .065) Only 7.5% of black children on CCG 2961 had an available family donor. In conclusion, Hispanic and black children with AML have worse survival than white children. Access to chemotherapy, differences in supportive care or leukemia phenotype, and reduced compliance are unlikely explanations for this difference because therapy was given intravenously according to CCG protocols. Fewer black children than expected had an available family marrow donor. (Blood. 2006;108:74-80) PMID:16537811

  3. Increased Body Mass Index during Therapy for Childhood Acute Lymphoblastic Leukemia: A Significant and Underestimated Complication.

    PubMed

    Atkinson, Helen C; Marsh, Julie A; Rath, Shoshana R; Kotecha, Rishi S; Gough, Hazel; Taylor, Mandy; Walwyn, Thomas; Gottardo, Nicholas G; Cole, Catherine H; Choong, Catherine S

    2015-01-01

    Objective & Design. We undertook a retrospective review of children diagnosed with acute lymphoblastic leukemia (ALL) and treated with modern COG protocols (n = 80) to determine longitudinal changes in body mass index (BMI) and the prevalence of obesity compared with a healthy reference population. Results. At diagnosis, the majority of patients (77.5%) were in the healthy weight category. During treatment, increases in BMI z-scores were greater for females than males; the prevalence of obesity increased from 10.3% to 44.8% (P < 0.004) for females but remained relatively unchanged for males (9.8% to 13.7%, P = 0.7). Longitudinal analysis using linear mixed-effects identified associations between BMI z-scores and time-dependent interactions with sex (P = 0.0005), disease risk (P < 0.0001), age (P = 0.0001), and BMI z-score (P < 0.0001) at diagnosis and total dose of steroid during maintenance (P = 0.01). Predicted mean BMI z-scores at the end of therapy were greater for females with standard risk ALL irrespective of age at diagnosis and for males younger than 4 years of age at diagnosis with standard risk ALL. Conclusion. Females treated on standard risk protocols and younger males may be at greatest risk of becoming obese during treatment for ALL. These subgroups may benefit from intervention strategies to manage BMI during treatment for ALL. PMID:26101530

  4. Maternal knowledge, attitude and practices regarding childhood acute respiratory infections in Kumasi, Ghana.

    PubMed

    Denno, D M; Bentsi-Enchill, A; Mock, C N; Adelson, J W

    1994-01-01

    Acute respiratory infections (ARI) are a major cause of paediatric mortality and morbidity, particularly when associated with delays in treatment. A study of mothers' knowledge, attitudes and practices regarding ARI in their children aged less than 5 years was conducted in an urban Ghanaian population. One hundred and forty-three women traders were interviewed in open air markers in Kumasi, Ghana. Based on Western standards, there was a poor maternal understanding of the aetiology of ARI. A variety of herbal and home care therapies, including some which have potentially harmful effects, were routinely employed for the prophylaxis and treatment of ARI. For example, castor oil and enemas (25.9%) were reported as agents to prevent ARI, and antibiotics were prescribed by the parents in 39.9% for treating coughs. While the mothers exhibited an understanding of symptoms which differentiate between mild and severe ARI, a substantial number indicated that they would delay accessing a health care facility in the presence of the following symptoms which signify severe respiratory distress: dyspnoea (11.2%); tachypnoea (18.9%); chest retraction (21.7%); cough, fever and anorexia (30.0%); and cough, fever and lethargy (57.3%). These findings support the need for an ARI health education programme in Ghana. PMID:7880091

  5. Feasibility and Initial Effectiveness of Home Exercise During Maintenance Therapy for Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Esbenshade, Adam J.; Friedman, Debra L.; Smith, Webb A.; Jeha, Sima; Pui, Ching-Hon; Robison, Leslie L.; Ness, Kirsten K.

    2014-01-01

    Purpose Children with acute lymphoblastic leukemia (ALL) are at increased risk of obesity and deconditioning from cancer therapy. This pilot study assessed feasibility/initial efficacy of an exercise intervention for ALL patients undergoing maintenance therapy. Methods Participants were children with ALL, age 5-10 years, receiving maintenance therapy, in first remission. A 6-month home-based intervention, with written and video instruction, was supervised with weekly calls from an exercise coach. Pre- and post-study testing evaluated strength, flexibility, fitness and motor function. Results Seventeen patients enrolled (participation 63%). Twelve (71%) finished the intervention, completing 81.7±7.2% of prescribed sessions. Improvements ≥5% occurred in 67% for knee and 75% for grip strength, 58% for hamstring/low-back and 83% for ankle flexibility, 75% for the 6-minute-walk-test, and 33% for performance on the Bruininks-Oseretsky Test of Motor Proficiency Version 2. Conclusions This pilot study demonstrated that exercise intervention during ALL therapy is feasible and has promise for efficacy. PMID:24979081

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

    PubMed Central

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

    2015-01-01

    Abstract 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. PMID:26705211

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

    PubMed

    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. PMID:26705211

  8. The long-term results of childhood acute lymphoblastic leukemia at two centers from Turkey: 15 years of experience with the ALL-BFM 95 protocol.

    PubMed

    Güneş, Adalet Meral; Oren, Hale; Baytan, Birol; Bengoa, Sebnem Yılmaz; Evim, Melike Sezgin; Gözmen, Salih; Tüfekçi, Ozlem; Karapınar, Tuba Hilkay; Irken, Gülersu

    2014-10-01

    Dramatic progress in the treatment of childhood acute lymphoblastic leukemia (ALL) has been achieved during the last two decades in Western countries, where the 5-year event-free survival (EFS) rate has risen from 30 to 85 %. However, similarly high cure rates have not always been achieved in all centers in developing countries due to limited sources. We evaluated the treatment results of the ALL-Berlin-Frankfurt-Münster (BFM) 95 protocol as used between 1995 and 2009 in the pediatric hematology departments of two university hospitals. A retrospective analysis of 343 children newly diagnosed with ALL (M/F 200/143, median age 6.8 years) was performed. The overall survival (OS) and EFS according to age, initial leukocyte count, immunophenotype, chemotherapy responses (on days 8, 15, and 33), and risk groups were analyzed by Kaplan-Meier survival analysis. Median follow-up time was 6.4 years. Complete remission was achieved in 97 % of children. Five-year EFS and OS were found to be 78.4 and 79.9 %, respectively. Children younger than 6 years old had significantly better EFS and OS (83.7 and 85.2 %) than children aged ≥6 years (71.4 and 72.8 %). Adolescents achieved 63 % EFS and 65 % OS. Patients who had initial leukocyte counts of <20 × 10(9)/L had better EFS and OS (82.2 and 84.6 %) than children with higher initial leukocyte counts (72.6 and 72.6 %). EFS for B-cell precursor and T-cell ALL was 81.5 and 66.7 %, respectively. Children with a good response to prednisolone on day 8 (87 %) achieved significantly better EFS and OS (81.2 and 81.9 % vs. 55.3 and 60.5 %). Children whose bone marrow on day 15 was in complete remission had higher EFS and OS (83.7 and 86.6.1 % vs. 56.4 and 61.5 %). Children in the standard-risk and medium-risk groups obtained statistically significantly higher EFS (95.5 and 82.7 %) and OS (97.7 and 82.3 %) compared to the high-risk group (EFS 56.3 %, OS 63.4 %). The relapse rate was 14.8 %. The median relapse time from diagnosis was 23

  9. Association between Methylenetetrahydrofolate Reductase (MTHFR) Gene Polymorphisms and Susceptibility to Childhood Acute Lymphoblastic Leukemia in an Iranian Population

    PubMed Central

    Bahari, Gholamreza; Hashemi, Mohammad; Naderi, Majid; Taheri, Mohsen

    2016-01-01

    Background: The present study was aimed to examine the possible association between methylene tetrahydrofolate reductase (MTHFR) gene polymorphisms and childhood acute lymphoblastic leukemia (ALL) in a sample of Iranian population. Subjects and Methods: A total of 220 subjects including 100 children diagnosed with ALL and 120 healthy children participated in the case-control study. The single nucleotide polymorphisms (SNPs) of MTHFR were determined by ARMS-PCR or PCR-RFLP method. Results: Our investigation revealed that rs13306561 both TC and TC + CC genotypes decreased the risk of ALL compared to TT genotype (OR=0.32, 95%CI=0.15-0.68, p=0.002 and OR=0.35, 95%CI=0.17-0.70, p=0.003, respectively). In addition, the rs13306561 C allele decreased the risk of ALL in comparison with T allele (OR=0.42, 95% CI=0.22-0.78, P=0.005). MTHFR rs1801131 (A1298C) polymorphism showed that the AC heterozygous genotype decreased the risk of ALL in comparison with AA homozygous genotype (OR=0.43, 95%CI=0.21-0.90, p=0.037). Neither the overall Chi-square comparison of cases and control subjects (𝜒2=5.54, p=0.063) nor the logistic regression analysis showed significant association between C677T polymorphism and ALL (OR=1.25, 95% CI=0.69-2.23, p=0.552; CT vs. CC). Conclusion: The current investigation findings showed that MTHFR rs1801131 and rs13306561 polymorphisms decreased the risk of ALL in the population which has been studied. Further studies with larger sample sizes and different ethnicities are required to validate our findings. PMID:27489588

  10. [Phenomenon of the evolution of clonal chromosomal abnormalities in childhood acute myeloid leukemia].

    PubMed

    Andreeva, S V; Drozdova, V D; Kavardakova, N V

    2010-01-01

    Analysis of chromosomal abnormalities in bone marrow cells in 116 children with diagnosis of acute myeloid leukemia (AML) was performed. Frequency of evolution of clonal chromosome abnormalities in AML constituted 42,3%. The most abundant among them were numerical abnormalities of chromosomes 8, 9, and 21 as well as secondary structural abnormalities in region 12p12, 9p22, 9q22, 9q34, 11q14-23, and 16q22. Numerical abnormalities were registered in 26,7% cases. The basic mechanism of leukemic clone evolution was trisomy, deletion and monosomy. The frequency of evolution was 7 times higher in the age group up to 2 years and twice higher in the age group up to 5 years. The high frequency of evolution was established at t(15;17)(q22;q22) and the absence at inv(16)(p13q22). The patients with clonal evolution died earlier, before reaching remission, that can be connected with heavy initial state and high frequency of relapse. Conception of abnormality clone evolution was proposed at some stages: I--appearance of balanced rearrangement; II--trisomy; III--lose of chromosomal material. Appearance of unbalanced genome in evolution possess an advantage in proliferate activity and can be connected with the answer on chemotherapy. Identity of abnormal chromosome structure at diagnosis and relapse of disease can be an evidence of the influence of chemical agent on establishment of some types of evolution of chromosome abnormalities in leukemic cells in AML in children. PMID:20608159

  11. Acute Lower Respiratory Infection in Childhood and Household Fuel Use in Bhaktapur, Nepal

    PubMed Central

    Bates, Michael N.; Chandyo, Ram K.; Valentiner-Branth, Palle; Pokhrel, Amod K.; Mathisen, Maria; Basnet, Sudha; Shrestha, Prakash S.; Strand, Tor A.

    2013-01-01

    Background: Globally, solid fuels are used by about 3 billion people for cooking. These fuels have been associated with many health effects, including acute lower respiratory infection (ALRI) in young children. Nepal has a high prevalence of use of biomass for cooking and heating. Objective: This case–control study was conducted among a population in the Bhaktapur municipality, Nepal, to investigate the relationship of cookfuel type to ALRI in young children. Methods: Cases with ALRI and age-matched controls were enrolled from an open cohort of children 2–35 months old, under active monthly surveillance for ALRI. A questionnaire was used to obtain information on family characteristics, including household cooking and heating appliances and fuels. The main analysis was carried out using conditional logistic regression. Population-attributable fractions (PAF) for stove types were calculated. Results: A total of 917 children (452 cases and 465 controls) were recruited into the study. Relative to use of electricity for cooking, ALRI was increased in association with any use of biomass stoves [odds ratio (OR) = 1.93; 95% CI: 1.24, 2.98], kerosene stoves (OR = 1.87; 95% CI: 1.24, 2.83), and gas stoves (OR = 1.62; 95% CI: 1.05, 2.50). Use of wood, kerosene, or coal heating was also associated with ALRI (OR = 1.45; 95% CI: 0.97, 2.14), compared with no heating or electricity or gas heating. PAFs for ALRI were 18.0% (95% CI: 8.1, 26.9%) and 18.7% (95% CI: 8.4%–27.8%), for biomass and kerosene stoves, respectively. Conclusions: The study supports previous reports indicating that use of biomass as a household fuel is a risk factor for ALRI, and provides new evidence that use of kerosene for cooking may also be a risk factor for ALRI in young children. PMID:23512278

  12. Altered erythrocyte membrane characteristics during anemia in childhood acute lymphoblastic leukemia.

    PubMed

    Ghosh, Shyamasree; Bandyopadhyay, Suman; Bhattacharya, Dilip K; Mandal, Chitra

    2005-02-01

    Anemia is a prominent feature in children with acute lymphoblastic leukemia (ALL). To investigate the erythrocyte features during anemia in these patients, we studied the altered characters of these cells and oxidative stress imposed in their serum. This investigation reveals that erythrocytes from ALL patients show (1) increased membrane fluidity detected by fluorescence anisotropy studies, increased osmotic fragility detected by hemolysis of erythrocytes in different saline concentrations, and increased hydrophobicity as measured by binding with 8-anilino-1-naphthalenesulfonic acid, (2) enhanced (approximately threefold) glycosylation and sialylation, monitored by digoxigenin enzyme assay, and (3) expression of disease-specific 210, 105, 83, 54, and 28 kDa 9-O-acetyl sialoglycoconjugates (9-O-AcSGs) demonstrated by Western blot analysis and fluorescence-activated cell sorter (FACS) analysis studies using Achatinin-H with specificity towards 9-O-AcSAalpha2-6GalNAc as the analytical probe. (4) In addition, induced oxidative stress was observed in the sera of these children as indicated by increased nitric oxide (approximately fourfold) and thiobarbituric acid (TBA) reactive species (twofold) as detected by Griess reaction and TBA assay, respectively. For all the experiments, erythrocytes from normal individuals served as controls. Thus, the altered membrane characteristics together with their exposure to induced oxidative stress in serum are found to be a few features restricted to diseased erythrocytes. Taken together, our results are suggestive of their interplay in the contribution to the observed anemia in these patients, which may be exploited for better management of the disease. PMID:15338196

  13. Epigenetic landscape correlates with genetic subtype but does not predict outcome in childhood acute lymphoblastic leukemia.

    PubMed

    Gabriel, Alem S; Lafta, Fadhel M; Schwalbe, Edward C; Nakjang, Sirintra; Cockell, Simon J; Iliasova, Alice; Enshaei, Amir; Schwab, Claire; Rand, Vikki; Clifford, Steven C; Kinsey, Sally E; Mitchell, Chris D; Vora, Ajay; Harrison, Christine J; Moorman, Anthony V; Strathdee, Gordon

    2015-01-01

    Although children with acute lymphoblastic leukemia (ALL) generally have a good outcome, some patients do relapse and survival following relapse is poor. Altered DNA methylation is highly prevalent in ALL and raises the possibility that DNA methylation-based biomarkers could predict patient outcome. In this study, genome-wide methylation analysis, using the Illumina Infinium HumanMethylation450 BeadChip platform, was carried out on 52 diagnostic patient samples from 4 genetic subtypes [ETV6-RUNX1, high hyperdiploidy (HeH), TCF3-PBX1 and dic(9;20)(p11-13;q11)] in a 1:1 case-control design with patients who went on to relapse (as cases) and patients achieving long-term remission (as controls). Pyrosequencing assays for selected loci were used to confirm the array-generated data. Non-negative matrix factorization consensus clustering readily clustered samples according to genetic subgroups and gene enrichment pathway analysis suggested that this is in part driven by epigenetic disruption of subtype specific signaling pathways. Multiple bioinformatics approaches (including bump hunting and individual locus analysis) were used to identify CpG sites or regions associated with outcome. However, no associations with relapse were identified. Our data revealed that ETV6-RUNX1 and dic(9;20) subtypes were mostly associated with hypermethylation; conversely, TCF3-PBX1 and HeH were associated with hypomethylation. We observed significant enrichment of the neuroactive ligand-receptor interaction pathway in TCF3-PBX1 as well as an enrichment of genes involved in immunity and infection pathways in ETV6-RUNX1 subtype. Taken together, our results suggest that altered DNA methylation may have differential impacts in distinct ALL genetic subtypes. PMID:26237075

  14. Mercaptopurine/Methotrexate maintenance therapy of childhood acute lymphoblastic leukemia: clinical facts and fiction.

    PubMed

    Schmiegelow, Kjeld; Nielsen, Stine N; Frandsen, Thomas L; Nersting, Jacob

    2014-10-01

    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 dosing. Because of significant interindividual and intraindividual variations in drug disposition and pharmacodynamics, vigorous dose adjustments are needed to obtain a target degree of myelosuppression. As the normal white blood cell counts vary by patients' ages and ethnicity, and also within age groups, identical white blood cell levels for 2 patients may not reflect the same treatment intensity. Measurements of intracellular levels of cytotoxic metabolites of 6MP and MTX can identify nonadherent patients, but therapeutic target levels remains to be established. A rise in serum aminotransferase levels during maintenance therapy is common and often related to high levels of methylated 6MP metabolites. However, except for episodes of hypoglycemia, serious liver dysfunction is rare, the risk of permanent liver damage is low, and aminotransferase levels usually normalize within a few weeks after discontinuation of therapy. 6MP and MTX dose increments should lead to either leukopenia or a rise in aminotransferases, and if neither is experienced, poor treatment adherence should be considered. The many genetic polymorphisms that determine 6MP and MTX disposition, efficacy, and toxicity have precluded implementation of pharmacogenomics into treatment, the sole exception being dramatic 6MP dose reductions in patients who are homozygous deficient for thiopurine methyltransferase, the enzyme that methylates 6MP and several of its metabolites. In conclusion, maintenance therapy is as important as the more intensive and toxic earlier treatment phases, and often more challenging. Ongoing research address the applicability of drug metabolite measurements for dose adjustments

  15. [THE EXPRESSION OF TLR-4 GENE MONONUCLEAR CELLS PERIPHERAL BLOOO IN PATIENTS BY HIGH RISK OF PURULENT-INFLAMMATORY COMPLICATIONS AFTER SURGERY FOR ACUTE DISEASES OF THE ABDOMINAL ORGANS].

    PubMed

    Sheyko, V D; Sytnik, D A; Pryhidko, R A; Shkurupiy, O A; Shlykova, O A; Izmailova, O V

    2015-06-01

    The specified level of gene expression TLR-4 in peripheral blood mononuclear cells in 77 patients operated on acute diseases of the abdominal organs in the 1st and the 4th day after surgery was determined. Established dynamic changes of gene expression TLR-4. Adverse course early postoperative period in patients initially high and medium risk of purulent-septic complications was accompanied by activation of gene expression TLR-4 in peripheral blood mononuclear cells. PMID:26521462

  16. Cyberbullying in those at Clinical High Risk for psychosis

    PubMed Central

    Magaud, Emilie; Nyman, Karissa; Addington, Jean

    2012-01-01

    Aim Several studies suggest an association between experiences of childhood trauma including bullying and the development of psychotic symptoms. The use of communications technology has created a new media for bullying called ‘cyberbullying’. Research has demonstrated associations between traditional bullying and cyberbullying. Negative effects of cyberbullying appear similar in nature and severity to the reported effects of traditional bullying. Our aim was to examine the prevalence and correlates of cyberbullying in those at clinical high risk (CHR) for psychosis. Methods Fifty young people at CHR for psychosis were administered the Childhood Trauma Questionnaire with added questions about cyberbullying. Results Cyberbullying was reported in 38% of the sample. Those who experienced cyberbullying also reported experiencing previous trauma. Conclusion It is possible that cyberbullying may be a problem for those at CHR of psychosis and due to the vulnerable nature of these young people, may have longitudinal implications. PMID:23343259

  17. Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    ClinicalTrials.gov

    2015-07-09

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma

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

    PubMed

    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. PMID:26215111

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

    ClinicalTrials.gov

    2016-06-28

    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

  20. Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2014-09-30

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

  1. Effectiveness of a pharmacist-led educational intervention to reduce the use of high-risk abbreviations in an acute care setting in Saudi Arabia: a quasi-experimental study

    PubMed Central

    Haseeb, Abdul; Winit-Watjana, Win; Bakhsh, Abdul-Rahman R; Elrggal, Mahmoud E; Hadi, Muhammad Abdul; Mously, Alaa A; Gadibalban, Asmaa Z; Al-Ibraheem, Bashayir F; Almubark, Rasha A; Ekram, Rawan A; Khan, Tahir Mehmood

    2016-01-01

    Objectives To evaluate the effectiveness of a pharmacist-led educational intervention to reduce the use of high-risk abbreviations (HRAs) by healthcare professionals. Design Quasi-experimental study consisting of a single group before-and-after study design. Setting A public emergency hospital in Mecca, Saudi Arabia. Participants 660 (preintervention) and then 498 (postintervention) handwritten physician orders, medication administration records (MRAs) and pharmacy dispensing sheets of 482 and 388 patients, respectively, from emergency wards, inpatient settings and the pharmacy department were reviewed. Intervention The intervention consisted of a series of interactive lectures delivered by an experienced clinical pharmacist to all hospital staff members and dissemination of educational tools (flash cards, printed list of HRAs, awareness posters) designed in line with the recommendations of the Institute for Safe Medical Practices and the US Food and Drug Administration. The duration of intervention was from April to May 2011. Main outcome Reduction in the incidence of HRAs use from the preintervention to postintervention study period. Findings The five most common abbreviations recorded prior to the interventions were ‘IJ for injection’ (28.6%), ‘SC for subcutaneous’ (17.4%), drug name and dose running together (9.7%), ‘OD for once daily’ (5.8%) and ‘D/C for discharge’ (4.3%). The incidence of the use of HRAs was highest in discharge prescriptions and dispensing records (72.7%) followed by prescriptions from in-patient wards (47.3%). After the intervention, the overall incidence of HRA was significantly reduced by 52% (ie, 53.6% vs 25.5%; p=0.001). In addition, there was a statistically significant reduction in the incidence of HRAs across all three settings: the pharmacy department (72.7% vs 39.3%), inpatient settings (47.3% vs 23.3%) and emergency wards (40.9% vs 10.7%). Conclusions Pharmacist-led educational interventions can significantly

  2. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-04-08

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  3. Vitamin D and Bone Minerals Status in the Long-term Survivors of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Reisi, Nahid; Iravani, Parisa; Raeissi, Pouran; Kelishadi, Roya

    2015-01-01

    Background: Low vitamin D and diminished bone minerals with the potential for fractures are one of the nonapparent late effects of acute lymphoblastic leukemia (ALL). Chemotherapy and radiation were known as two important risk factors. We evaluated these late effects in ALL survivors who were treated with chemotherapy or chemo plus cranial radiation therapy. Methods: In a case–control study, 33 of ALL survivors who were treated with chemotherapy (Group A), and 33 subjects who were treated with chemoplus cranial radiation (Group B) were compared against 33 matched age, sex, and pubertal stage of their healthy siblings (Group C). Standard anthropometric data were collected as well as Tanner staging for puberty, number of fractures since treatment, serum calcium (Ca), phosphorus (P), magnesium (Mg), alkaline phosphatase, parathyroid hormone, and 25-hydroxyvitamin D (25(OH) D). The independent t-test, one-way ANOVA, Chi-square test, and Tukey's test were used to analyze the data. Results: The findings indicated that the mean serum levels of 25(OH) D in ALL survivors (i.e. Groups A and B) with age mean score of 11.2 years and 12.3 years, average treatment length: 3.25 years and average time after treatment completion: 4 years, was lower compared to the controls group (12.94 ± 6.69, 14.6 ± 8.1, 20.16 ± 10.83, respectively, P < 0.001) but no significant difference was observed between Group A and B in this regard (P > 0.05). Other clinical and laboratory parameters had no significant differences between the survivors and control. Vitamin D deficiency (<20 ng/ml) was observed in 27% of group A and 24% of group B and vitamin D insufficiency (20–30 ng/ml) in 72.7% and 69.6% survivors of Group A and B and 48.5% of controls group (P = 0.003). 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

  4. High-risk sexual behaviors.

    PubMed

    Troussier, Thierry; Benghozi, Pierre; Ganem, Marc

    2012-01-01

    Adolescence is a time of life characterized by danger because of the many changes that occur, the many ties that are severed: ties to childhood, ties to the child's body as it begins to take on an adult appearance, ties to a once-familiar body image and psyche as hormones complete the transformation to adulthood, ties to an unconscious that is struggling to restructure itself anew. The creation of the romantic couple is a danger inherent in any human society. This text was written from the professional practices of each author in a multidisciplinary approach combining the approaches of public health, risk reduction, and sexual, psychological and clinical care of adolescents. How to help anticipate the dangers is to use preventive insurance verifying that security is guaranteed before committing. Risk-taking is accepting all the challenges that boost the self with oneself and with others. The risk is therefore also the commitment in love. It is still the risk to speak, to feel, to express feelings, choices, and refusal of unwanted sex. The ability of adolescents to play and defeat the risk by learning the ethical value not only to protect themselves from contracting AIDS, but also to protect others is part of the pedagogy of risk. This pedagogy of risk, as we have seen, includes three areas: information, care and initiation into love. Adolescents must be supported in their emergence by responsible people to protect them from the dangers ahead. The support is not only to prevent them from engaging in risky behavior, but to help them better manage their anxieties and support the fragility of their families in a network approach. Not knowing how to confront the risk stifles the chance of allowing the child to grow up to be independent and helps reassure parents who may resent being removed from the empowerment of their children. PMID:22846539

  5. Meta-analysis of the association between CCAAT/enhancer binding protein-ε polymorphism and the risk of childhood acute lymphoblastic leukemia

    PubMed Central

    Pan, Yangqiong; Chen, Hao; Liang, Hong; Wang, Xiaowen; Wang, Lingling

    2014-01-01

    CEBPE rs2239633 polymorphism has been implicated in susceptibility to childhood acute lymphoblastic leukemia (ALL) risk. Several studies investigated the association of this polymorphism with ALL in different populations. However, the results were contradictory. A meta-analysis was conducted to assess the association between CEBPE rs2239633 polymorphism and ALL susceptibility. Databases including Pubmed, EMBASE, Chinese National Knowledge Infrastructure (CNKI) and Wangfang were searched to find relevant studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of associations. A random-effects model was used. A significant association was found between CEBPE rs2239633 polymorphism and childhood ALL (OR = 1.19, 95% CI, 1.11-1.28). In the subgroup analyses by ethnicity, the significant association was found among Caucasians (OR = 1.19, 95% CI, 1.09-1.30) and Hispanics (OR = 1.39, 95% CI, 1.18-1.63), but not in Asians (OR = 1.05, 95% CI, 0.90-1.22). In the subgroup analysis by histology, B-cell ALL risk (OR = 1.29, 95% CI, 1.15-1.44) and B hyperdiploid ALL risk (OR = 1.84, 95% CI, 1.40-2.43) were increased. Our results suggested that CEBPE rs2239633 polymorphism conferred a risk factor of childhood ALL. PMID:25664070

  6. Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population

    PubMed Central

    2014-01-01

    Background The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL). Methods A case–control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility. Results No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015]. Conclusions The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population. PMID:24476575

  7. A Phase 1 study of the safety, pharmacokinetics and anti-leukemic activity of the anti-CD123 monoclonal antibody CSL360 in relapsed, refractory or high-risk acute myeloid leukemia.

    PubMed

    He, Simon Z; Busfield, Samantha; Ritchie, David S; Hertzberg, Mark S; Durrant, Simon; Lewis, Ian D; Marlton, Paula; McLachlan, Andrew J; Kerridge, Ian; Bradstock, Kenneth F; Kennedy, Glen; Boyd, Andrew W; Yeadon, Trina M; Lopez, Angel F; Ramshaw, Hayley S; Iland, Harry; Bamford, Simone; Barnden, Megan; DeWitte, Mark; Basser, Russell; Roberts, Andrew W

    2015-05-01

    Acute myeloid leukemia (AML) blasts express high levels of interlekin-3 (IL-3) receptor-α (CD123). CSL360 is a recombinant, chimeric immunoglobulin G1 (IgG1), anti-CD123 monoclonal antibody (MoAb) that neutralizes IL-3 and demonstrates anti-leukemic activity in vitro. This phase 1 study assessed safety, pharmacokinetics and bioactivity of weekly intravenous CSL360 for 12 weeks in 40 patients with advanced AML across five dose levels (0.1-10.0 mg/kg). Other than mild infusion reactions, CSL360 was well tolerated. The maximal tolerated dose was not reached. The half-life was 4.9 days, and the area under the curve (AUC) and maximum concentration (Cmax) increased proportionally with dose. Doses ≥ 3.0 mg/kg resulted in complete saturation and down-regulation of CD123 and abolition of ex vivo proliferative responsiveness to IL-3, indicating adequate blockade of IL-3 signaling. Two patients responded, with one remaining in complete remission after 17 doses. CSL360 bound CD123 specifically, but did not induce anti-leukemic activity in most patients. While safe, MoAb blockade of CD123 function is insufficient as a therapeutic strategy. PMID:25248882

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

    PubMed

    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. PMID:26625771

  9. World Kidney Day 2016: Averting the legacy of kidney disease-focus on childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-03-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early, or who are small-for-date newborns, have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, while only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy-makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:26884120

  10. Editorial: World Kidney Day 2016: Averting the Legacy of Kidney Disease--Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for-date newborns have a relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy including dialysis and transplantation, although only a minority of children may require this ultimate intervention. Because there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers, and caregivers about the needs and possibilities surrounding kidney disease in childhood. PMID:27085729

  11. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Irving, Julie A E; Enshaei, Amir; Parker, Catriona A; Sutton, Rosemary; Kuiper, Roland P; Erhorn, Amy; Minto, Lynne; Venn, Nicola C; Law, Tamara; Yu, Jiangyan; Schwab, Claire; Davies, Rosanna; Matheson, Elizabeth; Davies, Alysia; Sonneveld, Edwin; den Boer, Monique L; Love, Sharon B; Harrison, Christine J; Hoogerbrugge, Peter M; Revesz, Tamas; Saha, Vaskar; Moorman, Anthony V

    2016-08-18

    Somatic genetic abnormalities are initiators and drivers of disease and have proven clinical utility at initial diagnosis. However, the genetic landscape and its clinical utility at relapse are less well understood and have not been studied comprehensively. We analyzed cytogenetic data from 427 children with relapsed B-cell precursor ALL treated on the international trial, ALLR3. Also we screened 238 patients with a marrow relapse for selected copy number alterations (CNAs) and mutations. Cytogenetic risk groups were predictive of outcome postrelapse and survival rates at 5 years for patients with good, intermediate-, and high-risk cytogenetics were 68%, 47%, and 26%, respectively (P < .001). TP53 alterations and NR3C1/BTG1 deletions were associated with a higher risk of progression: hazard ratio 2.36 (95% confidence interval, 1.51-3.70, P < .001) and 2.15 (1.32-3.48, P = .002). NRAS mutations were associated with an increased risk of progression among standard-risk patients with high hyperdiploidy: 3.17 (1.15-8.71, P = .026). Patients classified clinically as standard and high risk had distinct genetic profiles. The outcome of clinical standard-risk patients with high-risk cytogenetics was equivalent to clinical high-risk patients. Screening patients at relapse for key genetic abnormalities will enable the integration of genetic and clinical risk factors to improve patient stratification and outcome. This study is registered at www.clinicaltrials.org as #ISCRTN45724312. PMID:27229005

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

    ClinicalTrials.gov

    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

  13. Endocrine Disorders in Childhood Cancer Survivors Treated with Haemopoietic Stem Cell Transplantation

    PubMed Central

    Wei, Christina; Albanese, Assunta

    2014-01-01

    The increasing number of haemopoietic stem cell transplantations (HSCT) taking place worldwide has offered a cure to many high risk childhood malignancies with an otherwise very poor prognosis. However, HSCT is associated with an increased risk of morbidity and premature death, and patients who have survived the acute complications continue to face lifelong health sequelae as a result of the treatment. Endocrine dysfunction is well described in childhood HSCT survivors treated for malignancies. The endocrine system is highly susceptible to damage from the conditioning therapy, such as, alkylating agents and total body irradiation, which is given prior stem cell infusion. Although not immediately life-threatening, the impact of these abnormalities on the long term health and quality of life in these patients may be considerable. The prevalence, risk factors, clinical approaches to investigations and treatments, as well as the implications of ongoing surveillance of endocrine disorders in childhood HSCT survivors, are discussed in this review.

  14. Enlarging Red Blood Cell Distribution Width During Hospitalization Identifies a Very High-Risk Subset of Acutely Decompensated Heart Failure Patients and Adds Valuable Prognostic Information on Top of Hemoconcentration

    PubMed Central

    Ferreira, João Pedro; Girerd, Nicolas; Arrigo, Mattia; Medeiros, Pedro Bettencourt; Ricardo, Miguel Bento; Almeida, Tiago; Rola, Alexandre; Tolpannen, Heli; Laribi, Said; Gayat, Etienne; Mebazaa, Alexandre; Mueller, Christian; Zannad, Faiez; Rossignol, Patrick; Aragão, Irene

    2016-01-01

    Abstract Red blood cell distribution width (RDW) may serve as an integrative marker of pathological processes that portend worse prognosis in heart failure (HF). The prognostic value of RDW variation (ΔRDW) during hospitalization for acute heart failure (AHF) has yet to be studied. We retrospectively analyzed 2 independent cohorts: Centro Hospitalar do Porto (derivation cohort) and Lariboisière hospital (validation cohort). In the derivation cohort a total of 170 patients (age 76.2 ± 10.3 years) were included and in the validation cohort 332 patients were included (age 76.4 ± 12.2 years). In the derivation cohort the primary composite outcome of HF admission and/or cardiovascular death occurred in 78 (45.9%) patients during the 180-day follow-up period. Discharge RDW and ΔRDW were both increased when hemoglobin levels were lower; peripheral edema was also associated with increased discharge RDW (all P < 0.05). Discharge RDW value was significantly associated with adverse events: RDW > 15% at discharge was associated with a 2-fold increase in event rate, HR = 1.95 (1.05–3.62), P = 0.04, while a ΔRDW >0 also had a strong association with outcome, HR = 2.47 (1.35–4.51), P = 0.003. The addition of both discharge RDW > 15% and ΔRDW > 0 to hemoconcentration was associated with a significant improvement in the net reclassification index, NRI = 18.3 (4.3–43.7), P = 0.012. Overlapping results were found in the validation cohort. As validated in 2 independent AHF cohorts, an in-hospital RDW enlargement and an elevated RDW at discharge are associated with increased rates of mid-term events. RDW variables improve the risk stratification of these patients on top of well-established prognostic markers. PMID:27057905

  15. Preferentially Expressed Antigen of Melanoma (PRAME) and Wilms’ Tumor 1 (WT 1) Genes Expression in Childhood Acute Lymphoblastic Leukemia, Prognostic Role and Correlation with Survival

    PubMed Central

    Khateeb, Engy El; Morgan, Dalia

    2014-01-01

    BACKGROUND: Acute lymphocytic leukemia (ALL) is the most common hematologic malignancy in children. In young children it is also largely curable, with more than 90% of afflicted children achieving long-term remission. PRAME (Preferentially expressed antigen of melanoma) gene belongs to Group 3 class I HLA-restricted widely expressed antigens in which genes encoding widely expressed tumor antigens have been detected in many normal tissues as well as in histologically different types of tumors with no preferential expression on a certain type of cancer. It has been found to be expressed in a variety of cancer cells as leukemia & lymphoma. PRAME monitoring can be useful for detection of minimal residual disease and subsequent relapses particularly those leukemias in which specific tumor markers are unavailable. Wilms’ tumor1 (WT1) gene was identified as a gene that plays an important role in normal kidney development and inactivation of its function was shown to result in the development of Wilms’ tumors in paediatric patients. Disruption of WT1 function has been implicated in the formation of many different tumor types. AIM: to study how PRAME & WT 1 genes expression patterns influence cancer susceptibility & prognosis. PATIENTS & METHODS: 50 patients with denovo childhood acute lymphoblastic leukemia, as well as 50 age and sex matched apparently healthy volunteers were genotyped for PRAME and WT1 genes expression by reverse transcription polymerase chain reaction (RT-PCR). RESULTS: PRAME gene was expressed in 34 of the patients (68%) and WT1 gene was expressed in 26 of the patients (52%). Expression of both genes was significantly higher compared to controls (P < 0.0001). Analysis of relapse free survival among our patients revealed that patients expressing PRAME gene or WT1 gene had better relapse free survival (p value=0.02 and 0.01 respectively). Relapse free survival increased significantly among patients coexpressing PRAME and WT 1(p value =0

  16. Strides Made in Treating Childhood Cancer: Report

    MedlinePlus

    ... For example, the five-year survival rate for neuroblastoma is currently 78 percent, but it is only 40 percent to 50 percent for high-risk neuroblastoma. The five-year survival rate for some childhood ...

  17. Nilotinib and Imatinib Mesylate After Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia

    ClinicalTrials.gov

    2014-12-09

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. Career goals in the high risk adolescent.

    PubMed

    Fleming, Charlene; Woods, Charles; Barkin, Shari L

    2006-10-01

    Possessing a career goal might serve as a protective factor for an adolescent's healthy development. This could be especially important in adolescents who engage in high risk behaviors. The relationship between high risk adolescents' future career goals and selected predictor variables were examined. Almost half (49%) the students indicated a career goal. Students who reported a job were 5.1-fold more likely to have listed a future career goal. Females, those aged 18 years, and those whose mothers were employed were twice as likely to have a career goal. Considerations for fostering career goals for high risk students are warranted. PMID:16968962

  19. Contribution of Polymorphisms in IKZF1 Gene to Childhood Acute Leukemia: A Meta-Analysis of 33 Case-Control Studies

    PubMed Central

    Dai, Yue-e; Tang, Linjun; Healy, Jasmine; Sinnett, Daniel

    2014-01-01

    Objective Two common polymorphisms in the IKZF1 gene (rs4132601 and rs11978267 variants) have been reported to be associated with childhood acute leukemia (AL) risk, however the results were inconsistent. Here, we conducted a meta-analysis to generate large-scale evidence on whether IKZF1 variants are risk factors for childhood AL. Methods The PubMed, Embase, EBSCO, and Web of Science were searched up to June 2, 2014 for studies on the association of IKZF1 polymorphisms with childhood AL risk. Data were extracted and the odd ratios (ORs) and95% confidence intervals (95% CIs) were calculated by a fixed-effects orrandom-effects model. Subgroup analysis by ethnicity and leukemia subtype, sensitivity and cumulative meta-analyses were performed. Moreover, publication bias was assessed by Begg's and Egger's tests. Results In total, 33 case control studies were finally included in this meta-analysis. For rs4132601 polymorphism, significantly increased AL risk was observed in all genetic models (the association was still significant when the p value was Bonferroni adjusted to 0.025). In the subgroup analysis by tumor type, statistical association was observed in B-cell precursor ALL (BCP-ALL). Additionally, when stratified by ethnicity, significantly increased AL risk was only observed in European subgroup, but not among African or mixed population subgroups. Finally, similar results were found forrs11978267 polymorphism. Conclusion In summary, this meta-analysis provides evidence that rs4132601 and rs11978267 polymorphisms in the IKZF1 gene mightcontribute to the occurrence of BCP-ALL, especially in European populations. Moreover, further studies with large sample size are required to clarify possibleroles of IKZF1 variants in other ethnic groups (e.g., Asians and Africans). PMID:25423013

  20. A unique complex translocation involving six different chromosomes in a case of childhood acute lymphoblastic leukemia with the Philadelphia chromosome and adverse prognosis.

    PubMed

    Achkar, Walid Al; Wafa, Abdulsamad; Mkrtchyan, Hasmik; Moassass, Faten; Liehr, Thomas

    2010-09-01

    Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy. Approximately 84% of cases of ALL are classified as B-precursor ALL, 14% of cases are T-cell and 2% of cases are B-cell (B-)ALL. About one third of B-ALL cases show an abnormal karyotype. Combining data obtained by immunophenotyping, karyotyping and molecular cytogenetic analyses allows for a better understanding of this heterogeneous disease. This study reports an exceptional B-ALL case with a poor prognosis and unique complex chromosomal aberrations not previously observed, i.e., a translocation involving the six chromosomal regions 1q42, 4q21, 4q24, 4q35 (twice), 8q22 and 10p15.3 besides 9q34 and 22q11.2. PMID:22966383

  1. Averting the Legacy of Kidney Disease-Focus on Childhood.

    PubMed

    Ingelfinger, Julie R; Kalantar-Zadeh, Kamyar; Schaefer, Franz; On Behalf Of The World Kidney Day Steering Committee

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. "For in every adult there dwells the child that was, and in every child there lies the adult that will be."-John Connolly, The Book of Lost Things. PMID:27417242

  2. Averting the Legacy of Kidney Disease—Focus on Childhood

    PubMed Central

    Ingelfinger, Julie R.; Kalantar-Zadeh, Kamyar; Schaefer, Franz

    2016-01-01

    World Kidney Day 2016 focuses on kidney disease in childhood and the antecedents of adult kidney disease that can begin in earliest childhood. Chronic kidney disease (CKD) in childhood differs from that in adults, as the largest diagnostic group among children includes congenital anomalies and inherited disorders, with glomerulopathies and kidney disease in the setting of diabetes being relatively uncommon. In addition, many children with acute kidney injury will ultimately develop sequelae that may lead to hypertension and CKD in later childhood or in adult life. Children born early or who are small-for date newborns have relatively increased risk for the development of CKD later in life. Persons with a high-risk birth and early childhood history should be watched closely in order to help detect early signs of kidney disease in time to provide effective prevention or treatment. Successful therapy is feasible for advanced CKD in childhood; there is evidence that children fare better than adults if they receive kidney replacement therapy, including dialysis and transplantation, while only a minority of children may require this ultimate intervention.  Since there are disparities in access to care, effort is needed so that those children with kidney disease, wherever they live, may be treated effectively, irrespective of their geographic or economic circumstances. Our hope is that World Kidney Day will inform the general public, policy makers and caregivers about the needs and possibilities surrounding kidney disease in childhood. “For in every adult there dwells the child that was, and in every child there lies the adult that will be.”—John Connolly, The Book of Lost Things. PMID:27417242

  3. A Heritable Missense Polymorphism in CDKN2A Confers Strong Risk of Childhood Acute Lymphoblastic Leukemia and Is Preferentially Selected during Clonal Evolution.

    PubMed

    Walsh, Kyle M; de Smith, Adam J; Hansen, Helen M; Smirnov, Ivan V; Gonseth, Semira; Endicott, Alyson A; Xiao, Jianqiao; Rice, Terri; Fu, Cecilia H; McCoy, Lucie S; Lachance, Daniel H; Eckel-Passow, Jeanette E; Wiencke, John K; Jenkins, Robert B; Wrensch, Margaret R; Ma, Xiaomei; Metayer, Catherine; Wiemels, Joseph L

    2015-11-15

    Genome-wide association studies (GWAS) have identified SNPs in six genes that are associated with childhood acute lymphoblastic leukemia (ALL). A lead SNP was found to occur on chromosome 9p21.3, a region that is deleted in 30% of childhood ALLs, suggesting the presence of causal polymorphisms linked to ALL risk. We used SNP genotyping and imputation-based fine-mapping of a multiethnic ALL case-control population (Ncases = 1,464, Ncontrols = 3,279) to identify variants of large effect within 9p21.3. We identified a CDKN2A missense variant (rs3731249) with 2% allele frequency in controls that confers three-fold increased risk of ALL in children of European ancestry (OR, 2.99; P = 1.51 × 10(-9)) and Hispanic children (OR, 2.77; P = 3.78 × 10(-4)). Moreover, of 17 patients whose tumors displayed allelic imbalance at CDKN2A, 14 preferentially retained the risk allele and lost the protective allele (PBinomial = 0.006), suggesting that the risk allele provides a selective advantage during tumor growth. Notably, the CDKN2A variant was not significantly associated with melanoma, glioblastoma, or pancreatic cancer risk, implying that this polymorphism specifically confers ALL risk but not general cancer risk. Taken together, our findings demonstrate that coding polymorphisms of large effect can underlie GWAS "hits" and that inherited polymorphisms may undergo directional selection during clonal expansion of tumors. PMID:26527286

  4. DNA Repair Gene Polymorphisms and Their Relation With DNA Damage, DNA Repair, and Total Antioxidant Capacity in Childhood Acute Lymphoblastic Leukemia Survivors.

    PubMed

    Dincer, Yildiz; Yüksel, Selin; Batar, Bahadir; Güven, Mehmet; Onaran, Ilhan; Celkan, Tiraje

    2015-07-01

    Oxidative stress and defective DNA repair are major contributory factors in the initiation and progression of carcinogenesis. Chemotherapy and radiotherapy cause oxidative DNA damage, consume antioxidant capacity, and impair DNA repair activity. These effects of chemotherapy and radiotherapy may be contributory factors in the development of secondary malignancy in cancer survivors. Basal, H2O2-induced, and postrepair DNA damage; urinary 8-hydroxydeoxyguanosine level as a marker of oxidatively damaged DNA; and serum total antioxidant capacity were measured; XPD Lys751Gln, XRCC1 Arg399Gln, and XRCC1 Arg194Trp polymorphisms were analyzed in childhood acute lymphoblastic leukemia (ALL) survivors. Basal and H2O2-induced DNA damage were found to be higher in the ALL survivor group versus the control group, however, there was no significant difference between the other parameters. No association was found between the examined parameters and polymorphisms of XPD 751 and XRCC1 399 and both the groups. XRCC1 194Trp allele was found to be associated with a low level of postrepair DNA damage in the ALL survivors. In conclusion, basal DNA damage and susceptibility to oxidation are high in childhood ALL survivors. This situation which may easily lead to occurrence of a secondary cancer does not seem to be a result of deficient DNA repair. PMID:24577548

  5. Association of ABCC2 −24C>T Polymorphism with High-Dose Methotrexate Plasma Concentrations and Toxicities in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Liu, Yan; Yin, You; Sheng, Qi; Lu, Xiaotong; Wang, Fang; Lin, Zhiyan; Tian, Huaiping; Xu, Ajing; Zhang, Jian

    2014-01-01

    Methotrexate (MTX) is a key agent for the treatment of childhood acute lymphoblastic leukemia (ALL). Increased MTX plasma concentrations are associated with a higher risk of adverse drug effects. ATP-binding cassette subfamily C member 2 (ABCC2) is important for excretion of MTX and its toxic metabolite. The ABCC2 −24C>T polymorphism (rs717620) reportedly contributes to variability of MTX kinetics. In the present study, we assessed the association between the ABCC2 −24C>T polymorphism and methotrexate (MTX) toxicities in childhood ALL patients treated with high-dose MTX. A total of 112 Han Chinese ALL patients were treated with high-dose MTX according to the ALL-Berlin-Frankfurt-Muenster 2000 protocol. Our results showed that presence of the −24T allele in ABCC2 gene led to significantly higher MTX plasma concentrations at 48 hours after the start of infusion, which would strengthen over repeated MTX infusion. The −24T allele in ABCC2 gene was significantly associated with higher risks of high-grade hematologic (leucopenia, anemia, and thrombocytopenia) and non-hematologic (gastrointestinal and mucosal damage/oral mucositis) MTX toxicities. This study provides the first evidence that the −24T allele in ABCC2 gene is associated with the severity of MTX toxicities, which add fresh insights into clinical application of high-dose MTX and individualization of MTX treatment. PMID:24404132

  6. Loci on 7p12.2, 10q21.2 and 14q11.2 are associated with risk of childhood acute lymphoblastic leukemia

    PubMed Central

    Papaemmanuil, Elli; Hosking, Fay J; Vijayakrishnan, Jayaram; Price, Amy; Olver, Bianca; Sheridan, Eammon; Kinsey, Sally E; Lightfoot, Tracy; Roman, Eve; Irving, Julie A E; Allan, James M.; Tomlinson, Ian P; Taylor, Malcolm; Greaves, Mel; Houlston, Richard S

    2016-01-01

    To identify risk variants for childhood acute lymphoblastic leukemia (ALL) we conducted a genome-wide association study of 2 case-control series, analyzing the genotypes of 291,423 tagging SNP genotypes in a total of 907 ALL cases and 2,398 controls. We identified risk loci for ALL at 7p12.2 (IKZF1, rs4132601; OR = 1.69, P = 1.20 x 10-19), 10q21.2 (ARIDB5, rs7089424; OR = 1.65, P = 6.69 x 10-19) and 14q11.2 (CEBPE, rs2239633; OR = 1.34, P = 2.88 x 10-7). The 10q21.2 (ARIDB5) risk association appears to be selective for the subset of B-cell precursor ALL with hyperdiploidy. These data show that common low-penetrance susceptibility alleles contribute to the risk of developing childhood ALL and provide novel insight into disease causation of this hematological cancer; notably all 3 risk variants map to genes involved in transcriptional regulation and differentiation of B-cell progenitors. PMID:19684604

  7. The high-risk myocardial infarction database initiative.

    PubMed

    Dickstein, Kenneth; Bebchuk, Judith; Wittes, Janet

    2012-01-01

    Coronary artery disease and myocardial infarction represent a major cause of morbidity and mortality. Four randomized, controlled, double-blind clinical trials--VALIANT, EPHESUS, OPTIMAAL, and CAPRICORN evaluated pharmacologic intervention in a total of 28,771 high-risk patients following acute MI complicated with signs of heart failure or evidence of left ventricular dysfunction. The demographic profiles of the 4 study cohorts were similar. The High-Risk MI Database Initiative constructed a common database by merging the data captured by these 4 large trials. The merged data set did not contain the randomized study treatment, so no comparisons could be made between the agents investigated. A total of more than 17,600 subjects experienced a cardiovascular end point. Approximately 5100 deaths occurred, and more than 15,700 subjects experienced a hospitalization. The primary objectives of this initiative were to use this large database to define more precisely the prognostic profile of this high-risk population, to perform rigorous, adequately-sized, subset analyses, to provide epidemiologic information and event rate estimation based on baseline demographics. The methodological challenges and limitations of such an analyses are discussed. It is proposed that some thoughtful foresight and planning could enable us to use the large number of clinical events that accrue during randomized clinical trials to address questions of scientific and clinical interest. PMID:22226005

  8. Childhood medulloblastoma.

    PubMed

    Massimino, Maura; Biassoni, Veronica; Gandola, Lorenza; Garrè, Maria Luisa; Gatta, Gemma; Giangaspero, Felice; Poggi, Geraldina; Rutkowski, Stefan

    2016-09-01

    Medulloblastoma accounts for 15-20% of childhood nervous system tumours. The risk of dying was reduced by 30% in the last twenty years. Patients are divided in risk strata according to post-surgical disease, dissemination, histology and some molecular features such as WNT subgroup and MYC status. Sixty to 70% of patients older than 3 years are assigned to the average-risk group. High-risk patients include those with disseminated and/or residual disease, large cell and/or anaplastic histotypes, MYC genes amplification. Current and currently planned clinical trials will: (1) evaluate the feasibility of reducing both the dose of craniospinal irradiation and the volume of the posterior fossa radiotherapy (RT) for those patients at low biologic risk, commonly identified as those having a medulloblastoma of the WNT subgroup; (2) determine whether intensification of chemotherapy (CT) or irradiation can improve outcome in patients with high-risk disease; (3) find target therapies allowing tailored therapies especially for relapsing patients and those with higher biological risk. PMID:27375228

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

    ClinicalTrials.gov

    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

  10. The efficacy and safety of a new reduced-toxicity conditioning with 4 days of once-daily 100 mg/m(2) intravenous busulfan associated with fludarabine and antithymocyte globulins prior to allogeneic stem cell transplantation in patients with high-risk myelodysplastic syndrome or acute leukemia.

    PubMed

    Wanquet, Anne; Crocchiolo, Roberto; Furst, Sabine; Granata, Angela; Faucher, Catherine; Devillier, Raynier; Harbi, Samia; Lemarie, Claude; Calmels, Boris; Vey, Norbert; Weiller, Pierre Jean; Chabannon, Christian; Castagna, Luca; Blaise, Didier; El-Cheikh, Jean

    2016-10-01

    The optimal intensity of myeloablation associated with a reduced-toxicity conditioning (RTC) regimen in order to decrease the relapse rate without increasing non-relapse mortality (NRM), is not well established yet. This retrospective analysis was done on 30 patients with hematological malignancies. The aim was to assess the safety of a RTC regimen based on the busulfan at a dose of 100 mg/m(2)/d intravenously for 4 d, fludarabine at a dose of 30 mg/m(2)/d for 5 d, and anti-thymoglobulins at a dose of 2.5 mg/kg/d for 2 d. The cumulative incidences of grade 2-4 acute graft-versus-host disease (GVHD) and all grades chronic GVHD were 37% and 42%, respectively. Median 1-year overall survival and disease-free survival were 66% and 50%, respectively. At 1 year, the cumulative incidence of relapse/disease progression was 33%. NRM was 3% and 17% at day 100 and 1 year, respectively. This RTC conditioning regimen can lead to a long-term disease control. Moreover, it appears to be safe with a low NRM rate among high-risk patients. PMID:26885686

  11. 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

    ClinicalTrials.gov

    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

  12. What is High Risk Surgery? Development of a List of High Risk Operations for Patients Age 65 and Older

    PubMed Central

    Schwarze, Margaret L.; Barnato, Amber E.; Rathouz, Paul J.; Zhao, Qianqian; Neuman, Heather B.; Winslow, Emily R.; Kennedy, Gregory D.; Hu, Yue-Yung; Dodgion, Christopher M.; Kwok, Alvin C.; Greenberg, Caprice C.

    2015-01-01

    Importance No consensus exists regarding the definition of “high risk” surgery in older adults. An inclusive and precise definition of high risk surgery may be useful for surgeons, patients, researchers and hospitals. Objectives To develop a list of “high risk” operations. Design 1) Retrospective cohort study; and 2) Modified Delphi procedure. Setting All Pennsylvania acute care hospitals (Pennsylvania Health Care Cost Containment Council [PHC4], 2001–2007) and a nationally-representative sample of U.S. acute care hospitals (Nationwide Inpatient Sample [NIS], HCUP, AHRQ 2001–2006). Patients Admissions 65 and older to PHC4 hospitals and admissions 18 and older to NIS hospitals. Methods We identified ICD-9 CM procedure codes associated with >1% inpatient mortality in PHC4. We used a modified Delphi technique with 5 board certified surgeons to further refine this list by excluding non-operative procedures and operations that were unlikely to be the proximate cause of mortality and were instead a marker of critical illness (e.g., tracheostomy). We then cross-validated this list of ICD-9CM codes in the NIS. Main Outcomes Measures 1) Delphi consensus of at least 4/5 panelists; 2) proportion agreement in the NIS. Results Among 4,739,522 admissions 65 and older in PHC4, 2,569,589 involved a procedure, encompassing 2,853 unique procedures. Of 1,130 procedures associated with a crude inpatient mortality of at least 1%, 264 achieved consensus as high risk operations by Delphi. The observed inpatient mortality in the NIS was ≥ 1% for 227/264 (86%) of the procedures in patients age 65 and older. The pooled inpatient mortality rate for these identified high risk procedures performed on patients age ≥65 was double the inpatient mortality for correspondingly identified high risk operations for patients less than 65 (6% vs. 3%). Conclusions We developed a list of procedure codes that can be used to identify “high risk” surgical procedures in claims data. This

  13. Effects of Methylphenidate on Attention Deficits in Childhood Cancer Survivors

    ClinicalTrials.gov

    2015-03-16

    ALL, Childhood; Leukemia, Lymphoblastic; Leukemia, Lymphoblastic, Acute; Leukemia, Lymphoblastic, Acute, L1; Leukemia, Lymphoblastic, Acute, L2; Leukemia, Lymphoblastic, Acute, Philadelphia-Positive; Leukemia, Lymphocytic, Acute; Leukemia, Lymphocytic, Acute, L1; Leukemia, Lymphocytic, Acute, L2; Lymphoblastic Leukemia; Lymphoblastic Leukemia, Acute; Lymphoblastic Leukemia, Acute, Childhood; Lymphoblastic Leukemia, Acute, L1; Lymphoblastic Leukemia, Acute, L2; Lymphoblastic Lymphoma; Lymphocytic Leukemia, Acute; Lymphocytic Leukemia, L1; Lymphocytic Leukemia, L2; Brain Tumors; Cancer of the Brain; Cancer of Brain; Malignant Primary Brain Tumors; Brain Neoplasms, Malignant

  14. Total Marrow and Lymphoid Irradiation and Chemotherapy Before Donor Transplant in Treating Patients With Myelodysplastic Syndrome or Acute Leukemia

    ClinicalTrials.gov

    2016-08-10

    Adult Acute Lymphoblastic Leukemia in Complete Remission; Acute Myeloid Leukemia in Remission; Previously Treated Myelodysplastic Syndrome; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Childhood Acute Lymphoblastic Leukemia in Complete Remission

  15. Parental predictors of pediatric panic disorder/agoraphobia: a controlled study in high-risk offspring.

    PubMed

    Biederman, Joseph; Petty, Carter; Faraone, Stephen V; Hirshfeld-Becker, Dina R; Henin, Aude; Dougherty, Meghan; Lebel, Teresa J; Pollack, Mark; Rosenbaum, Jerrold F

    2005-01-01

    Our objective was to evaluate parental risk factors for pediatric-onset panic disorder/agoraphobia (PD/AG) in offspring at high risk for PD/AG. Comparisons were made between parents with PD who had a child with PD or AG (N = 27) and parents with PD without children with PD or AG (N = 79). Comparisons were also made between the spouses of these parents with PD. Separation anxiety disorder, social phobia, obsessive-compulsive disorder, and bipolar disorder in the parents with PD and their spouses accounted for the risk for childhood onset PD/AG in the offspring. This risk was particularly high if both parents were affected with social phobia. These findings suggest that psychiatric comorbidity with other anxiety disorders and with bipolar disorder in parents with PD and their spouses confer a particularly high risk in their offspring to develop PD/AG in childhood. PMID:16193490

  16. Comparative study of quality of life of adult survivors of childhood acute lymphocytic leukemia and Wilms’ tumor

    PubMed Central

    de Souza, Clélia Marta Casellato; Cristofani, Lilian Maria; Cornacchioni, Ana Lucia Beltrati; Odone, Vicente; Kuczynski, Evelyn

    2015-01-01

    Abstract Objective To analyze and compare the health-related quality of life of adult survivors of acute lymphocytic leukemia and Wilms’ tumor amongst themselves and in relation to healthy participants. Methods Ninety participants aged above 18 years were selected and divided into three groups, each comprising 30 individuals. The Control Group was composed of physically healthy subjects, with no cancer history; and there were two experimental groups: those diagnosed as acute lymphocytic leukemia, and those as Wilms’ Tumor. Quality of life was assessed over the telephone, using the Medical Outcomes Study 36-Item Short Form Health Survey. Results Male survivors presented with better results as compared to female survivors and controls in the Vitality domain, for acute lymphocytic leukemia (p=0.042) and Wilms’ tumor (p=0.013). For acute lymphocytic leukemia survivors, in Social aspects (p=0.031), Mental health (p=0.041), and Emotional aspects (p=0.040), the latter also for survivors of Wilms’ tumor (p=0.040). The best results related to the Functional capacity domain were recorded for the experimental group that had a late diagnosis of acute lymphocytic leukemia. There were significant differences between groups except for the Social and Emotional domains for self-perceived health, with positive responses that characterized their health as good, very good, and excellent. Conclusion Survivors of acute lymphocytic leukemia showed no evidence of relevant impairment of health-related quality of life. The Medical Outcomes Study 36-Item Short Form Health Survey (via telephone) can be a resource to access and evaluate survivors. PMID:26537509

  17. Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

    ClinicalTrials.gov

    2015-10-20

    Childhood B Acute Lymphoblastic Leukemia; Childhood Burkitt Leukemia; Childhood Diffuse Large Cell Lymphoma; Mediastinal (Thymic) Large B-Cell Lymphoma; Stage III Childhood Large Cell Lymphoma; Stage IV Childhood Large Cell Lymphoma

  18. Results of the Japan Association of Childhood Leukemia Study (JACLS) NHL-98 protocol for the treatment of B-cell non-Hodgkin lymphoma and mature B-cell acute lymphoblastic leukemia in childhood.

    PubMed

    Fujita, Naoto; Kobayashi, Ryoji; Takimoto, Tetsuya; Nakagawa, Atsuko; Ueda, Kazuhiro; Horibe, Keizo

    2011-02-01

    The Japan Association of Childhood Leukemia Study (JACLS) NHL-98 is a multicenter study designed to evaluate treatment outcomes in Japanese children with B-cell non-Hodgkin lymphoma (B-NHL) and mature B-cell acute lymphoblastic leukemia (B-ALL). The study was supported by a central pathology review system and used a new, standardized protocol with short, intensive treatment regimens. From April 1998 to May 2002, 69 patients with B-NHL and B-ALL up to 16 years of age were enrolled in the NHL-98 study. Treatment was stratified by risk group; patients with limited disease were in groups A and B, and those with extensive disease were in groups C and D. Patients in groups B, C, and D received consolidation phases with high-dose methotrexate (HDMTX) followed by other multi-agent chemotherapy. Patients in group A did not receive either MTX or etoposide. Only patients in group D received etoposide. The event-free survival rates were 100% in groups A and B, 75.1% in group C, and 66.2% in group D. Overall, patients with limited disease had favorable results. For patients with extensive disease, additional treatment options such as increased doses of anticancer drugs warrant further investigation. PMID:21261497

  19. Metabolic syndrome in adults who received hematopoietic stem cell transplantation for acute childhood leukemia: an LEA study.

    PubMed

    Oudin, C; Auquier, P; Bertrand, Y; Contet, A; Kanold, J; Sirvent, N; Thouvenin, S; Tabone, M-D; Lutz, P; Ducassou, S; Plantaz, D; Dalle, J-H; Gandemer, V; Beliard, S; Berbis, J; Vercasson, C; Barlogis, V; Baruchel, A; Leverger, G; Michel, G

    2015-11-01

    We evaluated prospectively the incidence and risk factors of the metabolic syndrome (MS) and its components in 170 adult patients (mean age at evaluation: 24.8±5.4 years) who received an hematopoietic stem cell transplantation for childhood ALL, n=119, or AML, n=51. TBI was carried out in 124 cases; a busulfan-based conditioning was done in 30 patients. Twenty-nine patients developed a MS (17.1%, 95% confidence intervals: 11.7-23.6). The cumulative incidence was 13.4% at 25 years of age and 35.5% at 35 years of age. A higher body mass index (BMI) before transplantation and a growth hormone deficiency were associated with increased MS risk (P=0.002 and 0.01, respectively). MS risk was similar for patients who received TBI or busulfan-based conditioning. The TBI use increased the hyperglycemia risk (odds ratio (OR): 4.7, P=0.02). Women were at the risk of developing increased waist circumference (OR: 7.18, P=0.003) and low levels of high-density lipoprotein cholesterol (OR: 2.72, P=0.007). The steroid dose was not a risk factor. The MS occurs frequently among transplanted survivors of childhood leukemia. Its incidence increases with age. Both intrinsic (BMI, gender) and extrinsic factors (TBI, alkylating agents) contribute to its etiopathogenesis. PMID:26191949

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

    PubMed

    Baraz, Rana; Cisterne, Adam; Saunders, Philip O; Hewson, John; Thien, Marilyn; Weiss, Jocelyn; Basnett, Jordan; Bradstock, Kenneth F; Bendall, Linda J

    2014-01-01

    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. PMID:25014496

  1. mTOR Inhibition by Everolimus in Childhood Acute Lymphoblastic Leukemia Induces Caspase-Independent Cell Death

    PubMed Central

    Baraz, Rana; Cisterne, Adam; Saunders, Philip O.; Hewson, John; Thien, Marilyn; Weiss, Jocelyn; Basnett, Jordan; Bradstock, Kenneth F.; Bendall, Linda J.

    2014-01-01

    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. PMID:25014496

  2. Perforated Duodenal Ulcer in High Risk Patients: Is Percutaneous Drainage Justified?

    PubMed Central

    Saber, Aly; Gad, Mohammad A; Ellabban, Gouda M

    2012-01-01

    Background: Conservative treatment was recommended as the treatment of choice in perforated acute peptic ulcer. Here, we adjunct percutaneous peritoneal drainage with nonoperative conservative treatment in high risk elderly patients with perforated duodenal ulcer. Aim: The work was to study the efficacy of percutaneous peritoneal drainage under local anesthesia supported by conservative measures in high risk elderly patients, according to the American Society of Anesthesiologists grading, with perforated duodenal ulcer. Patients and Methods: Twenty four high risk patients with age >65 years having associated medical illness with evidence of perforated duodenal ulcer. Results: The overall morbidity and mortality were comparable with those treated by conservative measures alone. Conclusion: In high risk patients with perforated peptic ulcer and established peritonitis, percutaneous peritoneal drainage under local anesthesia seems to be effective with least operative trauma and mortality rate. PMID:22393546

  3. Neurological correlates of high-risk behavior: a case study of Alphonse Capone.

    PubMed

    Brewer-Smyth, Kathleen

    2006-12-01

    Neurological impairment, traumatic brain injury, and childhood trauma and abuse are all associated with violent and high-risk behaviors among prison inmates. This case study examines the medical history of a notorious criminal--Alphonse Capone. Records suggest an association between Capone's declining neurological condition and an increase in high-risk behaviors. Prison, criminal, media, and medical records from the National Archives and other sources were studied to identify relationships to current research data describing neurological abnormalities of prison inmates. Healthcare providers can play a critical role in identifying at-risk youths, potentially reducing the incidence of high-risk behaviors associated with both crime and infectious disease transmission. PMID:17233515

  4. Acute pyelonephritis in children.

    PubMed

    Morello, William; La Scola, Claudio; Alberici, Irene; Montini, Giovanni

    2016-08-01

    Acute pyelonephritis is one of the most serious bacterial illnesses during childhood. Escherichia coli is responsible in most cases, however other organisms including Klebsiella, Enterococcus, Enterobacter, Proteus, and Pseudomonas species are being more frequently isolated. In infants, who are at major risk of complications such as sepsis and meningitis, symptoms are ambiguous and fever is not always useful in identifying those at high risk. A diagnosis of acute pyelonephritis is initially made on the basis of urinalysis; dipstick tests for nitrites and/or leukocyte esterase are the most accurate indicators of infection. Collecting a viable urine sample for urine culture using clean voided methods is feasible, even in young children. No gold standard antibiotic treatment exists. In children appearing well, oral therapy and outpatient care is possible. New guidelines suggest less aggressive imaging strategies after a first infection, reducing radiation exposure and costs. The efficacy of antibiotic prophylaxis in preventing recurrence is still a matter of debate and the risk of antibiotic resistance is a warning against its widespread use. Well-performed randomized controlled trials are required in order to better define both the imaging strategies and medical options aimed at preserving long-term renal function. PMID:26238274

  5. Teaching Art to High Risk Groups.

    ERIC Educational Resources Information Center

    Rossol, Monona

    The role of art therapy is considered in working with such high risk groups as the institutionalized, mentally retarded, elderly, visually impaired, physically handicapped, asthmatic, hyper- and hypo-active children, hearing impaired, and patients on mind altering drugs. The special risks of infectious diseases (such as serum hepatitis), and…

  6. The High Risk Freshman Chemist Revisited

    ERIC Educational Resources Information Center

    Pickering, Miles

    1977-01-01

    Reports on the long term comparison between a group of "high risk" college freshmen who were given a supplemental chemistry course and another group who did not have the course. The supplemental course was found to produce only a short term rise in students' grades. (MR)

  7. Determination of high-risk cargo

    NASA Astrophysics Data System (ADS)

    Morris, Leo A.; Smith, Douglas E.; Khan, Siraj M.

    1994-10-01

    The approach and methodology used in the determination of the type of cargo containing concealments of commercial quantities of narcotics such as cocaine and heroin is described. This high-risk cargo enters the United States through border crossings at land, seaports and airports. The volume and variety of cargos make it a complex and challenging task for the U.S. Customs Service.

  8. Student Assistance Programs and High Risk Youth.

    ERIC Educational Resources Information Center

    Casale, Jenni

    This manual discusses a method for developing a comprehensive drug abuse prevention and intervention program for students in special education. The first section contains introductory material regarding high risk students in general and implications for special education. The second section outlines material on specific types of high-risk…

  9. Micronutrient requirements of high-risk infants

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Micronutrient requirements are well-established for healthy full-term infants. However, few such recommendations exist for high-risk infants, including full-term infants with a variety of medical disorders or very preterm infants. Key micronutrients considered in this review are calcium, phosphorus,...

  10. Utility of Global Longitudinal Strain by Echocardiography to Detect Left Ventricular Dysfunction in Long-Term Adult Survivors of Childhood Lymphoma and Acute Lymphoblastic Leukemia.

    PubMed

    Christiansen, Jon R; Massey, Richard; Dalen, Håvard; Kanellopoulos, Adriani; Hamre, Hanne; Fosså, Sophie D; Ruud, Ellen; Kiserud, Cecilie E; Aakhus, Svend

    2016-08-01

    Measuring left ventricular (LV) global longitudinal strain (GLS) is recommended in screening of long-term cancer survivors for cardiotoxicity. However, there are limited data on GLS in this setting, in particular in survivors with apparently normal LV function without risk factors of impaired GLS. In the present study, we measured GLS in 191 adult survivors of childhood lymphoma or acute lymphoblastic leukemia, with normal LV ejection fraction and fractional shortening (FS) and without known hypertension, diabetes mellitus, myocardial infarction, or stroke. We compared GLS in the survivors with 180 controls. Mean GLS was -19.0 ± 2.2% in the survivor group and -21.4 ± 2.0% in the controls (p <0.001). Impaired GLS, defined as mean - 1.96 SDs in the control group, occurred in 53 of 191 survivors (28%). We included survivors with impaired LV ejection fraction and/or FS or traditional risk factors (n = 231 in all) in multiple regression analyses to explore associations with previous cancer treatment. Survivors treated with mediastinal radiotherapy had an odds ratio of impaired GLS of 5.2 (95% confidence interval 2.2 to 12) compared with other survivors. Survivors treated with cumulative anthracycline doses >300 mg/m(2) had an odds ratio of 4.8 (95% confidence interval 1.7 to 14) of impaired GLS. In conclusion, this study demonstrates a high proportion of LV dysfunction assessed by GLS in apparently healthy adult survivors of childhood cancer. Impaired GLS was associated with previous exposure to mediastinal radiotherapy and high doses of anthracyclines. The prognostic role of measuring GLS in this specific patient population should be examined in prospective studies. PMID:27296561

  11. A Phase II Study Of The Farnesyltransferase Inhibitor ZANESTRA (R115777, NSC #702818, IND #58,359) In Complete Remission Following Induction And/Or Consolidation Chemotherapy In Adults With Poor-Risk Acute Myelogenous Leukemia (AML) And High-Risk Myelodysplasia (MDS)

    ClinicalTrials.gov

    2013-01-08

    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); de Novo Myelodysplastic Syndromes; Secondary Myelodysplastic Syndromes

  12. Clofarabine in combination with a standard remission induction regimen (cytosine arabinoside and idarubicin) in patients with previously untreated intermediate and bad-risk acute myelogenous leukemia (AML) or high-risk myelodysplastic syndrome (HR-MDS): phase I results of an ongoing phase I/II study of the leukemia groups of EORTC and GIMEMA (EORTC GIMEMA 06061/AML-14A trial).

    PubMed

    Willemze, R; Suciu, S; Muus, P; Halkes, C J M; Meloni, G; Meert, L; Karrasch, M; Rapion, J; Vignetti, M; Amadori, S; de Witte, T; Marie, J P

    2014-06-01

    This study aims to determine the maximum tolerated dose (MTD) of clofarabine combined with the EORTC-GIMEMA 3 + 10 induction regimen (idarubicin + cytosine arabinoside) in adults with untreated acute myelogenous leukemia or high-risk myelodysplastic syndrome. In this phase I trial, 25 patients (median age 56 years) received 5 days of clofarabine as 1-h infusion (arm A) or push injection (arm B) at the dose level of 5 × 10 or 5 × 15 mg/m(2)/day in an algorithmic dose escalation 3 + 3 design. A consolidation course (intermediate dose cytosine arabinoside, idarubicin) was planned for patients in complete remission (CR). Primary endpoint was safety and tolerance as measured by dose limiting toxicity (DLT); secondary endpoints were response rate, other grade III/IV toxicities, and hematological recovery after induction and consolidation. Five DLTs were observed (in arm A: one DLT at 10 mg/m(2)/day, three at 15 mg/m(2)/day; in arm B: one DLT at 15 mg/m(2)/day). Three patients receiving 15 mg/m(2)/day were withdrawn due to adverse events not classified as DLT. Prolonged hypoplasia was observed in five patients. CR + complete remission with incomplete recovery were achieved in 21 patients (11/12 (92 %) receiving clofarabine 10 mg/m(2)/day; 10/13 (77 %) receiving clofarabine 15 mg/m(2)/day). Clofarabine, 5 × 10 mg/m(2)/day, resulted in one DLT and no early treatment withdrawals. MTD of clofarabine combined with cytosine arabinoside and idarubicin is 5 × 10 mg/m(2)/day. PMID:24682421

  13. Developmental Outcome of Childhood Leukemia.

    ERIC Educational Resources Information Center

    Coniglio, Susan J.; Blackman, James A.

    1995-01-01

    Literature on developmental and psychosocial outcomes of childhood leukemia is reviewed, focusing on preschool-age children. Studies are categorized in terms of outcome measures: intelligence/achievement, neuropsychological, memory/attention, and psychosocial tests. Evidence suggests that preschool children with leukemia are at high risk for…

  14. Indoleamine 2,3-dioxygenase 1 (IDO1) activity in leukemia blasts correlates with poor outcome in childhood acute myeloid leukemia.

    PubMed

    Folgiero, Valentina; Goffredo, Bianca M; Filippini, Perla; Masetti, Riccardo; Bonanno, Giuseppina; Caruso, Roberta; Bertaina, Valentina; Mastronuzzi, Angela; Gaspari, Stefania; Zecca, Marco; Torelli, Giovanni F; Testi, Anna M; Pession, Andrea; Locatelli, Franco; Rutella, Sergio

    2014-04-30

    Microenvironmental factors contribute to the immune dysfunction characterizing acute myeloid leukemia (AML). Indoleamine 2,3-dioxygenase 1 (IDO1) is an interferon (IFN)-γ-inducible enzyme that degrades tryptophan into kynurenine, which, in turn, inhibits effector T cells and promotes regulatory T-cell (Treg) differentiation. It is presently unknown whether childhood AML cells express IDO1 and whether IDO1 activity correlates with patient outcome. We investigated IDO1 expression and function in 37 children with newly diagnosed AML other than acute promyelocytic leukemia. Blast cells were cultured with exogenous IFN-γ for 24 hours, followed by the measurement of kynurenine production and tryptophan consumption. No constitutive expression of IDO1 protein was detected in blast cells from the 37 AML samples herein tested. Conversely, 19 out of 37 (51%) AML samples up-regulated functional IDO1 protein in response to IFN-γ. The inability to express IDO1 by the remaining 18 AML samples was not apparently due to a defective IFN-γ signaling circuitry, as suggested by the measurement of signal transducer and activator of transcription 3 (STAT3) phosphorylation. Co-immunoprecipitation assays indicated the occurrence of physical interactions between STAT3 and IDO1 in AML blasts. In line with this finding, STAT3 inhibitors abrogated IDO1 function in AML blasts. Interestingly, levels of IFN-γ were significantly higher in the bone marrow fluid of IDO-expressing compared with IDO-nonexpressing AMLs. In mixed tumor lymphocyte cultures (MTLC), IDO-expressing AML blasts blunted the ability of allogeneic naïve T cells to produce IFN-γ and promoted Treg differentiation. From a clinical perspective, the 8-year event-free survival was significantly worse in IDO-expressing children (16.4%, SE 9.8) as compared with IDO-nonexpressing ones (48.0%, SE 12.1; p=0.035). These data indicate that IDO1 expression by leukemia blasts negatively affects the prognosis of childhood AML. Moreover

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

    ClinicalTrials.gov

    2016-08-23

    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

  16. Mammalian Target of Rapamycin (mTOR) Activity Dependent Phospho-Protein Expression in Childhood Acute Lymphoblastic Leukemia (ALL)

    PubMed Central

    Márk, Ágnes; Hajdu, Melinda; Kenessey, István; Sticz, Tamás; Nagy, Eszter; Barna, Gábor; Váradi, Zsófia; Kovács, Gábor; Kopper, László; Csóka, Monika

    2013-01-01

    Modern treatment strategies have improved the prognosis of childhood ALL; however, treatment still fails in 25–30% of patients. Further improvement of treatment may depend on the development of targeted therapies. mTOR kinase, a central mediator of several signaling pathways, has recently attracted remarkable attention as a potential target in pediatric ALL. However, limited data exists about the activity of mTOR. In the present study, the amount of mTOR activity dependent phospho-proteins was characterized by ELISA in human leukemia cell lines and in lymphoblasts from childhood ALL patients (n = 49). Expression was measured before and during chemotherapy and at relapses. Leukemia cell lines exhibited increased mTOR activity, indicated by phospho-S6 ribosomal protein (p-S6) and phosphorylated eukaryotic initiation factor 4E binding protein (p-4EBP1). Elevated p-4EBP1 protein levels were detected in ALL samples at diagnosis; efficacy of chemotherapy was followed by the decrease of mTOR activity dependent protein phosphorylation. Optical density (OD) for p-4EBP1 (ELISA) was significantly higher in patients with poor prognosis at diagnosis, and in the samples of relapsed patients. Our results suggest that measuring mTOR activity related phospho-proteins such as p-4EBP1 by ELISA may help to identify patients with poor prognosis before treatment, and to detect early relapses. Determining mTOR activity in leukemic cells may also be a useful tool for selecting patients who may benefit from future mTOR inhibitor treatments. PMID:23573198

  17. Prognostic factors of childhood and adolescent acute myeloid leukemia (AML) survival: evidence from four decades of US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li; Caywood, Emi H

    2015-10-01

    Growing insight into prognosis of pediatric acute myeloid leukemia (AML) survival has led to improved outcome over time and could be further enhanced through investigation using a large number of patients. To characterize the extent of the association of pediatric AML survival with its identified prognostic factors, we analyzed the United States population-based Surveillance Epidemiology and End Results (SEER) large dataset of 3442 pediatric AML patients diagnosed and followed between 1973 and 2011 using a Cox proportional hazards model stratified by year of diagnosis. Patients diagnosed between 10 and 19 years of age were at a higher risk of death compared to those diagnosed before age 10 (adjusted hazard ratio (aHR): 1.30, 95% confidence interval (CI): 1.17-1.44). African Americans (1.27, 1.09-1.48) and Hispanics (1.15, 1.00-1.32) had an elevated risk of mortality than Caucasians. Compared to the subtype acute promyelocytic leukemia, AML with minimal differentiation (2.44, 1.78-3.35); acute erythroid leukemia (2.34, 1.60-3.40); AML without maturation (1.87, 1.35-2.59); and most other AML subtypes had a higher risk of mortality, whereas AML with inv(16) had a substantially lower risk. Age at diagnosis, race-ethnicity, AML subtype, county level poverty and geographic region appeared as significant prognostic factors of pediatric AML survival in the US. Contrary to previous findings, the subtypes of AML with t(9;11)(p22;q23)MLLT3-MLL, AML without maturation and acute myelomonocytic leukemia emerged to be indicative of poor outcome. PMID:26159683

  18. Single dose rasburicase in the management of tumor lysis syndrome in childhood acute lymphoblastic leukemia: A case series

    PubMed Central

    Latha, S. M.; Krishnaprasadh, D.; Murugapriya, P.; Scott, J. X.

    2015-01-01

    Tumor lysis syndrome (TLS) occurs in malignancies with high proliferative potential and tumor burden, such as lymphomas and leukemias. TLS syndrome is an oncologic emergency, requiring prompt intervention. The metabolic derangements cause acute kidney failure and may lead to cardiac arrhythmias, seizures, and death. With the advent of rasburicase, a recombinant urate oxidase, there has been a decline in the TLS-mediated renal failure and the need for dialysis. The recommended regimen and doses pose a heavy financial burden for patients in developing countries like India. With data and studies proving a similar efficacy for the reduced dose and lesser number of rasburicase, we report here a case series of seven children with acute leukemias, whose TLS was managed by a single dose of rasburicase. A retrospective analysis of case records of seven children with acute lymphoblastic leukemia and TLS, admitted to our Pediatric Oncology Unit of our Hospital between the period 2011 and 2013, was done. All our patients responded to a single dose, indicating that in appropriately monitored patients, single dose followed by as-needed dosing can be cost-saving. PMID:25838646

  19. How I treat high-risk myeloma.

    PubMed

    Lonial, Sagar; Boise, Lawrence H; Kaufman, Jonathan

    2015-09-24

    The treatment of patients with myeloma has dramatically changed over the past decade due in part to the development of new agents and myeloma-specific targets. Despite these advancements, a group for whom the long-term benefit remains less clear are patients with genetically or clinically defined high-risk myeloma. In order to successfully treat these patients, it is important to first identify these patients, treat them with aggressive combination therapy, and employ the use of aggressive long-term maintenance therapy. Future directions include the use of new immune-based treatments (antibodies or cellular-based therapies) as well as target-driven approaches. Until these treatment approaches are better defined, this review will provide a potential treatment approach for standard- and high-risk myeloma that can be followed using agents and strategies that are currently available with the goal of improving progression-free and overall survival for these patients today. PMID:26272217

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

    PubMed

    Chen, Yun-Ju; Wu, Chieh-Shan; Shieh, Jeng-Jer; Wu, Jyh-Horng; Chen, Hsing-Yu; Chung, Ting-Wen; Chen, Yu-Kuo; Lin, Chi-Chen

    2013-01-01

    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. PMID:23476680

  1. The TGF-β/SMAD pathway is an important mechanism for NK cell immune evasion in childhood B acute lymphoblastic leukemia

    PubMed Central

    Rouce, Rayne H.; Shaim, Hila; Sekine, Takuya; Weber, Gerrit; Ballard, Brandon; Ku, Stephanie; Barese, Cecilia; Murali, Vineeth; Wu, Meng-Fen; Liu, Hao; Shpall, Elizabeth J.; Bollard, Catherine M.; Rabin, Karen R.; Rezvani, Katayoun

    2015-01-01

    Natural killer (NK) cells are key components of the innate immune system, providing potent antitumor immunity. Here, we show that the TGF-β/SMAD signaling pathway is an important mechanism for NK cell immune evasion in childhood B-acute lymphoblastic leukemia (ALL). We characterized NK cells in 50 consecutive children with B-ALL at diagnosis, end-Induction, and during maintenance therapy compared to age-matched controls. ALL-NK cells at diagnosis had an inhibitory phenotype associated with impaired function, most notably IFN-γ production and cytotoxicity. By maintenance, these phenotypic and functional abnormalities partially normalized, however, cytotoxicity against autologous blasts remained impaired. We identified ALL-derived TGF-β1 to be an important mediator of leukemia-induced NK cell dysfunction. The TGF-β/SMAD signaling pathway was constitutively activated in ALL-NK cells at diagnosis and end-induction when compared to healthy controls and patients during maintenance. Culture of ALL blasts with healthy NK cells induced NK dysfunction and an inhibitory phenotype, mediated by activation of the TGF-β/SMAD signaling pathway, and abrogated by blocking TGF-β. These data indicate that by regulating the TGF-β/SMAD pathway, ALL blasts induce changes in NK cells to evade innate immune surveillance, thus highlighting the importance of developing novel therapies to target this inhibitory pathway and restore antileukemic cytotoxicity. PMID:26621337

  2. Effects of radiation on testicular function in long-term survivors of childhood acute lymphoblastic leukemia: A report from the Children Cancer Study Group

    SciTech Connect

    Sklar, C.A.; Robison, L.L.; Nesbit, M.E.; Sather, H.N.; Meadows, A.T.; Ortega, J.A.; Kim, T.H.; Hammond, G.D. )

    1990-12-01

    Testicular function was evaluated in 60 long-term survivors of childhood acute lymphoblastic leukemia (ALL). All the patients were treated on two consecutive Children Cancer Study Group protocols and received identical chemotherapy and either 18 or 24 Gy radiation therapy (RT) to one of the following fields: craniospinal plus 12 Gy abdominal RT including the gonads (group 1); craniospinal (group 2); or cranial (group 3). The median age at the time of their last evaluation was 14.5 years (range, 10.5 to 25.7), which took place a median of 5.0 years (range, 1 to 10.3) after discontinuing therapy. The incidence of primary germ cell dysfunction as judged by raised levels of follicle-stimulating hormone (FSH) and/or reduced testicular volume was significantly associated with field of RT; 55% of group 1, 17% of group 2, and 0% of group 3 were abnormal (P = .002). Leydig cell function, as assessed by plasma concentrations of luteinizing hormone (LH) and testosterone, and pubertal development, was unaffected in the majority of subjects regardless of RT field. These data indicate that in boys undergoing therapy for ALL, germ cell dysfunction is common following testicular irradiation and can occur following exposure to scattered irradiation from craniospinal RT. In contrast, Leydig cell function appears resistant to direct irradiation with doses as high as 12 Gy.

  3. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on growth and craniofacial proportion

    SciTech Connect

    Schunior, A.; Zengel, A.E.; Mullenix, P.J.; Tarbell, N.J.; Howes, A.; Tassinari, M.S. )

    1990-10-15

    Many long term survivors of childhood acute lymphoblastic leukemia have short stature, as well as craniofacial and dental abnormalities, as side effects of central nervous system prophylactic therapy. An animal model is presented to assess these adverse effects on growth. Cranial irradiation (1000 cGy) with and without prednisolone (18 mg/kg i.p.) and methotrexate (2 mg/kg i.p.) was administered to 17- and 18-day-old Sprague-Dawley male and female rats. Animals were weighed 3 times/week. Final body weight and body length were measured at 150 days of age. Femur length and craniofacial dimensions were measured directly from the bones, using calipers. For all exposed groups there was a permanent suppression of weight gain with no catch-up growth or normal adolescent growth spurt. Body length was reduced for all treated groups, as were the ratios of body weight to body length and cranial length to body length. Animals subjected to cranial irradiation exhibited microcephaly, whereas those who received a combination of radiation and chemotherapy demonstrated altered craniofacial proportions in addition to microcephaly. Changes in growth patterns and skeletal proportions exhibited sexually dimorphic characteristics. The results indicate that cranial irradiation is a major factor in the growth failure in exposed rats, but chemotherapeutic agents contribute significantly to the outcome of growth and craniofacial dimensions.

  4. Slower early response to treatment and distinct expression profile of childhood high hyperdiploid acute lymphoblastic leukaemia with DNA index < 1.16.

    PubMed

    Zaliova, Marketa; Hovorkova, Lenka; Vaskova, Martina; Hrusak, Ondrej; Stary, Jan; Zuna, Jan

    2016-09-01

    Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes are defined as high hyperdiploid (HHD) and are generally associated with good prognosis. However, several studies show heterogeneity in HHD ALL and suggest that the favourable prognosis is associated rather with higher ploidy defined by DNA index (DNAi) ≥ 1.16 or with a presence of specific single or combined trisomies. HHD ALL with DNAi < 1.16 are only rarely studied separately. Using single nucleotide polymorphism array, we analysed 89 childhood HHD ALL patients divided into groups with lower (<1.16; n = 34) and higher (≥1.16; n = 55) DNAi. We assessed treatment response, presence of secondary aberrations, mutations in RAS pathway genes and CREBBP and also gene expression profile (GEP) to reveal differences between the two subgroups. Cases with 51-54 chromosomes had DNAi 1.1-1.16 and cases with 55-67 chromosomes had DNAi ≥ 1.16. The groups with lower and higher DNAi had distinct response to early treatment and distinct GEP. The better response of the group with higher DNAi was associated with specific trisomies (trisomy of chromosome 10 or combined with trisomies 4 and/or 17). Our results suggest that cytogenetically defined HHD ALL can in fact be divided into two biologically distinguishable subgroups and that DNAi 1.16 is a relevant value to separate between the two. © 2016 Wiley Periodicals, Inc. PMID:27163296

  5. The 9p21.3 risk of childhood acute lymphoblastic leukaemia is explained by a rare high-impact variant in CDKN2A

    PubMed Central

    Vijayakrishnan, Jayaram; Henrion, Marc; Moorman, Anthony V.; Fiege, Bettina; Kumar, Rajiv; Inacio da Silva Filho, Miguel; Holroyd, Amy; Koehler, Rolf; Thomsen, Hauke; Irving, Julie A.; Allan, James M.; Lightfoot, Tracy; Roman, Eve; Kinsey, Sally E.; Sheridan, Eamonn; Thompson, Pamela D.; Hoffmann, Per; Nöthen, Markus M.; Mühleisen, Thomas W.; Eisele, Lewin; Bartram, Claus R.; Schrappe, Martin; Greaves, Mel; Hemminki, Kari; Harrison, Christine J.; Stanulla, Martin; Houlston, Richard S.

    2015-01-01

    Genome-wide association studies (GWAS) have provided strong evidence for inherited predisposition to childhood acute lymphoblastic leukaemia (ALL) identifying a number of risk loci. We have previously shown common SNPs at 9p21.3 influence ALL risk. These SNP associations are generally not themselves candidates for causality, but simply act as markers for functional variants. By means of imputation of GWAS data and subsequent validation SNP genotyping totalling 2,177 ALL cases and 8,240 controls, we have shown that the 9p21.3 association can be ascribed to the rare high-impact CDKN2A p.Ala148Thr variant (rs3731249; Odds ratio = 2.42, P = 3.45 × 10−19). The association between rs3731249 genotype and risk was not specific to particular subtype of B-cell ALL. The rs3731249 variant is associated with predominant nuclear localisation of the CDKN2A transcript suggesting the functional effect of p.Ala148Thr on ALL risk may be through compromised ability to inhibit cyclin D within the cytoplasm. PMID:26463672

  6. Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    ClinicalTrials.gov

    2016-04-11

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia With 11q23 (MLL) Abnormalities; Adult Acute Myeloid Leukemia With Del(5q); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Large Cell Lymphoma; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Chronic Myelomonocytic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hepatosplenic T-cell Lymphoma; Intraocular Lymphoma; Juvenile Myelomonocytic Leukemia; Nodal Marginal Zone B-cell Lymphoma; Noncutaneous Extranodal Lymphoma; Peripheral T-cell Lymphoma; Polycythemia Vera; Post-transplant Lymphoproliferative Disorder; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Adult Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non

  7. Sex disparity in childhood and young adult acute myeloid leukemia (AML) survival: Evidence from US population data.

    PubMed

    Hossain, Md Jobayer; Xie, Li

    2015-12-01

    Sex variation has been persistently investigated in studies concerning acute myeloid leukemia (AML) survival outcomes but has not been fully explored among pediatric and young adult AML patients. We detected sex difference in the survival of AML patients diagnosed at ages 0-24 years and explored distinct effects of sex across subgroups of age at diagnosis, race-ethnicity and AML subtypes utilizing the United States Surveillance Epidemiology and End Results (SEER) population based dataset of 4865 patients diagnosed with AML between 1973 and 2012. Kaplan-Meier survival function, propensity scores and stratified Cox proportional hazards regression were used for data analyses. After controlling for other prognostic factors, females showed a significant survival advantage over their male counterparts, adjusted hazard ratio (aHR, 95% confidence interval (CI): 1.09, 1.00-1.18). Compared to females, male patients had substantially increased risk of mortality in the following subgroups of: ages 20-24 years at diagnosis (aHR1.30), Caucasian (1.14), acute promyelocytic leukemia (APL) (1.35), acute erythroid leukemia (AEL) (1.39), AML with inv(16)(p13.1q22) (2.57), AML with minimum differentiation (1.47); and had substantially decreased aHR in AML t(9;11)(p22;q23) (0.57) and AML with maturation (0.82). Overall, females demonstrated increased survival over males and this disparity was considerably large in patients ages 20-24 years at diagnosis, Caucasians, and in AML subtypes of AML inv(16), APL and AEL. In contrast, males with AML t(9;11)(p22;q23), AML with maturation and age at diagnosis of 10-14 years showed survival benefit. Further investigations are needed to detect the biological processes influencing the mechanisms of these interactions. PMID:26520618

  8. CD7 aberrant expression led to a lineage switch at relapsed childhood acute pre-B lymphoblastic leukemia.

    PubMed

    Fallah Azad, Vahid; Hedayati Asl, Amir Abbas; Tashvighi, Maryam; Niktoreh Mofrad, Naghmeh; Haghighi, Mansoureh; Mehrvar, Azim

    2016-03-01

    Immunophenotypic changes and lineage switch between diagnosis and relapse in acute lymphoblastic leukemia are uncommon and accompanied by poor outcomes. In this report, a 12-year-old boy with diagnosis of pre-B ALL with an aberrant expression of CD 7 is described. Patient was treated with the ALL-BFM 2000 protocol and suffered an episode of relapse with a lineage switch from pre-B ALL to T cell ALL. This report concludes that presence of aberrant expression of CD7 at diagnosis of pre-B ALL can have prognostic value of lineage switch to T cell ALL at relapse. PMID:26242204

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

    ClinicalTrials.gov

    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

  10. Antiplatelet therapy in populations at high risk of atherothrombosis.

    PubMed

    Faxon, David P; Nesto, Richard W

    2006-05-01

    Atherothrombosis is the most common cause of an acute ischemic event. Antiplatelet agents form the cornerstone of atherothrombosis prevention. The purpose of this article is to review the use of antiplatelet agents in patients that are at particularly high risk of atherothrombotic events. To undertake this review, we searched the literature to identify key studies on the use of antiplatelet agents in this group of patients. Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events. The routine use of aspirin is recommended, as it has been shown to reduce the risk of thrombotic events by approximately 25%. Additional benefit has been demonstrated with clopidogrel, both as a monotherapy and in combination with aspirin. In the CAPRIE trial, 19,185 patients with atherosclerotic vascular disease were randomized to receive clopidogrel (75 mg/day) or aspirin (325 mg/day) for a mean duration of follow-up of 1.91 years. Clopidogrel provided an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin. In the CURE trial, the addition of clopidogrel to background aspirin was associated with a 20% relative risk reduction in a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke compared with aspirin alone. In patients undergoing PCI as part of the PCI-CURE substudy, clopidogrel was associated with a 30% relative reduction in the incidence of cardiovascular events in the first 30 days after intervention compared with aspirin. The benefits of antiplatelet therapy continue to be investigated. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention is unknown. The ongoing CHARISMA trial aims to determine the relative efficacies of aspirin monotherapy and aspirin/clopidogrel combination therapy in a broad range of high-risk

  11. Antiplatelet therapy in populations at high risk of atherothrombosis.

    PubMed Central

    Faxon, David P.; Nesto, Richard W.

    2006-01-01

    Atherothrombosis is the most common cause of an acute ischemic event. Antiplatelet agents form the cornerstone of atherothrombosis prevention. The purpose of this article is to review the use of antiplatelet agents in patients that are at particularly high risk of atherothrombotic events. To undertake this review, we searched the literature to identify key studies on the use of antiplatelet agents in this group of patients. Antiplatelet agents, such as aspirin and clopidogrel, play a fundamental role in the treatment and management of secondary thrombotic events. The routine use of aspirin is recommended, as it has been shown to reduce the risk of thrombotic events by approximately 25%. Additional benefit has been demonstrated with clopidogrel, both as a monotherapy and in combination with aspirin. In the CAPRIE trial, 19,185 patients with atherosclerotic vascular disease were randomized to receive clopidogrel (75 mg/day) or aspirin (325 mg/day) for a mean duration of follow-up of 1.91 years. Clopidogrel provided an additional 8.7% relative risk reduction in the primary composite endpoint of ischemic stroke, myocardial infraction or vascular death compared with aspirin. In the CURE trial, the addition of clopidogrel to background aspirin was associated with a 20% relative risk reduction in a composite of death from cardiovascular causes, nonfatal myocardial infarction or stroke compared with aspirin alone. In patients undergoing PCI as part of the PCI-CURE substudy, clopidogrel was associated with a 30% relative reduction in the incidence of cardiovascular events in the first 30 days after intervention compared with aspirin. The benefits of antiplatelet therapy continue to be investigated. Whether dual antiplatelet therapy is superior to aspirin monotherapy for high-risk primary prevention is unknown. The ongoing CHARISMA trial aims to determine the relative efficacies of aspirin monotherapy and aspirin/clopidogrel combination therapy in a broad range of high-risk

  12. An animal model to study toxicity of central nervous system therapy for childhood acute lymphoblastic leukemia: Effects on behavior

    SciTech Connect

    Mullenix, P.J.; Kernan, W.J.; Tassinari, M.S.; Schunior, A.; Waber, D.P.; Howes, A.; Tarbell, N.J. )

    1990-10-15

    Central nervous system prophylactic therapy used in the treatment of acute lymphoblastic leukemia can reduce intelligence quotient scores and impair memory and attention in children. Cranial irradiation, intrathecal methotrexate, and steroids are commonly utilized in acute lymphoblastic leukemia therapy. How they induce neurotoxicity is unknown. This study employs an animal model to explore the induction of neurotoxicity. Male and female Sprague-Dawley rats at 17 and 18 days of age were administered 18 mg/kg prednisolone, 2 mg/kg methotrexate, and 1000 cGy cranial irradiation. Another 18-day-old group was administered 1000 cGy cranial irradiation but no drugs. Matching controls received saline and/or a sham exposure to radiation. All animals at 6 weeks and 4 months of age were tested for alterations in spontaneous behavior. A computer pattern recognition system automatically recorded and classified individual behavioral acts displayed during exploration of a novel environment. Measures of behavioral initiations, total time, and time structure were used to compare treated and control animals. A permanent sex-specific change in the time structure of behavior was induced by the prednisolone, methotrexate, and radiation treatment but not by radiation alone. Unlike hyperactivity, the effect consisted of abnormal clustering and dispersion of acts in a pattern indicative of disrupted development of sexually dimorphic behavior. This study demonstrates the feasibility of an animal model delineating the agent/agents responsible for the neurotoxicity of central nervous system prophylactic therapy.

  13. [Acute leukemia in childhood: present status of 100 cases after 7 years of complete remission (author's transl)].

    PubMed

    Schaison, G; Jacquillat, C; Lemercier, N; Weil, M; Alby, N; Auclerc, M F; Boiron, M; Bernard, J

    1980-01-01

    Amongst 1,200 leukemie children treated between 1958 and 1971, 60 are in complete remission for more than 10 years and 100 for more than 7 years. There were 96 acute lymphoid and 4 acute myeloid leukemias. Ten patients who have relapsed in the past have not done so lately. The F/M sex ratio is 1.5. Poor prognostic features were initially absent in 2/3 of cases. In 1/3 there was associated hyperleucocytosis and/or tumours. 93 children are in remission, their treatment having been stopped for 1 to 12 years. Five children relapsed and 4 are in a second remission for more than 2 years. Two children died in remission: one from a hepatocarcinoma and one from cardiac failure. These patients have been shown to have the following: 1) normal growth; 2) normal puberty: 8 patients have been able to reproduce, giving 10 children, one with multiple malformations; 3) school achievement and later socioprofessional behaviour has been normal. The patients have often sought a medical or paramedical career. Sequelae are minimal, psychological problems being minimal in the child. With the protocols used, mean remission curve shows a plateau after 9 years and complete definitive care is achieved in 92 per cent of patients surviving at 7 years. The very distant future outlook is not known. No other malignant haematological disease has occurred but one child died from a carcinoma. PMID:6931627

  14. PARC/CCL18 Is a Plasma CC Chemokine with Increased Levels in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Struyf, Sofie; Schutyser, Evemie; Gouwy, Mieke; Gijsbers, Klara; Proost, Paul; Benoit, Yves; Opdenakker, Ghislain; Van Damme, Jo; Laureys, Geneviève

    2003-01-01

    Chemokines play an important role in leukocyte mobilization, hematopoiesis, and angiogenesis. Tissue-specific expression of particular chemokines also influences tumor growth and metastasis. Here, the CC chemokine pulmonary and activation-regulated chemokine (PARC)/CCL18 was measured in pediatric patients with acute lymphoblastic leukemia (ALL) or acute myeloid leukemia (AML). Surprisingly, PARC immunoreactivity was consistently detected in plasma from healthy donors. After purification to homogeneity, the presence of intact PARC (1–69) and processed PARC (1–68) in normal human plasma was confirmed by sequence and mass spectrometry analysis. Furthermore, PARC serum levels were significantly increased in children with T-ALL and prepreB-ALL compared to control serum samples, whereas serum levels in AML and preB-ALL patients were not significantly different from controls. In contrast, the hemofiltrate CC chemokine-1 (HCC-1)/CCL14 was not found to be a biomarker in any of these patients’ strata, whereas the cytokine interleukin-6 (IL-6) was significantly decreased in AML and prepreB-ALL. Stimulated leukocytic cell lines or lymphoblasts from patients produced IL-8/CXCL8 or macrophage inflammatory protein-1α (MIP-1α/CCL3) but not PARC, not even after IL-4 or IL-10 treatment. However, PARC was produced by superantigen or IL-4 stimulated monocytes co-cultured with lymphocytes or lymphoblastic cells. Serum PARC levels thus constitute a novel leukemia marker, possibly reflecting tumor/host cell interactions in the circulation. PMID:14578205

  15. Minimal residual disease in peripheral blood at day 15 identifies a subgroup of childhood B-cell precursor acute lymphoblastic leukemia with superior prognosis

    PubMed Central

    Volejnikova, Jana; Mejstrikova, Ester; Valova, Tatana; Reznickova, Leona; Hodonska, Ladislava; Mihal, Vladimir; Sterba, Jaroslav; Jabali, Yahia; Prochazkova, Daniela; Blazek, Bohumir; Hak, Jiri; Cerna, Zdenka; Hrusak, Ondrej; Stary, Jan; Trka, Jan; Fronkova, Eva

    2011-01-01

    Background Most minimal residual disease-directed treatment interventions in current treatment protocols for acute lymphoblastic leukemia are based on bone marrow testing, which is a consequence of previous studies showing the superiority of bone marrow over peripheral blood as an investigational material. Those studies typically did not explore the prognostic impact of peripheral blood involvement and lacked samples from very early time points of induction. Design and Methods In this study, we employed real-time quantitative polymerase chain reaction analysis to examine minimal residual disease in 398 pairs of blood and bone marrow follow-up samples taken from 95 children with B-cell precursor acute lymphoblastic leukemia treated with the ALL IC-BFM 2002 protocol. Results We confirmed the previously published poor correlation between minimal residual disease in blood and marrow at early treatment time points, with levels in bone marrow being higher than in blood in most samples (median 7.9-fold, range 0.04–8,293-fold). A greater involvement of peripheral blood at diagnosis was associated with a higher white blood cell count at diagnosis (P=0.003) and with enlargement of the spleen (P=0.0004) and liver (P=0.05). At day 15, a level of minimal residual disease in blood lower than 10−4 was associated with an excellent 5-year relapse-free survival in 78 investigated patients (100% versus 69±7%; P=0.0003). Subgroups defined by the level of minimal residual disease in blood at day 15 (high-risk: ≥10−2, intermediate-risk: <10−2 and ≥10−4, standard-risk: <10−4) partially correlated with bone marrow-based stratification described previously, but the risk groups did not match completely. No other time point analyses were predictive of outcome in peripheral blood, except for a weak association at day 8. Conclusions Minimal residual disease in peripheral blood at day 15 identified a large group of patients with an excellent prognosis and added prognostic

  16. General Information about Childhood Central Nervous System Embryonal Tumors

    MedlinePlus

    ... System Embryonal Tumors Treatment (PDQ®)–Patient Version General Information About Childhood Central Nervous System Embryonal Tumors Go ... in patients with a high-risk tumor. The information from tests and procedures done to detect (find) ...

  17. Combination Chemotherapy With or Without Bortezomib in Treating Younger Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or Stage II-IV T-Cell Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-09-12

    Adult T Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Stage II Childhood Lymphoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  18. Pharmacological Management of High-risk Neuroblastoma in Children

    PubMed Central

    Ganeshan, Veena R.; Schor, Nina F.

    2015-01-01

    BACKGROUND Neuroblastoma is the most common extracranial solid tumor of childhood. It accounts for 15% of pediatric cancer deaths. Children with high-risk disease have a 3-year event-free survival rate of only 20%. Chemotherapy is the mainstay of the treatment of children with advanced neuroblastoma. OBJECTIVE To review and critically evaluate the pharmacotherapy of neuroblastoma. DATA SOURCES Peer-reviewed and review literature, 2000–2011. STUDY SELECTION All peer-reviewed, published human subjects studies of therapy for neuroblastoma in children were included. Animal model and in vitro studies were included only if they added to the understanding of the mechanism of a proposed or existing human neuroblastoma therapy. DATA SYNTHESIS Current therapeutic options for neuroblastoma involve insufficient differentiation of normal from neoplastic tissue. Critically needed new approaches will increasingly exploit targeting of therapy for unique characteristics of the neuroblastoma cell. CONCLUSIONS Pharmacotherapy for neuroblastoma still suffers from an inadequate therapeutic window. Enhancement of toxicity for tumor and safety for normal tissues will entail innovation in targeting neuroblastoma cells and rescuing or protecting normal tissue elements. PMID:21692548

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

    ClinicalTrials.gov

    2013-07-03

    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

  20. Gynecological surveillance in high risk women.

    PubMed

    Dilley, James; Gentry-Maharaj, Aleksandra; Menon, Usha

    2016-10-01

    In high-risk women, risk reducing surgery remains the cornerstone of prevention. However, the resulting premature menopause has led to continued efforts to develop effective screening strategies for those who wish to delay or avoid surgery. This review describes how the screening of women at risk of ovarian and endometrial cancer has evolved to its current state. Serial monitoring of CA125 is core to ovarian cancer screening and most recent studies have used the Risk of Ovarian Cancer Algorithm (ROCA) to interpret CA125 profile. The additional use of a second tumour marker, HE4, is reviewed. The results to date of key ovarian cancer screening studies in high-risk women are summarised ahead of their concluding findings due later in 2016. The role of both ultrasound and endometrial sampling in the management of women at increased risk of endometrial cancer is outlined. Exciting new methodology, which could help shape the future of screening is investigated. The article summarises the current recommendations and guidelines from recognised international bodies to aid the clinician with management of these women. PMID:26930388

  1. Intracranial hemorrhage in acute and chronic childhood immune thrombocytopenic purpura over a ten-year period: an Egyptian multicenter study.

    PubMed

    Elalfy, Mohsen; Elbarbary, Nancy; Khaddah, Normine; Abdelwahab, Magy; El Rashidy, Farida; Hassab, Hoda; Al-Tonbary, Youssef

    2010-01-01

    Intracranial hemorrhage (ICH) is a rare but major cause of death in immune thrombocytopenic purpura (ITP). The authors reviewed data of 1,840 patient with ITP, from 5 pediatric hematology centers in Egypt from 1997 to 2007, to study the incidence and risk factors of ICH. Ten cases of ICH were identified with a median age at presentation of 7.5 years; 4 patients had acute ITP, 2 persistent and 4 chronic. The platelet count was <10 x 10(9)/l in 7 cases, and only 1 patient had a history of head trauma. Seven children were on treatment prior to or at the time of occurrence of ICH and all were treated by pharmacotherapy. Two children died shortly afterwards due to late referral to a specialized center. Our results suggest that treatment does not prevent ICH and that it can occur at any time during the course of the disease. Delayed referral can be considered a risk factor for unfavorable outcome of ICH, highlighting the importance of teaching sessions for patients and their parents to minimize subsequent morbidity and mortality of ICH in children with ITP. PMID:19955713

  2. A six gene expression signature defines aggressive subtypes and predicts outcome in childhood and adult acute lymphoblastic leukemia

    PubMed Central

    Wang, Jin; Mi, Jian-Qing; Debernardi, Alexandra; Vitte, Anne-Laure; Emadali, Anouk; Meyer, Julia A.; Charmpi, Konstantina; Ycart, Bernard; Callanan, Mary B.; Carroll, William L.; Khochbin, Saadi; Rousseaux, Sophie

    2015-01-01

    Abnormal gene expression in cancer represents an under-explored source of cancer markers and therapeutic targets. In order to identify gene expression signatures associated with survival in acute lymphoblastic leukemia (ALL), a strategy was designed to search for aberrant gene activity, which consists of applying several filters to transcriptomic datasets from two pediatric ALL studies. Six genes whose expression in leukemic blasts was associated with prognosis were identified:three genes predicting poor prognosis (AK022211, FASTKD1 and STARD4) and three genes associated with a favorable outcome (CAMSAP1, PCGF6 and SH3RF3). Combining the expression of these 6 genes could successfully predict prognosis not only in the two discovery pediatric ALL studies, but also in two independent validation cohorts of adult patients, one from a publicly available study and one consisting of 62 newly recruited Chinese patients. Moreover, our data demonstrate that our six gene based test is particularly efficient in stratifying MLL or BCR.ABL negative patients. Finally, common biological traits characterizing aggressive forms of ALL in both children and adults were found, including features of dormant hematopoietic stem cells, suggesting new therapeutic strategies. PMID:26001296

  3. Obesity is associated with residual leukemia following induction therapy for childhood B-precursor acute lymphoblastic leukemia.

    PubMed

    Orgel, Etan; Tucci, Jonathan; Alhushki, Waseem; Malvar, Jemily; Sposto, Richard; Fu, Cecilia H; Freyer, David R; Abdel-Azim, Hisham; Mittelman, Steven D

    2014-12-18

    Obesity is associated with poorer event-free survival (EFS) in pediatric acute lymphoblastic leukemia (ALL). Persistent minimal residual disease (MRD) in the bone marrow as measured by multidimensional flow cytometry (MDF) is a key early prognostic indicator and is strongly associated with EFS. We therefore hypothesized that obesity during induction would be associated with positive end-of-induction MRD (≥0.01%). We analyzed MDF of end-induction bone marrow samples from a historical cohort of 198 children newly diagnosed with B-precursor ALL (BP-ALL) and treated with Children's Oncology Group induction regimens. We assessed the influence of body mass index on risk for positive end-induction MRD in the bone marrow. In our cohort of BP-ALL, 30 children (15.2%) were overweight and 41 (20.7%) were obese at diagnosis. Independent of established predictors of treatment response, obesity during induction was associated with significantly greater risk for persistent MRD (odds ratio, 2.57; 95% confidence interval, 1.19 to 5.54; P = .016). Obesity and overweight were associated with poorer EFS irrespective of end-induction MRD (P = .012). Obese children with newly diagnosed BP-ALL are at increased risk for positive end-induction MRD and poorer EFS. PMID:25349177

  4. Comparative genomic hybridization in childhood acute lymphoblastic leukemia: correlation with interphase cytogenetics and loss of heterozygosity analysis.

    PubMed

    Scholz, I; Popp, S; Granzow, M; Schoell, B; Holtgreve-Grez, H; Takeuchi, S; Schrappe, M; Harbott, J; Teigler-Schlegel, A; Zimmermann, M; Fischer, C; Koeffler, H P; Bartram, C R; Jauch, A

    2001-01-15

    We used comparative genomic hybridization (CGH) to study DNA copy number changes in 71 children with acute lymphoblastic leukemia (ALL) including 50 B-lineage and 21 T-ALLs. Forty-two patients (59%) showed genomic imbalances whereby gains were more frequently observed than losses (127 vs. 29). Gains most commonly affected the entire chromosomes 21 and 10 (19.7% each), 6, 14, 18, X (15.5% each), 17 (14.1%) and 4 (11.3%). Highly hyperdiploid karyotypes (chromosome number >50) occurred more frequently in B-lineage than in T-lineage ALL (24% vs. 4.8%). In both cell lineages deletions were mainly detected on 9p (14.1%) and 12p (8.4%), and on 6q in T-lineage ALL (4.2%). These findings were compared with loss of heterozygosity (LOH) of 6q, 9p, 11q, and 12p previously performed in 56 of the 71 patients. Among 54 sites of LOH, CGH revealed losses of the respective chromosome arms in 17 LOH-positive regions (31.5%). G-banding analysis and interphase cytogenetics with subregional probes for 14 loci confirmed the presence of genomic imbalances as detected by CGH. We, therefore, conclude that, in the absence of cytogenetic data, CGH represents a suitable method for identifying hyperdiploid karyotypes as well as prognostically relevant deletions in ALL patients. PMID:11172898

  5. Presence of FLT3-ITD and high BAALC expression are independent prognostic markers in childhood acute myeloid leukemia.

    PubMed

    Staffas, Anna; Kanduri, Meena; Hovland, Randi; Rosenquist, Richard; Ommen, Hans Beier; Abrahamsson, Jonas; Forestier, Erik; Jahnukainen, Kirsi; Jónsson, Ólafur G; Zeller, Bernward; Palle, Josefine; Lönnerholm, Gudmar; Hasle, Henrik; Palmqvist, Lars; Ehrencrona, Hans

    2011-11-24

    Mutation status of FLT3, NPM1, CEBPA, and WT1 genes and gene expression levels of ERG, MN1, BAALC, FLT3, and WT1 have been identified as possible prognostic markers in acute myeloid leukemia (AML). We have performed a thorough prognostic evaluation of these genetic markers in patients with pediatric AML enrolled in the Nordic Society of Pediatric Hematology and Oncology (NOPHO) 1993 or NOPHO 2004 protocols. Mutation status and expression levels were analyzed in 185 and 149 patients, respectively. Presence of FLT3-internal tandem duplication (ITD) was associated with significantly inferior event-free survival (EFS), whereas presence of an NPM1 mutation in the absence of FLT3-ITD correlated with significantly improved EFS. Furthermore, high levels of ERG and BAALC transcripts were associated with inferior EFS. No significant correlation with survival was seen for mutations in CEBPA and WT1 or with gene expression levels of MN1, FLT3, and WT1. In multivariate analysis, the presence of FLT3-ITD and high BAALC expression were identified as independent prognostic markers of inferior EFS. We conclude that analysis of the mutational status of FLT3 and NPM1 at diagnosis is important for prognostic stratification of patients with pediatric AML and that determination of the BAALC gene expression level can add valuable information. PMID:21967978

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

    PubMed Central

    Perez-Saldivar, Maria Luisa; Ortega-Alvarez, Manuel Carlos; Fajardo-Gutierrez, Arturo; Bernaldez-Rios, Roberto; del Campo-Martinez, Maria de los Angeles; Medina-Sanson, Aurora; Palomo-Colli, Miguel Angel; Paredes-Aguilera, Rogelio; Martínez-Avalos, Armando; Borja-Aburto, Victor Hugo; Rodriguez-Rivera, Maria de Jesus; Vargas-Garcia, Victor Manuel; Zarco-Contreras, Jesus; Flores-Lujano, Janet; Mejia-Arangure, Juan Manuel

    2008-01-01

    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 expert's opinion. Results The

  7. Analysis of factors influencing the overall effect of racecadotril on childhood acute diarrhea. Results from a real-world and post-authorization surveillance study in Venezuela

    PubMed Central

    Chacón, Jose

    2010-01-01

    Drug efficacy might differ from clinical trial results when performed in clinical daily conditions. Therefore, it is mandatory to conduct trials about effectiveness to improve external validity. This post-authorization, open-label, noncontrolled, prospective, multicenter, observational, and naturalistic trial was designed to search for factors influencing the racecadotril overall effect on childhood acute watery diarrhea in a real-world setting of Venezuela. There were 3,873 children with acute watery diarrhea treated with racecadotril, an enkephalin breakdown blocker plus oral rehydration therapy by 97 pediatricians. Evaluations were carried out daily until emission of two consecutive formed stools or absence of watery bowel movements for 24 hours. The primary end-point was time-to-relief, defined as the time from first racecadotril dose to the last watery bowel movement time. Age, gender, nursing type, nursing status during diarrhea, diarrhea severity, and co-medication were considered as factors in the statistical analysis. The primary end-point was evaluated by factors using UNIANOVA, and post-hoc tests were done. A multiple regression analysis was carried out to identify factors affecting drug performance, racecadotril effectiveness and tolerability overall assessment was searched by physicians and patients, and inter-observer agreement was evaluated by kappa statistics. The mean time-to-relief was 18.5 ± 12.5 hours [95% confidence interval 17.9–19.0] and the diarrhea severity was the only variable with significant and independent weight on racecadotril effectiveness explaining 23% of time-to-relief variance, but even in severe diarrhea cases this time was less than 24 hours. High agreement about satisfactory perception on effectiveness and tolerability was reached among physicians and patients. In conclusion, the racecadotril overall effect, evaluated in a real-world setting of Venezuela, was in agreement with results of some earlier controlled trials. It

  8. Information needs of parents for acute childhood illness: determining ‘what, how, where and when’ of safety netting using a qualitative exploration with parents and clinicians

    PubMed Central

    Jones, Caroline H D; Neill, Sarah; Lakhanpaul, Monica; Roland, Damian; Singlehurst-Mooney, Hayley; Thompson, Matthew

    2014-01-01

    Objective To explore the views of parents and clinicians regarding the optimal content, format and delivery of safety netting information for acute childhood illness. Design Qualitative study including semistructured focus groups and interviews. Setting First contact care settings, community centres, children's centres and nurseries in the Midlands, UK. Participants 27 parents from a travelling community, Asian British community and white British community. Sixteen clinicians including 10 doctors and 6 nurses from a general practice surgery, an out-of-hours service and two emergency departments (paediatric and combined adult and paediatric). Results Participants described a need for safety netting to contain information on signs and symptoms of serious and common illnesses, illness management and where and when to seek help. Resources should be basic, simple to use and contain simple symbols. A key criterion was professional endorsement of resources. Internet-based information was desired which is reliable, consistent and up-to-date. Participants described a need for different types of information: that which could be delivered during consultations, as well as more general information for parents to access before consulting a healthcare professional. Face-to-face education, written materials and digital media were suggested delivery mechanisms. Audiovisual material was preferred by families with low literacy. Participants commonly suggested internet-based and phone-based resources, but the travelling community was less comfortable with these approaches. Conclusions A multifaceted and tailored approach to safety netting is needed so that effective resources are available for parents with varying information needs, literacy levels and ability to use information technology. We have identified key aspects of content, quality criteria, format and delivery mechanisms for safety netting information from the perspectives of clinicians and parents. Resources should be

  9. Calcium and cholecalciferol supplementation provides no added benefit to nutritional counseling to improve bone mineral density in survivors of childhood acute lymphoblastic leukemia (ALL)

    PubMed Central

    Kaste, S.C.; An, Q.; Smith, K.; Surprise, H.; Lovorn, E.; Boyett, J.; Ferry, R.J.; Relling, M.V.; Shurtleff, S.A.; Pui, C.H.; Carbone, L.; Hudson, M.M.; Ness, K.K.

    2014-01-01

    Background We sought to improve lumbar spine bone mineral density (LS-BMD) in long-term survivors of childhood acute lymphoblastic leukemia (ALL) using calcium and cholecalciferol supplementation. Procedure This double-blind, placebo-controlled trial randomized 275 participants (median age, 17 (9 –36.1) years) with age- and gender-specific LS-BMD Z-scores < 0 to receive nutritional counseling with supplementation of 1000 mg/day calcium and 800 IU cholecalciferol or placebo for 2 years. The primary outcome was change in LS-BMD assessed by quantitative computerized tomography (QCT) at 24 months. Linear regression models were employed to identify the baseline risk factors for low LS-BMD and to compare LS-BMD outcomes. Results Pre-randomization LS-BMD below the mean was associated with male gender (p=0.0024), white race (p=0.0003), lower body mass index (p<0.0001), and cumulative glucocorticoid doses of ≥5,000 mg (p=0.0012). One hundred eighty-eight (68%) participants completed the study; 77% adhered to the intervention. Mean LS-BMD change did not differ between survivors randomized to supplements (0.33±0.57) or placebo (0.28±0.56). Participants aged 9 – 13 years and those 22–35 years had the greatest mean increases in LS-BMD (0.50±0.66 and 0.37±0.23, respectively). Vitamin D insufficiency [serum 25(OH)D <30 ng/mL] found in 296 (75%), was not associated with LS-BMD outcomes (p=0.78). Conclusion Cholecalciferol and calcium supplementation provides no added benefit to nutritional counseling for improving LS-BMD among adolescent and young adult survivors of ALL (93% of whom had LS-BMD Z-scores above the mean at study entry). PMID:24395288

  10. Inherent illnesses and attacks: an ethnographic study of interpretations of childhood Acute Respiratory Infections (ARIs) in Manhiça, southern Mozambique

    PubMed Central

    2011-01-01

    Background Pneumonia is a leading cause of childhood hospitalisation and child mortality in Africa. This study explores local interpretations of Acute Respiratory Infections (ARIs), focusing on caretakers of children under five in the context of hospital care seeking. Methods The study took place in Manhiça, southern Mozambique and used Focused Ethnographic Study tools (FES) including field exercises and interviews. Results Understandings of terms used to describe ARIs differed between caretakers and hospital staff. Children's sicknesses that hospital staff diagnosed as ARIs were interpreted by caretakers as intermittent "attacks" of xifuva, a permanent, inherent and incurable chest illness. Caretakers thought that it was possible to manage and treat the attacks, which were caused by immediate natural factors such as food or the weather, but not the underlying illness, which was seen as having more indirect and social causes. Explanations of illness could not be neatly separated into pluralistic categories, but were characterised by syncretism, with "lay" and "biomedical" terms and concepts intermingling in practical care-seeking interactions between caretakers and health staff. Conclusions Health promotion should take into account the syncretism involved in explanations of ARIs in the context of practical care seeking for children. In doing so, it should draw upon lay interpretations and terminologies in order to stress the importance of seeking hospital care for all xifuva-type illnesses as well as seeking care for any subsequent attacks of an already diagnosed xifuva. However, this should be undertaken with awareness that the meanings of the terms used in practical care-seeking interactions may change over time. Health communication about ARIs should therefore be ongoing and evidence-based, even if ARIs appear to be well understood. PMID:21752260

  11. Immunophenotype of adult and childhood acute lymphoblastic leukemia: changes at first relapse and clinico-prognostic implications.

    PubMed

    Guglielmi, C; Cordone, I; Boecklin, F; Masi, S; Valentini, T; Vegna, M L; Ferrari, A; Testi, A M; Foa, R

    1997-09-01

    The immunologic features of leukemic cells at the time of 1st hematologic relapse were compared to those obtained at initial diagnosis in 128 patients (69 children and 59 adults) with acute lymphoblastic leukemia (ALL) treated at a single institution. An immunophenotypic change was observed in 59 cases (46%), more frequently in T (20/25) than in B (39/103) lineage ALL (80 vs 38%, P=0.0008), but with a similar incidence in adults and children. Of these cases, 34 (24 B- and 10 T-ALL) changed at relapse their intralineage subgroup affiliation, although no complete shift from B to T lineage ALL, or vice versa, was observed. The myeloid antigens CD13 and/or CD33 were frequently lost (2/5 cases) or acquired (12/123 cases) at relapse. In 21 cases, the immunophenotype at relapse was more undifferentiated than at diagnosis, while it was more differentiated in 13 cases. Initial treatment intensity or preceding treatment with teniposide did not affect the phenotypic profile at relapse. Complete response (CR) rate to salvage therapy and event-free survival were not influenced by the immunophenotypic shifts, nor by the presence, at relapse, of leukemic cells expressing the myeloid antigens CD13 and/or CD33. Univariate analysis suggested that prognosis after relapse was dependent on the duration of 1st CR, patients' age and immunophenotype at the time of diagnosis, with a worse outcome for patients with T lineage ALL and for patients with the less differentiated subgroup of B lineage ALL (CD19+ and CD10-). Multivariate analysis showed that only two factors, duration of 1st CR and grade of immunologic differentiation at diagnosis, have independent prognostic value in relapsed ALL. PMID:9305605

  12. Minimal effects of E. coli and Erwinia asparaginase on the coagulation system in childhood acute lymphoblastic leukemia: a randomized study.

    PubMed

    Risseeuw-Appel, I M; Dekker, I; Hop, W C; Hählen, K

    1994-01-01

    A randomized study was done in twenty newly diagnosed children with acute lymphoblastic leukemia. Ten children were treated with Escherichia coli L-asparaginase, and ten with Erwinia chrysanthemi L-asparaginase. L-asparaginase (ASP) treatment started halfway during ALL-induction treatment with vincristine, prednisone, daunorubicin and intrathecal methotrexate. The mean activated partial thromboplastin time (APTT) level in all children demonstrated a significant fall (P < 0.001) from 28.25 sec at diagnosis to 23.0 sec at the start of ASP treatment. In this same time interval, the mean fibrinogen level declined markedly from 3 g/l to 1.2 g/l (P < 0.001), probably due to prednisone therapy. The APTT stayed shortened during ASP therapy, whereas the hypofibrinogenemia recovered significantly faster in the Erwinia group (P < or = 0.01). Factors (F) II, V, VII and X stayed within the normal range, while F VIII and F IX were elevated. During the entire period of induction therapy, the ATIII activity remained within the normal range in both treatment groups. The protein C values, however, demonstrated a steady decline from 140% at start of ASP treatment to a mean of 81% and 93%, respectively, at the end of the ASP therapy in the E. coli and Erwinia group. Five of the ten children treated with E. coli ASP demonstrated protein C levels below 70% at the end of ASP therapy, opposed to none of the Erwinia treated patients (P = 0.03). We suggest that the effect of ASP resulting in decreased coagulation factor synthesis is in part counterbalanced by the effect of prednisone on the coagulation system, when ASP is administered at the end of ALL induction treatment. The overall effect of ASP either of E. coli or of Erwinia on the hemorrhagic system reveals a slight imbalance towards thrombosis, mainly because of a gradual decrease in protein C activity. This imbalance is less pronounced in the Erwinia group. PMID:8058004

  13. Assessment of mercaptopurine (6MP) metabolites and 6MP metabolic key-enzymes in childhood acute lymphoblastic leukemia.

    PubMed

    Wojtuszkiewicz, Anna; Barcelos, Ana; Dubbelman, Boas; De Abreu, Ronney; Brouwer, Connie; Bökkerink, Jos P; de Haas, Valerie; de Groot-Kruseman, Hester; Jansen, Gerrit; Kaspers, Gertjan L; Cloos, Jacqueline; 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 pathway still remains unclear. This study attempted to determine which components of 6MP metabolism in leukemic blasts and red blood cells are important for 6MP's sensitivity and toxicity. In addition, changes in the enzymatic activities and metabolite levels during the treatment were analyzed. In a cohort (N=236) of pediatric ALL patients enrolled in the Dutch ALL-9 protocol, we studied the enzymes inosine-5'-monophosphate dehydrogenase (IMPDH), thiopurine S-methyltransferase (TPMT), hypoxanthine guanine phosphoribosyl transferase (HGPRT), and purine nucleoside phosphorylase (PNP) as well as thioguanine nucleotides (TGN) and methylthioinosine nucleotides (meTINs). Activities of selected enzymes and levels of 6MP derivatives were measured at various time points during the course of therapy. The data obtained and the toxicity related parameters available for these patients were correlated with each other. We found several interesting relations, including high concentrations of two active forms of 6MP--TGN and meTIN--showing a trend toward association with better in vitro antileukemic effect of 6MP. High concentrations of TGN and elevated activity of HGPRT were found to be significantly associated with grade III/IV leucopenia. However, a lot of data of enzymatic activities and metabolite concentrations as well as clinical toxicity were missing, thereby limiting the number of assessed relations. Therefore, although a complex study of 6MP metabolism in ALL patients is feasible, it warrants more robust and strict data collection in order to be able to draw more reliable conclusions. PMID:24940700

  14. Treatment of Acute Graft-versus-Host Disease in Childhood with Extracorporeal Photochemotherapy/Photopheresis: The Padova Experience.

    PubMed

    Calore, Elisabetta; Marson, Piero; Pillon, Marta; Tumino, Manuela; Tison, Tiziana; Mainardi, Chiara; De Silvestro, Giustina; Rossin, Sara; Franceschetto, Genny; Carraro, Elisa; Pescarin, Matilde; Varotto, Stefania; Destro, Roberta; Gazzola, Maria Vittoria; Basso, Giuseppe; Messina, Chiara

    2015-11-01

    Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic steroid treatment represents the first-line therapy for aGVHD and is associated with a response rate of 30% to 60%. Steroid-resistant patients have a poor prognosis with high transplantation-related mortality (TRM). Several second-line therapies have been proposed for the management of unresponsive aGVHD, without proven beneficial effects on patients' outcome or overall long-term survival. For these reasons, extracorporeal photochemotherapy/photopheresis (ECP), a cell-based approach to control GVHD that spares generalized immunosuppression, seems to be promising. In this study, we report the outcome of 72 consecutive pediatric patients treated with ECP between 1997 and 2013 for aGVHD. Among them, 21 patients had steroid-resistant aGVHD, 42 had steroid-dependent aGVHD, and 9 did not receive steroid as first-line therapy because of clinical contraindications. A complete response was obtained in 72% of patients, a partial response was observed in 11%, and there was no response in 17% of patients. At day +180, TRM was 4% in the whole cohort; TRM was 3% and 20% among responders and nonresponders to ECP, respectively (P < .0001). The 5-year overall survival was 71%, showing a difference between responders and nonresponders of 78% and 30%, respectively (P = .0004). The 5-year time to progression of primary disease was 81%, without any significant difference between the 2 groups. Moreover, the 5-year progression-free survival of primary disease was 72%, with a significant difference (P = .0007) between responders (79%) and nonresponders (30%) to ECP. In conclusion, this study demonstrates that ECP is highly effective in aGVHD without a negative impact on primary disease. PMID:26183078

  15. Stabilization of high-risk plaques

    PubMed Central

    Takata, Kohei; Zhang, Bo; Miura, Shin-ichiro; Saku, Keijiro

    2016-01-01

    The prevalence of atherosclerotic cardiovascular diseases (ASCVDs) is increasing globally and they have become the leading cause of death in most countries. Numerous experimental and clinical studies have been conducted to identify major risk factors and effective control strategies for ASCVDs. The development of imaging modalities with the ability to determine the plaque composition enables us to further identify high-risk plaque and evaluate the effectiveness of different treatment strategies. While intensive lipid-lowering by statins can stabilize or even regress plaque by various mechanisms, such as the reduction of lipid accumulation in a necrotic lipid core, the reduction of inflammation, and improvement of endothelial function, there are still considerable residual risks that need to be understood. We reviewed important findings regarding plaque vulnerability and some encouraging emerging approaches for plaque stabilization. PMID:27500090

  16. [High Risk Federal Program Areas]: An Overview. High-Risk Series.

    ERIC Educational Resources Information Center

    Comptroller General of the U.S., Washington, DC.

    This report reviews the status of government agencies and operations that have been identified as at "high risk" for waste, fraud, abuse, and mismanagement; describes successful progress in some agencies; and looks at recent reform legislation. Six categories being targeted include accountability of defense programs, ensuring that all revenues are…

  17. High risk register--an economical tool for early identification of hearing loss.

    PubMed

    D'Mello, J

    1995-01-01

    Deafness needs to be dignified nearly as its adverse effects increase with the degree and age of onset. The high risk register helps to alert the professional to suspect the presence of this hidden handicap. Histories of 281 hearing impaired children and 158 normal children was collected and analysed. Risk items that appeared significant were--rashes with fever during pregnancy, family history of childhood deafness, asphyxia at birth or blue baby, prematurity (less than 32-34 gestational weeks), low birth weight (less than 1200 gm), hyperbilirubinemia, birth defects of ear nose, throat and head, consanguineous marriage (cousin), parental concerns about their child's hearing. These high risk factors could help in identifying hearing impairment early and in envisaging quality habilitation programs. PMID:10829952

  18. Direct social support for young high risk children: relations with behavioral and emotional outcomes across time.

    PubMed

    Appleyard, Karen; Egeland, Byron; Sroufe, L Alan

    2007-06-01

    This study is unique in addressing developmental correlates of direct social support for young children in a high risk sample, in contrast to previous studies addressing social support for caregivers. Participants were drawn from a prospective, longitudinal study of at-risk children. Social support was rated from maternal interviews throughout early childhood. Support from the mother was assessed from mother-child observations. Outcomes included internalizing and externalizing behavior problems measured from first through tenth grades. The most common support providers were biological fathers, followed by grandparents and other providers. Using multilevel modeling, higher quantity, higher quality, and lower disruption of support predicted lower starting levels of behavior problems, controlling for support from the mother. Disruption was associated with change in slope. Gender differences were found for externalizing behavior intercepts. Social support provides a promotive factor for young high risk children. Implications include involving children's social support providers in prevention and intervention programs. PMID:17295063

  19. Evaluation of ETV6/RUNX1 Fusion and Additional Abnormalities Involving ETV6 and/or RUNX1 Genes Using FISH Technique in Patients with Childhood Acute Lymphoblastic Leukemia.

    PubMed

    Aydin, Cigdem; Cetin, Zafer; Manguoglu, Ayse Esra; Tayfun, Funda; Clark, Ozden Altiok; Kupesiz, Alphan; Akkaya, Bahar; Karauzum, Sibel Berker

    2016-06-01

    Childhood acute lymphoblastic leukemia (ALL) is the most common type of childhood leukemia. Specifically, ALL is a malignant disorder of the lymphoid progenitor cells, with a peak incidence among children aged 2-5 years. The t(12;21)(p13;q22) translocation occurs in 25 % of childhood B cell precursor ALL. In this study, bone marrow samples were obtained from 165 patients with childhood ALL. We analyzed the t(12;21) translocation and other related abnormalities using the fluorescent in situ hybridization (FISH) technique with the ETV6(TEL)/RUNX1(AML1) ES dual color translocation probe. Conventional cytogenetic analyses were also performed. ETV6 and RUNX1 related chromosomal abnormalities were found in 42 (25.5 %) of the 165 patients with childhood ALL. Among these 42 patients, structural changes were detected in 33 (78.6 %) and numerical abnormalities in 9 (21.4 %). The frequency of FISH abnormalities in pediatric ALL cases were as follows: 8.5 % for t(12;21)(p13;q22) ETV6/RUNX1 fusion, 6.0 % for RUNX1 amplification, 3.0 % for tetrasomy/trisomy 21, 1.8 % for ETV6 deletion, 1.21 % for ETV6 deletion with RUNX1 amplification, 1.21 % for ETV6 amplification with RUNX1 amplification, 0.6 % for polyploidy, 0.6 % for RUNX1 deletion, and 0.6 % for diminished ETV6 signal. The most common structural abnormality was the t(12;21) translocation, followed by RUNX1 amplification and ETV6 deletion, while the most commonly observed numerical abnormality was trisomy 21. PMID:27065576

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

    ClinicalTrials.gov

    2015-07-27

    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

  1. Early Childhood Caries

    PubMed Central

    Kawashita, Yumiko; Kitamura, Masayasu; Saito, Toshiyuki

    2011-01-01

    Dental caries is one of the most common childhood diseases, and people continue to be susceptible to it throughout their lives. Although dental caries can be arrested and potentially even reversed in its early stages, it is often not self-limiting and progresses without proper care until the tooth is destroyed. Early childhood caries (ECC) is often complicated by inappropriate feeding practices and heavy infection with mutans streptococci. Such children should be targeted with a professional preventive program that includes oral hygiene instructions for mothers or caregivers, along with fluoride and diet counseling. However, these strategies alone are not sufficient to prevent dental caries in high-risk children; prevention of ECC also requires addressing the socioeconomic factors that face many families in which ECC is endemic. The aim of this paper is to systematically review information about ECC and to describe why many children are suffering from dental caries. PMID:22007218

  2. Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-03-18

    Adult B Lymphoblastic Lymphoma; Childhood B Acute Lymphoblastic Leukemia; Childhood B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Childhood B Lymphoblastic Lymphoma; Down Syndrome; Stage I B Lymphoblastic Lymphoma; Stage II B Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  3. Nonoperative options for management of residual stones after cholecystostomy in high-risk patients

    NASA Astrophysics Data System (ADS)

    Reed, David M.; Daye, S. S.; Lincer, R. M.

    1993-05-01

    Cholecystostomy is frequently performed to obtain control of sepsis in high risk patients with acute cholecystitis. Retained stones in the gallbladder may cause future clinical problems. We present two patients with cholecystostomy tubes managed non-operatively. A review of other reported methods for stone extraction or destruction is also presented. Knowledge of safe and effective techniques for removal of these stones, using minimally invasive techniques is useful to the general surgeon.

  4. Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia

    PubMed Central

    Núñez-Enríquez, J C; Fajardo-Gutiérrez, A; Buchán-Durán, E P; Bernáldez-Ríos, R; Medina-Sansón, A; Jiménez-Hernández, E; Amador-Sanchez, R; Peñaloza-Gonzalez, J G; Paredes-Aguilera, R; Alvarez-Rodriguez, F J; Bolea-Murga, V; de Diego Flores-Chapa, J; Flores-Lujano, J; Bekker-Mendez, V C; Rivera-Luna, R; del Carmen Rodriguez-Zepeda, M; Rangel-López, A; Dorantes-Acosta, E M; Núñez-Villegas, N; Velazquez-Aviña, M M; Torres-Nava, J R; Reyes-Zepeda, N C; Cárdenas-Cardos, R; Flores-Villegas, L V; Martinez-Avalos, A; Salamanca-Gómez, F; Gorodezky, C; Arellano-Galindo, J; Mejía-Aranguré, J M

    2013-01-01

    Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. Odds ratios (OR) were calculated. Results: Asthma was positively associated with AL development (OR=4.18; 95% confidence interval (CI): 1.47–11.87), whereas skin allergies were negatively associated (OR=0.42; 95% CI: 0.20–0.91). Conclusion: Our findings suggest that allergies and AL in children with DS share biological and immune mechanisms. To our knowledge, this is the first study reporting associations between allergies and AL in children with DS. PMID:23695017

  5. High risk factors of pancreatic carcinoma.

    PubMed

    Camara, Soriba Naby; Yin, Tao; Yang, Ming; Li, Xiang; Gong, Qiong; Zhou, Jing; Zhao, Gang; Yang, Zhi-Yong; Aroun, Tajoo; Kuete, Martin; Ramdany, Sonam; Camara, Alpha Kabinet; Diallo, Aissatou Taran; Feng, Zhen; Ning, Xin; Xiong, Jiong-Xin; Tao, Jing; Qin, Qi; Zhou, Wei; Cui, Jing; Huang, Min; Guo, Yao; Gou, Shan-Miao; Wang, Bo; Liu, Tao; Olivier, Ohoya Etsaka Terence; Conde, Tenin; Cisse, Mohamed; Magassouba, Aboubacar Sidiki; Ballah, Sneha; Keita, Naby Laye Moussa; Souare, Ibrahima Sory; Toure, Aboubacar; Traore, Sadamoudou; Balde, Abdoulaye Korse; Keita, Namory; Camara, Naby Daouda; Emmanuel, Dusabe; Wu, He-Shui; Wang, Chun-You

    2016-06-01

    Over the past decades, cancer has become one of the toughest challenges for health professionals. The epidemiologists are increasingly directing their research efforts on various malignant tumor worldwide. Of note, incidence of cancers is on the rise more quickly in developed countries. Indeed, great endeavors have to be made in the control of the life-threatening disease. As we know it, pancreatic cancer (PC) is a malignant disease with the worst prognosis. While little is known about the etiology of the PC and measures to prevent the condition, so far, a number of risk factors have been identified. Genetic factors, pre-malignant lesions, predisposing diseases and exogenous factors have been found to be linked to PC. Genetic susceptibility was observed in 10% of PC cases, including inherited PC syndromes and familial PC. However, in the remaining 90%, their PC might be caused by genetic factors in combination with environmental factors. Nonetheless, the exact mechanism of the two kinds of factors, endogenous and exogenous, working together to cause PC remains poorly understood. The fact that most pancreatic neoplasms are diagnosed at an incurable stage of the disease highlights the need to identify risk factors and to understand their contribution to carcinogenesis. This article reviews the high risk factors contributing to the development of PC, to provide information for clinicians and epidemiologists. PMID:27376795

  6. High risk groups in oil shale workforce

    SciTech Connect

    Gratt, L.B.; Perry, B.W.; Marine, W.M.; Savitz, D.A.

    1984-04-01

    The workforce risks of a hypothetical one million barrels-per-day oil shale industry were estimated. The risks for the different workforce segments were compared and high risk groups were identified. Accidents and injuries were statistically described by rates for fatalities, for accidents with days lost from work, and for accidents with no days lost from work. Workforce diseases analyzed were cancers, silicosia, pneumoconiosis, chronic bronchitis, chronic airway obstruction, and high frequency hearing loss. A comparison of the workforce groups under different risk measures (occurrence, fatality, and life-loss expectancy) was performed. The miners represented the group with the largest fatality and the most serious accident rate, although the estimated rates were below the average industry-wide underground mining experience. Lung disease from inhalation exposure of about the nuisance dust threshold limit value presents a significant risk for future concerns. If future environmental dust exposure is at the 100 ..mu..g/m/sup 3/ alpha-quartz level, safety improvements in the mining sector are of prime importance to reduce the oil shale worker's life-loss expectancy. 11 references, 1 figure, 11 tables.

  7. Developmental Pathways to Sexual Risk Behavior in High-Risk Adolescent Boys

    PubMed Central

    Brennan, Lauretta M.; Forbes, Erika; Shaw, Daniel S.

    2014-01-01

    OBJECTIVE: Adolescent boys’ involvement in pregnancy and sexual risk behavior is a public health concern. Although research has identified predictors of sexual risk behavior during adolescence, few studies have investigated precursors to boys’ sexual risk behavior beginning in early childhood, the identification of which could serve to inform interventions and help reduce involvement in pregnancy. Our goal was to identify early developmental pathways associated with sexual risk behavior in a sample of low-income adolescent boys. METHODS: Data from a prospective longitudinal study in 310 at-risk boys were used to examine externalizing problems, mothers’ depressive symptoms, and low-nurturant parenting in early childhood (1.5, 2, and 3.5 years old) and daring, externalizing, parental monitoring, and deviant peer affiliation during emerging adolescence (11 and 12 years old) as precursors of sexual risk behavior between the ages 15 and 20 years. Structural equation modeling was used to explore pathways associated with later high-risk sexual behavior (HRSB). RESULTS: In multivariate analyses, adolescent daring and deviant peer affiliation at age 12 were associated with later HRSB. Furthermore, deviant peer affiliation during emerging adolescence mediated the relationship between mothers’ depressive symptoms and nurturant parenting during early childhood and later adolescent HRSB. CONCLUSIONS: Family-based risk factors in early childhood are predictive of HRSB in adolescence but are also influenced, and in some cases mediated, by relationships with peers and child characteristics during emerging adolescence. PMID:24819568

  8. Roles of Genetic Polymorphisms in the Folate Pathway in Childhood Acute Lymphoblastic Leukemia Evaluated by Bayesian Relevance and Effect Size Analysis

    PubMed Central

    Lautner-Csorba, Orsolya; Gézsi, András; Erdélyi, Dániel J.; Hullám, Gábor; Antal, Péter; Semsei, Ágnes F.; Kutszegi, Nóra; Kovács, Gábor; Falus, András; Szalai, Csaba

    2013-01-01

    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 supplementary to

  9. ARID5B, IKZF1 and Non-Genetic Factors in the Etiology of Childhood Acute Lymphoblastic Leukemia: The ESCALE Study

    PubMed Central

    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

  10. High-risk sex offenders may not be high risk forever.

    PubMed

    Hanson, R Karl; Harris, Andrew J R; Helmus, Leslie; Thornton, David

    2014-10-01

    This study examined the extent to which sexual offenders present an enduring risk for sexual recidivism over a 20-year follow-up period. Using an aggregated sample of 7,740 sexual offenders from 21 samples, the yearly recidivism rates were calculated using survival analysis. Overall, the risk of sexual recidivism was highest during the first few years after release, and decreased substantially the longer individuals remained sex offense-free in the community. This pattern was particularly strong for the high-risk sexual offenders (defined by Static-99R scores). Whereas the 5-year sexual recidivism rate for high-risk sex offenders was 22% from the time of release, this rate decreased to 4.2% for the offenders in the same static risk category who remained offense-free in the community for 10 years. The recidivism rates of the low-risk offenders were consistently low (1%-5%) for all time periods. The results suggest that offense history is a valid, but time-dependent, indicator of the propensity to sexually reoffend. Further research is needed to explain the substantial rate of desistance by high-risk sexual offenders. PMID:24664250

  11. The Psychosis High-Risk State

    PubMed Central

    Fusar-Poli, Paolo; Borgwardt, Stefan; Bechdolf, Andreas; Addington, Jean; Riecher-Rössler, Anita; Schultze-Lutter, Frauke; Keshavan, Matcheri; Wood, Stephen; Ruhrmann, Stephan; Seidman, Larry J.; Valmaggia, Lucia; Cannon, Tyrone; Velthorst, Eva; De Haan, Lieuwe; Cornblatt, Barbara; Bonoldi, Ilaria; Birchwood, Max; McGlashan, Thomas; Carpenter, William; McGorry, Patrick; Klosterkötter, Joachim; McGuire, Philip; Yung, Alison

    2014-01-01

    Context During the past 2 decades, a major transition in the clinical characterization of psychotic disorders has occurred. The construct of a clinical high-risk (HR) state for psychosis has evolved to capture the prepsychotic phase, describing people presenting with potentially prodromal symptoms. The importance of this HR state has been increasingly recognized to such an extent that a new syndrome is being considered as a diagnostic category in the DSM-5. Objective To reframe the HR state in a comprehensive state-of-the-art review on the progress that has been made while also recognizing the challenges that remain. Data Sources Available HR research of the past 20 years from PubMed, books, meetings, abstracts, and international conferences. Study Selection and Data Extraction Critical review of HR studies addressing historical development, inclusion criteria, epidemiologic research, transition criteria, outcomes, clinical and functional characteristics, neurocognition, neuroimaging, predictors of psychosis development, treatment trials, socioeconomic aspects, nosography, and future challenges in the field. Data Synthesis Relevant articles retrieved in the literature search were discussed by a large group of leading worldwide experts in the field. The core results are presented after consensus and are summarized in illustrative tables and figures. Conclusions The relatively new field of HR research in psychosis is exciting. It has the potential to shed light on the development of major psychotic disorders and to alter their course. It also provides a rationale for service provision to those in need of help who could not previously access it and the possibility of changing trajectories for those with vulnerability to psychotic illnesses. PMID:23165428

  12. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    ClinicalTrials.gov

    2016-07-18

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

  13. A rare type of secondary cancer in a child with acute lymphoblastic leukemia: malignant fibrous histiocytoma.

    PubMed

    Incesoy Özdemir, Sonay; Balkaya, Eda; Ören, Ayşe C; Bozkurt, Ceyhun; Sahin, Gürses; Ünlü, Ramazan E; Ertem, Ayşe U

    2014-03-01

    Secondary cancers which are related with treatment of childhood acute lymphoblastic leukemia (ALL) is a significant problem with longer term. For development of secondary cancer after treatment, the latency period varies between 5 and 10 years. In this case, a 13 year-old-boy diagnosed as high-risk ALL was treated with chemotherapy and prophylactic cranial radiotherapy at a dose of 1800 cGy. Six years after the end of treatment he developed a 5 × 5 × 4 cm mass at the right temporal region of the cranium. The mass was excised totally with clear surgical margin. Pathology of mass has been diagnosed as malignant fibrous histiocytoma (MFH), recently referred to as an undifferentiated pleomorphic sarcoma (UPS). After treatment of childhood ALL, reported cases of secondary MFH is extremely rare in the literature. Herein we present a case of MFH/UPS that developed as a secondary cancer 6 years after the end of ALL treatment. PMID:24096378

  14. Management of acute childhood fevers.

    PubMed

    Teuten, Polly; Paul, Siba Prosad; Heaton, Paul Anthony

    2015-01-01

    Feverish illnesses commonly affect children and are the second most frequent reason for a child to be admitted to hospital. Most cases are viral in origin, usually with a good prognosis. Fever can be caused by severe and rapidly progressive illness which needs urgent referral to hospital for potentially life-saving treatment, and community practitioners must be able to identify such cases showing 'red flag'features. The fear of serious disease among parents and carers may result in 'fever phobia' leading to minor illnesses being managed inappropriately. Community practitioners are well placed to reassure and support families, and to provide education regarding the facts about fever, the appropriate use of antipyretic medication, how to avoid dehydration, and the beneficial role of immunisation in preventing infection. PMID:26387247

  15. Hepatic Sinusoidal Obstruction Syndrome During Chemotherapy for Childhood Medulloblastoma: Report of a Case and Review of the Literature

    PubMed Central

    Buckland, Amy; Phillips, Marianne B.; Cole, Catherine H.; Gottardo, Nicholas G.

    2014-01-01

    Hepatic sinusoidal obstruction syndrome (HSOS), also known as veno-occlusive disease, is a well-recognized toxic complication after autologous and allogeneic hematopoietic stem cell transplant, during treatment of Wilms tumor and rhabdomyosarcoma associated with actinomycin-D, and during acute lymphoblastic leukemia therapy due to oral 6-thioguanine. However, its occurrence in the context of chemotherapy regimens for other childhood malignancies is rare. We report a 5-year-old girl with high-risk anaplastic medulloblastoma, who developed severe HSOS during her second cycle of maintenance chemotherapy, consisting of vincristine, cisplatin, and cyclophosphamide. She was treated with defibrotide with complete resolution of the HSOS. These findings and a review of the literature, highlight the occurrence of HSOS in children outside the established settings of hematopoietic stem cell transplantation, Wilms tumor, rhabdomyosarcoma, and acute lymphoblastic leukemia. PMID:24276042

  16. Evaluating a Comprehensive Strategy to Improve Engagement to Group-Based Behavioral Parent Training for High-Risk Families of Children with ADHD

    ERIC Educational Resources Information Center

    Chacko, Anil; Wymbs, Brian T.; Chimiklis, Alyssa; Wymbs, Frances A.; Pelham, William E.

    2012-01-01

    Behavioral parent training (BPT) is an evidence-based intervention for the treatment of attention-deficit/hyperactivity disorder (ADHD) and related disruptive behavioral disorders of childhood. Despite convincing data on effectiveness, engagement to BPT, particularly for high-risk families, has been a long standing, yet understudied, issue. Data…

  17. Treatment Options for Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  18. Stages of Adult Acute Myeloid Leukemia

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  19. Treatment Option Overview (Adult Acute Myeloid Leukemia)

    MedlinePlus

    ... Treatment Childhood AML Treatment Research Adult Acute Myeloid Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Myeloid Leukemia Go to Health Professional Version Key Points Adult ...

  20. Social work services in a high-risk nursery.

    PubMed

    Sheridan, M S; Johnson, D R

    1976-05-01

    Why should a social worker be on the team of a neonatal intensive-care nursery? Helping parents cope with the crises that arise with high-risk births is only one important reason. Ameliorating staff stress is another. Also, by following up the high-risk babies, the social worker has an opportunity to play a preventive role. PMID:185126

  1. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 15 Commerce and Foreign Trade 1 2011-01-01 2011-01-01 false High risk special award conditions. 14.14 Section 14.14 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM...-PROFIT, AND COMMERCIAL ORGANIZATIONS Pre-Award Requirements § 14.14 High risk special award...

  2. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 15 Commerce and Foreign Trade 1 2013-01-01 2013-01-01 false High risk special award conditions. 14.14 Section 14.14 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM...-PROFIT, AND COMMERCIAL ORGANIZATIONS Pre-Award Requirements § 14.14 High risk special award...

  3. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 15 Commerce and Foreign Trade 1 2012-01-01 2012-01-01 false High risk special award conditions. 14.14 Section 14.14 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM...-PROFIT, AND COMMERCIAL ORGANIZATIONS Pre-Award Requirements § 14.14 High risk special award...

  4. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 15 Commerce and Foreign Trade 1 2014-01-01 2014-01-01 false High risk special award conditions. 14.14 Section 14.14 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM...-PROFIT, AND COMMERCIAL ORGANIZATIONS Pre-Award Requirements § 14.14 High risk special award...

  5. 15 CFR 14.14 - High risk special award conditions.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 15 Commerce and Foreign Trade 1 2010-01-01 2010-01-01 false High risk special award conditions. 14.14 Section 14.14 Commerce and Foreign Trade Office of the Secretary of Commerce UNIFORM...-PROFIT, AND COMMERCIAL ORGANIZATIONS Pre-Award Requirements § 14.14 High risk special award...

  6. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2010-07-01 2010-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  7. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2014-07-01 2014-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  8. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2012-07-01 2012-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  9. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2011-07-01 2011-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  10. 40 CFR 35.6790 - High risk recipients.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... described in 40 CFR 31.12. Requirements for Administering a Superfund State Contract (SSC) ... 40 Protection of Environment 1 2013-07-01 2013-07-01 false High risk recipients. 35.6790 Section... Actions Other Administrative Requirements for Cooperative Agreements § 35.6790 High risk recipients....

  11. 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

    PubMed Central

    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

  12. 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.

    PubMed

    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; Rangel-López, Angélica; 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

  13. Childhood Obesity: Prediction and Prevention.

    ERIC Educational Resources Information Center

    Miller, Michael D.

    Obesity in children is a problem both insidious and acute. Childhood obesity has been indicated as a forerunner of adult obesity; it is also an immediate problem for the child. Given the lack of evidence for long term maintenance of any weight loss, this paper investigates the etiology of the disorder as a prelude to prevention. Upon review of the…

  14. Lenalidomide maintenance for high-risk multiple myeloma after allogeneic hematopoietic cell transplantation.

    PubMed

    Alsina, Melissa; Becker, Pamela S; Zhong, Xiaobo; Adams, Alexia; Hari, Parameswaran; Rowley, Scott; Stadtmauer, Edward A; Vesole, David H; Logan, Brent; Weisdorf, Daniel; Qazilbash, Muzaffar; Popplewell, Leslie L; McClune, Brian; Bensinger, William; Riches, Marcie; Giralt, Sergio A; Pasquini, Marcelo C

    2014-08-01

    Allogeneic hematopoietic cell transplantation (alloHCT) with reduced-intensity conditioning is an appealing option for patients with high-risk multiple myeloma (MM). However, progression after alloHCT remains a challenge. Maintenance therapy after alloHCT may offer additional disease control and allow time for a graft-versus-myeloma effect. The primary objective of this clinical trial was to determine the tolerability and safety profile of maintenance lenalidomide (LEN) given on days 1 to 21 of 28 days cycles, with intrapatient dose escalation during 12 months/cycles after alloHCT. Thirty alloHCT recipients (median age, 54 years) with high-risk MM were enrolled at 8 centers between 2009 and 2012. The median time from alloHCT to LEN initiation was 96 days (range, 66 to 171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%). Most common reasons for discontinuation were acute graft-versus-host disease (GVHD) (37%) and disease progression (37%). Cumulative incidence of grades III to IV acute GVHD from time of initiation of LEN was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplantation-related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN after alloHCT is feasible at lower doses, although it is associated with a 38% incidence of acute GVHD. Survival outcomes observed in this high-risk MM population warrant further study of this approach. PMID:24769014

  15. Transforming the legacies of childhood trauma in couple and family therapy.

    PubMed

    Basham, Kathryn

    2004-01-01

    A multi-theoretical couple/family therapy clinical social work practice model synthesizes various social, family, trauma, and psychodynamic theories to inform a biopsychosocial assessment that guides clinical interventions. The client population involves adult partners who have negotiated the impact of childhood trauma, i.e., physical, sexual, and emotional abuses, including culturally sanctioned trauma. Couples may also be dealing with the aftermath of acute trauma related to interpersonal violence, political conflict, and/or the dislocations related to refugee or new immigrant status. Clinical examples demonstrate the usefulness of the model as well as contraindications when active physical violence is present. The construct of resilience remains a central focus in assessment and treatment. Specific attention to cultural and racial diversity enriches both assessment and treatment interventions with these high-risk couples and families. This practice model will be explicated in depth in an upcoming publication from Columbia University Press titled Transforming the Legacies of Trauma in Couple Therapy. PMID:15774396

  16. Acute myelogenous leukemia (AML) -- children

    MedlinePlus

    ... Leung WH, Pounds S, Cao X, e t al. Definition of cure in childhood acute myeloid leukemia. Cancer . 2014 Aug ... MD, Medical Oncologist, Fresno, CA. Review provided by VeriMed Healthcare Network. Also reviewed by ...

  17. Toddlers at High Risk of Chemical Eye Burns

    MedlinePlus

    ... fullstory_160258.html Toddlers at High Risk of Chemical Eye Burns: Study Access to household cleaning products ... and 2 years have relatively high rates of chemical eye burns, with everyday cleaners a common cause, ...

  18. Treating Patients with High-Risk Smoldering Myeloma

    Cancer.gov

    In this phase III clinical trial, patients with smoldering myeloma classified as high risk for progression will be randomly assigned to undergo standard observation or six 4-week courses of treatment with the drug lenalidomide.

  19. Understanding Suicide Risk: Identification of High Risk Groups during High Risk Times

    PubMed Central

    Overholser, James C.; Braden, Abby; Dieter, Lesa

    2012-01-01

    Background The assessment of suicide risk is a complex task for mental health professionals. Certain demographic groups are associated with completed suicide including males, divorced adults, and Caucasians. However, demographic variables alone provide a crude assessment of suicide risk. Psychiatric diagnosis and recent life events may improve the identification of high risk individuals. Method The current study evaluated 148 individuals who died by suicide compared to 257 adults who died suddenly from accidents or medical problems. Psychological autopsy was used to assess Axis I psychiatric diagnosis and recent stressful life events. Results Suicide completers were significantly more likely than comparison subjects to have a depressive disorder, a substance abuse disorder, and to have experienced interpersonal conflict in the months leading up to their death. A discriminant function analysis revealed that the combination of demographic variables, recent stressful life events, and psychiatric diagnoses best discriminated between suicide completers and comparison subjects. Conclusions Proper assessment of suicide risk should include a comprehensive evaluation of demographic characteristics, recent life stressors, and psychiatric diagnosis. PMID:22140004

  20. Management of High-Risk Cutaneous Squamous Cell Carcinoma

    PubMed Central

    Jennings, Lorraine

    2010-01-01

    Cutaneous squamous cell carcinoma is an increasing public health concern, representing the second most common cancer in the United States. High-risk cutaneous squamous cell carcinoma represents a subgroup of this disease, where patients are at higher risk of metastasis and death. To date, there are no accepted criteria for defining or managing these patients. This review discusses the current state of knowledge of high-risk cutaneous squamous cell carcinoma and outlines reasonable management strategies based on available data. PMID:20725546

  1. A multidisciplinary QA program for enteral nutrition in high-risk patients.

    PubMed

    D'Addario, V; Danek, M

    1991-01-01

    An increase in elderly patients and severity of illness rates means greater use of nasogastric feeding tubes for both high-risk acutely ill and chronically ill patients. When the QA screening process at Booth Memorial Medical Center revealed a certain percentage of complications with small bore, weight-tipped feeding tubes inserted through the nares, a multidisciplinary peer review committee (MPRC) was formed to review the enteral nutrition program. After a literature review to determine possible complications, the MPRC identified lung perforations due to tube misplacement, tube feeding aspiration into the lungs leading to possible aspiration pneumonia, and an internal tip separation from the tube product failure. Unconscious incubated patients on ventilators were shown as at high risk for feeding tube misplacement in an initial MPRC patient study. A second study evaluated several different feeding tube products in the medical, respiratory and surgical ICU. The MPRC established a credentialing process for physician assistants, interns and residents in feeding tube placement. The MPRC proceedings were presented to the hospital-wide QA committee for review, endorsement and recommendations on all policy and procedure changes. The conclusions were that a more concerted effort must be made to improve medical management and encourage ongoing education in the administration of enteral feedings to high-risk patients. PMID:10113670

  2. Factors and Outcomes Associated with MRCP Use prior to ERCP in Patients at High Risk for Choledocholithiasis

    PubMed Central

    Anand, Gobind; Patel, Yuval A.; Yeh, Hsin-Chieh; Khashab, Mouen A.; Lennon, Anne Marie; Shin, Eun Ji; Canto, Marcia I.; Okolo, Patrick I.; Kalloo, Anthony N.; Singh, Vikesh K.

    2016-01-01

    Background. Consensus guidelines recommend that patients at high risk for choledocholithiasis undergo endoscopic retrograde cholangiopancreatography (ERCP) without additional imaging. This study evaluates factors and outcomes associated with performing magnetic resonance cholangiopancreatography (MRCP) prior to ERCP among patients at high risk for choledocholithiasis. Methods. An institutional administrative database was searched using diagnosis codes for choledocholithiasis, cholangitis, and acute pancreatitis and procedure codes for MRCP and ERCP. Patients categorized as high risk for choledocholithiasis were evaluated. Results. 224 patients classified as high risk, of whom 176 (79%) underwent ERCP only, while 48 (21%) underwent MRCP prior to ERCP. Patients undergoing MRCP experienced longer time to ERCP (72 hours versus 35 hours, p < 0.0001), longer length of stay (8 days versus 6 days, p = 0.02), higher hospital charges ($23,488 versus $19,260, p = 0.08), and higher radiology charges ($3,385 versus $1,711, p < 0.0001). The presence of common bile duct stone(s) on ultrasound was the only independent factor associated with less use of MRCP (OR 0.09, p < 0.0001). Conclusions. MRCP use prior to ERCP in patients at high risk for choledocholithiasis is common and associated with greater length of hospital stay, higher radiology charges, and a trend towards higher hospital charges. PMID:27446845

  3. Umbilical cord blood transplant from unrelated HLA-mismatched donors in children with high risk leukemia.

    PubMed

    Arcese, W; Guglielmi, C; Iori, A P; Screnci, M; Carmini, D; Testi, A M; Moleti, M L; Mengarelli, A; Del Giudice, I; Cimino, G; Elia, L; Rapanotti, M C; Perrone, P; Laurenti, L; Gentile, G; Boecklin, F; Romano, A; De Felice, L; Mandelli, F

    1999-03-01

    In the last 3 years, 14 children with high-risk leukemia (11 ALL, 2 AML and 1 CML) underwent cord blood transplantation from unrelated HLA-mismatched donors at a median of 99 days from the start of search. Eight patients were transplanted in second CR, one in accelerated phase, three at relapse and two patients in first CR. Conditioning regimen (fractionated TBI, etoposide, CY and anti-lymphocyte serum) and prophylaxis of GVHD (CsA and 6-methylprednisolone) were identical for all patients. Neutrophils >0.5x10(9)/l were reached at a median of 33 days from transplant, but in four cases we observed an autologous hematopoietic reconstitution (three spontaneous, one after autologous BM rescue). Acute and chronic GVHD were observed in 10/14 and 3/8 evaluable cases, respectively. Three patients died of transplant-related toxicity and three patients relapsed. The probabilities of event-free, disease-free and overall survival were 50, 53 and 64%, respectively. Cord blood transplant from HLA-mismatched unrelated donor is a valid option for the treatment of children with high-risk leukemia. With our eligibility criteria, conditioning regimen and prophylaxis of graft-versus-host disease, the main obstacles to successful transplant were represented by graft failure and fatal acute GVHD. PMID:10217184

  4. Childhood Leukemia

    MedlinePlus

    Leukemia is cancer of the white blood cells. It is the most common type of childhood cancer. ... blood cells help your body fight infection. In leukemia, the bone marrow produces abnormal white blood cells. ...

  5. Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-03-25

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

  6. Brachytherapy boost and cancer-specific mortality in favorable high-risk versus other high-risk prostate cancer

    PubMed Central

    Muralidhar, Vinayak; Xiang, Michael; Orio, Peter F.; Martin, Neil E.; Beard, Clair J.; Feng, Felix Y.; Hoffman, Karen E.

    2016-01-01

    Purpose Recent retrospective data suggest that brachytherapy (BT) boost may confer a cancer-specific survival benefit in radiation-managed high-risk prostate cancer. We sought to determine whether this survival benefit would extend to the recently defined favorable high-risk subgroup of prostate cancer patients (T1c, Gleason 4 + 4 = 8, PSA < 10 ng/ml or T1c, Gleason 6, PSA > 20 ng/ml). Material and methods We identified 45,078 patients in the Surveillance, Epidemiology, and End Results database with cT1c-T3aN0M0 intermediate- to high-risk prostate cancer diagnosed 2004-2011 treated with external beam radiation therapy (EBRT) only or EBRT plus BT. We used multivariable competing risks regression to determine differences in the rate of prostate cancer-specific mortality (PCSM) after EBRT + BT or EBRT alone in patients with intermediate-risk, favorable high-risk, or other high-risk disease after adjusting for demographic and clinical factors. Results EBRT + BT was not associated with an improvement in 5-year PCSM compared to EBRT alone among patients with favorable high-risk disease (1.6% vs. 1.8%; adjusted hazard ratio [AHR]: 0.56; 95% confidence interval [CI]: 0.21-1.52, p = 0.258), and intermediate-risk disease (0.8% vs. 1.0%, AHR: 0.83, 95% CI: 0.59-1.16, p = 0.270). Others with high-risk disease had significantly lower 5-year PCSM when treated with EBRT + BT compared with EBRT alone (3.9% vs. 5.3%; AHR: 0.73; 95% CI: 0.55-0.95; p = 0.022). Conclusions Brachytherapy boost is associated with a decreased rate of PCSM in some men with high-risk prostate cancer but not among patients with favorable high-risk disease. Our results suggest that the recently-defined “favorable high-risk” category may be used to personalize therapy for men with high-risk disease. PMID:26985191

  7. Underreporting High-Risk Prescribing Among Medicare Advantage Plans

    PubMed Central

    Cooper, Alicia L.; Kazis, Lewis E.; Dore, David D.; Mor, Vincent; Trivedi, Amal N.

    2016-01-01

    Background Although Medicare Advantage plans are required to report clinical performance using Healthcare Effectiveness Data and Information Set (HEDIS) quality indicators, the accuracy of plan-reported performance rates is unknown. Objective To compare calculated and reported rates of high-risk prescribing among Medicare Advantage plans. Design Cross-sectional comparison. Setting 172 Medicare Advantage plans. Patients A random sample of beneficiaries in 172 Medicare Advantage plans in 2006 (n = 177 227) and 2007 (n = 173 655). Measurements Plan-reported HEDIS rates of high-risk prescribing among elderly persons were compared with rates calculated from Medicare Advantage plans’ Part D claims by using the same measure specifications and source population. Results The mean rate of high-risk prescribing derived from Part D claims was 26.9% (95% CI, 25.9% to 28.0%), whereas the mean plan-reported rate was 21.1% (CI, 20.0% to 22.3%). Approximately 95% of plans underreported rates of high-risk prescribing relative to calculated rates derived from Part D claims. The differences in the calculated and reported rates negatively affected quality rankings for the plans that most accurately reported rates. For example, the 9 plans that reported rates of high-risk prescribing within 1 percentage point of calculated rates were ranked 43.4 positions lower when reported rates were used instead of calculated rates. Among 103 680 individuals present in both the sample of Part D claims and HEDIS data in 2006, Medicare Advantage plans incorrectly excluded 10.3% as ineligible for the HEDIS high-risk prescribing measure. Among those correctly included in the high-risk prescribing denominator, the reported rate of high-risk prescribing was 21.9% and the calculated rate was 26.2%. Limitation A single quality measure was assessed. Conclusion Medicare Advantage plans underreport rates of high-risk prescribing, suggesting a role for routine audits to ensure the validity of publicly reported

  8. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols.

    PubMed

    Paulsson, Kajsa; Forestier, Erik; Andersen, Mette K; Autio, Kirsi; Barbany, Gisela; Borgström, Georg; Cavelier, Lucia; Golovleva, Irina; Heim, Sverre; Heinonen, Kristiina; Hovland, Randi; Johannsson, Johann H; Kjeldsen, Eigil; Nordgren, Ann; Palmqvist, Lars; Johansson, Bertil

    2013-09-01

    Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1-15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age of patients with "classic" high hyperdiploidy was lower than that of patients with translocation-positive high hyperdiploidy (P<0.001). Cases with triple trisomies (+4, +10, +17), comprising 50%, had higher modal numbers than the triple trisomy-negative cases (P<0.0001). The probabilities of event-free survival and overall survival were lower for those with white blood cell counts ≥ 50 × 10(9)/L (P=0.017/P=0.009), ≥ 5% bone marrow blasts at day 29 (P=0.001/0.002), and for high-risk patients (P<0.001/P=0.003), whereas event-free, but not overall, survival, was higher for cases with gains of chromosomes 4 (P<0.0001), 6 (P<0.003), 17 (P=0.010), 18 (P=0.049), and 22 (P=0.040), triple trisomies (P=0.002), and modal numbers >53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by a particularly favorable outcome. PMID:23645689

  9. High modal number and triple trisomies are highly correlated favorable factors in childhood B-cell precursor high hyperdiploid acute lymphoblastic leukemia treated according to the NOPHO ALL 1992/2000 protocols

    PubMed Central

    Paulsson, Kajsa; Forestier, Erik; Andersen, Mette K.; Autio, Kirsi; Barbany, Gisela; Borgström, Georg; Cavelier, Lucia; Golovleva, Irina; Heim, Sverre; Heinonen, Kristiina; Hovland, Randi; Johannsson, Johann H.; Kjeldsen, Eigil; Nordgren, Ann; Palmqvist, Lars; Johansson, Bertil

    2013-01-01

    Between 1992 and 2008, 713 high hyperdiploid acute lymphoblastic leukemias in children aged 1–15 years were diagnosed and treated according to the Nordic Society for Pediatric Hematology and Oncology acute lymphoblastic leukemia 1992/2000 protocols. Twenty (2.8%) harbored t(1;19), t(9;22), der(11q23), or t(12;21). The median age of patients with “classic” high hyperdiploidy was lower than that of patients with translocation-positive high hyperdiploidy (P<0.001). Cases with triple trisomies (+4, +10, +17), comprising 50%, had higher modal numbers than the triple trisomy-negative cases (P<0.0001). The probabilities of event-free survival and overall survival were lower for those with white blood cell counts ≥50×109/L (P=0.017/P=0.009), ≥5% bone marrow blasts at day 29 (P=0.001/0.002), and for high-risk patients (P<0.001/P=0.003), whereas event-free, but not overall, survival, was higher for cases with gains of chromosomes 4 (P<0.0001), 6 (P<0.003), 17 (P=0.010), 18 (P=0.049), and 22 (P=0.040), triple trisomies (P=0.002), and modal numbers >53/55 (P=0.020/0.024). In multivariate analyses, modal number and triple trisomies were significantly associated with superior event-free survival in separate analyses with age and white blood cell counts. When including both modal numbers and triple trisomies, only low white blood cell counts were significantly associated with superior event-free survival (P=0.009). We conclude that high modal chromosome numbers and triple trisomies are highly correlated prognostic factors and that these two parameters identify the same subgroup of patients characterized by a particularly favorable outcome. PMID:23645689

  10. The Linkages among Childhood Maltreatment, Adolescent Mental Health, and Self-Compassion in Child Welfare Adolescents

    ERIC Educational Resources Information Center

    Tanaka, Masako; Wekerle, Christine; Schmuck, Mary Lou; Paglia-Boak, Angela

    2011-01-01

    Objectives: Childhood maltreatment is a robust risk factor for poor physical and mental health. Child welfare youths represent a high-risk group, given the greater likelihood of severe or multiple types of maltreatment. This study examined the relationship between childhood maltreatment and self-compassion--a concept of positive acceptance of…

  11. Thromboembolism Prophylaxis in Hip Arthroplasty: Routine and High Risk Patients.

    PubMed

    Nam, Denis; Nunley, Ryan M; Johnson, Staci R; Keeney, James A; Clohisy, John C; Barrack, Robert L

    2015-12-01

    This study's purpose was to present the use of a risk stratification protocol in which "routine" risk patients receive a mobile compression device with aspirin and "high" risk patients receive warfarin for thromboprophylaxis after hip arthroplasty. 1859 hip arthroplasty patients were prospectively enrolled (1402 routine risk--75.4%, 457 high risk--24.6%). The cumulative rate of venous thromboembolism events was 0.5% in the routine versus 0.5% in the high-risk cohort within 6weeks postoperatively (P=1.00). Patients in the routine risk cohort had a lower rate of major bleeding (0.5% versus 2.0%, P=0.006) and wound complications (0.2% versus 1.2%, P=0.01). Use of our risk stratification protocol allowed the avoidance of more aggressive anticoagulation in 75% of patients while achieving a low overall incidence of symptomatic VTE. PMID:26182980

  12. High-risk prostate cancer: the role of surgical management.

    PubMed

    Morlacco, Alessandro; Karnes, R Jeffrey

    2016-06-01

    High-risk prostate cancer (HR Pca) is a highly heterogeneous disease from a biological and clinical standpoint, and it carries a significant chance of morbidity and mortality. Despite the impact of PSA screening, a significant number of men continue to present with high risk disease and need adequate management: clinical evidence shows that a considerable fraction on men with HR PCa can be actually cured with either uni- or multi-modality approaches. Surgical treatment, once considered unfeasible in this setting, is acquiring more and more diffusion in modern clinical practice. Herein we discuss the main treatment strategies for high-risk prostate cancer, providing an expert opinion on the role of surgical management and its outcomes in the most recent literature. PMID:27155934

  13. Telomerase activation by genomic rearrangements in high-risk neuroblastoma

    PubMed Central

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L.; Sand, Frederik; Heuckmann, Johannes M.; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Glöckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R.; Savelyeva, Larissa; Watkins, Simon C.; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H.; Herrmann, Carl; O’Sullivan, Roderick J.; Westermann, Frank; Thomas, Roman K.; Fischer, Matthias

    2016-01-01

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system1. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive2–4. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type1,2,5. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  14. Telomerase activation by genomic rearrangements in high-risk neuroblastoma.

    PubMed

    Peifer, Martin; Hertwig, Falk; Roels, Frederik; Dreidax, Daniel; Gartlgruber, Moritz; Menon, Roopika; Krämer, Andrea; Roncaioli, Justin L; Sand, Frederik; Heuckmann, Johannes M; Ikram, Fakhera; Schmidt, Rene; Ackermann, Sandra; Engesser, Anne; Kahlert, Yvonne; Vogel, Wenzel; Altmüller, Janine; Nürnberg, Peter; Thierry-Mieg, Jean; Thierry-Mieg, Danielle; Mariappan, Aruljothi; Heynck, Stefanie; Mariotti, Erika; Henrich, Kai-Oliver; Gloeckner, Christian; Bosco, Graziella; Leuschner, Ivo; Schweiger, Michal R; Savelyeva, Larissa; Watkins, Simon C; Shao, Chunxuan; Bell, Emma; Höfer, Thomas; Achter, Viktor; Lang, Ulrich; Theissen, Jessica; Volland, Ruth; Saadati, Maral; Eggert, Angelika; de Wilde, Bram; Berthold, Frank; Peng, Zhiyu; Zhao, Chen; Shi, Leming; Ortmann, Monika; Büttner, Reinhard; Perner, Sven; Hero, Barbara; Schramm, Alexander; Schulte, Johannes H; Herrmann, Carl; O'Sullivan, Roderick J; Westermann, Frank; Thomas, Roman K; Fischer, Matthias

    2015-10-29

    Neuroblastoma is a malignant paediatric tumour of the sympathetic nervous system. Roughly half of these tumours regress spontaneously or are cured by limited therapy. By contrast, high-risk neuroblastomas have an unfavourable clinical course despite intensive multimodal treatment, and their molecular basis has remained largely elusive. Here we have performed whole-genome sequencing of 56 neuroblastomas (high-risk, n = 39; low-risk, n = 17) and discovered recurrent genomic rearrangements affecting a chromosomal region at 5p15.33 proximal of the telomerase reverse transcriptase gene (TERT). These rearrangements occurred only in high-risk neuroblastomas (12/39, 31%) in a mutually exclusive fashion with MYCN amplifications and ATRX mutations, which are known genetic events in this tumour type. In an extended case series (n = 217), TERT rearrangements defined a subgroup of high-risk tumours with particularly poor outcome. Despite a large structural diversity of these rearrangements, they all induced massive transcriptional upregulation of TERT. In the remaining high-risk tumours, TERT expression was also elevated in MYCN-amplified tumours, whereas alternative lengthening of telomeres was present in neuroblastomas without TERT or MYCN alterations, suggesting that telomere lengthening represents a central mechanism defining this subtype. The 5p15.33 rearrangements juxtapose the TERT coding sequence to strong enhancer elements, resulting in massive chromatin remodelling and DNA methylation of the affected region. Supporting a functional role of TERT, neuroblastoma cell lines bearing rearrangements or amplified MYCN exhibited both upregulated TERT expression and enzymatic telomerase activity. In summary, our findings show that remodelling of the genomic context abrogates transcriptional silencing of TERT in high-risk neuroblastoma and places telomerase activation in the centre of transformation in a large fraction of these tumours. PMID:26466568

  15. Integration of HIV Care into Community Management of Acute Childhood Malnutrition Permits Good Outcomes: Retrospective Analysis of Three Years of a Programme in Lusaka

    PubMed Central

    Amadi, Beatrice; Imikendu, Mercy; Sakala, Milika; Banda, Rosemary; Kelly, Paul

    2016-01-01

    Background While HIV has had a major impact on health care in southern Africa, there are few data on its impact on acute malnutrition in children in the community. We report an analysis of outcomes in a large programme of community management of acute malnutrition in the south of Lusaka. Programme Activities and Analysis Over 3 years, 68,707 assessments for undernutrition were conducted house-to-house, and children with severe acute malnutrition (SAM) or moderate acute malnutrition (MAM) were enrolled into either Outpatient Therapeutic Programme (OTP) or Supplementary Feeding Programme (SFP) respectively. Case records were analysed using tabulation and unconditional logistic regression. Findings 1,859 children (889 boys, 970 girls; median age 16 months) with MAM (n = 664) or SAM (n = 1,195) were identified. Of 1,796 children whose parents consented to testing, 185 (10.3%) were HIV positive. Altogether 1,163 (62.6%) were discharged as recovered from acute malnutrition. Case fatality while in the programme was 4.2% in children with SAM and 0.5% in those with MAM (RR of SAM 10.9; 95%CI 3.4,34.8; P<0.0001), and higher in children with HIV infection (RR 5.2, 95%CI 2.9, 9.0; P<0.0001). In multivariate analysis, HIV (OR 5.2; 95%CI 2.6, 10.1; P<0.0001), MUAC <11.5cm (OR 4.1; 95%CI 2.2, 7.4; P<0.0001) and the first year of the programme (OR 1.9; 95%CI 1.0, 3.4; P = 0.04) all increased mortality. Children with HIV infection who were able to initiate antiretroviral therapy had lower mortality (RR 0.23; 95%CI 0.10, 0.57; P = 0.0008). Interpretation Our programme suggests that a comprehensive community malnutrition programme, incorporating HIV care, can achieve low mortality even in a population heavily affected by HIV. PMID:26943124

  16. Fludarabine Phosphate, Cyclophosphamide, Tacrolimus, Mycophenolate Mofetil, Total-Body Irradiation, and Donor Bone Marrow Transplant in Treating Patients With High-Risk Hematologic Cancer

    ClinicalTrials.gov

    2014-02-27

    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); Adult Nasal Type Extranodal NK/T-cell Lymphoma; Anaplastic Large Cell Lymphoma; Angioimmunoblastic T-cell Lymphoma; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia; Childhood Myelodysplastic Syndromes; Childhood Nasal Type Extranodal NK/T-cell Lymphoma; Cutaneous B-cell Non-Hodgkin Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Hematopoietic/Lymphoid Cancer; 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 Burkitt Lymphoma; Recurrent Adult Diffuse Large Cell Lymphoma; Recurrent Adult Diffuse Mixed Cell Lymphoma; Recurrent Adult Diffuse Small Cleaved Cell Lymphoma; Recurrent Adult Grade III Lymphomatoid Granulomatosis; Recurrent Adult Hodgkin Lymphoma; Recurrent Adult Immunoblastic Large Cell Lymphoma; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Adult T-cell Leukemia/Lymphoma; Recurrent Childhood Anaplastic Large Cell Lymphoma; Recurrent Childhood Grade III Lymphomatoid Granulomatosis; Recurrent Childhood Large Cell Lymphoma; Recurrent Childhood Lymphoblastic Lymphoma; Recurrent Childhood Small Noncleaved Cell Lymphoma; Recurrent Cutaneous T-cell Non-Hodgkin Lymphoma; Recurrent Grade 1 Follicular Lymphoma; Recurrent Grade 2 Follicular Lymphoma

  17. Caudate Volume in Offspring at Ultra High Risk for Alcohol Dependence: COMT Val158Met, DRD2, Externalizing Disorders, and Working Memory*

    PubMed Central

    Hill, Shirley Y.; Lichenstein, Sarah; Wang, Shuhui; Carter, Howard; McDermott, Michael

    2014-01-01

    Background There is emerging evidence that the increased susceptibility to developing alcohol and substance use disorders in those with a family history of Alcohol Dependence (AD) may be related to structural differences in brain circuits that influence the salience of rewards or modify the efficiency of information processing. Externalizing disorders of childhood including Attention Deficit Hyperactivity Disorder, Conduct and Oppositional Disorders are a prominent feature of those with a positive family history. The caudate nuclei have been implicated in both the salience of rewards and in the pathophysiology of alcohol dependence and these often antecedent childhood disorders. Methods Adolescent/young adult high and low-risk for AD offspring (N = 130) were studied using magnetic resonance imaging. Volumes of the caudate nucleus were obtained using manual tracing with BRAINS2 software and neuropsychological functioning determined. Childhood disorders were assessed as part of a long-term longitudinal follow-up that includes young adult assessment. Dopaminergic variation was assessed using genotypic variation in the catechol-O-methyltransferase (COMT) and DRD2 genes. Results High-risk subjects showed poorer Working Memory functioning. Cau-date volume did not differ between high and low-risk subjects, but those with externalizing disorders of childhood showed reduced caudate volume. Variation in COMT and DRD2 genes was associated with Working Memory performance and caudate volume. Conclusions Caudate volume is reduced in association with externalizing disorders of childhood/adolescence. Working Memory deficits appear in familial high-risk offspring and those with externalizing disorders of childhood. The dopaminergic system appears to be involved in both working memory performance and externalizing disorders of childhood. PMID:25364629

  18. iTunes song-gifting is a low-cost, efficient recruitment tool to engage high-risk MSM in internet research.

    PubMed

    Holland, Christine M; Ritchie, Natalie D; Du Bois, Steve N

    2015-10-01

    This brief report describes methodology and results of a novel, efficient, and low-cost recruitment tool to engage high-risk MSM in online research. We developed an incentivization protocol using iTunes song-gifting to encourage participation of high-risk MSM in an Internet-based survey of HIV status, childhood sexual abuse, and adult behavior and functioning. Our recruitment methodology yielded 489 participants in 4.5 months at a total incentive cost of $1.43USD per participant. The sample comprised a critically high-risk group of MSM, including 71.0 % who reported recent condomless anal intercourse. We offer a "how-to" guide to aid future investigators in using iTunes song-gifting incentives. PMID:26174208

  19. High Risk Drinking among Non-Affiliated College Students

    ERIC Educational Resources Information Center

    Smith, Margaret; Finneran, John; Droppa, Marj

    2014-01-01

    This study investigated the high risk drinking practices of unaffiliated college students who are not involved in formal athletics, fraternities, or sororities. Using a qualitative research design, the investigators interviewed students at a northeast public college in fall 2010 to learn about unaffiliated students' drinking experiences and…

  20. Confronting Worst Case Scenarios: Education and High Risk Offenders.

    ERIC Educational Resources Information Center

    Duguid, Stephen

    1997-01-01

    Predicted vs. actual recidivism of 119 high-risk offenders aged 20-29 who had completed postsecondary prison education was compared. Despite a low predicted success rate, they achieved higher grade point averages, acquired more postrelease education, and had less recidivism. Success factors included a culture of academic achievement and student…

  1. Distribution of influenza vaccine to high-risk groups.

    PubMed

    Ompad, Danielle C; Galea, Sandro; Vlahov, David

    2006-01-01

    Vaccine distribution programs have historically targeted individuals at high risk of complications due to influenza. Despite recommendations from the Advisory Committee on Immunization Practices, vaccination coverage among high-risk populations has been generally low. This review systematically summarizes the recent literature evaluating programs in different settings, from within medical settings to venue-based and community-based approaches, in an effort to identify successful program components. The published literature was identified by using the MEDLINE database from 1990 to 2006 covering studies that reported on interventions or programs aimed at vaccinating high-risk populations. The authors reviewed 56 studies. In the United States, the Healthy People 2010 goals included 90% vaccination coverage for adults aged > or = 65 years and 60% for high-risk adults aged 18-64 years. Only a handful of the studies reviewed managed to meet those goals. Interventions that increased vaccination coverage to Healthy People 2010 goals included advertising, provider and patient mailings, registry-based telephone calls, patient and staff education, standing orders coupled with standardized forms, targeting of syringe exchange customers, and visiting nurses. Few studies evaluated the impact of vaccination programs by race/ethnicity and socioeconomic status. Few studies targeted individuals outside of the health-care and social services sectors. Given the growing disparities in health and health-care access, understanding the way in which interventions can remedy disparities is crucial. PMID:16707648

  2. ORGANOPHOSPHATE PESTICIDE EXPOSURES - WHERE ARE THE HIGH RISK CHILDREN?

    EPA Science Inventory

    Methods to identify children at high-risk for organophosphate (OP) pesticide exposure are difficult to develop because biological markers reflect only recent "snapshots" of exposure due to the short half-life of OP compounds (generally about 24 hours). We conducted a series of p...

  3. Staying Alive! Training High-Risk Teams for Self Correction

    NASA Technical Reports Server (NTRS)

    Slack, Kelley; Noe, Raymond; Weaver, Sallie

    2011-01-01

    Research examining teams working in high-risk operations has been lacking. The present symposium showcases research on team training that helps to optimize team performance in environments characterized by life or death situations arising spontaneously after long periods of mundane activity by pulling experts from diverse areas of industry: space flight, health care, and medical simulation.

  4. The High-Risk (Disturbed and Disturbing) College Student

    ERIC Educational Resources Information Center

    Hollingsworth, Kathy R.; Dunkle, John H.; Douce, Louise

    2009-01-01

    The disturbed and disturbing college student causes the most vexing concerns for student affairs administrators. The Assessment-Intervention of Student Problems (AISP) model offers a useful and easily understood framework for dealing with the various challenges of this high-risk student population. This chapter focuses on changes that have…

  5. Explorations in High-Risk Stimulation: Two Modalities in Mothering.

    ERIC Educational Resources Information Center

    Gochman, Eva R. Grubler; Aisenstein, Clara

    An exploratory study of high-risk mothers' interactions with their infants studied modalities of stimulation; vestibular and auditory. It was hypothesized that stimulation would be lower for non-paranoid than for paranoid types, and than for control mothers. Mothers recruited from inner city gynecological clinics were screened for probable…

  6. Alleviating Stress in Parents of High-Risk Preterm Infants.

    ERIC Educational Resources Information Center

    Lowenthal, Barbara

    1989-01-01

    Possible sources of stress for parents of preterm high-risk infants are reviewed from a research perspective. Stages of parental attachment to their premature baby are spelled out. Strategies for special education teachers to use in alleviating parental stress are described. (JDD)

  7. Prediction of Violence Perpetration Among High-Risk Youth

    ERIC Educational Resources Information Center

    Sussman, Steve; Skara, Silvana; Weiner, Michelle D.; Dent, Clyde W.

    2004-01-01

    Objectives: To prospectively examine demographic background, personality, perceived environment, and behavior as violence perpetration predictors in emerging adulthood among high-risk adolescents using problem-behavior theory as a conceptual perspective. Methods: Self-report questionnaires were administered 5 years apart to 676 participants.…

  8. Suicide Prevention for High-Risk Persons Who Refuse Treatment

    ERIC Educational Resources Information Center

    Motto, Jerome A.

    1976-01-01

    Patients (N=3,006) admitted to a psychiatric in-patient service because of a suicidal state were contacted to determine if post-discharge plans were followed. Half of those who refused treatment were contacted by telephone or letter on a set schedule. Evidence is that a high-risk population for suicide can be identified. (Author)

  9. Comorbidity and Inflammatory Markers May Contribute to Predict Mortality of High-Risk Patients With Chronic Obstructive Pulmonary Disease Exacerbation

    PubMed Central

    Kim, Yu Jin; Lim, Byeongwoo; Kyung, Sun Young; Park, Jeong-woong; Jeong, Sung Hwan

    2016-01-01

    Background Acute exacerbation of chronic obstructive pulmonary disease (COPD) causes not only an accelerated disease progression, but also an increased mortality rate. The purpose of this study was to analyze the factors associated with clinical features, comorbidities and mortality in patients at high risk for acute COPD exacerbation who had been hospitalized at least once in a year. Methods The study enrolled 606 patients who had been diagnosed with and were being treated for COPD at university affiliated hospital. Among them, there were 61 patients at high risk for acute exacerbation of COPD who had been hospitalized at least once in a year. A retrospective analysis was conducted to examine the factors affecting mortality. The analysis divided the patients into non-survivor and survivor groups, and reviewed their medical records for clinical aspects, comorbidities, pulmonary function tests and blood tests. Results In the high-risk group, the number of comorbidities at diagnosis (P = 0.020) and the Charlson comorbidity index value (P = 0.018) were higher in the non-survivor group than in the survivor group. During hospitalization, the non-survivor group had a significantly higher neutrophil (%) and a significantly lower lymphocyte (%) in complete blood count. Under stable conditions, the high-sensitivity C-reactive protein (hsCRP) concentration in blood plasma and neutrophil (%) were significantly higher (P = 0.025 and P = 0.036), while the lymphocyte (%) was significantly lower (P = 0.005) in the non-survivor group. A pulmonary function test revealed no statistically significant differences between the two groups. Conclusion The number of comorbidities, neutrophil (%), lymphocyte (%) in complete blood cell (CBC) and hsCRP in blood plasma concentration among the groups at high risk for COPD exacerbation are associated with increased mortality. PMID:27298662

  10. Obesity and Metabolic Disease After Childhood Cancer.

    PubMed

    Barnea, Dana; Raghunathan, Nirupa; Friedman, Danielle Novetsky; Tonorezos, Emily S

    2015-11-01

    As care for the childhood cancer patient has improved significantly, there is an increasing incidence of treatment-related late effects. Obesity and type 2 diabetes mellitus are common and significant metabolic conditions in some populations of adult survivors of childhood cancer. Results from the Childhood Cancer Survivor Study and other large cohorts of childhood cancer survivors reveal that long-term survivors of acute lymphoblastic leukemia and those who received total body irradiation or abdominal radiotherapy are at highest risk. The potential mechanisms for the observed increase in risk, including alterations in leptin and adiponectin, pancreatic insufficiency, poor dietary habits, sedentary lifestyle, and perhaps changes in the composition of the gut microbiota, are reviewed. Discussion of exercise and diet intervention studies shows that further research about the barriers to a healthy lifestyle and other interventions in childhood cancer survivors is warranted. PMID:26568532

  11. High-risk corneal allografts: A therapeutic challenge.

    PubMed

    Yu, Tian; Rajendran, Vijayalakshmi; Griffith, May; Forrester, John V; Kuffová, Lucia

    2016-03-24

    Corneal transplantation is the most common surgical procedure amongst solid organ transplants with a high survival rate of 86% at 1-year post-grafting. This high success rate has been attributed to the immune privilege of the eye. However, mechanisms originally thought to promote immune privilege, such as the lack of antigen presenting cells and vessels in the cornea, are challenged by recent studies. Nevertheless, the immunological and physiological features of the cornea promoting a relatively weak alloimmune response is likely responsible for the high survival rate in "low-risk" settings. Furthermore, although corneal graft survival in "low-risk" recipients is favourable, the prognosis in "high-risk" recipients for corneal graft is poor. In "high-risk" grafts, the process of indirect allorecognition is accelerated by the enhanced innate and adaptive immune responses due to pre-existing inflammation and neovascularization of the host bed. This leads to the irreversible rejection of the allograft and ultimately graft failure. Many therapeutic measures are being tested in pre-clinical and clinical studies to counter the immunological challenge of "high-risk" recipients. Despite the prevailing dogma, recent data suggest that tissue matching together with use of systemic immunosuppression may increase the likelihood of graft acceptance in "high-risk" recipients. However, immunosuppressive drugs are accompanied with intolerance/side effects and toxicity, and therefore, novel cell-based therapies are in development which target host immune cells and restore immune homeostasis without significant side effect of treatment. In addition, developments in regenerative medicine may be able to solve both important short comings of allotransplantation: (1) graft rejection and ultimate graft failure; and (2) the lack of suitable donor corneas. The advances in technology and research indicate that wider therapeutic choices for patients may be available to address the worldwide

  12. Biological markers of Pseudomonas aeruginosa epidemic high-risk clones.

    PubMed

    Mulet, Xavier; Cabot, Gabriel; Ocampo-Sosa, Alain A; Domínguez, M Angeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis; Oliver, Antonio

    2013-11-01

    A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies. PMID:23979744

  13. Biological Markers of Pseudomonas aeruginosa Epidemic High-Risk Clones

    PubMed Central

    Mulet, Xavier; Cabot, Gabriel; Ocampo-Sosa, Alain A.; Domínguez, M. Angeles; Zamorano, Laura; Juan, Carlos; Tubau, Fe; Rodríguez, Cristina; Moyà, Bartolomé; Peña, Carmen; Martínez-Martínez, Luis

    2013-01-01

    A limited number of Pseudomonas aeruginosa genotypes (mainly ST-111, ST-175, and ST-235), known as high-risk clones, are responsible for epidemics of nosocomial infections by multidrug-resistant (MDR) or extensively drug-resistant (XDR) strains worldwide. We explored the potential biological parameters that may explain the success of these clones. A total of 20 isolates from each of 4 resistance groups (XDR, MDR, ModR [resistant to 1 or 2 classes], and MultiS [susceptible to all antipseudomonals]), recovered from a multicenter study of P. aeruginosa bloodstream infections performed in 10 Spanish hospitals, were analyzed. A further set of 20 XDR isolates belonging to epidemic high-risk clones (ST-175 [n = 6], ST-111 [n = 7], and ST-235 [n = 7]) recovered from different geographical locations was also studied. When unknown, genotypes were documented through multilocus sequence typing. The biological parameters evaluated included twitching, swimming, and swarming motility, biofilm formation, production of pyoverdine and pyocyanin, spontaneous mutant frequencies, and the in vitro competition index (CI) obtained with a flow cytometry assay. All 20 (100%) XDR, 8 (40%) MDR, and 1 (5%) ModR bloodstream isolate from the multicenter study belonged to high-risk clones. No significant differences were observed between clonally diverse ModR and MultiS isolates for any of the parameters. In contrast, MDR/XDR high-risk clones showed significantly increased biofilm formation and mutant frequencies but significantly reduced motility (twitching, swimming, and swarming), production of pyoverdine and pyocyanin, and fitness. The defined biological markers of high-risk clones, which resemble those resulting from adaptation to chronic infections, could be useful for the design of specific treatment and infection control strategies. PMID:23979744

  14. High event-free survival rate with minimum-dose-anthracycline treatment in childhood acute promyelocytic leukaemia: a nationwide prospective study by the Japanese Paediatric Leukaemia/Lymphoma Study Group.

    PubMed

    Takahashi, Hiroyuki; Watanabe, Tomoyuki; Kinoshita, Akitoshi; Yuza, Yuki; Moritake, Hiroshi; Terui, Kiminori; Iwamoto, Shotaro; Nakayama, Hideki; Shimada, Akira; Kudo, Kazuko; Taki, Tomohiko; Yabe, Miharu; Matsushita, Hiromichi; Yamashita, Yuka; Koike, Kazutoshi; Ogawa, Atsushi; Kosaka, Yoshiyuki; Tomizawa, Daisuke; Taga, Takashi; Saito, Akiko M; Horibe, Keizo; Nakahata, Tatsutoshi; Miyachi, Hayato; Tawa, Akio; Adachi, Souichi

    2016-08-01

    We evaluated the efficacy of treatment using reduced cumulative doses of anthracyclines in children with acute promyelocytic leukaemia (APL) in the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-P05 study. All patients received two and three subsequent courses of induction and consolidation chemotherapy respectively, consisting of all-trans retinoic acid (ATRA), cytarabine and anthracyclines, followed by maintenance therapy with ATRA. Notably, a single administration of anthracyclines was introduced in the second induction and all consolidation therapies to minimize total doses of anthracycline. The 3-year event-free (EFS) and overall survival rates for 43 eligible children were 83·6% [95% confidence interval (CI): 68·6-91·8%] and 90·7% (95% CI: 77·1-96·4%), respectively. Although two patients died of intracranial haemorrhage or infection during induction phases, no cardiac adverse events or treatment-related deaths were observed during subsequent phases. Patients not displaying M1 marrow after the first induction therapy, or those under 5 years of age at diagnosis, showed inferior outcomes (3-year EFS rate; 33·3% (95% CI: 19·3-67·6%) and 54·6% (95% CI: 22·9-78·0%), respectively). In conclusion, a single administration of anthracycline during each consolidation phase was sufficient for treating childhood APL. In younger children, however, conventional ATRA and chemotherapy may be insufficient so that alternative therapies should be considered. PMID:27029412

  15. The impact of childhood acute rotavirus gastroenteritis on the parents’ quality of life: prospective observational study in European primary care medical practices

    PubMed Central

    2012-01-01

    Background Rotavirus (RV) is the commonest cause of acute gastroenteritis in infants and young children worldwide. A Quality of Life study was conducted in primary care in three European countries as part of a larger epidemiological study (SPRIK) to investigate the impact of paediatric rotavirus gastroenteritis (RVGE) on affected children and their parents. Methods A self-administered questionnaire was linguistically validated in Spanish, Italian and Polish. The questionnaire was included in an observational multicentre prospective study of 302 children aged <5 years presenting to a general practitioner or paediatrician for RVGE at centres in Spain, Italy or Poland. RV infection was confirmed by polymerase chain reaction (PCR) testing (n = 264). The questionnaire was validated and used to assess the emotional impact of paediatric RVGE on the parents. Results Questionnaire responses showed that acute RVGE in a child adversely affects the parents’ daily life as well as the child. Parents of children with RVGE experience worry, distress and impact on their daily activities. RVGE of greater clinical severity (assessed by the Vesikari scale) was associated with higher parental worries due to symptoms and greater changes in the child’s behaviour, and a trend to higher impact on parents’ daily activities and higher parental distress, together with a higher score on the symptom severity scale of the questionnaire. Conclusions Parents of a child with acute RVGE presenting to primary care experience worry, distress and disruptions to daily life as a result of the child’s illness. Prevention of this disease through prophylactic vaccination will improve the daily lives of parents and children. PMID:22650611

  16. Birth Weight and Cognitive Ability in Childhood: A Systematic Review

    ERIC Educational Resources Information Center

    Shenkin, Susan D.; Starr, John M.; Deary, Ian J.

    2004-01-01

    Individual differences in cognitive ability may in part have prenatal origins. In high-risk (low birth weight/premature) babies, birth weight correlates positively with cognitive test scores in childhood, but it is unclear whether this holds for those with birth weights in the normal range. The authors systematically reviewed literature on the…

  17. Busulfan and Etoposide Followed by Peripheral Blood Stem Cell Transplant and Low-Dose Aldesleukin in Treating Patients With Acute Myeloid Leukemia

    ClinicalTrials.gov

    2015-08-04

    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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Childhood Acute Myeloid Leukemia in Remission; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia

  18. Validation of the High-Risk Pregnancy Stress Scale in a sample of hospitalized Greek high-risk pregnant women.

    PubMed

    Gourounti, Kleanthi; Karpathiotaki, Natassa; Karapanou, Vassiliki; Antzaklis, Panos; Daskalakis, Georgios

    2016-01-01

    The aim of the authors in this study was to determine the psychometric properties of the Greek adaptation of the High-Risk Pregnancy Stress Scale (HRPSS) in a sample of high-risk hospitalized pregnant women. The sample consisted of 133 high-risk pregnant women with gestational age from 9 to 37 weeks. Data were collected between