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Sample records for high-risk childhood acute

  1. High-Risk Childhood Acute Lymphoblastic Leukemia

    PubMed Central

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

    2009-01-01

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

  2. 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

  3. 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

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

    PubMed

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

    2013-07-01

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

  5. 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

  6. Improved outcome in high-risk childhood acute lymphoblastic leukemia defined by prednisone-poor response treated with double Berlin-Frankfurt-Muenster protocol II.

    PubMed

    Aricò, Maurizio; Valsecchi, Maria Grazia; Conter, Valentino; Rizzari, Carmelo; Pession, Andrea; Messina, Chiara; Barisone, Elena; Poggi, Vincenzo; De Rossi, Giulio; Locatelli, Franco; Micalizzi, Maria Concetta; Basso, Giuseppe; Masera, Giuseppe

    2002-07-15

    One hundred ninety-eight children and adolescents were entered in the Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP)-ALL95 study for high-risk acute lymphoblastic leukemia (ALL). Inclusion criteria were poor response to initial prednisone/intrathecal methotrexate (prednisone-poor response [PPR]), resistance to induction therapy, translocation t(9;22), infants with the t(4;11), or CD10(-) ALL. The event-free survival (EFS) rate at 4 years was 56.5% (SE, 3.9%) for the entire group. The overall EFS rate in the current study was significantly better (P =.002) than that obtained in a comparable group of patients treated in the early 1990s in the AIEOP-ALL91 study. In particular, patients with PPR had a 4-year EFS of 61.1% (SE, 4.4%) versus 42.8% (SE, 5.4%) in the ALL 91 study (P =.008). Among PPR patients, those who were PPR-only (60.1%)-that is, they achieved CR and were negative for t(9;22) and t(4;11) translocations-had the best outcomes with this intensive treatment, even when additional adverse features (hyperleukocytosis, T phenotype) were present (4-year EFS, 70.1%; SE, 4.7%). We attribute this improvement to the replacement of 6 alternating blocks of non-cross-resistant drugs with an 8-drug reinduction regimen (Berlin-Frankfurt-Muenster [BFM] protocol II), repeated twice, in the context of a standard BFM-type intensive chemotherapy for high-risk ALL. This modified therapy may lead to high cure rates for patients defined as at high risk for intrinsic resistance to corticosteroids only.

  7. Allogeneic bone marrow transplantation versus chemotherapy in high-risk childhood acute lymphoblastic leukaemia in first remission. Associazione Italiana di Ematologia ed Oncologia Pediatrica (AIEOP) and the Gruppo Italiano Trapianto di Midollo Osseo (GITMO).

    PubMed

    Uderzo, C; Valsecchi, M G; Balduzzi, A; Dini, G; Miniero, R; Locatelli, F; Rondelli, R; Pession, A; Arcese, W; Bacigalupo, A; Polchi, P; Andolina, M; Messina, C; Conter, V; Aricó, M; Galimberti, S; Masera, G

    1997-02-01

    We compared the outcome of children with high-risk acute lymphoblastic leukaemia (HR-ALL) in first complete remission (first CR) treated with chemotherapy (CHEMO) or with allogeneic bone marrow transplantation (BMT) in a multicentre study. All children treated by the Italian Paediatric Haematology Oncology Association for HR-ALL in first CR between 1986 and 1994 were eligible for the study. 30 children were given BMT at a median of 4 months from first CR, with preparative regimens including total-body irradiation (n = 25/30). 130 matched controls for BMT patients were identified among 397 HR-ALL CHEMO patients. Matching on main prognostic factors and duration of first CR was adopted to control the selection and time-to-transplant biases. The comparative analysis was based on the results of a stratified Cox model. The estimated hazard ratios of BMT versus CHEMO at 6 months, 1 year and 2 years after CR were 1.38 (CI 0.59-3.24), 0.69 (CI 0.27-1.77) and 0.35 (CI 0.06-1.91), with an overall non-significant difference between the two groups (P = 0.34). With a median follow-up of 4 years, the disease-free survival was 58.5% (SE 9.3) in the BMT group and 47.7% (SE 4.8) in the CHEMO group, at 4 years from CR. Non-leukaemic death occurred in 4% of CHEMO and 10% of BMT patients. In the BMT group the estimated cumulative incidence of relapse at 1.5 years from CR was 31.5% (SE 8.8) and did not change thereafter, whereas in the CHEMO group the corresponding figure was 29.2% (SE 4.1) and the incidence continued to increase thereafter (48.2% (SE 4.8) at 4 years from CR). The results of this study suggest that, with respect to the CHEMO group, the higher risk of early failure in the BMT group is outweighed by the lower risk of relapse after 1 year. Results prompt the need for a prospective study, in order to demonstrate the likely advantage of BMT in HR childhood ALL in first CR.

  8. High-risk acute myelogenous leukemia: treatment today ... and tomorrow.

    PubMed

    Schiller, Gary J

    2013-01-01

    High-risk acute myelogenous leukemia (AML) constitutes a distinct subset of disease based on clinical and biological characteristics and comprises a significant percentage of all cases of adult AML. Biologic features such as distinct clonal cytogenetic and molecular abnormalities identify a subgroup of AML patients characterized by poor response to induction chemotherapy and poor long-term survival after treatment with consolidation chemotherapy. Clinical variables that predict for poor response include AML relapsed after less than 1 year of remission and AML characterized by resistance to conventional agents. We review here our understanding of the defining biologic subtypes of AML and discuss how adequate initial evaluation can be used to inform the choice of treatment. By defining high-risk biologic and clinical variables, a strong case can be made for treating patients with investigational agents, with treatment directed at distinct cytogenetic or molecular abnormalities. Allogeneic transplantation is the only form of therapy available outside of the setting of a clinical trial that may offer a chance for long-term survival for patients with high-risk AML.

  9. 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 ...

  10. 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 ...

  11. 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 ...

  12. 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 ...

  13. 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

  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. Evolving treatment strategies in patients with high-risk acute myeloid leukemia.

    PubMed

    Schiller, Gary J

    2014-11-01

    Acute myeloid leukemia (AML) is defined by a set of biologically distinct diseases characterized by maturation arrest and clonal proliferation of myeloid cells. Recommendations for post-remission therapy depend on assessing the leukemia risk characteristics, such as cytogenetics and molecular features present at diagnosis. Patients with high-risk disease include those whose leukemia is characterized by monosomal karyotype or poor-risk cytogenetic or molecular abnormalities, patients with antecedent hematologic disorders or therapy-related AML, and presence of adverse host factors, such as comorbidities, impaired performance status or older age. Older patients are more likely to have these adverse features. High-risk AML responds poorly to available induction treatment and is likely to relapse despite consolidation therapy. Current data support an increasing understanding of prognosis but have not yet resulted in effective therapies for patients with high-risk disease. This review discusses current therapies and evolving treatment strategies for high-risk AML.

  16. High Risk Pediatric Acute Lymphoblastic Leukemia: To Transplant or Not to Transplant?

    PubMed Central

    Pulsipher, Michael A.; Peters, Christina; Pui, Ching-Hon

    2010-01-01

    Because survival with both chemotherapy and allogeneic hematopoietic stem cell transplantation (HSCT) approaches to high risk pediatric acute lymphoblastic leukemia (ALL) generally improves through the years, regular comparisons of outcomes with either approach for a given indication are needed to decide when HSCT is indicated. Improvements in risk classification are allowing clinicians to identify patients at high risk for relapse early in their course of therapy. Whether patients defined as high risk by new methods will benefit from HSCT requires careful testing. Standardization and improvement of transplant approaches has led to equivalent survival outcomes with matched sibling and well-matched unrelated donors, however, survival using mismatched and haploidentical donors is generally worse. Trials comparing chemotherapy and HSCT must obtain sufficient data about therapy and stratify the analysis to assess the outcomes of best-chemotherapy with best-HSCT approaches. PMID:21195303

  17. Ras/Raf/MEK/ERK Pathway Activation in Childhood Acute Lymphoblastic Leukemia and Its Therapeutic Targeting

    PubMed Central

    Knight, Thomas; Irving, Julie Anne Elizabeth

    2014-01-01

    Deregulation of the Ras/Raf/MEK/extracellular signal-regulated kinase pathway is a common event in childhood acute lymphoblastic leukemia and is caused by point mutation, gene deletion, and chromosomal translocation of a vast array of gene types, highlighting its importance in leukemia biology. Pathway activation can be therapeutically exploited and may guide new therapies needed for relapsed acute lymphoblastic leukemia and other high risk subgroups. PMID:25009801

  18. 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.

  19. 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

  20. 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

  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

    2016-08-16

    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.

  2. 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

  3. 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…

  4. History of childhood physical trauma is related to cognitive decline in individuals with ultra-high risk for psychosis.

    PubMed

    Üçok, Alp; Kaya, Hatice; Uğurpala, Can; Çıkrıkçılı, Uğur; Ergül, Ceylan; Yokuşoğlu, Çağdaş; Bülbül, Öznur; Direk, Nese

    2015-12-01

    The aim of this study was to investigate the relationship between childhood trauma (CT) and cognitive functioning in individuals with ultra-high risk for psychosis (UHR). Fifty-three individuals at UHR for psychosis were administered a neurocognitive battery that assessed attention, processing speed, verbal learning, memory, working memory, interference inhibition, and sustained attention. The CT was assessed using the short-version Childhood Trauma Questionnaire (CTQ). We dichotomized the sample by using cut-off scores for the presence of emotional, physical and sexual trauma, and physical and emotional neglect. Those with a history of physical trauma performed worse on the Digit Span Forward test, Trail making B (time), Stroop test (difference between color and word reading times), and completed categories of the Wisconsin Card Sorting Test (WCST). Physical trauma scores were correlated with WCST-completed categories, Digit Span Forward and Stroop test scores. Physical neglect scores were negatively correlated with Digit Span Forward Test scores. Most of the significant dose–response relationships between cognitive impairment and different subtypes of CT were found only in men. There was no difference between those with and without other kinds of childhood abuse or neglect in terms of cognitive impairment. Our findings suggest that a history of physical trauma has a negative impact on cognitive function in individuals at UHR for psychosis.

  5. 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.

  6. 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

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

    ClinicalTrials.gov

    2016-11-02

    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. 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

  9. Dasatinib, Cytarabine, and Idarubicin in Treating Patients With High-Risk Acute Myeloid Leukemia

    ClinicalTrials.gov

    2016-04-08

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

  10. Bortezomib in Treating Patients With High-Risk Acute Myeloid Leukemia in Remission

    ClinicalTrials.gov

    2014-10-30

    Acute Myeloid Leukemia With Multilineage Dysplasia Following Myelodysplastic Syndrome; Adult Acute Minimally Differentiated Myeloid Leukemia (M0); 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 t(15;17)(q22;q12); Adult Acute Myeloid Leukemia With t(16;16)(p13;q22); Adult Acute Promyelocytic Leukemia (M3); Adult Erythroleukemia (M6a); Adult Pure Erythroid Leukemia (M6b); Secondary Acute Myeloid Leukemia

  11. Hospital transfer for primary coronary angioplasty in high risk patients with acute myocardial infarction

    PubMed Central

    Straumann, E; Yoon, S; Naegeli, B; Frielingsdorf, J; Gerber, A; Schuiki, E; Bertel, O

    1999-01-01

    , respectively. Only one hospital survivor (group A) died during follow up.
CONCLUSION—Interhospital transport for primary PTCA in high risk patients with acute myocardial infarction is safe and feasible within a reasonable period of time. Short and medium term outcome is favourable. Optimising the decision process and transport logistics may further improve outcome by reducing the total time of ischaemia.


Keywords: acute myocardial infarction; primary percutaneous transluminal coronary angioplasty; hospital transfer; time delay PMID:10490552

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

    PubMed

    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.

  13. Childhood Acute Lymphoblastic Leukemia: Progress Through Collaboration

    PubMed Central

    Yang, Jun J.; Hunger, Stephen P.; Pieters, Rob; Schrappe, Martin; Biondi, Andrea; Vora, Ajay; Baruchel, André; Silverman, Lewis B.; Schmiegelow, Kjeld; Escherich, Gabriele; Horibe, Keizo; Benoit, Yves C.M.; Izraeli, Shai; Yeoh, Allen Eng Juh; Liang, Der-Cherng; Downing, James R.; Evans, William E.; Relling, Mary V.; Mullighan, Charles G.

    2015-01-01

    Purpose To review the impact of collaborative studies on advances in the biology and treatment of acute lymphoblastic leukemia (ALL) in children and adolescents. Methods A review of English literature on childhood ALL focusing on collaborative studies was performed. The resulting article was reviewed and revised by the committee chairs of the major ALL study groups. Results With long-term survival rates for ALL approaching 90% and the advent of high-resolution genome-wide analyses, several international study groups or consortia were established to conduct collaborative research to further improve outcome. As a result, treatment strategies have been improved for several subtypes of ALL, such as infant, MLL-rearranged, Philadelphia chromosome–positive, and Philadelphia chromosome–like ALL. Many recurrent genetic abnormalities that respond to tyrosine kinase inhibitors and multiple genetic determinants of drug resistance and toxicities have been identified to help develop targeted therapy. Several genetic polymorphisms have been recognized that show susceptibility to developing ALL and that help explain the racial/ethnic differences in the incidence of ALL. Conclusion The information gained from collaborative studies has helped decipher the heterogeneity of ALL to help improve personalized treatment, which will further advance the current high cure rate and the quality of life for children and adolescents with ALL. PMID:26304874

  14. 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

  15. Reduced intensity conditioning followed by peripheral blood stem cell transplantation for adult patients with high-risk acute lymphoblastic leukemia

    PubMed Central

    Stein, Anthony S.; Palmer, Joycelynne M.; O'Donnell, Margaret R.; Kogut, Neil M.; Spielberger, Ricardo T.; Slovak, Marilyn L.; Tsai, Ni-Chun; Senitzer, David; Snyder, David S.; Thomas, Sandra H.; J.Forman, Stephen

    2009-01-01

    Acute lymphoblastic leukemia (ALL) with high-risk features has a poor prognosis in adults despite aggressive chemotherapy. Reduced-intensity conditioning (RIC) is a lower toxicity alternative for high-risk patients requiring hematopoietic cell transplantation (HCT), however it has not been widely used for ALL. We conducted a retrospective study of 24 high-risk adult ALL patients who received an RIC regimen of fludarabine/melphalan prior to allogeneic peripheral blood stem cell transplant between 6/14/02 and 6/15/07 at City of Hope. Indications for the RIC regimen were: 1) age 50 or older (42%), 2) compromised organ function (54%), or 3) recipient of a previous HCT (37.5%). Patients had a median age of 47.5 years and the median follow-up was 28.5 months for living patients. Both overall survival and disease-free survival at two years was 61.5%. Relapse incidence was 21.1% and non-relapse mortality was 21.5% at two years. cGVHD developed in 86% of evaluable patients. In this series, no significant correlations were made between outcomes and patient age, presence of Philadelphia chromosome, relatedness of donor source or prior HCT. These high survival rates for high-risk ALL patients following RIC HCT may offer a promising option for patients not eligible for a standard myeloablative transplant. PMID:19822300

  16. 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...

  17. 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.

  18. Mediators of Childhood Sexual Abuse and High-Risk Sex Among Men-Who-Have-Sex-With-Men

    PubMed Central

    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% prevalence of CSA was reported. For MSM in secondary sexual relationships, our modeling work identified two over-arching but inter-related pathways (e.g., both pathways include effects on interpersonal skills) linking CSA and high-risk behavior: 1) CSA-Motivation-Scripts-Skills-Risk Behavior, and 2) CSA-Motivation-Coping-Risk Appraisal-Skills-Risk Behavior. For men in primary relationships, there was one over-arching pathway including CSA-Motivation-Coping-Risk Appraisal- Risk Behavior processes. Exploratory analyses indicated that men with a history of CSA in only primary relationships vs only secondary relationships had, for example, fewer motivational problems, and better coping and interpersonal skills. Conclusions CSA contributes to the ongoing HIV epidemic among MSM by distorting or undermining critical motivational, coping, and interpersonal factors that, in turn, influence adult sexual risk behavior. Further, the type of adult relationships men engage serve as markers for adult CSA-related problems. The findings are discussed in the context of current theory and HIV prevention strategies. Practice Implications Direct extrapolation from our findings to practice is limited. However, there are general implications that may be drawn. First, the complex challenges faced by men with severe CSA experiences may limit the effectiveness of typical short-term HIV risk reduction programs; more intensive treatment may be needed. Secondly, Clinical Psychologists and Psychiatrists with MSM patients with CSA histories should, if not already, routinely consider issues of sexual health; patterns and types of sexual partners may be useful

  19. Blood Spotlight on iAMP21 acute lymphoblastic leukemia (ALL), a high-risk pediatric disease.

    PubMed

    Harrison, Christine J

    2015-02-26

    Intrachromosomal amplification of chromosome 21 (iAMP21) defines a distinct cytogenetic subgroup of childhood B-cell precursor acute lymphoblastic leukemia. Breakage-fusion-bridge cycles followed by chromothripsis and other complex structural rearrangements of chromosome 21 underlie the mechanism giving rise to iAMP21. Patients with iAMP21 are older (median age 9 years), with a low white cell count. They have a high relapse rate when treated as standard risk. Recent studies have shown improved outcome on intensive therapy. Molecular targets for therapy are being sought.

  20. 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...

  1. 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

  2. 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

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

    PubMed

    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.

  4. Childhood Acute Lymphoblastic Leukemia: Integrating Genomics into Therapy

    PubMed Central

    Tasian, Sarah K; Loh, Mignon L; Hunger, Stephen P

    2015-01-01

    Acute lymphoblastic leukemia (ALL), the most common malignancy of childhood, is a genetically complex entity that remains a major cause of childhood cancer-related mortality. Major advances in genomic and epigenomic profiling during the past decade have appreciably enhanced knowledge of the biology of de novo and relapsed ALL and have facilitated more precise risk stratification of patients. These achievements have also provided critical insights regarding potentially targetable lesions for development of new therapeutic approaches in the era of precision medicine. This review delineates the current genetic landscape of childhood ALL with emphasis upon patient outcomes with contemporary treatment regimens, as well as therapeutic implications of newly identified genomic alterations in specific subsets of ALL. PMID:26194091

  5. [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

  6. Advances in therapy for Philadelphia-positive acute lymphoblastic leukaemia of childhood and adolescence.

    PubMed

    Bleckmann, Kirsten; Schrappe, Martin

    2016-03-01

    The presence of the BCR/ABL1 fusion gene in childhood acute lymphoblastic leukaemia (ALL) is a rare finding and has been an adverse prognostic factor associated with a high risk of therapeutic failure. The current key components of treatment are intensive polychemotherapy and a BCR/ABL1 kinase domain inhibitor. This treatment approach has been applied in a few clinical trials by paediatric leukaemia study groups. Thus, this subtype of ALL serves as the first model system for truly targeted treatment. The role of haematopoietic stem cell transplantation (HSCT) is increasingly called into question, at least in a favourable, though not yet clearly defined, subset of patients. Currently, the choice of the most effective tyrosine kinase inhibitor is not yet settled, in particular, in view of potential reduction of overall treatment intensity.

  7. Acute abdominal pain in childhood, with special reference to cases not due to acute appendicitis.

    PubMed

    Jones, P F

    1969-02-01

    Appendicitis is not the only common cause of acute abdominal pain in childhood. Almost equally common is an acute episode which in its early stages resembles acute appendicitis but which subsides without treatment in 24 to 48 hours. The clinical features of this syndrome are contrasted with those of appendicitis. The two conditions cannot always be distinguished on clinical grounds, leading to admission to hospital for observation and the finding of a normal appendix in 14% of operations for suspected appendicitis. Reasons are given for abandoning attempts to diagnose acute mesenteric adenitis at the bedside.

  8. Stability and change in autism spectrum disorder diagnosis from age 3 to middle childhood in a high-risk sibling cohort.

    PubMed

    Brian, Jessica; Bryson, Susan E; Smith, Isabel M; Roberts, Wendy; Roncadin, Caroline; Szatmari, Peter; Zwaigenbaum, Lonnie

    2016-10-01

    Considerable evidence on autism spectrum disorder emergence comes from longitudinal high-risk samples (i.e. younger siblings of children with autism spectrum disorder). Diagnostic stability to age 3 is very good when diagnosed as early as 18-24 months, but sensitivity is weaker, and relatively little is known beyond toddlerhood. We examined stability and change in blinded, clinical best-estimate diagnosis from age 3 to middle childhood (mean age = 9.5 years) in 67 high-risk siblings enrolled in infancy. Good agreement emerged for clinical best-estimate diagnoses (89.6% overall; kappa = 0.76, p < 0.001, 95% confidence interval = 0.59-0.93). At age 3, 18 cases (26.9%) were classified with "autism spectrum disorder": 17 retained their autism spectrum disorder diagnosis (94.4%; 13 boys, 4 girls) and 1 no longer met autism spectrum disorder criteria at follow-up. Among "non-autism spectrum disorder" cases at age 3, 43/49 remained non-autism spectrum disorder at follow-up (87.8%; 22 boys, 21 girls) and 6/49 met lower autism symptomatology criteria ("Later-Diagnosed"; 3 boys, 3 girls). Later-diagnosed cases had significantly lower autism spectrum disorder symptomatology and higher receptive language at age 3 and trends toward lower autism symptoms and higher cognitive abilities at follow-up. Emerging developmental concerns were noted in all later-diagnosed cases, by age 3 or 5. High-risk children need to be followed up into middle childhood, particularly when showing differences in autism-related domains.

  9. 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%…

  10. Family history of autoimmune thyroid disease and childhood acute leukemia.

    PubMed

    Perillat-Menegaux, Florence; Clavel, Jacqueline; Auclerc, Marie-Françoise; Baruchel, André; Leverger, Guy; Nelken, Brigitte; Philippe, Noël; Sommelet, Danièle; Vilmer, Etienne; Hémon, Denis

    2003-01-01

    The association between a familial history of autoimmune disease and childhood acute leukemia was investigated in a French case-control study that, overall, was designed to assess the role of perinatal, infectious, environmental, and genetic factors in the etiology of childhood acute leukemia. Familial histories of autoimmune disease in first- and second-degree relatives were compared in 279 incident cases, 240 cases of acute lymphocytic leukemia (ALL) and 39 cases of acute non-lymphoblastic leukemia (ANLL), and 285 controls. Recruitment was frequency matched by age, gender, hospital, and ethnic origin. Odds ratios (OR) were estimated using an unconditional regression model taking into account the stratification variables, socioeconomic status, and familial structure. A statistically significant association between a history of autoimmune disease in first- or second-degree relatives and ALL (OR, 1.7; 95% confidence interval (CI), 1.0-2.8) was found. A relationship between thyroid diseases overall and ALL (OR, 2.0; 95% CI, 1.0-3.9) was observed. This association was more pronounced for potentially autoimmune thyroid diseases (Grave's disease and/or hyperthyroidism and Hashimoto's disease and/or hypothyroidism) (OR, 3.5; 95% CI, 1.1-10.7 and OR, 5.6; 95% CI, 1.0-31.1, respectively for ALL and ANLL), whereas it was not statistically significant for the other thyroid diseases (thyroid goiter, thyroid nodule, and unspecified thyroid disorders) (OR, 1.6; 95% CI, 0.7-3.5 and OR, 1.3; 95% CI, 0.2-7.0, respectively, for ALL and ANLL). The results suggest that a familial history of autoimmune thyroid disease may be associated with childhood acute leukemia.

  11. A protective genetic variant for adverse environments? The role of childhood traumas and serotonin transporter gene on resilience and depressive severity in a high-risk population.

    PubMed

    Carli, V; Mandelli, L; Zaninotto, L; Roy, A; Recchia, L; Stoppia, L; Gatta, V; Sarchiapone, M; Serretti, A

    2011-11-01

    Genetic aspects may influence the effect of early adverse events on psychological well being in adulthood. In particular, a common polymorphism within the serotonin transporter gene (5-HTTLPR short/long) has been associated to the risk for stress-induced psychopathology. In the present study we investigated the role of childhood traumas and 5-HTTLPR on measures of psychological resilience and depression in a sample of individuals at a high risk for psychological distress (763 male prisoners). The 5-HTTLPR genotype did not influence resilience and depressive severity. However, a significant interaction was observed between 5-HTTLPR and childhood traumas on both resilience and depressive severity. In particular, among subjects exposed to severe childhood trauma only, the long-allele was associated to lower resilience scores and increased current depressive severity as compared to short/short homozygous. Sex specific effects, difference in type and duration of stressors and the specific composition of the sample may explain discrepancy with many studies reporting the short-allele as a vulnerability factor for reactivity to stress. We here speculated that in males the long-allele may confer lower resilience and therefore higher vulnerability for depressive symptoms in subjects exposed to early stress and currently living in stressful environments.

  12. Reticulocyte count is the most important predictor of acute cerebral ischemia and high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

    PubMed

    Belisário, André Rolim; Sales, Rahyssa Rodrigues; Toledo, Nayara Evelin; Muniz, Maristela Braga de Sousa Rodrigues; Velloso-Rodrigues, Cibele; Silva, Célia Maria; Viana, Marcos Borato

    2016-10-01

    Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children's records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell count and reticulocyte count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high reticulocyte count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy. PMID:27520094

  13. Reticulocyte count is the most important predictor of acute cerebral ischemia and high-risk transcranial Doppler in a newborn cohort of 395 children with sickle cell anemia.

    PubMed

    Belisário, André Rolim; Sales, Rahyssa Rodrigues; Toledo, Nayara Evelin; Muniz, Maristela Braga de Sousa Rodrigues; Velloso-Rodrigues, Cibele; Silva, Célia Maria; Viana, Marcos Borato

    2016-10-01

    Stroke is a severe clinical manifestation of sickle cell anemia (SCA). Despite the prognostic relevance of transcranial Doppler (TCD), more accurate tools to assess stroke risk in children with SCA are required. Here, we describe the effect of clinical, laboratory, and molecular features on the risk of stroke and high-risk TCD in children from the newborn cohort of Minas Gerais, Brazil. Outcomes studied were acute cerebral ischemia and high-risk TCD. Clinical and hematological data were retrieved from children's records. Genetic markers, which were known for their association with stroke risk, were genotyped by polymerase chain reaction/restriction fragment length polymorphism and sequencing. The cumulative incidence of acute cerebral ischemia by the age of 8 years was 7.4 % and that of high-risk TCD by the age of 11.5 years was 14.2 %. The final multivariate model for acute cerebral ischemia risk included high white blood cell count and reticulocyte count, acute chest syndrome rate, and the single nucleotide polymorphisms (SNPs) TEK rs489347 and TNF-α rs1800629. The model for high-risk TCD included high reticulocyte count and the SNPs TEK rs489347 and TGFBR3 rs284875. Children with risk factors should be considered for intensive risk monitoring and for intervention therapy.

  14. 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

  15. Pharmacogenetics of childhood acute lymphoblastic leukemia.

    PubMed

    Lopez-Lopez, Elixabet; Gutierrez-Camino, Angela; Bilbao-Aldaiturriaga, Nerea; Pombar-Gomez, Maria; Martin-Guerrero, Idoia; Garcia-Orad, Africa

    2014-07-01

    Acute lymphoblastic leukemia (ALL) is the major pediatric cancer in developed countries. Although treatment outcome has improved owing to advances in chemotherapy, there is still a group of patients for which therapy fails while some patients experience severe toxicity. In the last few years, several pharmacogenetic studies have been performed to search for markers of outcome and toxicity in pediatric ALL. However, to date, TPMT is the only pharmacogenetic marker in ALL with clinical guidelines for drug dosing. In this article, we will provide an overview of the most important findings carried out in pharmacogenetics for pediatric ALL, such as the interest drawn by methotrexate transporters in the context of methotrexate treatment. Even if most of the studies are centered on coding genes, we will also point to new approaches focusing on noncoding regions and epigenetic variation that could be interesting for consideration in the near future.

  16. 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

  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

    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

  18. Reducing length of stay for acute diabetic foot episodes: employing an extended scope of practice podiatric high-risk foot coordinator in an acute foundation trust hospital

    PubMed Central

    2013-01-01

    Background To enhance the acute management of people with diabetic foot disease requiring admission, an extended scope of practice, podiatric high-risk foot coordinator position, was established at the Great Western Hospital, Swindon in 2010. The focus of this new role was to facilitate more efficient and timely management of people with complex diabetic foot disease. The aim of this project was to investigate the impact of the podiatric high-risk foot coordinator role on length of stay, rate of re-admission and bed cost. Method This study evaluated the difference in length of stay and rate of re-admission between an 11- month pre-pilot period (November 2008 to October 2009) and a 10-month pilot period (August 2010 to June 2011). The estimated difference in bed cost between the pre-pilot and pilot audits was also calculated. Inclusion criteria were restricted to inpatients admitted with a diabetic foot ulcer, gangrene, cellulitis or infection as the primary cause for admission. Eligible records were retrieved using ICD-10 (V9) coding via the hospital clinical audit department for the pre-pilot period and a unique database was used to source records for the pilot phase. Results Following the introduction of the podiatric high-risk foot coordinator, the average length of stay reduced from 33.7 days to 23.3 days (mean difference 10.4 days, 95% CI 0.0 to 20.8, p = 0.050). There was no statistically significant difference in re-admission rate between the two study periods, 17.2% (95% CI 12.2% to 23.9%) in the pre-pilot phase and 15.4% (95% CI 12.0% to 19.5%) in the pilot phase (p = 0.820). The extrapolated annual cost saving following the implementation of the new coordinator role was calculated to be £234,000 for the 2010/2011 year. Conclusions This audit found that the extended scope of practice coordinator role may have a positive impact on reducing length of stay for diabetic foot admissions. This paper advocates the role of a podiatric high-risk foot

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

    PubMed

    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

    2015-06-01

    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).

  20. 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

  1. 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

  2. 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.

  3. [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.

  4. Disabling pansclerotic morphea of childhood poses a high risk of chronic ulceration of the skin and squamous cell carcinoma.

    PubMed

    Wollina, Uwe; Buslau, Michael; Heinig, Birgit; Petrov, Ivailo; Unger, Eleonore; Kyriopoulou, Eugenia; Koch, André; Köstler, Erich; Schönlebe, Jaqueline; Haroske, Gunther; Doede, Thorsten; Pramatarov, Kyrill

    2007-12-01

    Disabling pansclerotic morphea of childhood (DPMC) is a rare and severe variant of scleroderma. This report presents 3 cases that presented to the authors and studies 25 patients from the literature (English language only) for the presence of chronic nonhealing ulcers of skin and skin cancer. The authors identified a total of 30 patients (9 male and 21 female) aged between 1 and 37 years at time of presentation. All cases were less than 14 years old when the disease started. The majority of patients had an aggressive course with deep sclerotic lesions leading to joint contractures and immobility. Five patients suffered from chronic nonhealing leg ulcers (17%), but ulcers were present on other parts of the body (upper limbs, trunk, head) as well (n = 6). Four patients died because of complications of the disease such as sepsis or gangrene. Two patients developed a squamous cell carcinoma at the age of 16 years and 19 years, respectively (6.7%). The available treatment of DMPC-associated ulcers is unsatisfying. Only temporary improvements have been seen in a minority of patients. We report on marked improvement of chronic leg ulcers by a combination of sildenafil 3 x 20 mg/day and repeated application of a porcine small intestinal submucosal acellular matrix. PMID:18048875

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

    ClinicalTrials.gov

    2016-09-16

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

  6. 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

  7. 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

  8. Childhood pancreatitis.

    PubMed

    Uretsky, G; Goldschmiedt, M; James, K

    1999-05-01

    Acute pancreatitis is a rare finding in childhood but probably more common than is generally realized. This condition should be considered in the evaluation of children with vomiting and abdominal pain, because it can cause significant morbidity and mortality. Clinical suspicion is required to make the diagnosis, especially when the serum amylase concentration is normal. Recurrent pancreatitis may be familial as a result of inherited biochemical or anatomic abnormalities. Patients with hereditary pancreatitis are at high risk for pancreatic cancer.

  9. The role of matched sibling donor allogeneic stem cell transplantation in pediatric high-risk acute myeloid leukemia: results from the AML-BFM 98 study

    PubMed Central

    Klusmann, Jan-Henning; Reinhardt, Dirk; Zimmermann, Martin; Kremens, Bernhard; Vormoor, Josef; Dworzak, Michael; Creutzig, Ursula; Klingebiel, Thomas

    2012-01-01

    Background The role of allogeneic stem cell transplantation in post-remission management of children with high-risk acute myeloid leukemia remains controversial. In the multi-center AML-BFM 98 study we prospectively evaluated the impact of allogeneic stem cell transplantation in children with high-risk acute myeloid leukemia in first complete remission. Design and Methods HLA-typed patients with high-risk acute myeloid leukemia, who achieved first complete remission (n=247), were included in this analysis. All patients received double induction and consolidation. Based on the availability of a matched-sibling donor, patients were allocated by genetic chance to allogeneic stem cell transplantation (n=61) or chemotherapy-only (i.e. intensification and maintenance therapy; n=186). The main analysis was done on an intention-to-treat basis according to this allocation. Results Intention-to-treat analysis did not show a significantly different 5-year disease-free survival (49±6% versus 45±4%, Plog rank=0.44) or overall survival (68±6% versus 57±4%, Plog rank=0.17) between the matched-sibling donor and no-matched-sibling donor groups, whereas late adverse effects occurred more frequently after allogeneic stem cell transplantation (72.5% versus 31.8%, PFischer<0.01). These results were confirmed by as-treated analysis corrected for the time until transplantation (5-year overall survival: 72±8% versus 60±4%, PMantel-Byar 0.21). Subgroup analysis demonstrated improved survival rates for patients with 11q23 aberrations allocated to allogeneic stem cell transplantation (5-year overall survival: 94±6% versus 52±7%, Plog-rank=0.01; n=18 versus 49) in contrast to patients without 11q23 aberrations (5-year overall survival: 58±8% versus 55±5%, Plog-rank=0.66). Conclusions Our analyses defined a genetic subgroup of children with high-risk acute myeloid leukemia who benefited from allogeneic stem cell transplantation in the prospective multi-center AML-BFM 98 study. For

  10. 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.

  11. 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

  12. 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

  13. The ecology of early childhood risk: a canonical correlation analysis of children's adjustment, family, and community context in a high-risk sample.

    PubMed

    Vilsaint, Corrie L; Aiyer, Sophie M; Wilson, Melvin N; Shaw, Daniel S; Dishion, Thomas J

    2013-08-01

    The ecology of the emergence of psychopathology 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.

  14. Inherited genetic variants associated with childhood acute lymphoblastic leukemia risk.

    PubMed

    Takagi, Masatoshi; Urayama, Kevin

    2016-07-01

    Numerous efforts have been made to elucidate the roles of individual genetic background factors in the risk of childhood acute lymphoblastic leukemia. Most have taken the form of case-control studies focusing on specific candidate gene polymorphisms. Recently, a more rigorous and comprehensive approach referred to as a genome-wide association study (GWAS) has been widely utilized and has achieved success. Case-control studies evaluating candidate gene associations have shown cumulative evidence of a role for folate metabolism and xenobiotic metabolism/transport pathway genetic variants. In addition, single nucleotide polymorphism (SNP)s identified by GWAS appear to indicate a strong role for genes encoding transcription factors involved in cellular differentiation. Further studies are needed to clarify the accumulating evidence obtained from both candidate gene and genome-wide investigations. PMID:27498736

  15. 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.

  16. 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 Central

    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

    2015-01-01

    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; 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; 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

  17. 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

  18. 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

  19. 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

  20. 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 ...

  1. 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

  2. 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

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

    PubMed Central

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

    2009-01-01

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

  4. A Revised Definition for Cure of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Pui, CH; Pei, D; Campana, D; Cheng, C; Sandlund, JT; Bowman, WP; Hudson, MM; Ribeiro, RC; Raimondi, SC; Jeha, S; Howard, SC; Bhojwani, D; Inaba, H; Rubnitz, JE; Metzger, ML; Gruber, TA; Coustan-Smith, E; Downing, JR; Leung, WH; Relling, MV; Evans, WE

    2014-01-01

    With improved contemporary therapy, we re-assess long-term outcome in patients completing treatment for childhood acute lymphoblastic leukemia to determine when cure can be declared with a high degree of confidence. In 6 successive clinical trials between 1984 and 2007, 1291(84.5%) patients completed all therapy 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 off 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 acute lymphoblastic leukemia may relapse after completion of treatment, and those who remain in remission at 4 years post-treatment may be considered cured (i.e., less than 1 % chance of relapse). PMID:24781017

  5. Early Complications of Hyperleukocytosis and Leukapheresis in Childhood Acute Leukemias.

    PubMed

    Abla, Oussama; Angelini, Paola; Di Giuseppe, Giancarlo; Kanani, Mohamed F; Lau, Wendy; Hitzler, Johann; Sung, Lillian; Naqvi, Ahmed

    2016-03-01

    Hyperleukocytosis in children with acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) is associated with early morbidity and mortality. The benefit from leukapheresis is controversial, and its complications are not well defined. We analyzed the frequency of early complications in children with ALL and AML presenting with white blood cell (WBC) count >100 × 10(9)/L, and the type and frequency of complications related to leukapheresis. During a 12-year period, 84 of 634 (13%) ALL and 18 of 143 (12.5%) AML patients presented with hyperleukocytosis. Leukapheresis was performed in 18 ALL and 12 AML patients. The median initial WBC was 474 × 10(9)/L in the leukapheresis group compared with 175 × 10(9)/L in the nonleukapheresis group. Neurological leukostasis occurred in 6 ALL (7.1%) and 4 AML (22.2%) patients. Pulmonary leukostasis occurred in 16 ALL (19%) and 4 AML patients (22.2%). Neurological symptoms improved in few patients after leukapheresis, except in patients with very high WBC (>650 × 10(9)/L in ALL and >400 × 10(9)/L in AML). Leukapheresis improved respiratory symptoms in some patients but caused worsening symptoms in others. Early death was associated with neurological complications, AML diagnosis, and coagulopathy. Leukapheresis did not delay initiation of chemotherapy, nor did it impact early response to chemotherapy or long-term survival. Complications included femoral vein thrombosis, electrolyte imbalances, and hemodynamic instability, which were all reversible. The role of leukapheresis as a cytoreductive procedure in childhood hyperleukocytic leukemia remains to be well defined.

  6. Definition of Cure in Childhood Acute Myeloid Leukemia

    PubMed Central

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

    2014-01-01

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

  7. 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

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

    PubMed

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

    2005-08-15

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

  9. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.

    PubMed

    Tartaglia, Marco; Martinelli, Simone; Iavarone, Ivano; Cazzaniga, Giovanni; Spinelli, Monica; Giarin, Emanuela; Petrangeli, Valentina; Carta, Claudio; Masetti, Riccardo; Aricò, Maurizio; Locatelli, Franco; Basso, Giuseppe; Sorcini, Mariella; Pession, Andrea; Biondi, Andrea

    2005-05-01

    Somatic mutations in PTPN11, the gene encoding the transducer SHP-2, have emerged as a novel class of lesions that upregulate RAS signalling and contribute to leukaemogenesis. In a recent study of 69 children and adolescents with de novo acute myeloid leukaemia (AML), we documented a non-random distribution of PTPN11 mutations among French-American-British (FAB) subtypes. Lesions were restricted to FAB-M5 cases, where they were relatively common (four of 12 cases). Here, we report on the results of a molecular screening performed on 181 additional unselected patients, enrolled in participating institutions of the Associazione Italiana Ematologia Oncologia Pediatrica-AML Study Group, to provide a more accurate picture of the prevalence, spectrum and distribution of PTPN11 mutations in childhood AML and to investigate their clinical relevance. We concluded that PTPN11 defects do not represent a frequent event in this heterogeneous group of malignancies (4.4%), although they recur in a considerable percentage of patients with FAB-M5 (18%). PTPN11 lesions rarely occur in other subtypes. Within the FAB-M5 group no clear association of PTPN11 mutations with any clinical variable was evident. Nearly two third of the patients with this subtype were found to harbour an activating mutation in PTPN11, NRAS, KRAS2 or FLT3.

  10. [Percutaneous rheolytic thrombectomy in the treatment of high-risk acute pulmonary embolism: Initial experience of a single center].

    PubMed

    Faria, Rita; Oliveira, Márcia; Ponte, Marta; Pires-Morais, Gustavo; Sousa, Marta; Fernandes, Paula; Rodrigues, Alberto; Braga, Pedro; Gonçalves, Manuel; Gama, Vasco

    2014-06-01

    For years, the treatment of high-risk pulmonary embolism (PE) was based on two well-defined strategies: thrombolysis, whose benefits have been documented in randomized trials, and surgical embolectomy. However, mechanical reperfusion by percutaneous techniques is used in an increasing number of patients, and is a valid therapeutic option when there is a formal contraindication to thrombolysis, as rescue therapy when thrombolysis fails to improve hemodynamics, and/or when emergency surgical thrombectomy is unavailable or contraindicated. This article discusses the indications for the use of percutaneous techniques in PE, reports the initial experience of our center with the AngioJet® thrombectomy device (Possis Medical Inc, Minneapolis, MN, USA) and reviews the available evidence, the most recent recommendations and the main complications associated with this procedure.

  11. 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

  12. High Risk of Herpes Zoster among Patients with Advance Acute Kidney Injury--A Population-Based Study.

    PubMed

    Yang, Wei-Shun; Hu, Fu-Chang; Chen, Meng-Kan; Ko, Wen-Je; Chen, Likwang; Wu, Kwan-Dun; Wu, Vin-Cent

    2015-09-03

    The risk for herpes zoster (HZ) in acute kidney injury (AKI) survivors was never explored. We identified 2,387 adults in the Taiwan National Health Insurance Research Database who recovered from dialysis-requiring AKI and matched them with non-recovery and non-AKI patients by propensity score. During a mean follow-up of 2.7 years, the incidences of HZ were 6.9, 8.2 and 4.8 episodes per 1,000 person-years in AKI-non-recovery, AKI-recovery and non-AKI group, respectively. The recovery group was more likely to develop herpes zoster than those without acute kidney injury [incidence-rate ratios 1.71, 95% confidence interval 1.16-2.52; p = 0.007]. Patients without acute kidney injury were less likely to develop herpes zoster than those AKI, recovered from dialysis or not (hazard ratio HR 0.66, 95% CI 0.46-0.95). Dialysis-requiring acute kidney injury poses a long-term risk of herpes zoster after hospital discharge. Even patients who have recovered from dialysis still carry a significantly higher risk of developing herpes zoster.

  13. 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

  14. Tolerability and feasibility of eptifibatide in acute coronary syndrome in patients at high risk for cardiovascular disease: A retrospective analysis*

    PubMed Central

    Azzam, Zaher S.; Sa'ad, Elias; Jabareen, Amal; Eilam, Oron; Bartha, Petru; Hadad, Salim; Krivoy, Norberto

    2005-01-01

    Background: Despite the beneficial effects of glycoprotein (GP) IIb/IIIa antagonists in patients with unstable angina and non-ST-segment elevation myocardial infarction (UA/NSTEMI), GP IIb/IIIa antagonists are rarely administered in general internal medicine wards in Israel, where most patients with UA/ NSTEMI are admitted, due to lack of adequate monitoring and safety concerns. Objective: The aims of this study were to compare the prevalence of bleeding complications in patients with UA/NSTEMI receiving combination treatment with eptifibatide (a GP IIb/IIIa antagonist), the low-molecular-weight heparin enoxaparin, and acetylsalicylic acid (ASA) versus that in patients receiving enoxaparin and ASA in internal medicine wards in Israel, and to identify risk factors for bleeding complications. Methods: This retrospective analysis included information from the database at Rambam Medical Center, Haifa, Israel. The database provided information from 4 of the 5 wards (the ward from which data were unavailable did not routinely use eptifibatide). Data were included from patients aged ≥l.8 years who were admitted to the center with a diagnosis of UA/NSTEMI, were at high risk for death and/or nonfatal ischemic events based on American College of Cardiology/American Heart Association guidelines, were to undergo coronary intervention, and who had a Thrombosis in Myocardial Infarction risk score ≥3 (moderate to high risk). Patients in the eptifibatide group received eptifibatide IV (180-μg/kg bolus followed by a continuous infusion of 2 μg/kg · min up to 72 hours), enoxaparin SC (2 mg/kg · d), and ASA (100 mg/d). Patients in the control group received enoxaparin SC (2 mg/kg - d up to 96 hours) and ASA (100 mg/d). The prevalence of bleeding events was assessed using data up to 24 hours after the end of study drug administration. Major bleeding was defined as life-threatening bleeding at any site, intracranial hemorrhage, or bleeding accompanied by a decrease in plasma

  15. Herbo-mineral ayurvedic treatment in a high risk acute promyelocytic leukemia patient with second relapse: 12 years follow up

    PubMed Central

    Prakash, Balendu; Parikh, Purvish M.; Pal, Sanjoy K.

    2010-01-01

    A 47 year old diabetic male patient was diagnosed and treated for high risk AML-M3 at Tata Memorial Hospital (BJ 17572), Mumbai in September 1995. His bone marrow aspiration cytology indicated 96% promyelocytes with abnormal forms, absence of lymphocytic series and myeloperoxide test 100% positive. Initially treated with ATRA, he achieved hematological remission on day 60, but cytogenetically the disease persisted. The patient received induction and consolidated chemotherapy with Daunorubicin and Cytarabine combination from 12.01.96 to 14.05.96, following which he achieved remission. However, his disease relapsed in February 97. The patient was given two cycles of chemotherapy with Idarubicine and Etoposide, after which he achieved remission. His disease again relapsed in December 97. The patient then refused more chemotherapy and volunteered for a pilot Ayurvedic study conducted by the Central Council for Research in Ayurveda and Siddha, New Delhi. The patient was treated with a proprietary Ayurvedic medicine Navajeevan, Kamadudha Rasa and Keharuba Pisti for one year. For the subsequent 5 years the patient received three months of intermittent Ayurvedic treatment every year. The patient achieved complete disease remission with the alternative treatment without any adverse side effects. The patient has so far completed 13 years of survival after the start of Ayurvedic therapy. PMID:21547051

  16. Herbo-mineral ayurvedic treatment in a high risk acute promyelocytic leukemia patient with second relapse: 12 years follow up.

    PubMed

    Prakash, Balendu; Parikh, Purvish M; Pal, Sanjoy K

    2010-07-01

    A 47 year old diabetic male patient was diagnosed and treated for high risk AML-M3 at Tata Memorial Hospital (BJ 17572), Mumbai in September 1995. His bone marrow aspiration cytology indicated 96% promyelocytes with abnormal forms, absence of lymphocytic series and myeloperoxide test 100% positive. Initially treated with ATRA, he achieved hematological remission on day 60, but cytogenetically the disease persisted. The patient received induction and consolidated chemotherapy with Daunorubicin and Cytarabine combination from 12.01.96 to 14.05.96, following which he achieved remission. However, his disease relapsed in February 97. The patient was given two cycles of chemotherapy with Idarubicine and Etoposide, after which he achieved remission. His disease again relapsed in December 97. The patient then refused more chemotherapy and volunteered for a pilot Ayurvedic study conducted by the Central Council for Research in Ayurveda and Siddha, New Delhi. The patient was treated with a proprietary Ayurvedic medicine Navajeevan, Kamadudha Rasa and Keharuba Pisti for one year. For the subsequent 5 years the patient received three months of intermittent Ayurvedic treatment every year. The patient achieved complete disease remission with the alternative treatment without any adverse side effects. The patient has so far completed 13 years of survival after the start of Ayurvedic therapy. PMID:21547051

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

    PubMed Central

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

    2013-01-01

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

  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. Treatment Outcome in Older Patients with Childhood Acute Myeloid Leukemia

    PubMed Central

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

    2013-01-01

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

  20. 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

  1. Monitoring minimal residual disease in children with high-risk relapses of acute lymphoblastic leukemia: prognostic relevance of early and late assessment.

    PubMed

    Eckert, C; Hagedorn, N; Sramkova, L; Mann, G; Panzer-Grümayer, R; Peters, C; Bourquin, J-P; Klingebiel, T; Borkhardt, A; Cario, G; Alten, J; Escherich, G; Astrahantseff, K; Seeger, K; Henze, G; von Stackelberg, A

    2015-08-01

    The prognosis for children with high-risk relapsed acute lymphoblastic leukemia (ALL) is poor. Here, we assessed the prognostic importance of response during induction and consolidation treatment prior to hematopoietic stem cell transplantation (HSCT) aiming to evaluate the best time to assess minimal residual disease (MRD) for intervention strategies and in future trials in high-risk ALL relapse patients. Included patients (n=125) were treated uniformly according to the ALL-REZ BFM (Berlin-Frankfurt-Münster) 2002 relapse trial (median follow-up time=4.8 years). Patients with MRD ⩾10(-3) after induction treatment (76/119, 64%) or immediately preceding HSCT (19/71, 27%) had a significantly worse probability of disease-free survival 10 years after relapse treatment begin, with 26% (±6%) or 23% (±7%), respectively, compared with 58% (±8%) or 48% (±7%) for patients with MRD <10(-3). Conventional intensive consolidation treatment reduced MRD to <10(-3) before HSCT in 63% of patients, whereas MRD remained high or increased in the rest of this patient group. Our data support that MRD after induction treatment can be used to quantify the activity of different induction treatment strategies in phase II trials. MRD persistence at ⩾10(-3) before HSCT reflects a disease highly resistant to conventional intensive chemotherapy and requiring prospective controlled investigation of new treatment strategies and drugs. PMID:25748682

  2. 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

  3. Predictions in the face of clinical reality: HistoCheck versus high-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease.

    PubMed

    Askar, Medhat; Sobecks, Ronald; Morishima, Yasuo; Kawase, Takakazu; Nowacki, Amy; Makishima, Hideki; Maciejewski, Jaroslaw

    2011-09-01

    HLA polymorphism remains a major hurdle for hematopoietic stem cell transplantation (HSCT). In 2004, Elsner et al. proposed the HistoCheck Web-based tool to estimate the allogeneic potential between HLA-mismatched stem cell donor/recipient pairs expressed as a sequence similarity matching (SSM). SSM is based on the structure of HLA molecules and the functional similarity of amino acids. According to this algorithm, a high SSM score represents high dissimilarity between MHC molecules, resulting in a potentially more deleterious impact on stem cell transplant outcomes. We investigated the potential of SSM to predict high-risk HLA allele mismatch combinations responsible for severe acute graft-versus-host disease (aGVHD grades III and IV) published by Kawase et al., by comparing SSM in low- and high-risk combinations. SSM was calculated for allele mismatch combinations using the HistoCheck tool available on the Web (www.histocheck.org). We compared ranges and means of SSM among high-risk (15 combinations observed in 722 donor/recipient pairs) versus low-risk allele combinations (94 combinations in 3490 pairs). Simulation scenarios were created where the recipient's HLA allele was involved in multiple allele mismatch combinations with at least 1 high-risk and 1 low-risk mismatch combination. SSM values were then compared. The mean SSM for high- versus low-risk combinations were 2.39 and 2.90 at A, 1.06 and 2.53 at B, 16.60 and 14.99 at C, 4.02 and 3.81 at DRB1, and 7.47 and 6.94 at DPB1 loci, respectively. In simulation scenarios, no predictable SSM association with high- or low-risk combinations could be distinguished. No DQB1 combinations met the statistical criteria for our study. In conclusion, our analysis demonstrates that mean SSM scores were not significantly different, and SSM distributions were overlapping among high- and low-risk allele combinations within loci HLA-A, B, C, DRB1, and DPB1. This analysis does not support selecting donors for HSCT recipients

  4. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    PubMed Central

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

    2012-01-01

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

  5. 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

  6. 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...

  7. Murine B-1 B Cell Progenitors Initiate B-Acute Lymphoblastic Leukemia With Features of High Risk Disease1

    PubMed Central

    Montecino-Rodriguez, Encarnacion; Li, Katy; Fice, Michael; Dorshkind, Kenneth

    2014-01-01

    B-1 and B-2 B cells derive from distinct progenitors that emerge in overlapping waves of development. The number of murine B-1 progenitors peaks during fetal development while B-2 B cell production predominates in adult bone marrow. Many genetic mutations that underlie B-acute lymphoblastic leukemia (B-ALL) occur in the fetus, at which time B-1 progenitor numbers are high. However, whether B-ALL can initiate in B-1 progenitors is unknown. We now report that BCR-ABL transformed murine B-1 progenitors can be B-ALL cells of origin and demonstrate that they initiate disease more rapidly than oncogene expressing B-2 progenitors. We further demonstrate that B-1 progenitors exhibit relative resistance to apoptosis and undergo significant growth following oncogene expression and propose that these properties underlie the accelerated kinetics with which they initiate leukemia. These results provide a developmental perspective on the origin of B-ALL and indicate B cell lineage as a factor influencing disease progression. PMID:24752443

  8. TP53 mutation in patients with high-risk acute myeloid leukaemia treated with allogeneic haematopoietic stem cell transplantation.

    PubMed

    Middeke, Jan M; Herold, Sylvia; Rücker-Braun, Elke; Berdel, Wolfgang E; Stelljes, Matthias; Kaufmann, Martin; Schäfer-Eckart, Kerstin; Baldus, Claudia D; Stuhlmann, Reingard; Ho, Anthony D; Einsele, Hermann; Rösler, Wolf; Serve, Hubert; Hänel, Mathias; Sohlbach, Kristina; Klesse, Christian; Mohr, Brigitte; Heidenreich, Falk; Stölzel, Friedrich; Röllig, Christoph; Platzbecker, Uwe; Ehninger, Gerhard; Bornhäuser, Martin; Thiede, Christian; Schetelig, Johannes

    2016-03-01

    Treatment success in patients with acute myeloid leukaemia (AML) is heterogeneous. Cytogenetic and molecular alterations are strong prognostic factors, which have been used to individualize treatment. Here, we studied the impact of TP53 mutations on the outcome of AML patients with adverse cytogenetic risk treated with allogeneic haematopoietic stem cell transplantation (HSCT). Samples of 97 patients with AML and adverse-risk cytogenetics who had received a HSCT within three randomized trials were analysed. Complete sequencing of the TP53 coding region was performed using next generation sequencing. The median age was 51 years. Overall, TP53 mutations were found in 40 patients (41%). With a median follow up of 67 months, the three-year probabilities of overall survival (OS) and event-free survival for patients with TP53 wild type were 33% [95% confidence interval (CI), 21% to 45%] and 24% (95% CI, 13% to 35%) compared to 10% (95% CI, 0% to 19%) and 8% (95% CI, 0% to 16%) (P = 0·002 and P = 0·007) for those with mutated TP53, respectively. In multivariate analysis, the TP53-mutation status had a negative impact on OS (Hazard Ratio = 1·7; P = 0·066). Mutational analysis of TP53 might be an important additional tool to predict outcome after HSCT in patients with adverse karyotype AML.

  9. 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

  10. 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

  11. 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

    2016-09-26

    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

  12. 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

  13. Stability and Change in Autism Spectrum Disorder Diagnosis from Age 3 to Middle Childhood in a High-Risk Sibling Cohort

    ERIC Educational Resources Information Center

    Brian, Jessica; Bryson, Susan E.; Smith, Isabel M.; Roberts, Wendy; Roncadin, Caroline; Szatmari, Peter; Zwaigenbaum, Lonnie

    2016-01-01

    Considerable evidence on autism spectrum disorder emergence comes from longitudinal high-risk samples (i.e. younger siblings of children with autism spectrum disorder). Diagnostic stability to age 3 is very good when diagnosed as early as 18-24 months, but sensitivity is weaker, and relatively little is known beyond toddlerhood. We examined…

  14. 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…

  15. Vaccination and the risk of childhood acute leukaemia: the ESCALE study (SFCE)

    PubMed Central

    Mallol-Mesnard, Nathalie; Menegaux, Florence; Auvrignon, Anne; Auclerc, Marie-Françoise; Bertrand, Yves; Nelken, Brigitte; Robert, Alain; Michel, Gérard; Margueritte, Geneviève; Perel, Yves; Méchinaud, Françoise; Bordigoni, Pierre; Leverger, Guy; Baruchel, André; Hémon, Denis; Clavel, Jacqueline

    2007-01-01

    Background In 2002, a poster alerted the French health authorities to the possibility that the risk of childhood leukaemia might be increased by hepatitis B vaccination. Elucidating the role of vaccination in the etiology of childhood acute leukaemia was therefore included in the objectives of an ongoing national study. Methods The ESCALE study was a French national population-based case-control study conducted in France in 2003 and 2004 in order to investigate the role of infectious, environmental and genetic factors in 4 childhood neoplastic diseases (leukaemia, lymphoma, neuroblastoma, and brain tumor). The controls were randomly selected from the French population and age and gender frequency matched with the cases. A total of 776 cases of acute leukaemia (91% of the eligible cases) and 1681 controls (69% of the eligible controls) were included. In a specific standardized telephone interview, which was the same for both the cases and controls, each mother was asked to read out her child’s complete vaccination record. Results No association between vaccination and the risk of childhood acute leukaemia (ALL or AML) was observed. No relationship between the risk of leukaemia and the type of vaccine, number of doses of each vaccine, total number of injections, total number of vaccine doses or number of early vaccinations was evidenced. No confounding factor was observed. Conclusion The study did not show any evidence of a role of vaccination in the etiology of childhood leukaemia. PMID:17227780

  16. The seventh international childhood acute lymphoblastic leukemia workshop report: Palermo, Italy, January 29--30, 2005.

    PubMed

    Aricó, M; Baruchel, A; Bertrand, Y; Biondi, A; Conter, V; Eden, T; Gadner, H; Gaynon, P; Horibe, K; Hunger, S P; Janka-Schaub, G; Masera, G; Nachman, J; Pieters, R; Schrappe, M; Schmiegelow, K; Valsecchi, M G; Pui, C-H

    2005-07-01

    Between 1995 and 2004, six International Childhood Acute Lymphoblastic Leukemia (ALL) Workshop have been held, and the completion of several collaborative projects has established the clinical relevance and treatment options for several specific genetic subtypes of ALL. This meeting report summarizes the data presented in the seventh meeting and the discussion.

  17. 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

  18. Quantitative assessments of indoor air pollution and the risk of childhood acute leukemia in Shanghai.

    PubMed

    Gao, Yu; Zhang, Yan; Kamijima, Michihiro; Sakai, Kiyoshi; Khalequzzaman, Md; Nakajima, Tamie; Shi, Rong; Wang, Xiaojin; Chen, Didi; Ji, Xiaofan; Han, Kaiyi; Tian, Ying

    2014-04-01

    We investigated the association between indoor air pollutants and childhood acute leukemia (AL). A total of 105 newly diagnosed cases and 105 1:1 gender-, age-, and hospital-matched controls were included. Measurements of indoor pollutants (including nitrogen dioxide (NO2) and 17 types of volatile organic compounds (VOCs)) were taken with diffusive samplers for 64 pairs of cases and controls. Higher concentrations of NO2 and almost half of VOCs were observed in the cases than in the controls and were associated with the increased risk of childhood AL. The use of synthetic materials for wall decoration and furniture in bedroom was related to the risk of childhood AL. Renovating the house in the last 5 years, changing furniture in the last 5 years, closing the doors and windows overnight in the winter and/or summer, paternal smoking history and outdoor pollutants affected VOC concentrations. Our results support the association between childhood AL and indoor air pollution.

  19. 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.

  20. A cost utility analysis of interdisciplinary early intervention versus treatment as usual for high-risk acute low back pain patients.

    PubMed

    Rogerson, Mark D; Gatchel, Robert J; Bierner, Samuel M

    2010-01-01

    Chronic pain is a costly and debilitating condition that has proven difficult to treat, solely with medical interventions, due to the complex interplay of biological, psychological, and social factors in its onset and persistence. Many studies have demonstrated the effectiveness of interdisciplinary treatment that includes psychosocial interventions for low back pain. Nevertheless, these interventions continue to be under-utilized due to concerns of cost and applicability. The present study utilized a cost utility analysis to evaluate effectiveness and associated costs of interdisciplinary early intervention for individuals with acute low back pain that was identified as high-risk for becoming chronic. Treatment effectiveness was evaluated using a standard pain measure and quality-adjusted life years, and associated medical and employment costs were gathered for 1 year. Results indicated that subjects improved significantly from pretreatment to 1-year follow-up, and that the early intervention group reported fewer health-care visits and missed workdays than the treatment as usual group. The majority of 1,000 bootstrapped samples demonstrated the dominance of the early intervention program as being both more effective and less costly from a societal perspective. The early intervention treatment was the preferred option in over 85% of samples within an established range of acceptable costs. These results are encouraging evidence for the cost-effectiveness of interdisciplinary intervention and the benefits of targeted early treatment. PMID:20384967

  1. 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

  2. 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

  3. 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.

  4. 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

  5. NF-kappaB inhibition sensitizes to starvation-induced cell death in high-risk myelodysplastic syndrome and acute myeloid leukemia.

    PubMed

    Fabre, C; Carvalho, G; Tasdemir, E; Braun, T; Adès, L; Grosjean, J; Boehrer, S; Métivier, D; Souquère, S; Pierron, G; Fenaux, P; Kroemer, G

    2007-06-14

    CD34(+) bone marrow blasts from high-risk myelodysplastic syndrome (MDS) patients as well as MDS patient-derived cell lines (P39 and MOLM13) constitutively activate the nuclear factor-kappaB (NF-kappaB) pathway and undergo apoptosis when NF-kappaB is inhibited. Here, we show that the combination of conventional chemotherapeutic agents (daunorubicin, mitoxantrone, 5-azacytidine or camptothecin) with the NF-kappaB inhibitor BAY11-7082 did not yield a synergistic cytotoxicity. In contrast, BAY11-7082 (which targets the NF-kappaB-activating I-kappaB kinase (IKK) complex) or knockdown of essential components of the NF-kappaB system (such as the IKK1 and IKK2 subunits of the IKK complex and the p65 subunit of NF-kappaB), by small interfering RNAs sensitized MDS cell lines to starvation-induced apoptosis. The combination of BAY11-7082 and nutrient depletion synergistically killed the acute myeloid leukemia (AML) cell line U937 as well as primary CD34(+) bone marrow blasts from AML and high-risk MDS patients. The synergistic killing by BAY11-7082, combined with nutrient depletion, led to cell death accompanied by all hallmarks of apoptosis, including an early loss of the mitochondrial transmembrane potential, the release of cytochrome c and apoptosis-inducing factor (AIF) from mitochondria, activation of caspase-3, phosphatidylserine exposure on the plasma membrane surface and nuclear chromatin condensation. Transmission electron microscopy revealed the presence of numerous autophagic vacuoles in the cytoplasm before cells underwent nuclear apoptosis. Nonetheless, cell death was neither inhibited by the pan-caspase inhibitor z-VAD-fmk nor by knockdown of AIF or of essential components of the autophagy pathway (ATG5, ATG6/Beclin-1, ATG10, ATG12). In contrast, external supply of glucose, insulin or insulin-like growth factor-I could retard the cell death induced by BAY11-7082 combined with starvation. These results suggest that in MDS cells, NF-kappaB inhibition can

  6. Duration of eptifibatide infusion after percutaneous coronary intervention and outcomes among high-risk patients with non-ST-segment elevation acute coronary syndrome: insights from EARLY ACS

    PubMed Central

    Hess, Connie N; Schulte, Phillip J; Steg, Philippe Gabriel; Dalby, Anthony J; Schweiger, Marc J; Lewis, Basil S; Armstrong, Paul W; Califf, Robert M; van de Werf, Frans; Harrington, Robert A

    2013-01-01

    Background and Objectives: Eptifibatide is indicated during percutaneous coronary intervention (PCI) with continuation for 18–24 hours post procedure but is associated with bleeding. We examined the efficacy and safety of shorter post-PCI eptifibatide infusions in high-risk non-ST-segment elevation acute coronary syndrome (NSTE ACS) patients. Methods: EARLY ACS patients treated with PCI and eptifibatide were grouped by post-procedure infusion duration: <10, 10–13, 13–17, and 17–25 (per protocol) hours. Adjusted estimated event rates for 96-hour death/myocardial infarction (MI)/recurrent ischaemia requiring urgent revascularization (RIUR), 30-day death/MI, post-PCI packed red blood cell (PRBC) transfusion, and GUSTO (Global Utilization of Streptokinase and Tissue Plasminogen Activator for Occluded Coronary Arteries) moderate/severe bleeding were obtained using inverse-propensity weighting to account for informative censoring of infusions. Results: Among 3271 eptifibatide-treated PCI patients, there were 66 96-hour death/MI/RIUR events, 94 30-day death/MI events, 127 PRBC transfusions, and 115 GUSTO moderate/severe bleeds. Compared with per protocol, patients receiving post-PCI infusions <10 hours had similar adjusted estimated rates of 96-hour death/MI/RIUR (absolute difference 0.021 higher; 0.040 vs. 0.019, 95% CI −0.023 to 0.064; p=0.35) and 30-day death/MI (0.020 higher; 0.046 vs. 0.026, 95% CI −0.021 to 0.062; p=0.34). There were also no differences in ischaemic outcomes between infusions of 10–17 hours and per-protocol infusions. Adjusted estimated rates of PRBC transfusion were higher for the <10-hour infusion group compared with per protocol (0.048 higher; 0.079 vs. 0.031, 95% CI 0.005 to 0.091, p=0.03) but were similar for other groups. Adjusted GUSTO moderate/severe bleeding rates were similar to per-protocol rates for all groups. Conclusions: In high-risk NSTE ACS patients, post-PCI eptifibatide infusions <18 hours were not associated with

  7. Tosedostat in Combination With Cytarabine or Decitabine in Treating Patients With Newly Diagnosed Acute Myeloid Leukemia or High-Risk Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-06-09

    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 t(15;17)(q22;q12); de Novo Myelodysplastic Syndromes; Previously Treated Myelodysplastic Syndromes; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Untreated Adult Acute Myeloid Leukemia

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

    PubMed

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

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

  9. 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

  10. Fetal growth and body size genes and risk of childhood acute lymphoblastic leukemia.

    PubMed

    Chokkalingam, Anand P; Metayer, Catherine; Scelo, Ghislaine; Chang, Jeffrey S; Schiffman, Joshua; Urayama, Kevin Y; Ma, Xiaomei; Hansen, Helen M; Feusner, James H; Barcellos, Lisa F; Wiencke, John K; Wiemels, Joseph L; Buffler, Patricia A

    2012-09-01

    Accumulating evidence suggests that childhood acute lymphoblastic leukemia (ALL) may be initiated in utero or early in the postnatal period. High birth weight (or rapid fetal growth) is associated with risk of ALL, but the mechanisms are not understood. In a population-based epidemiologic study of childhood ALL, we utilized a haplotype-based approach to assess the role of eight genes involved in fetal growth and body size regulation in 377 childhood ALL cases and 448 controls. We found significant haplotype associations with risk of childhood ALL for IGF1 among non-Hispanics and Hispanics together (p = 0.002), for IGF2 among Hispanics (p = 0.040), and for IGF2R among Hispanics and non-Hispanics (p = 0.051 and 0.009, respectively). No haplotype associations were observed for IGF1R or the studied genes involved in body size regulation, including LEP, LEPR, GHRL, and NPY. Our study is the first to identify an association between the genes involved in the IGF axis and risk of childhood ALL. These findings for childhood ALL emphasize the importance of fetal growth, when lymphoid progenitor cells are not yet fully differentiated and therefore more susceptible to malignant transformation. Additional studies are needed to confirm these findings and identify specific causal variants.

  11. 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.

  12. 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

    2016-08-23

    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

  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.

  15. 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

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

    PubMed

    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

    2015-07-01

    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.

  17. 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.

  18. Pyrethroid pesticide exposure and risk of childhood acute lymphocytic leukemia in Shanghai.

    PubMed

    Ding, Guodong; Shi, Rong; Gao, Yu; Zhang, Yan; Kamijima, Michihiro; Sakai, Kiyoshi; Wang, Guoquan; Feng, Chao; Tian, Ying

    2012-12-18

    Significant amounts of pyrethroid pesticides are used throughout China. Previous studies have suggested that exposure to pesticides may increase the risk of childhood cancer; however, few studies have focused on pyrethroid metabolites. We investigated five nonspecific metabolites of pyrethroid pesticides found in children's urine and examined the correlation with childhood leukemia. We conducted a hospital-based case-control study of childhood acute lymphocytic leukemia (ALL) in Shanghai between 2010 and 2011. The study included 176 children aged 0-14 years and 180 controls matched for age and sex. Compared with those in the lowest quartiles of total and individual metabolites, the highest quartiles were associated with an approximate 2-fold increased risk of ALL [total metabolites: odds ratio (OR) = 2.75, 95% confidence interval (CI), 1.43-5.29; cis-DCCA: OR = 2.21, 95% CI, 1.16-4.19; trans-DCCA: OR = 2.33, 95% CI, 1.23-4.41; and 3-PBA: OR = 1.84, 95% CI, 1.00-3.38], and most of the positive trends were significant (p < 0.05). Our findings suggest that urinary levels of pyrethroid metabolites may be associated with an elevated risk of childhood ALL and represent a previously unreported quantitative exposure assessment for childhood leukemia.

  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

    2016-10-18

    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. Lymphocyte aromatic hydrocarbon responsiveness in acute leukemia of childhood

    SciTech Connect

    Blumer, J.L.; Dunn, R.; Esterhay, M.D.; Yamashita, T.S.; Gross, S.

    1981-12-01

    Aryl hydrocarbon hydroxylase (AHH) activity and inducibility were examined in mitogen-stimulated cultured lymphocytes from children with acute leukemia in remission, with nonleukemic malignancies, and with no family or personal history of malignant disease. Neither morphological differences nor differences in mitogen responsivelness were observed among the three sources of cells studied. Levels of constitutive and dibenzanthracene-induced AHH activity were found to be similar among the three groups by analysis of variance. However, when results were analyzed in terms of inducibility ratios, it was found that cells from leukemic children were significantly less inducible (p < 0.005) than cells from unaffected children or children with nonleukemic malignancies. The reason for this difference became apparent when statistical criteria were employed for the phenotypic separation of individuals who were highly aromatic hydrocarbon responsive and minimally responsive. A significantly larger proportion (p < 0.001) of leukemic children than unaffected children or children with nonleukemic malignancy were found to be minimally aromatic hydrocarbon responsive. Moreover, in patients with acute lymphoblastic leukemia relapsing while on therapy, longer durations of the first remission were correlated (r = 0.63, p < 0.05) with the highly inducible AHH phenotype.

  2. Higher risk for acute childhood lymphoblastic leukaemia in Swedish population centres 1973-94

    PubMed Central

    Hjalmars, U; Gustafsson, G

    1999-01-01

    A population-based sample of acute childhood leukaemia cases in Sweden 1973–94 was analysed by a geographical information system (GIS) for spatial leukaemia distribution in relation to population density. The annual incidence rate for acute lymphoblastic leukaemia (ALL) was 3.6, and for acute non-lymphoblastic leukaemia (ANLL) 0.7, cases per 100 000 children. Incidence rates in population centres, constituting 1.3% of Sweden's land area and approximately 80% of the population, compared with the rest of Sweden showed a statistically significant excess of ALL [odds ratio (OR) 1.68; 95% confidence interval (CI) 1.44–1.95], but not ANLL (OR 1.13; 95% CI 0.98–1.32). An increasing trend, however not statistically significant, was found for ALL incidence with both increasing population density in parishes and increasing degree of urbanity in municipalities. These findings support the theories that some environmental factors associated with high population density, such as infectious agents, may be of aetiological importance for childhood acute lymphoblastic leukaemia. © 1999 Cancer Research Campaign PMID:10408689

  3. 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.

  4. Association between childhood acute lymphoblastic leukemia and use of electrical appliances during pregnancy and childhood.

    PubMed

    Hatch, E E; Linet, M S; Kleinerman, R A; Tarone, R E; Severson, R K; Hartsock, C T; Haines, C; Kaune, W T; Friedman, D; Robison, L L; Wacholder, S

    1998-05-01

    As part of a comprehensive study of residential magnetic field exposure in nine midwestern and mid-Atlantic states, we evaluated the use of appliances by 640 patients with acute lymphoblastic leukemia, 0-14 years of age, diagnosed between 1989 and 1993, and 640 matched control children. Mothers were interviewed regarding use of electrical appliances during their pregnancy with the subject and the child's postnatal use. The risk of acute lymphoblastic leukemia was elevated in children whose mothers reported use of an electric blanket or mattress pad during pregnancy [odds ratio (OR) = 1.59; 95% confidence interval (CI) = 1.11-2.29] but was reduced for use of sewing machines during pregnancy (OR = 0.76; 95% CI = 0.59-0.98). The risk of acute lymphoblastic leukemia was increased with children's use of electric blankets or mattress pads (OR = 2.75; 95% CI = 1.52-4.98) and three other electrical appliances (hair dryers, video machines in arcades, and video games connected to a television), but the patterns of risk for duration in years of use and frequency of use were inconsistent for most appliances used by children. Risks rose with increasing number of hours per day children spent watching television, but risks were similar regardless of the usual distance from the television. The inconsistency in the dose-response patterns for many appliances, reporting and selection bias, and the lack of an effect for measured 60 Hertz magnetic fields or wire codes in our companion study must be considered before ascribing these associations to exposures from magnetic fields.

  5. Molecular analysis of childhood acute lymphoblastic leukemia in Israel.

    PubMed

    Blau, O; Avigad, S; Frisch, A; Kilim, Y; Stark, B; Kodman, Y; Luria, D; Cohen, I J; Zaizov, R

    1998-06-01

    Ninety-two Israeli children with acute lymphoblastic leukemia (ALL) (67 B-lineage and 25 T-lineage) were analyzed for the immunological antigen receptor gene configuration. Thirty-nine of the patients (27 B-lineage and 12 T-lineage) relapsed. The incidence of the identified rearrangements within the immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)beta, gamma and delta genes, at diagnosis, was in accordance with previous studies from other countries. Furthermore, the clinical relevance of bi/oligoclonal status, at diagnosis, and clonal selection was determined in this long-term follow-up study (median 112 months). A similar relapse rate was observed among the B-lineage patients with bi/oligoclonal and monoclonal patterns indicated by IgH gene rearrangement. Based on our results, we suggest that bi/oligoclonality has no prognostic significance (P=0.8533). Clonal variations between diagnosis and subsequent relapses were detected in 60% (12/20) of the patients; 64% (7/11) B-lineage and 55% (5/9) T-lineage. Clonal selection significantly correlated with shorter duration of remission and earlier recurrence (P=0.0025).

  6. 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

  7. Risk-adapted treatment of acute promyelocytic leukemia based on all-trans retinoic acid and anthracycline with addition of cytarabine in consolidation therapy for high-risk patients: further improvements in treatment outcome.

    PubMed

    Sanz, Miguel A; Montesinos, Pau; Rayón, Chelo; Holowiecka, Alexandra; de la Serna, Javier; Milone, Gustavo; de Lisa, Elena; Brunet, Salut; Rubio, Vicente; Ribera, José M; Rivas, Concha; Krsnik, Isabel; Bergua, Juan; González, José; Díaz-Mediavilla, Joaquín; Rojas, Rafael; Manso, Félix; Ossenkoppele, Gert; González, José D; Lowenberg, Bob

    2010-06-24

    A risk-adapted strategy based on all-trans retinoic acid (ATRA) and anthracycline monochemotherapy (PETHEMA LPA99 trial) has demonstrated a high antileukemic efficacy in acute promyelocytic leukemia. We designed a new trial (LPA2005) with the objective of achieving stepwise improvements in outcome. Between July 2005 and April 2009, low- and intermediate-risk patients (leukocytes < 10 x 10(9)/L) received a reduced dose of mitoxantrone for the second consolidation course, whereas high- risk patients younger than 60 years of age received cytarabine combined with ATRA and idarubicin in the first and third consolidation courses. Of 372 patients attaining complete remission after ATRA plus idarubicin (92.5%), 368 proceeded to consolidation therapy. For low- and intermediate-risk patients, duration of neutropenia and thrombocytopenia and hospital stay were significantly reduced without sacrificing antileukemic efficacy, compared with the previous LPA99 trial. For high-risk patients, the 3-year relapse rate was significantly lower in the LPA2005 trial (11%) than in the LPA99 (26%; P = .03). Overall disease-free survival was also better in the LPA2005 trial (P = .04). In conclusion, the lower dose of mitoxantrone resulted in a significant reduction of toxicity and hospital stay while maintaining the antileukemic activity, and the combination of ATRA, idarubicin, and cytarabine for high-risk acute promyelocytic leukemia significantly reduced the relapse rate in this setting. Registered at http://www.clinicaltrials.gov as NCT00408278.

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

    PubMed

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

    2009-02-01

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

  9. 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

  10. 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

    2016-09-29

    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

  11. 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

  12. 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

  13. 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

  14. 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.

  15. 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

  16. TET2 Promoter DNA Methylation and Expression in Childhood Acute Lymphoblastic Leukemia.

    PubMed

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

    2016-01-01

    The ten-eleven-translocation-2 (TET2) gene is a novel tumor suppressor gene involved in several hematological malignancies of myeloid and lymphoid origin. Besides loss-of-function mutations and deletions, hypermethylation of the CpG island at the TET2 promoter has been found in human cancers. The TET2 encoded protein regulates DNA methylation. The present study aimed to examine DNA promoter methylation of TET2 in 100 childhood acute lymphoblastic leukemia (ALL) cases and 120 healthy children in southeast Iran. In addition, mRNA expression levels were assessed in 30 new cases of ALL and 32 controls. Our findings indicated that promoter methylation of TET2 significantly increases the risk of ALL (OR=2.60, 95% CI=1.31-5.12, p=0.0060) in comparison with absent methylation. Furthermore, the TET2 gene was significantly downregulated in childhood ALL compared to healthy children (p=0.0235). The results revealed that hypermethylation and downregulation of TET2 gene may play a role in predisposition to childhood ALL. Further studies with larger sample sizes and different ethnicities are needed to confirm our findings. PMID:27644645

  17. 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.

  18. 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

  19. 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

  20. Benign acute childhood myositis--a rare cause of abnormal gait.

    PubMed

    Hall, Gregory; Schranz, Craig I

    2014-02-01

    Benign acute childhood myositis is a rare postviral myositis seen in school-aged children after a common upper respiratory infection (URI), most commonly caused by influenza [J Microbiol Immunol Infect 2004;37:95-98]. Predominantly seen in boys, this condition causes bilateral calf tenderness and pain with ambulation, often presenting as a refusal to bear weight. To avoid activation within the gastroc-soleus complex, the child will frequently compensate with a “Frankenstein gait,” described as a stiff-legged posture with shuffling gait [CMAJ 2009;181:711-713]. The child may also walk on his toes or refuse to walk at all. This refusal to bear weight can be alarming to both providers and parents, resulting in extensive workups. We present the case of a 5-year-old boy who presented to the emergency department with a chief complaint of leg pain and refusal to walk. Further history revealed a resolved URI approximately 5 days prior. He was noted to have an elevated creatinine kinase with no evidence of renal insufficiency. He had no progression or complications, and his symptoms resolved spontaneously with minimal supportive treatment. Benign acute childhood myositis should be considered within the broad differential that surrounds a limping child or one who refuses to bear weight. Having insight into the condition with its characteristic gait abnormalities and associated URI history can often prevent extensive workups and be treated supportively in the outpatient setting. PMID:24126025

  1. 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.

  2. 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

  3. Molecular analysis of the leukaemic B cell in adult and childhood acute lymphoblastic leukaemia.

    PubMed

    Coyle, L A; Papaioannou, M; Yaxley, J C; Chim, J S; Attard, M; Hoffbrand, A V; Foroni, L

    1996-09-01

    Immunoglobulin heavy chain gene (IgH gene) rearrangements are found in the majority of cases of B-lineage acute lymphoblastic leukaemia (ALL). We have examined bone marrow samples taken at presentation or relapse from 109 patients (79 adults and 30 children) and have performed sequence analysis of the complementarity determining region 3 (CDR3) on 65 alleles from 54 patients. We aimed to define immunoglobulin heavy chain (IgH) variable segment family use and investigate biological and structural features of the B cell in adult and childhood ALL. Using the FR1 fingerprinting method, a rearranged band was identified in 70 (89%) of 79 adult ALL and in 29 (97%) of 30 childhood ALL. This study found no preferential use or selection of IgH VH genes and no statistically significant structural differences between normal and leukaemic B cells in either adult and childhood ALL. An equal proportion of amplifiable cases of adult and childhood ALL uses more than one VH family gene (24/70, 34%, and 8/29, 27.5%, respectively). There were no significant differences in the structure or size of the CDR3 region and the variable (V) or joining (J) segment use in ALL patients compared to normal B cells. We observed that the N2 region was shorter than N1 in children whereas the opposite was observed in adults (not statistically significant). The J4 segment was a more common rearrangement in children than in adults, and in both groups J4 was more frequently associated with multiple D segment VDJ rearrangements. An increase in VH6 use in leukaemic alleles compared to normal B lymphocytes (2%) was observed but it was not statistically significant in our group of patients. Amongst children and adults, in-frame CDR3 junctions occurred in 78% and 64% of rearranged alleles, respectively, compared to 75% of in-frame sequences reported by others to occur among normal B cells.

  4. Stroma-supported culture in childhood B-lineage acute lymphoblastic leukemia cells predicts treatment outcome.

    PubMed Central

    Kumagai, M; Manabe, A; Pui, C H; Behm, F G; Raimondi, S C; Hancock, M L; Mahmoud, H; Crist, W M; Campana, D

    1996-01-01

    We developed a stroma cell culture system that suppresses apoptosis of malignant cells from cases of B-lineage acute lymphoblastic leukemia. By multiparameter flow cytometric measurements of cell recovery after culture on stromal layers, we assessed the growth potential of 70 cases of newly diagnosed B-lineage acute lymphoblastic leukemia and related the findings of treatment outcome in a single program of chemotherapy. The numbers of leukemic cells recovered after 7 d of culture ranged from < 1 to 292% (median, 91%). The basis of poor cell recoveries from stromal layers appeared to be a propensity of the lymphoblasts to undergo apoptosis. The probability of event-free survival at 4 yr of follow-up was 50 +/- 9% (SE) among patients with higher cell recoveries ( > 91%), and 94 +/- 6% among those with reduced cell recoveries (+/- 91%; P = 0.0003). The prognostic value of leukemic cell recovery after culture exceeded estimates for all other recognized high-risk features and remained the most significant after adjustment with all competing covariates. Thus, the survival ability of leukemic cells on bone marrow-derived stromal layers reflects aggressiveness of the disease and is a powerful, independent predictor of treatment outcome in children with B-lineage acute lymphoblastic leukemia. PMID:8609232

  5. The role of limbic system irritability in linking history of childhood maltreatment and psychiatric outcomes in low-income, high-risk women: moderation by FK506 binding protein 5 haplotype.

    PubMed

    Dackis, Melissa N; Rogosch, Fred A; Oshri, Assaf; Cicchetti, Dante

    2012-11-01

    Childhood maltreatment is associated with lasting changes in neuroendocrine regulation, alterations in brain structure and function, and symptoms of "limbic irritability." Limbic irritability symptoms include somatic, sensory, and behavioral phenomena and may stem from increased excitatory neurotransmission following maltreatment. We tested the hypotheses that child maltreatment is indirectly associated with depressive and dissociative symptomatology via indicators of limbic irritability and that variation within the FK506 binding protein 5 gene (FKBP5), a gene involved in glucorticoid receptor functioning, moderates these effects. The sample consisted of high-risk, low-income women (N = 236) living in an inner-city environment. Child maltreatment, limbic irritability, and symptoms of depression and dissociation were measured cross-sectionally using self-report assessments. Haplotype analyses were conducted across four FKBP5 single nucleotide polymorphisms: rs3800373, rs9296158, rs1360870, and rs9470080. Path analysis using bootstrapping procedures was performed to test hypotheses regarding indirect and conditional indirect effects. We found significant indirect effects of maltreatment on depression (β = 0.088, p < .01) and dissociation (β = 0.105, p < .01) via limbic irritability. In addition, variation within FKBP5 moderated these significant indirect effects. For individuals with one to two copies of the CATT haplotype, the indirect effects of maltreatment on depression (β = 0.137, p < .01) and dissociation (β = 0.132, p < .01) via limbic irritability were significant, whereas the indirect paths were not significant for individuals with no copies of this haplotype (depression: β = 0.037, p > .05; dissociation: β = 0.002, p > .05). These results add to the growing evidence that child maltreatment may lead to symptoms of internalizing psychopathology through its impact on the limbic system. In addition, this study revealed a potential role of FKBP5 gene

  6. 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

  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. 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 ...

  10. A Multicenter Experience from Lebanon in Childhood and Adolescent Acute Myeloid Leukemia: High rate of Early Death in Childhood Acute Promyelocytic Leukemia

    PubMed Central

    Farah, Roula A.; Horkos, Jessy G.; Bustros, Youssef D.; Farhat, Hussein Z.; Abla, Oussama

    2015-01-01

    , including faster ATRA administration and, aggressive transfusions, easy access to stem cell transplant for high-risk AML patients and the need for a national homogenous treatment strategy for children with AML. PMID:25574371

  11. Implication of IRF4 aberrant gene expression in the acute leukemias of childhood.

    PubMed

    Adamaki, Maria; Lambrou, George I; Athanasiadou, Anastasia; Tzanoudaki, Marianna; Vlahopoulos, Spiros; Moschovi, Maria

    2013-01-01

    The most frequent targets of genetic alterations in human leukemias are transcription factor genes with essential functions in normal blood cell development. The Interferon Regulatory Factor 4 (IRF4) gene encodes a transcription factor important for key developmental stages of hematopoiesis, with known oncogenic implications in multiple myeloma, adult leukemias and lymphomas. Very few studies have reported an association of IRF4 with childhood malignancy, whereas high transcript levels have been observed in the more mature immunophenotype of ALL. Our aim was to investigate the expression levels of IRF4 in the diagnostic samples of pediatric leukemias and compare them to those of healthy controls, in order to determine aberrant gene expression and whether it extends to leukemic subtypes other than the relatively mature ALL subpopulation. Quantitative real-time RT-PCR methodology was used to investigate IRF4 expression in 58 children with acute leukemias, 4 leukemic cell lines and 20 healthy children. We show that aberrant IRF4 gene expression is implicated in a variety of leukemic subtypes; higher transcript levels appear in the more immature B-common ALL subtype and in T-cell than in B-cell leukemias, with the highest expression levels appearing in the AML group. Interestingly, we show that childhood leukemia, irrespective of subtype or cell maturation stage, is characterised by a minimum of approximately twice the amount of IRF4 gene expression encountered in healthy children. A statistically significant correlation also appeared to exist between high IRF4 expression and relapse. Our results show that ectopic expression of IRF4 follows the reverse expression pattern of what is encountered in normal B-cell development and that there might be a dose-dependency of childhood leukemia for aberrantly expressed IRF4, a characteristic that could be explored therapeutically. It is also suggested that high IRF4 expression might be used as an additional prognostic marker of

  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. 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

  14. Clonal analysis of childhood acute lymphoblastic leukemia with "cytogenetically independent" cell populations.

    PubMed Central

    Pui, C H; Raskind, W H; Kitchingman, G R; Raimondi, S C; Behm, F G; Murphy, S B; Crist, W M; Fialkow, P J; Williams, D L

    1989-01-01

    Acute lymphoblastic leukemia (ALL) is generally regarded as a clonal disease in which a single abnormal progenitor cell gives rise to neoplastic progeny. Five of 463 cases of childhood ALL with adequately banded leukemic cells were found to have two cytogenetically independent cell populations. In addition, two of the four cases tested had more than two rearranged immunoglobulin genes and (or) T cell receptor genes. To investigate the clonality of these unusual leukemias, we examined the neoplastic cells for X-linked markers extrinsic to the disease. Leukemic cells from each of the three patients heterozygous for an X-linked, restriction fragment length polymorphism showed a single active parental allele, suggesting that both apparently independent cell populations developed from a common progenitor. These cases provide evidence that leukemogenesis involves a multistep process of mutation and suggest that karyotypic abnormalities may be a late event of malignant transformation. Images PMID:2566623

  15. 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

  16. 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.

  17. 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.

  18. 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

  19. Altered neutrophil immunophenotypes in childhood B-cell precursor acute lymphoblastic leukemia

    PubMed Central

    Oliveira, Elen; Bacelar, Thiago S.; Ciudad, Juana; Ribeiro, Maria Cecília M.; Garcia, Daniela R.N.; Sedek, Lukasz; Maia, Simone F.; Aranha, Daniel B.; Machado, Indyara C.; Ikeda, Arissa; Baglioli, Bianca F.; Lopez-Duarte, Nathalia; Teixeira, Lisandra A. C.; Szczepanski, Tomasz; Silva, Maria Luiza M.; Land, Marcelo G.P.

    2016-01-01

    An increasing number of evidences suggest a genetic predisposition in acute lymphoblastic leukemia (ALL) that might favor the occurrence of the driver genetic alterations. Such genetic background might also translate into phenotypic alterations of residual hematopoietic cells. Whether such phenotypic alterations are present in bone marrow (BM) cells from childhood B-cell precursor (BCP)-ALL remains to be investigated. Here we analyzed the immunophenotypic profile of BM and peripheral blood (PB) maturing/matured neutrophils from 118 children with BCP-ALL and their relationship with the features of the disease. Our results showed altered neutrophil phenotypes in most (77%) BCP-ALL cases. The most frequently altered marker was CD10 (53%), followed by CD33 (34%), CD13 (15%), CD15/CD65 (10%) and CD123 (7%). Of note, patients with altered neutrophil phenotypes had younger age (p = 0.03) and lower percentages of BM maturing neutrophils (p = 0.004) together with greater BM lymphocyte (p = 0.04), and mature B-cell (p = 0.03) counts. No significant association was found between an altered neutrophil phenotype and other disease features. These findings point out the potential existence of an altered residual hematopoiesis in most childhood BCP-ALL cases. PMID:27028865

  20. Formation of trisomies and their parental origin in hyperdiploid childhood acute lymphoblastic leukemia.

    PubMed

    Paulsson, Kajsa; Panagopoulos, Ioannis; Knuutila, Sakari; Jee, Kowan Ja; Garwicz, Stanislaw; Fioretos, Thoas; Mitelman, Felix; Johansson, Bertil

    2003-10-15

    High hyperdiploidy, common in childhood acute lymphoblastic leukemia (ALL) with a favorable prognosis, is characterized by specific trisomies. Virtually nothing is known about its formation or pathogenetic impact. We evaluated 10 patients with ALL using 38 microsatellite markers mapped to 18 of the 24 human chromosomes to investigate the mechanisms underlying hyperdiploidy and to ascertain the parental origin of the trisomies. Based on the results, doubling of a near-haploid clone and polyploidization with subsequent losses of chromosomes could be excluded. The finding of equal allele dosage for tetrasomy 21 suggests that hyperdiploidy originates in a single aberrant mitosis, though a sequential gain of chromosomes other than 21 in consecutive cell divisions remains a possibility. Our study, the first to address experimentally the parental origin of trisomies in ALL, revealed no preferential duplication of maternally or paternally inherited copies of X, 4, 6, 9, 10, 17, 18, and 21. Trisomy 8 was of paternal origin in 4 of 4 patients (P =.125), and +14 was of maternal origin in 7 of 8 patients (P =.0703). Thus, the present results indicate that imprinting is not pathogenetically important in hyperdiploid childhood ALL, with the possible exception of the observed parental skewness of +8 and +14. PMID:12829594

  1. 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

  2. Acute childhood leukaemia and environmental exposure to potential sources of benzene and other hydrocarbons; a case-control study

    PubMed Central

    Steffen, C; Auclerc, M; Auvrignon, A; Baruchel, A; Kebaili, K; Lambilliotte, A; Leverger, G; Sommelet, D; Vilmer, E; Hemon, D; Clavel, J

    2004-01-01

    Aim: To analyse the association between potential environmental exposure to hydrocarbons and the risk of acute childhood leukaemia. Methods: A hospital based multicentre case control study, stratified on centre, age, and sex, with 280 leukaemia cases and 285 controls was carried out. Data were collected by a standardised interview of the mothers. Results: No clear association was seen between maternal occupational exposure to hydrocarbons during pregnancy and leukaemia, or between residential traffic density and leukaemia. There was an association between dwellings neighbouring a petrol station or a repair garage during childhood and the risk of childhood leukaemia (OR 4.0, 95% CI 1.5 to 10.3), with a duration trend. The association, which appeared particularly strong for acute non-lymphocytic leukaemia (OR 7.7, 95% CI 1.7 to 34.3), was not altered by adjustment for potential confounding factors. Conclusions: Results showed an association between acute childhood leukaemia and dwellings neighbouring auto repair garages and petrol stations, which are benzene emitting sources. These findings could be due to chance, although the strength of the association and the duration trend are arguments for a causal association. PMID:15317919

  3. In vivo infusion of anti-LFA-1 and anti-CD2 antibodies prevents graft failure after HLA partially incompatible bone marrow transplantation in children with high risk acute lymphoblastic leukaemia.

    PubMed

    Cavazzana-Calvo, M; Jabado, N; Bordigoni, P; Michel, G; Haddad, E; Mechinaud, F; Landman-Parker, J; Leblanc, T; Plouvier, E; Baruchel, A; Stephan, J L; Souillet, G; Vilmer, E; Wijdenes, J; Le Deist, F; Fischer, A

    1997-12-01

    Bone marrow transplantation (BMT) from matched sibling donors is the therapy of choice for children with high-risk acute lymphoblastic leukaemia in children. It is however not available to more than two-thirds of patients who lack a matched donor. Here, we review the outcome of 28 patients with high-risk ALL who were transplanted in France with alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives. For these patients, we tested the possibility to prevent T-depleted marrow graft rejection by infusing in vivo two monoclonal antibodies directed against adhesion receptors i.e., LFA-1 and CD2. Two previous multicenter trials in children transplanted with partially incompatible bone marrow for inborn errors of metabolism showed their efficacy in this setting. Twenty eight patients were enrolled in this study and followed for a median of 4.4 years. Bone marrow engraftment occurred in 81% of the evaluable patients. Post-transplantation leukaemic relapse was the most frequent cause of death in this group of patients, and occurred in 39% of patients. The second most frequent complication was infectious disease, while an EBV-induced B-lymphocyte proliferative disorder occurred in four patients. In conclusion, T-cell-depletion combined with infusion of anti-LFA-1 and anti-CD2 antibodies is efficient in preventing graft failure and GVHD in this group of children with high-risk leukaemia undergoing partially incompatible BMT. The overall DFS is not improved in contrast to what has been previously observed in patients with immunodeficiencies transplanted with a similar rejection prophylaxis. Other approaches are therefore needed aiming either at preserving donor T-cell mediated immunity or accelerating immune reconstitution.

  4. Clinical heterogeneity in childhood acute lymphoblastic leukemia with 11q23 rearrangements.

    PubMed

    Pui, C-H; Chessells, J M; Camitta, B; Baruchel, A; Biondi, A; Boyett, J M; Carroll, A; Eden, O B; Evans, W E; Gadner, H; Harbott, J; Harms, D O; Harrison, C J; Harrison, P L; Heerema, N; Janka-Schaub, G; Kamps, W; Masera, G; Pullen, J; Raimondi, S C; Richards, S; Riehm, H; Sallan, S; Sather, H; Shuster, J; Silverman, L B; Valsecchi, M G; Vilmer, E; Zhou, Y; Gaynon, P S; Schrappe, M

    2003-04-01

    To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed separate analyses according to age younger or older than 12 months for the various cytogenetic subsets. Infants with t(4;11) ALL had an especially dismal prognosis when their disease was characterized by a poor early response to prednisone (P=0.0005 for overall comparison; 5-year event-free survival (EFS), 0 vs 23+/-+/-12% s.e. for those with good response), or age less than 3 months (P=0.0003, 5-year EFS, 5+/-+/-5% vs 23.4+/-+/-4% for those over 3 months). A poor prednisone response also appeared to confer a worse outcome for older children with t(4;11) ALL. Hematopoietic stem cell transplantation failed to improve outcome in either age group. Among patients with t(11;19) ALL, those with a T-lineage immunophenotype, who were all over 1 year of age, had a better outcome than patients over 1 year of age with B-lineage ALL (overall comparison, P=0.065; 5-year EFS, 88+/-+/-13 vs 46+/-14%). In the heterogeneous subgroup with del(11)(q23), National Cancer Institute-Rome risk criteria based on age and leukocyte count had prognostic significance (P=0.04 for overall comparison; 5-year EFS, 64+/-+/-8% (high risk) vs 83+/-+/-6% (standard risk)). This study illustrates the marked clinical heterogeneity among and within subgroups of infants or older children with ALL and specific 11q23 abnormalities, and identifies patients at particularly high risk of failure who may benefit from innovative therapy.

  5. Geographical and ecological analyses of childhood acute leukaemias and lymphomas in north-west England.

    PubMed

    McNally, Richard J Q; Alston, Robert D; Cairns, Donal P; Eden, Osborn B; Birch, Jillian M

    2003-10-01

    Childhood leukaemias and lymphomas have been associated with exposure to environmental factors, including infections, which show geographical variation. This study examined the geographical distribution of the incidence of acute leukaemia and lymphoma using Manchester Children's Tumour Registry (MCTR) data 1976-2000. A total of 910 children were included, all of whom had histologically and/or cytologically verified leukaemia or lymphoma. At the time of their diagnoses, all the children were aged 0-14 years and were resident in the counties of Greater Manchester or Lancashire. Standardized morbidity ratios were calculated. Poisson regression was used to examine the relationship between incidence rates and small-area (census ward) population density, ethnic composition and deprivation index. There was a monotonic relationship between acute lymphoblastic leukaemia (ALL) incidence and population density (P = 0.05). Higher rates were seen in more densely populated areas. There was evidence for a monotonic relationship between the incidence of the mixed cellularity subtype of Hodgkin's disease (HD) and the Townsend deprivation score (P = 0.001). Markedly higher incidence was associated with greater levels of unemployment and household overcrowding. The results for ALL and mixed cellularity HD support the involvement of environmental factors, such as infections, in disease aetiology.

  6. 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.

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

    PubMed Central

    Gooley, Theodore A.; Rajendran, Joseph; Fisher, Darrell R.; Wilson, Wendy A.; Sandmaier, Brenda M.; Matthews, Dana C.; Deeg, H. Joachim; Gopal, Ajay K.; Martin, Paul J.; Storb, Rainer F.; Press, Oliver W.; Appelbaum, Frederick R.

    2009-01-01

    We conducted a study to estimate the maximum tolerated dose (MTD) of 131I–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 131I-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 131I-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. PMID:19786617

  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. Long-term results of the Italian Association of Pediatric Hematology and Oncology (AIEOP) Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia.

    PubMed

    Conter, V; Aricò, M; Basso, G; Biondi, A; Barisone, E; Messina, C; Parasole, R; De Rossi, G; Locatelli, F; Pession, A; Santoro, N; Micalizzi, C; Citterio, M; Rizzari, C; Silvestri, D; Rondelli, R; Lo Nigro, L; Ziino, O; Testi, A M; Masera, G; Valsecchi, M G

    2010-02-01

    We analyzed the long-term outcome of 4865 patients treated in Studies 82, 87, 88, 91 and 95 for childhood acute lymphoblastic leukemia (ALL) of the Italian Association of Pediatric Hematology and Oncology (AIEOP). Treatment was characterized by progressive intensification of systemic therapy and reduction of cranial radiotherapy. A progressive improvement of results with reduction of isolated central nervous system relapse rate was obtained. Ten-year event-free survival increased from 53% in Study 82 to 72% in Study 95, whereas survival improved from 64 to 82%. Since 1991, all patients were treated according to Berlin-Frankfurt-Muenster (BFM) ALL treatment strategy. In Study 91, reduced treatment intensity (25%) yielded inferior results, but intensification of maintenance with high-dose (HD)-L-asparaginase (randomized) allowed to compensate for this disadvantage; in high-risk patients (HR, 15%), substitution of intensive polychemotherapy blocks for conventional BFM backbone failed to improve results. A marked improvement of results was obtained in HR patients when conventional BFM therapy was intensified with three polychemotherapy blocks and double delayed intensification (Study 95). The introduction of minimal residual disease monitoring and evaluation of common randomized questions by AIEOP and BFM groups in the protocol AIEOP-BFM-ALL 2000 are expected to further ameliorate treatment of children with ALL.

  10. Cost-utility analysis of genotype-guided antiplatelet therapy in patients with moderate-to-high risk acute coronary syndrome and planned percutaneous coronary intervention

    PubMed Central

    Patel, Vardhaman; Lin, Fang-Ju; Ojo, Olaitan; Rao, Sapna; Yu, Shengsheng; Zhan, Lin; Touchette, Daniel R.

    2014-01-01

    Background Prasugrel is recommended over clopidogrel in poor/intermediate CYP2C19 metabolizers with acute coronary syndrome (ACS) and planned percutaneous coronary intervention (PCI), reducing the risk of ischemic events. CYP2C19 genetic testing can guide antiplatelet therapy in ACS patients. Objective The purpose of this study was to evaluate the cost-utility of genotype-guided treatment, compared with prasugrel or generic clopidogrel treatment without genotyping, from the US healthcare provider’s perspective. Methods A decision model was developed to project lifetime economic and humanistic burden associated with clinical outcomes (myocardial infarction [MI], stroke and major bleeding) for the three strategies in patients with ACS. Probabilities, costs and age-adjusted quality of life were identified through systematic literature review. Incremental cost-utility ratios (ICURs) were calculated for the treatment strategies, with quality-adjusted life years (QALYs) as the primary effectiveness outcome. Relative risk of developing myocardial infarction and stroke between patients with and without variant CYP2C19 when receiving clopidogrel were estimated to be 1.34 and 3.66, respectively. One-way and probabilistic sensitivity analyses were performed. Results Clopidogrel cost USD19,147 and provided 10.03 QALYs versus prasugrel (USD21,425, 10.04 QALYs) and genotype-guided therapy (USD19,231, 10.05 QALYs). The ICUR of genotype-guided therapy compared with clopidogrel was USD4,200. Genotype-guided therapy provided more QALYs at lower costs compared with prasugrel. Results were sensitive to the cost of clopidogrel and relative risk of myocardial infarction and stroke between CYP2C19 variant vs. non-variant. Net monetary benefit curves showed that genotype-guided therapy had at least 70% likelihood of being the most cost-effective alternative at a willingness-to-pay of USD100,000/QALY. In comparison with clopidogrel, prasugrel therapy was more cost-effective with <21

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

    PubMed Central

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

    2013-01-01

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

  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. A phase II study of decitabine and gemtuzumab ozogamicin in newly diagnosed and relapsed acute myeloid leukemia and high-risk myelodysplastic syndrome.

    PubMed

    Daver, N; Kantarjian, H; Ravandi, F; Estey, E; Wang, X; Garcia-Manero, G; Jabbour, E; Konopleva, M; O'Brien, S; Verstovsek, S; Kadia, T; Dinardo, C; Pierce, S; Huang, X; Pemmaraju, N; Diaz-Pines-Mateo, M; Cortes, J; Borthakur, G

    2016-02-01

    Decitabine may open the chromatin structure of leukemia cells making them accessible to the calicheamicin epitope of gemtuzumab ozogamicin (GO). A total of 110 patients (median age 70 years; range 27-89 years) were treated with decitabine and GO in a trial designed on model-based futility to accommodate subject heterogeneity: group 1: relapsed/refractory acute myeloid leukemia (AML) with complete remission duration (CRD) <1 year (N=28, 25%); group 2: relapsed/refractory AML with CRD ⩾1 year (N=5, 5%); group 3: untreated AML unfit for intensive chemotherapy or untreated myelodysplastic syndrome (MDS) or untreated myelofibrosis (MF; N=57, 52%); and group 4: AML evolving from MDS or relapsed/refractory MDS or MF (N=20, 18%). Treatment consisted of decitabine 20 mg/m(2) daily for 5 days and GO 3 mg/m(2) on day 5. Post-induction therapy included five cycles of decitabine+GO followed by decitabine alone. Complete remission (CR)/CR with incomplete count recovery was achieved in 39 (35%) patients; group 1= 5/28 (17%), group 2=3/5 (60%), group 3=24/57 (42%) and group 4=7/20 (35%). The 8-week mortality in groups 3 and 4 was 16% and 10%, respectively. Common drug-related adverse events included nausea, mucositis and hemorrhage. Decitabine and GO improved the response rate but not overall survival compared with historical outcomes in untreated AML ⩾60 years.

  14. 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

  15. 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

  16. 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

  17. Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow.

    PubMed

    Selvaggi, K J; Wilson, J W; Mills, L E; Cornwell, G G; Hurd, D; Dodge, W; Gingrich, R; Martin, S E; McMillan, R; Miller, W

    1994-03-15

    We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM.

  18. Improved outcome for high-risk acute myeloid leukemia patients using autologous bone marrow transplantation and monoclonal antibody-purged bone marrow.

    PubMed

    Selvaggi, K J; Wilson, J W; Mills, L E; Cornwell, G G; Hurd, D; Dodge, W; Gingrich, R; Martin, S E; McMillan, R; Miller, W

    1994-03-15

    We have conducted a 9-year multicenter trial of autologous bone marrow transplantation (ABMT) for acute myeloid leukemia (AML). Remission BM was purged in vitro using monoclonal antibodies (MoAbs; PM-81, AML-2-23) and complement targeting myeloid differentiation antigens (CD15, CD14). In 1988, the preparative regimen changed from 60 mg/kg/d cyclophosphamide x 2 and fractionated total body irradiation (TBI) total dose, 1,200 cGy (Cy/fTBI), to 4 mg/kg/d busulfan x 4 and 60 mg/kg/d Cy x 2 (Bu/Cy2). Recent analysis (October 1, 1993) shows that the Bu/Cy2 regimen along with the same MoAb purging method yields an improved outcome. Seven first complete-remission (CR) (CR1), 45 second- or third-CR (CR2/3), and 11 first-relapse (R1) patients were treated with chemotherapy and TBI or chemotherapy alone followed by ABMT with MoAb-purged BM. Median age at ABMT for those patients in CR 2/3 and R1 patients was 36 years. Twenty-nine CR 2/3 and R1 patients were conditioned with Cy/fTBI, and 27 CR2/3 and R1 patients were conditioned with Bu/CY. Using the Kaplan-Meier method, the CY/fTBI, CR2/3, and R1 patients have a 3-year disease-free survival (DFS) of 21%. On the other hand, the Bu/Cy2, CR2/3, and R1 patients have a 3-year DFS of 48%. Nineteen CR2/3 and R1 patients relapsed post-ABMT. On analysis by conditioning regimen, those treated with Cy/fTBI have a 3-year relapse rate (RR) of 58%, whereas the patients conditioned with Bu/Cy2 have a 39% 3-year RR. Long-term DFS can be achieved in about 50% of patients with advanced remissions and relapsed AML using Bu/Cy2 with MoAb-purged BM. PMID:8123862

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

    PubMed Central

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

    2014-01-01

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

  20. 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

  1. Features of Childhood Acute Myeloid Leukemia in Iran: a Report from Double Center Study.

    PubMed

    Mehrvar, Azim; Rahiminejad, Mohammad Saeid; Hedayati Asl, Amir Abbas; Tashvighi, Maryam; Faranoush, Mohammad; Alebouyeh, Mardawig; Kuchakzadeh, Leili; Ramyar, Asghar; Sabery Nejad, Javad; Mehrvar, Narjes

    2015-12-01

    Acute Myeloblastic Leukemia is one of the important malignancies in children. For better managing the prognosis of this disease, there should be enough information about common features of this malignancy. The aim of this study was to evaluate these common features in children with Acute Myeloblastic Leukemia. A total of 104 eligible children less than 15-year-old have been referred from 2007-2011 to two referral centers for childhood malignancies. Basic epidemiological information recorded in checklists for each individual. Analyzes have been done by SPSS version 22. Out of patients, 57 cases were males (54.8%). The male/female ratio was 1.2. The mean age of patients was 6.5 ± 4.3 years. The majority subtypes of patients were M3, M4, non-M3, and M2, respectively. The common molecular abnormalities were t (15;17) and inv (16). Of patients, 19.2% had an early relapse. The mean age of relapse in patients was 6.7 ± 3.9 years. Sixty patients (57.7%) were alive, and 44 cases (42.3%) died during or after therapy. The three years overall survival rate of patients was 42% in this study. According to our data, AML has the same frequency as compared with data from developing countries. But different epidemiological characteristic was a lower rate of three years overall survival in patients. These data may serve the health authorities for more effective environmental and preventive measurements, purposeful allocation of resources for facilitating up-to-date diagnostic and treatment modalities, psychological support programs for respective family members and educational purposes. PMID:26749231

  2. Day-care, early common infections and childhood acute leukaemia: a multicentre French case–control study

    PubMed Central

    Perrillat, F; Clavel, J; Auclerc, M F; Baruchel, A; Leverger, G; Nelken, B; Philippe, N; Schaison, G; Sommelet, D; Vilmer, E; Hémon, D

    2002-01-01

    We conducted a case–control study to investigate the role of early infections in the aetiology of childhood acute leukaemias. The study included 280 incident cases (240 acute lymphoblastic leukaemia and 40 acute non-lymphoblastic leukaemia) and 288 hospital controls, frequency matched by age, gender, hospital, catchment area of the hospital and ethnic origin. Data were obtained from standardised face-to-face interviews of the mothers. The interviews included questions on early common infections, day-care attendance, breast-feeding, birth order and infantile diseases. Odds ratios were estimated using an unconditional regression model including the stratification variables, parental socio-economic status and perinatal characteristics. Birth order was not associated with childhood leukaemia (acute lymphoblastic or acute non-lymphoblastic). A statistically-significant inverse association was observed between childhood leukaemia and day-care attendance (odds ratio=0.6, 95% Confidence Interval=(0.4–1.0)), repeated early common infections (⩾4 per year before age two, odds ratio=0.6 (0.4–1.0)), surgical procedures for ear–nose–throat infections before age two (odds ratio=0.5 (0.2–1.0)) and prolonged breast-feeding (⩾6 months, odds ratio=0.5 (0.2–1.0)). In the multivariate model including day-care attendance, early common infections and breast-feeding, results concerning breast-feeding remained unchanged. A statistically significant interaction between day-care attendance and repeated early common infections was observed. When the interaction was taken into account, the simple effects of day-care and early common infections disappeared (odds ratio=1.1 (0.5–2.3) and odds ratio=0.8 (0.5–1.3), respectively) while the joint effect of day-care attendance and early common infections was negatively associated with childhood leukaemia (odds ratio=0.3 (0.1–0.8)). All the above associations were observed both for acute lymphoblastic leukaemia and acute non

  3. Differential microRNA expression in childhood B-cell precursor acute lymphoblastic leukemia.

    PubMed

    Ju, Xiuli; Li, Dong; Shi, Qing; Hou, Huaishui; Sun, Nianzheng; Shen, Baijun

    2009-01-01

    MiRNAs play important roles in the development of both hematopoiesis and leukemogenesis. The analysis of differential microRNA expression profiles may be a powerful tool to allow us insight on the mechanisms of childhood B-cell precursor acute lymphoblastic leukemia (pre-B-ALL). The present study provides an informative profile of the expression of miRNAs in pre-B-ALL using two independent and quantitative methods: miRNA chip and qRT-PCR of mature miRNA from 40 newly diagnosed pre-B-ALL children. Additionally, putative hematopoiesis-specific target genes were analyzed with informatics technique. Both approaches showed that miR-222, miR-339, and miR-142-3p were dramatically overexpressed in pre-B-ALL patients, and downregulation of hsa-miR-451 and hsa-miR-373* was confirmed. The results of this study offer a comprehensive and quantitative profile of miRNA expression in pre-B-ALL and their healthy counterpart, suggesting that miRNAs could play a primary role in the disease itself.

  4. 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

  5. Chromosomal aberrations in childhood acute lymphoblastic leukemia: 15-year single center experience.

    PubMed

    Jarosova, Marie; Volejnikova, Jana; Porizkova, Ilona; Holzerova, Milena; Pospisilova, Dagmar; Novak, Zbynek; Vrbkova, Jana; Mihal, Vladimir

    2016-01-01

    Genetic analysis of leukemic cells significantly impacts prognosis and treatment stratification in childhood acute lymphoblastic leukemia (ALL). Our retrospective single center study of 86 children with ALL enrolled into three consecutive treatment protocols (ALL-BFM 90, ALL-BFM 95 and ALL IC-BFM 2002) between 1991 and 2007 demonstrates the importance of conventional cytogenetics and fluorescence in situ hybridization (FISH). Cytogenetic and FISH examinations were performed successfully in 82/86 (95.3%) patients and chromosomal changes were detected in 78 of the 82 (95.1%) patients: in 69/73 patients with B-cell precursor (BCP)-ALL and in 9/9 patients with T-lineage ALL (T-ALL). The most frequent chromosomal changes in subgroups divided according to WHO classification independent of treatment protocol and leukemia subtype were hyperdiploidy in 36 patients (with ≥50 chromosomes in 23 patients, with 47-49 chromosomes 13 patients) followed by translocation t(12;21) with ETV6/RUNX1 fusion detected by FISH in 18 (22%) patients. Additional changes were detected in 16/18 (88.8%) ETV6/RUNX1-positive ALL patients with predominant deletion or rearrangement of untranslocated ETV6 allele. Unique aberrations were detected in 4 patients and dicentric chromosomes in 8 patients, one with T-ALL. These results demonstrate that cytogenetics and FISH successfully provided important prognostic information and revealed not only recurrent but also new and rare rearrangements requiring further investigation in terms of prognostic significance. PMID:27341996

  6. 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

  7. 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

  8. 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.

  9. A Treatment Planning and Acute Toxicity Comparison of Two Pelvic Nodal Volume Delineation Techniques and Delivery Comparison of Intensity-Modulated Radiotherapy Versus Volumetric Modulated Arc Therapy for Hypofractionated High-Risk Prostate Cancer Radiotherapy

    SciTech Connect

    Myrehaug, Sten; Chan, Gordon; Craig, Tim; Weinberg, Vivian; Cheng, Chun; Roach, Mack; Cheung, Patrick; Sahgal, Arjun

    2012-03-15

    Purpose: To perform a comparison of two pelvic lymph node volume delineation strategies used in intensity-modulated radiotherapy (IMRT) for high risk prostate cancer and to determine the role of volumetric modulated arc therapy (VMAT). Methods and Materials: Eighteen consecutive patients accrued to an ongoing clinical trial were identified according to either the nodal contouring strategy as described based on lymphotropic nanoparticle-enhanced magnetic resonance imaging technology (9 patients) or the current Radiation Therapy Oncology Group (RTOG) consensus guidelines (9 patients). Radiation consisted of 45 Gy to prostate, seminal vesicles, and lymph nodes, with a simultaneous integrated boost to the prostate alone, to a total dose of 67.5 Gy delivered in 25 fractions. Prospective acute genitourinary and gastrointestinal toxicities were compared at baseline, during radiotherapy, and 3 months after radiotherapy. Each patient was retrospectively replanned using the opposite method of nodal contouring, and plans were normalized for dosimetric comparison. VMAT plans were also generated according to the RTOG method for comparison. Results: RTOG plans resulted in a significantly lower rate of genitourinary frequency 3 months after treatment. The dosimetric comparison showed that the RTOG plans resulted in both favorable planning target volume (PTV) coverage and lower organs at risk (OARs) and integral (ID) doses. VMAT required two to three arcs to achieve adequate treatment plans, we did not observe consistent dosimetric benefits to either the PTV or the OARs, and a higher ID was observed. However, treatment times were significantly shorter with VMAT. Conclusion: The RTOG guidelines for pelvic nodal volume delineation results in favorable dosimetry and acceptable acute toxicities for both the target and OARs. We are unable to conclude that VMAT provides a benefit compared with IMRT.

  10. 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

  11. 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

  12. [Clinical efficacy of decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen on elderly patients with high risk myelodysplastic syndrome and acute myeloid leukemia].

    PubMed

    Dou, Li-Ping; Jing, Yu; Wang, Quan-Shun; Mei, Jun-Hui; Yu, Li

    2013-06-01

    This study was aimed to observe the clinical efficacy and adverse effects of decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen on elderly patients with myelodysplastic syndrome (MDS) and acute myeloid leukemia (AML). Five elderly patients with MDS and AML were treated with decitabine plus improved CAG chemotherapy and donor peripheral lymphocyte infusion regimen. Examinations on liver and renal function, electrocardiogram and bone marrow analysis were performed before and after treatment, and adverse effects were observed. The results indicated that after a course of treatment by decitabine plus improved CAG chemotherapy and haplo-identical donor peripheral lymphocyte infusion regimen, the total effective rate was 100%, and 4 patients (80%) achieved complete remission, 1 patient achieved partial remission. The dominant clinical adverse effect was bone marrow depression, the median time of neutrophil>0.5×10(9)/L and platelet>20×10(9)/L was 15 d and 16 d respectively for patients without previous MDS. It is concluded that decitabine plus improved CAG chemotherapy and haploid-identical donor peripheral lymphocyte infusion regimen may be effective with less adverse effects for elderly primary AML and high risk MDS patients, it is a promising therapeutic methods and worthy to deeply study.

  13. [A comparative cytogenetic analysis in large scale between adult and childhood patients with acute lymphoblastic leukemia].

    PubMed

    Liu, Xu-Ping; Zhu, Xiao-Fan; Wang, Jian-Xiang; Mi, Ying-Chang; Zou, Yao; Chen, Yu-Mei; Li, Cheng-Wen; Dai, Yun; Qin, Shuang; Xiao, Ji-Gang; Xu, Fang-Yun; Gong, Jin-Ying; Wang, Si-Ping; Yu, Cheng-Long; Fan, Jing

    2009-12-01

    This study was purposed to comparatively analyze the cytogenetic characteristics between 566 cases of adult acute lymphoblastic leukemia (aALL) and 586 cases of childhood acute lymphoblastic leukemia (cALL). The cytogenetic analysis of all the patients was performed, and the FISH detection for partial patients was carried out. The result showed that the difference of chromosome abnormality between cALL and aALL was statistically significant. The percentage of abnormal karyotypes in aALL was 62.0%, including mainly t(9;22)(q34;q11), hypodiploidy, hyperdiploidy (47 - 50), abn(6q), abn(9p) and -7, most of which conferring an unfavorable prognosis. The percentage of abnormal karyotypes in cALL was 39.2%, composed mainly of high hyperdiploidy, hypodiploidy, TEL/AML1(+), +8, hyperdiploidy (47 - 50) and +21, etc, most of which conferring a favorable prognosis. The incidences of abnormal karyotypes, total hypodiploidy, total hyperdiploidy (47 - 50), t(9;22)(q34;q11), -7, abn(7q), abn(14q32) and +Ph in aALL were significantly higher than those of cALL (p < 0.05), whereas the incidences of normal karyotype (N), high hyperdiploidy, +8, +21*2 and TEL/AML1(+) in cALL were significantly higher than those of aALL (p < 0.05). 20.5% of aALL were Ph+ aALL, with 63.8% of which being with additional abnormalities, composed mainly of +Ph, -7, i (9q+), 9p-, +8, +21, +X, 6q-, abn(14q32) and +14. In contrast, only 4.4% of cALL were Ph+ aALL, with 42.3% of which being with additional abnormalities, including mainly abn(9p), abn(7p), -7, 17p- and +21. It is concluded that almost every chromosome is involved in the numerical and structural abnormalities and complex karyotypes are common. The significant difference of chromosome abnormality exists between aALL and cALL.

  14. 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

  15. Salivirus in Children and Its Association with Childhood Acute Gastroenteritis: A Paired Case-Control Study.

    PubMed

    Yu, Jie-Mei; Ao, Yuan-Yun; Liu, Na; Li, Li-Li; Duan, Zhao-Jun

    2015-01-01

    Salivirus was recently discovered in children with gastroenteritis and in sewage. Though a causative role for salivirus in childhood gastroenteritis was suggested in the previous study, the relationship between salivirus and acute gastroenteritis has not yet been clearly clarified. The sewage strain reported by Ng, although represented by incomplete genome sequencing data, was distinct from previously reported saliviruses, and had not previously been detected in humans. A case-control study examining 461 paired stool samples from children with diarrhea and healthy controls (1:1) was conducted in this study. Also, common diarrheal viruses were detected and complete genome of a salivirus was determined. Results showed that salivirus was detected in 16 (3.5%) and 13 (2.8%) of the case and control samples, respectively; no differences in detection rates (p=0.571) or mean values of viral loads (p=0.400) were observed between the groups. Multivariate Cox regression revealed no association between salivirus and gastroenteritis (p=0.774). The data also demonstrated that salivirus infection did not exacerbate clinical symptoms of gastroenteritis in children. Furthermore, complete genome sequence of a salivirus recovered from the feces of a child with diarrhea (i.e., SaliV-FHB) shared a 99% nucleotide identity with the sewage strain. In conclusion, a paired case-control study did not support a causative role for salivirus strains detected in this study with pediatric gastroenteritis. This study also demonstrated that all known saliviruses can be detected in the feces of children with or without gastroenteritis.

  16. Polymorphism of CYP1A1 gene and susceptibility to childhood acute lymphoblastic leukemia in Egypt.

    PubMed

    Agha, Adel; Shabaan, Howyda; Abdel-Gawad, Eman; El-Ghannam, Doaa

    2014-03-01

    The origin of acute lymphoblastic leukemia (ALL) may be explained by a combination of genetic susceptibility and environmental exposure. We aimed to study the frequency of CYP1A1 allelic variants in Egyptian patients with ALL, to evaluate their role in the development of ALL and to correlate these allelic variants with clinical and biological characteristics of the patients. Polymorphism of CYP1A1*2A, *2B and *4 alleles was examined in 186 Egyptian children with ALL and 200 normal individuals using polymerase chain reaction-single stranded conformation polymorphism (PCR-SSCP). A higher prevalence of the CYP1A1*4 allele was found in patients with ALL than in the normal population (19.4%vs. 10.0%, odds ratio [OR] = 2.160, 95% confidence interval [CI] = 1.200-3.89, p = 0.01), especially in the homozygous variant (OR = 6.6, 95% CI = 2.23-19.58, p = 0.001) and in male patients (p = 0.005), particularly those aged 2-10 years (OR = 5.214, 95% CI = 1.535-17.706, p = 0.008). CYP1A1*2A showed a significant difference between age groups (p = 0.046), with a higher incidence in the 10-17-year-old group (21.1%). Multivariate analysis showed that only the CYP1A1*4 allele remained as a probable independent risk factor for ALL development (OR = 2.250, 95% CI = 1.244-4.069; p = 0.007). Our results suggest that polymorphic variants in the CYP1A1*4 gene may increase the risk of childhood ALL, particularly in male patients aged 2-10 years.

  17. 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

  18. Investigating CD99 Expression in Leukemia Propagating Cells in Childhood T Cell Acute Lymphoblastic Leukemia

    PubMed Central

    Cox, Charlotte V.; Diamanti, Paraskevi; Moppett, John P.; Blair, Allison

    2016-01-01

    A significant number of children with T-lineage acute lymphoblastic leukemia (T-ALL) fail to respond to therapy and experience early relapse. CD99 has been shown to be overexpressed on T-ALL cells and is considered to be a reliable detector of the disease. However, the relevance of CD99 overexpression in ALL has not been investigated in a functional context. The aim of this study was to investigate the functional capacity of CD99+ cells in childhood ALL and determine the suitability of CD99 as a therapeutic target. Flow cytometric analyses confirmed higher expression of CD99 in ALL blasts (81.5±22.7%) compared to normal hemopoietic stem cells (27.5±21.9%) and T cells (3.1±5.2%, P≤0.004). When ALL cells were sorted and assessed in functional assays, all 4 subpopulations (CD34+/CD99+, CD34+/CD99-, CD34-/CD99+ and CD34-/CD99-) could proliferate in vitro and establish leukemia in NSG mice. Leukemia propagating cell frequencies ranged from 1 in 300 to 1 in 7.4x104 but were highest in the CD34+/CD99- subpopulation. In addition, all four subpopulations had self-renewal ability in secondary NSG mice. Cells in each subpopulation contained patient specific TCR rearrangements and karyotypic changes that were preserved with passage through serial NSG transplants. Despite high levels of CD99 antigen on the majority of blast cells, leukemia initiating capacity in vivo was not restricted to cells that express this protein. Consequently, targeting CD99 alone would not eliminate all T-ALL cells with the ability to maintain the disease. The challenge remains to develop therapeutic strategies that can eliminate all leukemia cells with self-renewal capacity in vivo. PMID:27764235

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

    PubMed

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

    2011-08-01

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

  20. [The Ross procedure in the acute phase of infectious endocarditis in childhood].

    PubMed

    Di Filippo, S; Bozio, A; Champsaur, G; Sassolas, F; Debost, B; Perroux, V

    1999-05-01

    The Ross procedure of aortic valve replacement with a pulmonary autograft has several advantages in childhood over mechanical prostheses or homografts, especially in infectious endocarditis requiring early surgery. Between January 1997 and July 1998, 3 children with no known previous cardiac disease, aged 14 months, 10 and 11 years, had aortic valve infectious endocarditis. The causal organism was not identified in 1 case and the other two were due to staphylococcus aureus and corynebacterium diphteriae. All children had severe, rapidly progressive aortic regurgitation complicated by pulmonary oedema in the baby and systemic emboli in the two older children. Surgery was performed within 9 days, 1.5 month and 2 months after the onset of the disease. The postoperative course was uncomplicated in the 3 cases. Postoperative Doppler echocardiography showed absence of autograft dysfunction or stenosis, with the presence of pulmonary regurgitation in 1 case. Pulmonary autograft has the advantages of not requiring anticoagulation, of allowing growth of the aortic ring, of not being limited by the age of the patient and of having a low risk of degeneration and infectious endocarditis. Therefore, it seems particularly indicated for cases of complicated infectious endocarditis requiring early aortic valve replacement. The early (4.8%) and late (4.3%) mortality rates were comparable to those of other techniques and are lower than those associated with valve replacement with mechanical prostheses in cases of endocarditis (8.5% versus 40%). The secondary morbidity is 18.8% with dysfunction of the autograft and/or stenosis of the pulmonary homograft. Despite a limited follow-up, aortic valve replacement by a pulmonary homograft seems better than aortic valve replacement with a homograft or mechanical prosthesis, especially in cases of complicated infectious endocarditis requiring surgery in the acute phase. Further studies are required to confirm these encouraging results.

  1. 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

  2. Double-blind, placebo-controlled Phase II studies of the protease-activated receptor 1 antagonist E5555 (atopaxar) in Japanese patients with acute coronary syndrome or high-risk coronary artery disease

    PubMed Central

    Goto, Shinya; Ogawa, Hisao; Takeuchi, Masaru; Flather, Marcus D.; Bhatt, Deepak L.

    2010-01-01

    Aims Two multicentre, randomized, double-blind, placebo-controlled Phase II studies assessed the safety and efficacy of the oral protease-activated receptor 1 (PAR-1) antagonist E5555 in addition to standard therapy in Japanese patients with acute coronary syndrome (ACS) or high-risk coronary artery disease (CAD). Methods and results Patients with ACS (n = 241) or high-risk CAD (n = 263) received E5555 (50, 100, or 200 mg) or placebo once daily for 12 (ACS patients) or 24 weeks (CAD patients). The incidence of TIMI major, minor, and minimal bleeds requiring medical attention was similar in the placebo and combined E5555 (atopaxar) groups (ACS: 6.6% placebo vs. 5.0% E5555; CAD: 1.5% placebo vs. 1.5% E5555). There were no TIMI major bleeds and three CURE major bleeds (two with placebo; one with 100 mg E5555). There was a numerical increase in ‘any’ TIMI bleeding with the E5555 200 mg dose (ACS: 16.4% placebo vs. 23.0% E5555, P = 0.398; CAD: 4.5% placebo vs. 13.2% E5555, P = 0.081). The rate of major cardiovascular adverse events in the combined E5555 group was not different from placebo (ACS: 6.6% placebo vs. 5.0% E5555, P = 0.73; CAD: 4.5% placebo vs. 1.0% E5555, P = 0.066). There was a statistically significant dose-dependent increase in liver function abnormalities and QTcF with E5555. At trough dosing levels in both populations, mean inhibition of platelet aggregation was >90% with 100 and 200 mg E5555, and 20–60% with 50 mg E5555. Conclusion E5555 (50, 100, and 200 mg) did not increase clinically significant bleeding, although there was a higher rate of any TIMI bleeding with the highest two doses. All doses tested achieved a significant level of platelet inhibition. There was a significant dose-dependent increase in liver function abnormalities and QTcF. Although further study is needed, PAR-1 antagonism may have the potential to be a novel pathway for platelet inhibition to add on to the current standard of care therapy. PMID:20805115

  3. 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

  4. Troubled Relationships: High-Risk Latina Adolescents and Nonresident Fathers

    ERIC Educational Resources Information Center

    Lopez, Vera; Corona, Rosalie

    2012-01-01

    This qualitative study explored 18 high-risk adolescent Latinas' perceptions of their relationships with nonresident fathers. A number of interrelated factors--early childhood memories, mothers' interpretations, and fathers' behaviors--shaped girls' perceptions, which in turn, influenced how they interacted with fathers. Some girls struggled to…

  5. 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…

  6. The Eighth International Childhood Acute Lymphoblastic Leukemia Workshop ('Ponte di legno meeting') report: Vienna, Austria, April 27-28, 2005.

    PubMed

    Gadner, H; Masera, G; Schrappe, M; Eden, T; Benoit, Y; Harrison, C; Nachman, J; Pui, C H

    2006-01-01

    The International Acute Lymphoblastic Leukemia Working Group, the so-called 'Ponte di Legno Workshop' has led to substantial progress in international collaboration in leukemia research. On April 27-28, 2005, the 8th Meeting was held in Vienna, Austria, to continue the discussions about special common treatment elements in randomized clinical trials, ethical and clinical aspects of therapy. Furthermore, collaborative projects of clinical relevance with special emphasis on rare genetic subtypes of Childhood ALL were established. The following report summarizes the achievements and aspects of possible future cooperation.

  7. 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

    2016-09-26

    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

  8. 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

  9. 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

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

    ClinicalTrials.gov

    2016-10-24

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

  11. The human equilibrative nucleoside transporter 1 mediates in vitro cytarabine sensitivity in childhood acute myeloid leukaemia

    PubMed Central

    Hubeek, I; Stam, R W; Peters, G J; Broekhuizen, R; Meijerink, J P P; Wering, E R van; Gibson, B E S; Creutzig, U; Zwaan, C M; Cloos, J; Kuik, D J; Pieters, R; Kaspers, G J L

    2005-01-01

    Cytarabine (ara-C) is the most effective agent for the treatment of acute myeloid leukaemia (AML). Aberrant expression of enzymes involved in the transport/metabolism of ara-C could explain drug resistance. We determined mRNA expression of these factors using quantitative-real-time-PCR in leukemic blasts from children diagnosed with de novo AML. Expression of the inactivating enzyme pyrimidine nucleotidase-I (PN-I) was 1.8-fold lower in FAB-M5 as compared to FAB-M1/2 (P=0.007). In vitro sensitivity to deoxynucleoside analogues was determined using the MTT-assay. Human equilibrative nucleoside transporter-1 (hENT1) mRNA expression and ara-C sensitivity were significantly correlated (rp=−0.46; P=0.001), with three-fold lower hENT1 mRNA levels in resistant patients (P=0.003). hENT1 mRNA expression also seemed to correlate inversely with the LC50 values of cladribine (rp=−0.30; P=0.04), decitabine (rp=−0.29; P=0.04) and gemcitabine (rp=−0.33; P=0.02). Deoxycytidine kinase (dCK) and cytidine deaminase (CDA) mRNA expression seemed to correlate with in vitro sensitivity to gemcitabine (rp=−0.31; P=0.03) and decitabine (rp=0.33; P=0.03), respectively. The dCK/PN-I ratio correlated inversely with LC50 values for gemcitabine (rp=−0.45, P=0.001) and the dCK/CDA ratio seemed to correlate with LC50 values for decitabine (rp=−0.29; 0.04). In conclusion, decreased expression of hENT1, which transports ara-C across the cell membrane, appears to be a major factor in ara-C resistance in childhood AML. PMID:16333246

  12. Childhood acute lymphoblastic leukemia: genetic determinants of susceptibility and disease outcome.

    PubMed

    Krajinovic, M; Labuda, D; Sinnett, D

    2001-01-01

    The origin of acute lymphoblastic leukemia (ALL), the most common pediatric cancer, can be explained by a combination of genetic factors and environmental exposure. The environmental toxicants to which an individual is exposed are biotransformed and eliminated from the body after metabolic conversion mediated by Phase I and Phase II xenobiotic-metabolizing enzymes. Phase I enzymes catalyze hydroxylation, reduction and oxidation reactions of xenobiotics (carcinogens/drugs), often converting them into more active or toxic compounds. Phase II enzymes catalyze conjugation reactions (glucuronidation, acetylation, methylation), thereby converting the metabolites into non-reactive, water-soluble products that are eliminated from the organism. The genetic polymorphism underlying the variation in enzyme activity can modify susceptibility to diverse adult cancers, probably by influencing the activation and removal of toxicants or drugs. Here we present an overview of the role of genetic variants of certain Phase I and Phase II enzymes in the development of childhood ALL, a good model for such studies because of its short latency period. The genetic contribution to the development of ALL is examined by association studies that analyze the loci of Phase I enzymes (cytochrome P-450, myeloperoxidase) and Phase II enzymes (quinone-oxidoreductase, glutathione-S-transferase, N-acetyltransferase). The loci of the enzyme variants CYPlA1, CYP2E1, NQO1, GSTM1, GSTP1, NAT2 are associated with disease development, and evidence of gene-gene interactions has emerged as well. Despite the improvements in treatment, resistant cases of ALL remain a leading cause of cancer-related death in children. Although the underlying mechanism of drug resistance is not well understood, differences in the capacity of ALL patients to process drugs and environmental carcinogens could play a role by modifying the risk of recurrent malignancy, as well as the response to therapy. Therefore, polymorphic genes

  13. 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

  14. Molecular analysis of HLA-DQB1 alleles in childhood common acute lymphoblastic leukaemia.

    PubMed Central

    Dearden, S. P.; Taylor, G. M.; Gokhale, D. A.; Robinson, M. D.; Thompson, W.; Ollier, W.; Binchy, A.; Birch, J. M.; Stevens, R. F.; Carr, T.; Bardsley, W. G.

    1996-01-01

    Epidemiological studies suggest that childhood common acute lymphoblastic leukaemia (c-ALL) may be the rare outcome of early post-natal infection with a common infectious agent. One of the factors that may determine whether a child succumbs to c-ALL is how it responds to the candidate infection. Since immune responses to infection are under the partial control of (human leucocyte antigen) HLA genes, an association between an HLA allele and c-ALL could provide support for an infectious aetiology. To define the limit of c-ALL susceptibility within the HLA region, we have compared HLA-DQB1 allele frequencies in a cohort of 62 children with c-ALL with 76 newborn controls, using group-specific polymerase chain reaction (PCR) amplification, and single-strand conformation polymorphism (SSCP) analysis. We find that a significant excess of children with c-ALL type for DQB1*05 [relative risk (RR): 2.54, uncorrected P=0.038], and a marginal excess with DQB1*0501 (RR: 2.18; P=0.095). Only 3 of the 62 children with c-ALL have the other susceptibility allele, DPB1*0201 as well as DQB1*0501, whereas 15 had one or the other allele. This suggests that HLA-associated susceptibility may be determined independently by at least two loci, and is not due to linkage disequilibrium. The combined relative risk of the two groups of children with DPB1*0201 and/or DQB1*0501 is 2.76 (P=0.0076). Analysis of amino acids encoded by exon 2 of DQB1 reveal additional complexity, with significant (P<0.05) or borderline-significant increases in Gly26, His30, Val57, Glu66-Val67 encoding motifs in c-ALL compared with controls. Since these amino acids are not restricted to DQB1*0501, our results suggest that, as with DPB1, the increased risk of c-ALL associated with DQB1 is determined by specific amino acid encoding motifs rather than by an individual allele. These results also suggest that HLA-associated susceptibility to c-ALL may not be restricted to the region bounded by DPB1 and DQB1. Images Figure 2

  15. A case-only study of interactions between metabolic enzyme polymorphisms and industrial pollution in childhood acute leukemia.

    PubMed

    Yang, You; Tian, Ying; Jin, Xingming; Yan, Chonghuai; Jiang, Fan; Zhang, Yiwen; Tang, Jingyan; Shen, Xiaoming

    2009-09-01

    Cancer risk is modulated by gene-environment interactions between toxic exposure and genetic variation in carcinogen metabolism. Our objective was to assess interactions between exposure to industrial pollutants and polymorphisms affecting cytochrome P450s (CYP1A1 and CYP2E1) and glutathione S-transferases (GSTP1 and GSTT) in childhood acute leukemia (AL). A case-only design was conducted in 123 Chinese children with sporadic AL. Industrial plants in the vicinity were recorded and, if present, their size and proximity to the usual place of residence of AL children was evaluated. Unconditional logistic regression analysis was performed across the AL study group adjusting for age, gender, parental education, occupation and smoking, indoor and outdoor pesticide use, presence of television sets, refrigerators, microwave ovens and furniture material in children's rooms, and electric transformers, power lines, and telecommunication transmitters within 500 m. This analysis revealed an interaction between the GSTT null allele and industrial plants within 500 m of the residences of childhood AL patients (interaction odds ratio, COR=2.96, 95% CI: 1.09-8.01). Furthermore, the COR for the interaction between GSTT null and industrial plants within 50 m was 5.99 (95% CI: 1.41-25.45). Our results suggest an association between proximity to industrial plants and the GSTT null allele in patients with childhood AL.

  16. Chromosomal Aberrations in ETV6/RUNX1-positive Childhood Acute Lymphoblastic Leukemia using 244K Oligonucleotide Array Comparative Genomic Hybridization

    PubMed Central

    2012-01-01

    Background Acute lymphoblastic leukemia (ALL) is a heterogeneous form of hematological cancer consisting of various subtypes. We are interested to study the genetic aberration in precursor B-cell ALL with specific t(12;21) translocation in childhood ALL patients. A high resolution 244K array-based Comparative Genomic Hybridization (array-CGH) was used to study eleven ETV6/RUNX1-positive childhood acute lymphoblastic leukemia (ALL) patients. Result 155 chromosomal aberrations (119 losses, 36 gains) were reported in the array findings, corresponding to 76.8% deletions and 23.2% amplifications. The ETV6 gene deletion occurred in 4 of the patients, corresponding to 45% of the sample. The most common alterations above 1 Mb were deletion 6q (13%), 12p (12%) and 9p (8%), and duplication 4q (6%) and Xq (4%). Other genes important in ALL were also identified in this study including RUNX1, CDKN2A, FHIT, and PAX5. The array-CGH technique was able to detect microdeletion as small as 400 bp. Conclusion The results demonstrate the usefulness of high resolution array-CGH as a complementary tool in the investigation of ALL. PMID:23151340

  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. 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

  19. Repetitive genomic elements and overall DNA methylation changes in acute myeloid and childhood B-cell lymphoblastic leukemia patients.

    PubMed

    Bujko, Mateusz; Musialik, Ewa; Olbromski, Rafał; Przestrzelska, Marta; Libura, Marta; Pastwińska, Anna; Juszczyński, Przemysław; Zwierzchowski, Lech; Baranowski, Paweł; Siedlecki, Janusz Aleksander

    2014-07-01

    Aberrant epigenetic regulation is a hallmark of neoplastic cells. Increased DNA methylation of individual genes' promoter regions and decreases in overall DNA methylation level are both generally observed in cancer. In solid tumors, this global DNA hypomethylation is related to reduced methylation of repeated DNA elements (REs) and contributes to genome instability. The aim of the present study was to assess methylation level of LINE-1 and ALU REs and total 5-methylcytosine (5metC) content in adult acute myeloid leukemia (AML) (n = 58), childhood B-cell acute lymphoblastic leukemia (ALL) (n = 32), as the most frequent acute leukemias in two age categories and in normal adult bone marrow and children's blood samples. DNA pyrosequencing and ELISA assays were used, respectively. Global DNA hypomethylation was not observed in leukemia patients. Results revealed higher DNA methylation of LINE-1 in AML and ALL samples compared to corresponding normal controls. Elevated methylation of ALU and overall 5metC level were also observed in B-cell ALL patients. Differences of REs and global DNA methylation between AML cytogenetic-risk groups were observed, with the lowest methylation levels in intermediate-risk/cytogenetically normal patients. B-cell ALL is characterized by the highest DNA methylation level compared to AML and controls and overall DNA methylation is correlated with leukocyte count.

  20. 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

  1. Vincristine and Prednisone for the Induction of Remissions in Acute Childhood Leukaemia

    PubMed Central

    Hardisty, R. M.; McElwain, T. J.; Darby, Caryl W.

    1969-01-01

    A total of 65 children with acute lymphoblastic leukaemia and seven with other types of acute leukaemia received treatment with a combination of vincristine and prednisone. In all 122 courses of treatment were given. Of 22 patients with acute lymphoblastic leukaemia who received this as their first treatment, all achieved complete remission. The complete remission rates were 82% for patients with acute lymphoblastic leukaemia in their first relapse, 63% in the second relapse, and much lower in subsequent relapses and in the patients with other types of acute leukaemia. Alopecia and gastrointestinal and neuromuscular toxicity occurred respectively in 51%, 29%, and 21% of instances, only the last of these side-effects of vincristine being dose-related. Most of the complete remissions were obtained with a total dose of vincristine which carried only a low risk of neurotoxicity. PMID:5254045

  2. 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

  3. Isolated Ocular Relapse in Childhood Acute Lymphoblastic Leukemia during Second Interim Maintenance Phase of Chemotherapy: Case Report.

    PubMed

    Monsereenusorn, Chalinee; Rujkijyanont, Piya; Srimanan, Worapot; Traivaree, Chanchai

    2015-11-01

    More than 80% of acute lymphoblastic leukemia (ALL) in pediatric population is curable by using combinations of chemotherapy. However, 20% of the cases still suffer from disease relapse. The most common site of relapse is bone marrow. Relapse of childhood ALL involving the eyeball is rare. However, it occurs in 2.2% of relapsing children. The authors described a 10-year-old Thai boy with underlying ALL on therapy, presented with a one-month history of progressive visual loss of his right eye. The clinical and imaging studies strongly suggested the diagnosis of isolated ocular relapse. In this report, the authors presented the findings from successfully specific treatment consisting of systemic chemotherapy and radiation therapy on the affected eye. From other studies, the outcome was more favorable in cases of ocular relapse off therapy. In our study, one case of isolated ocular relapse ALL was reported.

  4. 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

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

    PubMed

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

    2016-10-01

    Acute lymphoblastic leukemia (ALL) is the most common type of leukemia in children that can be affected by maternal diet. The aim of this study was to evaluate maternal dietary risk factors of ALL. We searched MEDLINE, Cochrane Library, Springer Link, Wiley Online, Science Direct, Mosby, ISI Web of Science, OVID, ProQuest, and Scopus from database inception until February 2, 2016. Two reviewers scanned titles, abstracts, and keywords of articles after excluding duplicates. We included case-control studies evaluating the relationship between maternal diet during pregnancy and childhood ALL. The search resulted in 2,940 papers, of which 11 full-text articles met the criteria for inclusion in the review and were analyzed. The finding of these studies suggest that maternal diet composed largely of vegetables, fruits, and protein sources before and during pregnancy can reduce the risk of ALL in offspring. Maternal alcohol intake had no effect. Nevertheless, inherent limitations of case-control studies like measurement error, random error, recall bias, and selection bias preclude conclusive evidence. Persuading pregnant women to follow a healthy diet rich in fruits, vegetables, and protein may reduce the risk of childhood ALL. Avoiding alcohol intake seems prudent. PMID:27472187

  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. 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

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

    PubMed

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

    2016-10-01

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

  9. 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

  10. 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

  11. An Overview. High Risk Series.

    ERIC Educational Resources Information Center

    General Accounting Office, Washington, DC.

    This report provides an overview of efforts undertaken by the U.S. General Accounting Office (GAO) in 1990 to review and report on federal program areas its work identified as high risk because of vulnerabilities to waste, fraud, abuse, and mismanagement. It reviews the current status of efforts to address these concerns. The six categories of…

  12. Perceptions of high risk sports.

    PubMed

    Pedersen, D M

    1997-10-01

    High risk sports were rated as to risk, appeal, and likelihood of participation by 282 men and 162 women. Ascending order of perceived risk was skiing, scuba diving, bungee jumping, rock climbing, motorcycle racing, hang gliding, cliff jumping, and skydiving. Profile analysis showed stated likelihood of participation to be directly related to appeal and inversely related to perceived risk.

  13. HOXA9 and MEIS1 gene overexpression in the diagnosis of childhood acute leukemias: Significant correlation with relapse and overall survival.

    PubMed

    Adamaki, Maria; Lambrou, George I; Athanasiadou, Anastasia; Vlahopoulos, Spiros; Papavassiliou, Athanasios G; Moschovi, Maria

    2015-08-01

    Homeobox genes HOXA9 and MEIS1 are evolutionarily conserved transcription factors with essential roles in both hematopoiesis and leukemogenesis. They act as dominant cooperating oncoproteins that cause acute leukemias bearing MLL translocations and to a lesser extent T-cell acute lymphocytic leukemia (ALL) characterized by other gene fusions. Overexpression is associated with an adverse prognosis in adults. In childhood, the genes have only been investigated in leukemias bearing MLL translocations. The aim of this study was to determine whether overexpression extends to leukemic subtypes other than the MLL-positive subtype in childhood. We use quantitative real-time PCR methodology to investigate gene expression in 100 children with acute leukemias and compare them to those of healthy controls. We show that abnormally high HOXA9 and MEIS1 gene expression is associated with a variety of leukemic subtypes, including various maturation stages of B-cell ALL and cytogenetic types other than the MLL-positive population, thus suggesting that the genes are implicated in the development of a broad range of leukemic subtypes in childhood. In addition, we show that HOXA9 and MEIS1 overexpression are inversely correlated with relapse and overall survival, so the genes could become useful predictive markers of the clinical course of pediatric acute leukemias.

  14. Psychological characteristics in high-risk MSM in China

    PubMed Central

    2012-01-01

    Background Men who have sex with men (MSM) have become a high-risk group of HIV infection in China. To date, little is known regarding the behavioral, social and psychological characteristics in Chinese MSM, which makes the implementation of preventive and therapeutic strategies for this high-risk subpopulation of people extremely difficult. Methods A total of 714 questionnaires were retrieved from the database of a Chinese government-sponsored National Key Research Project titled "Risk Analysis and Strategic Prevention of HIV Transmission from MSM to the General Population in China". The respondents were categorized into a high-risk group and a control group. Their behavioral, social and psychological characteristics were comparatively analyzed. Results Of the 714 MSM analyzed, 59 (8.26%) had high-risk homosexual behaviors. This sub-group of MSM had a higher in-marriage rate, a higher monthly income, heavier alcohol consumption and more serious problems with sexual abuse in childhood, intentional suicide attempts and mistaken assumption on condom's role in protecting HIV infection, as compared with the control group (P < 0.05). In contrast, the two groups did not differ significantly the sexual orientation, level of education, types of profession, drug use, condom use and experience of social stigma and discrimination (P > 0.05). A vast majority of the individuals in both behavior categories expressed support of legally protected gay clubs as well as gay marriage legislation in China. There was a strong correlation between high-risk behaviors and sexual abuse in childhood, alcohol drinking, income level and a mistaken belief in perfect HIV protection through the use of condoms. Conclusions MSM with and without high-risk homosexual behaviors have different social and psychological characteristics, which should be taken into account when implementing behavioral and therapeutic interventions aimed at preventing HIV/AIDS transmission among MSM as well as from MSM to

  15. Multicenter trial of cefpodoxime proxetil vs. amoxicillin-clavulanate in acute lower respiratory tract infections in childhood. International Study Group.

    PubMed

    Klein, M

    1995-04-01

    Acute lower respiratory tract infections in children are a worldwide public health problem, with an estimated 4 million potentially preventable deaths every year. Until recently, penicillin and related drugs were the treatment of choice for empiric therapy of paediatric lower respiratory tract infections. However, concerns over the emergence of penicillin-resistant strains of Streptococcus pneumoniae and beta-lactamase-producing strains of Haemophilus influenzae and Moraxella catarrhalis have led physicians to turn increasingly towards alternatives, such as the third generation cephalosporins. The oral extended spectrum cephalosporin cefpodoxime proxetil is highly active against the bacterial pathogens commonly associated with childhood lower respiratory tract infections. In order to evaluate its clinical efficacy in children with acute febrile lower respiratory tract infections, an international, multicenter, comparative, randomized open study was conducted in children ages 3 months to 11.5 years. Of 348 cases enrolled, 234 were randomized to cefpodoxime proxetil (8 mg/kg/day twice daily) and 114 to amoxicilin/clavanulate (amoxicillin 40 mg/kg/day 3 times a day). The duration of treatment was 10 days. Pretreatment diagnosis was pneumonia in 292 patients, bronchiolitis in 19 patients and acute bronchitis in 37 patients. Pathogens isolated from 59 cases included H. influenzae (47.5%), S. pneumoniae (23.7%), M. catarrhalis (11.9%) and Haemophilus parainfluenzae (6.8%). Clinical efficacy was evaluable in 278 children at the end of treatment when 95.2% of patients in the cefpodoxime proxetil group and 96.7% of patients in the amoxicillin/clavanulate group showed a satisfactory clinical response (cured or improved). The improvement was sustained at the follow-up visit, 10 to 20 days after completion of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

  16. 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

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

    ClinicalTrials.gov

    2016-10-14

    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

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

    PubMed Central

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

    2012-01-01

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

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

    PubMed Central

    Aberuyi, N; Rahgozar, S; Moafi, A

    2014-01-01

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

  20. 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

  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. Evolution of modern treatment of childhood acute leukemia and cancer: adventures and battles in the 1970s and 1980s.

    PubMed

    Ravindranath, Yaddanapudi

    2015-02-01

    This article summarizes the adventures and explorations in the 1970s and 1980s in the treatment of children with leukemia and cancer that paved the way for the current success in childhood cancers. Indeed, these were adventures and bold steps into unchartered waters. Because childhood leukemia the most common of the childhood cancers, success in childhood leukemia was pivotal in the push toward cure of all childhood cancers. The success in childhood leukemia illustrates how treatment programs were designed using clinical- and biology-based risk factors seen in the patients.

  3. 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

  4. 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

  5. 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

  6. 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

  7. A rare metabolic complication of acute lymphoblastic leukemia in childhood: lactic acidosis.

    PubMed

    Gökçe, Müge; Unal, Sule; Gülşen, Hayriye; Başaran, Ozge; Cetin, Mualla; Gümrük, Fatma; Beşbaş, Nesrin; Gürgey, Aytemiz

    2012-01-01

    A 13-year-old boy presented with nausea, fatigue, weight loss, and bone pain for two months. Complete blood count and serum renal and liver function tests were all normal. Blood gas analysis revealed severe metabolic acidosis with high anion gap. Lactate level was 61.2 mmol/L. Abdominal ultrasonography yielded bilateral nephromegaly and hepatomegaly with increased echogenicity. Peripheral blood smear revealed 2% blasts. Bone marrow aspiration showed 'Common ALL Antigen'-negative acute lymphoblastic leukemia by flow cytometric analysis. Metabolic acidosis dissolved as soon as chemotherapy was begun. Lactic acidosis at the presentation of acute lymphoblastic leukemia--especially with low tumor burden--is a very rare and almost always fatal complication. Our patient is still alive and in remission, which is a point of interest in this child.

  8. 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

  9. Randomized trial of combined modality therapy of childhood non-Hodgkin's lymphoma. [Acute and delayed complications

    SciTech Connect

    Murphy, S.B.; Hustu, H.O.

    1980-02-15

    From 1975 to 1978, 69 children with non-Hodgkin's lymphoma were staged and treated in a randomized protocol to determine the contribution of involved-field radiotherapy (IF-RT) to an effective drug regimen in Stages III to IV and the efficacy of prophylactic treatment of the central nervous system with cranial irradiation and intrathecal methotrexate in Stages II to IV. Induction therapy for Stages I to II was vincristine, prednisone, cyclophosphamide and IF-RT (3000 to 3500 rad). Stages III to IV received the same three drugs plus adriamycin, and were randomized to receive or not receive IF-RT. The complete remission rate was 88%. After randomization to receive CNS prophylaxis or not, all children received oral mercaptopurine and methotrexate for 18 months. The two-year actuarial estimate of disease-free survival for all responders is 55% and is significantly influenced by stage. (Ninety percent disease-free survival for Stages I to II, versus 38.8% for III to IV, P < .05). We observed no benefit but added toxicity from IF-RT in Stages III to IV. Efforts at CNS prophylaxis in high-risk children are warranted, since only 1 of 18 children randomized to receive prophylaxis developed CNS disease as the site of first relapse, whereas 4 of 16 receiving no prophylaxis did so.

  10. Quantification of TEL-AML1 transcript for minimal residual disease assessment in childhood acute lymphoblastic leukaemia.

    PubMed

    Drunat, S; Olivi, M; Brunie, G; Grandchamp, B; Vilmer, E; Bièche, I; Cavé, H

    2001-08-01

    Strategies currently used for residual disease detection in acute lymphoblastic leukaemia (ALL) rely on polymerase chain reaction (PCR) detection of immunoglobulin and T-cell receptor rearrangements. The TEL-AML1 fusion transcript, which is associated with t(12;21) (p13;q22), is found in 25% of childhood B-cell precursor ALL, and represents an interesting alternative target. We compared two methods for quantitating TEL-AML1 fusion transcripts: competitive PCR and real-time PCR. These techniques showed similar sensitivity (5 x 10(-5)) and reproducibility. Giving highly correlated results, both techniques can be conveniently used for TEL-AML1 transcript quantification. The constancy of TEL-AML1 expression was evaluated by measuring TEL-AML1 transcripts at different steps of the cell cycle, and in 21 cases of ALL at diagnosis. No major variation in TEL-AML1 expression was observed during the cell cycle or in 20/21 of the ALL patients. Residual disease was then determined after completion of induction therapy in 20 patients with a TEL-AML1-positive ALL. Seven patients out of 20 (35%) were still positive, including two patients with high level of residual blasts (close to or beyond 10(-2)). When comparison was possible, results obtained using TEL-AML1 quantification were in accordance with those obtained using T-cell receptor rearrangements analysis.

  11. Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

    PubMed

    Yotnda, P; Garcia, F; Peuchmaur, M; Grandchamp, B; Duval, M; Lemonnier, F; Vilmer, E; Langlade-Demoyen, P

    1998-07-15

    Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense.

  12. Cytotoxic T cell response against the chimeric ETV6-AML1 protein in childhood acute lymphoblastic leukemia.

    PubMed Central

    Yotnda, P; Garcia, F; Peuchmaur, M; Grandchamp, B; Duval, M; Lemonnier, F; Vilmer, E; Langlade-Demoyen, P

    1998-01-01

    Cytotoxic T lymphocytes (CTL) are potent effector cells that could provide long term antitumor immunity if induced by appropriate vaccines. CTL recognize 8-14 amino acid-long peptides processed intracellularly and presented by MHC class I molecules. A well-characterized example of a potential tumor antigen in childhood pre-B Acute Lymphoblastic Leukemia (ALL) results from the chromosomal translocation 12;21 leading to the fusion of the ETV6 and AML1 genes. This translocation is observed in > 25% of ALL-patients. In this study, we have examined whether the chimeric ETV6-AML1 protein could serve as a tumor specific antigen for CTL in HLA-A2.1 individuals. We have identified a nonapeptide (RIAECILGM), encoded by the fusion region of the ETV6-AML1 protein, that binds to HLA-A2.1 molecules and induces specific primary CTL in peripheral blood lymphocytes from healthy donors. These CTL specifically lysed HLA-A2.1 tumor cells endogeneously expressing the ETV6-AML fusion protein. CTL with similar functional capacities were found with high frequencies and cloned from one patient's bone marrow indicating that ETV6-AML1-specific anti-ALL CTL are, at least in some patients, spontaneously stimulated and might participate to host antileukemia defense. PMID:9664088

  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.

  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. Outcome of childhood relapsed or refractory mature B-cell non-Hodgkin lymphoma and acute lymphoblastic leukemia.

    PubMed

    Anoop, Parameswaran; Sankpal, Sushama; Stiller, Charles; Tewari, Sanjay; Lancaster, Donna L; Khabra, Komel; Taj, Mary M

    2012-10-01

    Patients with childhood relapsed and refractory mature B-cell non-Hodgkin lymphoma (B-NHL) and acute lymphoblastic leukemia (B-ALL) are rare and have a dismal prognosis. The previous UK national analysis of 26 children over a 7-year period prior to 1996 had highlighted the poor outcome, with only three survivors. This 10-year multicenter study evaluated recent data, since 2000. Of 33 children, nine survived (27.3%), with a median follow-up of 4.3 years. On exclusion of six children treated with palliative intent, the survival was one-third (nine of 27; 33.3%). All patients with primary refractory disease (n = 7) and all except one with early relapse (n = 11) died. Administration of four doses of 375 mg/m(2) of rituximab was associated with a longer survival (p = 0.006). Response to reinduction (p < 0.001) and autologous hematopoietic stem cell transplant (auto-HSCT) (p = 0.003) were significant on multivariate analysis. Patients with a time to relapse of at least 6 months are potentially curable and must be offered intensive treatment with salvage chemotherapy, rituximab and auto-HSCT. PMID:22448922

  16. 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.

  17. 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.

  18. 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.

  19. 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

  20. 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

  1. 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

  2. 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

  3. Deletion of chromosomal region 13q14.3 in childhood acute lymphoblastic leukemia.

    PubMed

    Cavé, H; Avet-Loiseau, H; Devaux, I; Rondeau, G; Boutard, P; Lebrun, E; Méchinaud, F; Vilmer, E; Grandchamp, B

    2001-03-01

    Deletion of the 13q14 chromosomal region is frequent in B cell chronic lymphocytic leukemia (B-CLL) and is believed to inactivate a tumor supressor gene (TSG) next to RB1. We studied microsatellite markers spanning the 13q14 chromosomal region in 138 children with acute lymphoblastic leukemia (ALL). Allelic loss was demonstrated in six cases (4.3%). Deletion did not include RB1 in two cases. In five patients, the deleted region overlapped that described in B-CLL. A sixth patient harbored a smaller deletion, slightly more telomeric than minimal deleted regions reported in B-CLL. Apparent differences in the delineation of the minimal deleted region could be due to the fact that the putative TSG is a very large gene, with some deletions affecting only a part of it. Our present findings suggest that at least some of its exons lie within a region of less than 100 kb more telomeric that previously thought.

  4. 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

  5. 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.

  6. Arsenic-contaminated water and extent of acute childhood malnutrition (wasting) in rural Bangladesh.

    PubMed

    Minamoto, Keiko; Mascie-Taylor, C G Nicholas; Moji, Kazuhiko; Karim, Enamul; Rahman, Mahmudur

    2005-01-01

    To investigate whether children's nutritional status, especially the extent of wasting [acute malnutrition as measured by weight-for-height Z (WHZ) score] is associated with arsenic contamination of drinking water, a survey was carried out in two discrete rural areas located less than 30 km southeast and northeast of Dhaka, the capital of Bangladesh. 761 children between 7 and 14 years of age were randomly selected, one child per household. The arsenic concentration in the tube well water used by each child and the prevalence and intensity of infection of three geo-helminths [Ascaris lumbricoides, Trichuris trichiura and hookworm (Ancylostoma duodenale or Necator americanus)] were determined. Each child had their height and weight measured and WHZ score determined using the World Health Organization (WHO) reference values. Basic socio-demographic data and knowledge of arsenic poisoning were collected using a questionnaire. 62.2% of the households studied were using well water with arsenic concentrations above the 0.01 mg/L WHO guideline (i.e. arsenic-contaminated households). The mean WHZ score of all the 761 children was -0.843 (sd 1.227) but children living in contaminated households were significantly more wasted than children living in noncontaminated households (mean difference = -0.361, p 0.001). When the effects of the differences in socio-economic status and prevalence of geo-helminths were also taken into account, the difference in means remained highly significant (-0.330, p = 0.006). This study suggests that arsenic contamination has a negative impact on children's acute nutritional status.

  7. Neurologic morbidity and quality of life in survivors of childhood acute lymphoblastic leukemia: a prospective cross-sectional study

    PubMed Central

    Khan, Raja B.; Hudson, Melissa M.; Ledet, Davonna S.; Morris, E. Brannon; Pui, Ching-Hon; Howard, Scott C.; Krull, Kevin R.; Hinds, Pamela S.; Crom, Debbie; Browne, Emily; Zhu, Liang; Rai, Shesh; Srivastava, Deokumar; Ness, Kirsten K.

    2014-01-01

    Purpose Childhood acute lymphoblastic leukemia (ALL) is treated with potentially neurotoxic drugs and neurologic complications in long-term survivors are inadequately studied. This study investigated neurologic morbidity and its effect on quality of life in long-term survivors of childhood ALL. Methods Prospective, single institution, cross-sectional, institutional review board-approved study of long-term ALL survivors. Participants were recruited from institutional clinics. Participants answered an investigator-administered questionnaire followed by evaluation by a neurologist. Quality of life (QOL) was also assessed. Results Of the 162 participants recruited over a 3-year period, 83.3 % reported at least one neurologic symptom of interest, 16.7 % had single symptom, 11.1 % had two symptoms, and 55.6 % had three or more symptoms. Symptoms were mild and disability was low in the majority of participants with neurologic symptoms. Median age at ALL diagnosis was 3.9 years (0.4–18.6), median age at study enrollment was 15.7 years (6.9–28.9), and median time from completion of ALL therapy was 7.4 years (1.9–20.3). On multivariable analyses, female sex correlated with presence of dizziness, urinary incontinence, constipation, and neuropathy; use of≥10 doses of triple intrathecal chemotherapy correlated with uri-nary incontinence, back pain, and neuropathy; cranial radiation with ataxia; history of ALL relapse with fatigue; and CNS leukemia at diagnosis with seizures. Decline in mental QOL was associated with migraine and tension type headaches, while physical QOL was impaired by presence of dizziness and falls. Overall, good QOL and physical function was maintained by a majority of participants. Conclusions Neurologic symptoms were present in 83 % long-term ALL survivors. Symptoms related morbidity and QOL impairment is low in majority of survivors. Female sex, ≥10 doses of intrathecal chemotherapy, and history of ALL relapse predispose to impaired QOL

  8. 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...

  9. 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

  10. 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

  11. 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

  12. 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.

  13. 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.

  14. Patterns of hematopoietic chimerism following bone marrow transplantation for childhood acute lymphoblastic leukemia from volunteer unrelated donors.

    PubMed

    Molloy, K; Goulden, N; Lawler, M; Cornish, J; Oakhill, A; Pamphilon, D; Potter, M; Steward, C; Langlands, K; Humphries, P; McCann, S R

    1996-04-01

    Hematopoietic chimerism was analyzed in serial bone marrow samples taken from 28 children following T-cell depleted unrelated donor bone marrow transplants (UD BMT) for acute lymphoblastic leukemia (ALL). Chimeric status was determined by polymerase chain reaction (PCR) of simple tandem repeat (STR) sequences (maximal sensitivity, 0.1%). At least two serial samples were examined in 23 patients. Of these, two had evidence of complete donor engraftment at all times and eight showed stable low level mixed chimerism (MC) (<1% recipient hematopoiesis). All 10 of these patients remain in remission with a minimum follow-up of 24 months. By contrast, 13 patients demonstrated a progressive return of recipient hematopoiesis. Five of these relapsed (4 to 9 months post BMT), one died of cytomegalovirus pneumonitis and seven remain in remission with a minimum follow-up of 24 months. Five children were excluded from serial analysis as two serial samples were not collected before either relapse (3) or graft rejection (2). We conclude that as with sibling transplants, ex vivo T depleted UD BMT in children with ALL is associated with a high incidence of MC. Stable donor engraftment and low level MC always correlated with continued remission. However, detection of a progressive return of recipient cells did not universally correlate with relapse, but highlighted those patients at greatest risk. Serial chimerism analysis by PCR of STRs provides a rapid and simple screening technique for the detection of relapse and the identification of patients with progressive MC who might benefit from detailed molecular analysis for minimal residual disease following matched volunteer UD BMT for childhood ALL.

  15. Deficient Innate Immunity, Thymopoiesis, and Gene Expression Response to Radiation in Survivors of Childhood Acute Lymphoblastic Leukemia

    PubMed Central

    Leung, Wing; Neale, Geoffrey; Behm, Fred; Iyengar, Rekha; Finkelstein, David; Kastan, Michael B.; Pui, Ching-Hon

    2010-01-01

    Background Survivors of childhood acute lymphoblastic leukemia (ALL) are at an increased risk of developing secondary malignant neoplasms. Radiation and chemotherapy can cause mutations and cytogenetic abnormalities and induce genomic instability. Host immunity and appropriate DNA damage responses are critical inhibitors of carcinogenesis. Therefore, we sought to determine the long-term effects of ALL treatment on immune function and response to DNA damage. Methods Comparative studies on 14 survivors in first complete remission and 16 siblings were conducted. Results In comparison to siblings on the cells that were involved in adaptive immunity, the patients had either higher numbers (CD19+ B cells and CD4+CD25+ T regulatory cells) or similar numbers (αβT cells and CD45RO+/RA− memory T cells) in the blood. In contrast, patients had lower numbers of all lymphocyte subsets involved in innate immunity (γδT cells and all NK subsets, including KIR2DL1+ cells, KIR2DL2/L3+ cells, and CD16+ cells), and lower natural cytotoxicity against K562 leukemia cells. Thymopoiesis was lower in patients, as demonstrated by less CD45RO−/RA+ Naïve T cell and less SjTREC levels in the blood, whereas the Vβ spectratype complexity score was similar. Array of gene expression response to low-dose radiation showed that about 70% of the probesets had a reduced response in patients. One of these genes, SCHIP-1, was also among the top-ranked single nucleotide polymorphisms (SNPs) during the whole genome scanning by SNP microarray analysis. Conclusion ALL survivors were deficient in innate immunity, thymopoiesis, and DNA damage responses to radiation. These defects may contribute to their increased likelihood of second malignancy. PMID:20413363

  16. 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

  17. 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

  18. 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

  19. 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

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

    PubMed Central

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

    2015-01-01

    Comprehensive clinical studies of patients with acute megakaryoblastic leukemia (AMKL) are lacking. We performed an international retrospective study on 490 patients (age ≤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

  1. 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

  2. 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

  3. Fever without apparent source on clinical examination, lower respiratory infections in children, other infectious diseases, and acute gastroenteritis and diarrhea of infancy and early childhood.

    PubMed

    McCarthy, P L; Klig, J E; Shapiro, E D; Baron, M A

    1996-02-01

    This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews recent literature about lower respiratory tract infection in children. Eugene Shapiro discusses recent developments in the literature concerning several infectious diseases commonly facing practitioners in the office. Michael Baron reviews recent literature about gastroenteritis and diarrhea of infancy and early childhood.

  4. Fever without apparent source on clinical examination, lower respiratory infections in children, other infectious diseases, and acute gastroenteritis and diarrhea of infancy and early childhood.

    PubMed

    McCarthy, P L; Klig, J E; Kahn, J S; Shapiro, E D; Baron, M A

    1997-02-01

    This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. Jean Klig reviews recent literature about lower respiratory tract infection in children. Jeffrey Kahn and Eugene Shapiro discuss literature concerning several infectious diseases commonly seen in office settings and concerning which recent developments are of interest. Michael Baron reviews recent literature about gastroenteritis and diarrhea of infancy and early childhood.

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

    ClinicalTrials.gov

    2016-08-25

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

  6. 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

  7. 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

  8. 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

  9. 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

  10. 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

  11. Differences in meiotic recombination rates in childhood acute lymphoblastic leukemia at an MHC class II hotspot close to disease associated haplotypes.

    PubMed

    Thompson, Pamela; Urayama, Kevin; Zheng, Jie; Yang, Peng; Ford, Matt; Buffler, Patricia; Chokkalingam, Anand; Lightfoot, Tracy; Taylor, Malcolm

    2014-01-01

    Childhood Acute Lymphoblastic Leukemia (ALL) is a malignant lymphoid disease of which B-cell precursor- (BCP) and T-cell- (T) ALL are subtypes. The role of alleles encoded by major histocompatibility loci (MHC) have been examined in a number of previous studies and results indicating weak, multi-allele associations between the HLA-DPB1 locus and BCP-ALL suggested a role for immunosusceptibility and possibly infection. Two independent SNP association studies of ALL identified loci approximately 37 kb from one another and flanking a strong meiotic recombination hotspot (DNA3), adjacent to HLA-DOA and centromeric of HLA-DPB1. To determine the relationship between this observation and HLA-DPB1 associations, we constructed high density SNP haplotypes of the 316 kb region from HLA-DMB to COL11A2 in childhood ALL and controls using a UK GWAS data subset and the software PHASE. Of four haplotype blocks identified, predicted haplotypes in Block 1 (centromeric of DNA3) differed significantly between BCP-ALL and controls (P = 0.002) and in Block 4 (including HLA-DPB1) between T-ALL and controls (P = 0.049). Of specific common (>5%) haplotypes in Block 1, two were less frequent in BCP-ALL, and in Block 4 a single haplotype was more frequent in T-ALL, compared to controls. Unexpectedly, we also observed apparent differences in ancestral meiotic recombination rates at DNA3, with BCP-ALL showing increased and T-ALL decreased levels compared to controls. In silico analysis using LDsplit sotware indicated that recombination rates at DNA3 are influenced by flanking loci, including SNPs identified in childhood ALL association studies. The observed differences in rates of meiotic recombination at this hotspot, and potentially others, may be a characteristic of childhood leukemia and contribute to disease susceptibility, alternatively they may reflect interactions between ALL-associated haplotypes in this region.

  12. World Kidney Day 2016: 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.

  13. 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

  14. 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

  15. Integration of genetic and clinical risk factors improves prognostication in relapsed childhood B-cell precursor acute lymphoblastic leukemia

    PubMed Central

    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

    2016-01-01

    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

  16. 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

  17. 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

  18. 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. PMID:27417467

  19. 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

  20. 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 ...

  1. 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

  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. 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

  4. Delineation of a 6 cM commonly deleted region in childhood acute lymphoblastic leukemia on the 6q chromosomal arm.

    PubMed

    Gérard, B; Cavé, H; Guidal, C; Dastugue, N; Vilmer, E; Grandchamp, B

    1997-02-01

    Deletion of the long arm of human chromosome 6 in acute lymphoblastic leukemia (ALL) has been shown by cytogenetic studies in 4-11% of cases. To characterize further the region of deletion and to precisely establish its frequency, we studied loss of heterozygosity (LOH) in 120 children with ALL using polymorphic markers located from the 6q14-15 chromosomal band to the telomere. LOH was detected in eight patients. A single region of LOH, flanked distally by D6S1594 and proximally by D6S301 was detected. These DNA markers are separated by 6 cM and are approximately located at the 6q21-22 band. Our present results delineate a region that is likely to contain a tumor-suppressor gene involved in a subset of childhood ALLs.

  5. Fever without apparent source on clinical examination, lower respiratory infections in children, bacterial infections, and acute gastroenteritis and diarrhea of infancy and early childhood.

    PubMed

    McCarthy, P L; Bachman, D T; Shapiro, E D; Baron, M A

    1995-02-01

    This section focuses on issues in infectious disease that are commonly encountered in pediatric office practice. Paul McCarthy discusses recent literature regarding the evaluation and management of acute fevers without apparent source on clinical examination in infants and children and the evaluation of children with prolonged fevers of unknown origin. David Bachman reviews recent literature about lower respiratory tract infection in children and focuses on community-acquired lower respiratory infections and respiratory syncytial virus. Eugene Shapiro discusses literature concerning several infectious diseases commonly seen in office settings and concerning which recent developments are of interest: the hemolytic-uremic syndrome and enterohemorrhagic Escherichia coli. Streptococcus pneumoniae resistant to penicillin, infections in day care centers, and new antimicrobial drugs. Michael Baron reviews recent literature about gastroenteritis and diarrhea of infancy and early childhood and discusses diagnosis, complications, pathogenesis and physiology, epidemiology, and treatment.

  6. Treatment outcome of CRLF2-rearranged childhood acute lymphoblastic leukaemia: a comparative analysis of the AIEOP-BFM and UK NCRI-CCLG study groups.

    PubMed

    Attarbaschi, Andishe; Morak, Maria; Cario, Gunnar; Cazzaniga, Giovanni; Ensor, Hannah M; te Kronnie, Truus; Bradtke, Jutta; Mann, Georg; Vendramini, Elena; Palmi, Chiara; Schwab, Claire; Russell, Lisa J; Schrappe, Martin; Conter, Valentino; Mitchell, Christopher D; Strehl, Sabine; Zimmermann, Martin; Pötschger, Ulrike; Harrison, Christine J; Stanulla, Martin; Panzer-Grümayer, Renate; Haas, Oskar A; Moorman, Anthony V

    2012-09-01

    The prognostic relevance of CRLF2 -rearrangements in childhood acute B-cell precursor lymphoblastic leukaemia (ALL), was assessed by a comparative analysis of 114 non-Down-syndrome patients (99 P2RY8-CRLF2+ , 15 IGH@-CRLF2+ ), 76 from the AIEOP-BFM ALL 2000 and 38 from the MRC ALL97 trials. The 6-year cumulative relapse incidence of P2RY8-CRLF2+ patients treated on the two trials was not statistically different: 0·37 ± 0·06 vs. 0·25 ± 0·08 (P = 0·194). In contrast, 0/9 IGH@-CRLF2+ AIEOP-BFM, but 5/6 ALL97 patients relapsed. Conclusively, P2RY8-CRLF2+ patients had an intermediate protocol-independent outcome while the different prognosis of IGH@-CRLF2+ patients could be related to the different structures of the applied treatment protocols.

  7. Delivering asthma education to special high risk groups.

    PubMed

    FitzGerald, J M; Turner, M O

    1997-12-01

    Patients at high risk from their asthma and therefore worthy of more focused asthma education are those at risk of fatal and near fatal asthma(NFA). In recent years the characteristics of these patients have been better defined. The most important risk factor appears to be a prior history of NFA. Other important features include prior emergency room visits or hospitalization for asthma. Excess use of beta-agonists, especially in the absence of inhaled corticosteroids, also confers increased risk. High risk groups also share similar psychosocial barriers as well as economic deprivation. The benefits of asthma education in these groups have been assessed in a number of studies. In general, asthma education has been shown to have an impact on these patients. Greater effects have been achieved where there has been consistent follow-up by the same physician. Patients require frequent reinforcement of their asthma management, especially regarding their response to acute exacerbations. A sub-group of patients with more severe asthma appear to have a problem perceiving dyspnoea and may therefore benefit from peak flow monitoring but the problem of compliance with this intervention is significant. Behaviour modification plays an important role as does ensuring the patient has adequate resources to purchase medications especially the more expensive anti-inflammatory therapy. Future studies should focus on optimizing the potential benefits of educating high risk patients as they are not only those at greatest risk of death but also consume a disproportionate amount of health care resources.

  8. 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

  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. 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

  11. Prognostic significance of the BAALC isoform pattern and CEBPA mutations in pediatric acute myeloid leukemia with normal karyotype: a study by the Japanese Childhood AML Cooperative Study Group.

    PubMed

    Mizushima, Yasuhiro; Taki, Tomohiko; Shimada, Akira; Yui, Yoshihiro; Hiraumi, Yoshimi; Matsubara, Hiroshi; Watanabe, Motonobu; Watanabe, Ken-ichiro; Kamitsuji, Yuri; Hayashi, Yasuhide; Tsukimoto, Ichiro; Kobayashi, Ryoji; Horibe, Keizo; Tawa, Akio; Nakahata, Tatsutoshi; Adachi, Souichi

    2010-06-01

    High BAALC (brain and acute leukemia, cytoplasmic) gene expression may indicate an adverse prognosis for adults who have acute myeloid leukemia (AML) and a normal karyotype, but its prognostic significance for pediatric AML cases is unclear. Whether different BAALC isoform patterns are of prognostic significance is also unclear. Newly diagnosed AML patients with normal karyotype who were treated by the Japanese Childhood AML Cooperative Treatment Protocol AML 99 were analyzed in terms of their BAALC expression levels (n = 29), BAALC isoforms (n = 29), and CEBPA mutations (n = 49). Eleven and 18 patients exhibited high and low BAALC expression, respectively, but these groups did not differ significantly in terms of overall survival (54.6 vs. 61.1%, P = 0.55) or event-free survival (61.4 vs. 50.0%, P = 0.82). Three of these 29 patients (10.3%) expressed the exon 1-5-6-8 BAALC isoform along with the expected 1-6-8 isoform and had adverse clinical outcomes. Novel CEBPA mutations were also identified in four of 49 patients (8.2%). All four patients have maintained complete remission for at least 5 years. Thus, 1-5-6-8 isoform expression may be associated with an adverse prognosis in pediatric AML with normal karyotype. CEBPA mutations may indicate a favorable prognosis.

  12. 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

  13. 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

  14. 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

  15. 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

  16. 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.

  17. Guaranteed Student Loans: GAO High Risk Series.

    ERIC Educational Resources Information Center

    Comptroller General of the U.S., Washington, DC.

    As part of a larger program to identify and analyze federal programs at high risk for waste, fraud, abuse and mismanagement, this publication presents an evaluation of the Federal Family Education Loan Program (FFELP), formerly the Guaranteed Student Loan Program. The analysis argues that the program has not been successful in protecting the…

  18. 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,...

  19. Creating Profiles of High Risk Students.

    ERIC Educational Resources Information Center

    Higbee, Jeanne L.; Dwinell, Patricia L.

    Measures used at the Division of Developmental Studies at the University of Georgia in constructing a student profile (specifically, of high-risk college freshmen) are discussed. The areas measured concern: goals; learning styles; career exploration; stress and academic anxiety; developmental tasks; and locus of control. The goals checklist…

  20. Frequency and Clinical Characteristics of Intrachromosomal Amplification of Chromosome 21 in Korean Childhood B-lineage Acute Lymphoblastic Leukemia

    PubMed Central

    Kim, Jieun; Lyu, Chuhl Joo; Choi, Jong Rak

    2016-01-01

    Background Intrachromosomal amplification of chromosome 21 (iAMP21) is known to be associated with poor prognosis in B-cell ALL (B-ALL). To determine the frequency and clinical characteristics of iAMP21 in Korean B-ALL patients, we performed FISH and multiplex ligation-dependent probe amplification (MLPA) analyses. Methods A total of 102 childhood B-ALL patients were screened with ETV6-RUNX1 FISH probes (Abbott Molecular, USA). The presence of an iAMP21 was confirmed by using MLPA P327 iAMP21-ERG probemix (MRC Holland, The Netherlands). Results iAMP21 was detected in one of the screened B-ALL patients (1/102 patients, 1.0%) who presented the ALL immunophenotype and complex karyotype at initial diagnosis. The patient relapsed twice after bone marrow transplantation. MLPA showed 12.5-Mb and 4.28-Mb regions of amplification and deletion, respectively. Conclusions The frequency of iAMP21 is considerable in Korean pediatric patients. Our report suggests that iAMP21 in childhood B-ALL has very unfavorable impact on patient's prognosis. Additional methods such as MLPA analysis is essential to rule out patients with equivocal interphase FISH results. PMID:27374714

  1. Combination Chemotherapy With or Without Rituximab in Treating Younger Patients With Stage III-IV Non-Hodgkin Lymphoma or B-Cell Acute Leukemia

    ClinicalTrials.gov

    2016-10-24

    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

  2. Childhood osteomyelitis-incidence and differentiation from other acute onset musculoskeletal features in a population-based study

    PubMed Central

    Riise, Øystein Rolandsen; Kirkhus, Eva; Handeland, Kai Samson; Flatø, Berit; Reiseter, Tor; Cvancarova, Milada; Nakstad, Britt; Wathne, Karl-Olaf

    2008-01-01

    Background Osteomyelitis can be difficult to diagnose and there has previously not been a prospective approach to identify all children in a defined geographic area. The aim of this study was to assess the annual incidence of osteomyelitis in children, describe the patient and disease characteristics in those with acute (< 14 days disease duration) and subacute osteomyelitis (≥ 14 days disease duration), and differentiate osteomyelitis patients from those with other acute onset musculoskeletal features. Methods In a population-based Norwegian study physicians were asked to refer all children with suspected osteomyelitis. Children with osteomyelitis received follow-up at six weeks, six months and thereafter as long as clinically needed. Results The total annual incidence rate of osteomyelitis was 13 per 100 000 (acute osteomyelitis 8 and subacute osteomyelitis 5 per 100 000). The incidence was higher in patients under the age of 3 than in older children (OR 2.9, 95%: CI 2.3–3.7). The incidence of non-vertebral osteomyelitis was higher than the incidence of vertebral osteomyelitis (10 vs. 3 per 100 000; p = .002). Vertebral osteomyelitis was more frequent in girls than in boys (OR 7.0, 95%: CI 3.3–14.7). ESR ≥ 40 mm/hr had the highest positive predictive laboratory value to identify osteomyelitis patients at 26% and MRI had a positive predictive value of 85%. Long-bone infection was found in 16 (43%) patients. ESR, CRP, white blood cell count, neutrophils and platelet count were higher for patients with acute osteomyelitis than for patients with subacute osteomyelitis. Subacute findings on MRI and doctor's delay were more common in subacute osteomyelitis than in acute osteomyelitis patients. Blood culture was positive in 26% of the acute osteomyelitis patients and was negative in all the subacute osteomyelitis patients. Conclusion The annual incidence of osteomyelitis in Norway remains high. ESR values and MRI scan may help to identify osteomyelitis patients

  3. 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

  4. Intrauterine exposure to fine particulate matter as a risk factor for increased susceptibility to acute broncho-pulmonary infections in early childhood.

    PubMed

    Jedrychowski, Wiesław A; Perera, Frederica P; Spengler, John D; Mroz, Elzbieta; Stigter, Laura; Flak, Elżbieta; Majewska, Renata; Klimaszewska-Rembiasz, Maria; Jacek, Ryszard

    2013-07-01

    Over the last decades many epidemiologic studies considered the morbidity patterns for respiratory diseases and lung function of children in the context of ambient air pollution usually measured in the postnatal period. The main purpose of this study is to assess the impact of prenatal exposure to fine particulate matter (PM2.5) on the recurrent broncho-pulmonary infections in early childhood. The study included 214 children who had measurements of personal prenatal PM2.5 exposure and regularly collected data on the occurrence of acute bronchitis and pneumonia diagnosed by a physician from birth over the seven-year follow-up. The effect of prenatal exposure to PM2.5 was adjusted in the multivariable logistic models for potential confounders, such as prenatal and postnatal ETS (environmental tobacco smoke), city residence area as a proxy of postnatal urban exposure, children's sensitization to domestic aeroallergens, and asthma. In the subgroup of children with available PM2.5 indoor levels, the effect of prenatal exposure was additionally adjusted for indoor exposure as well. The adjusted odds ratio (OR) for incidence of recurrent broncho-pulmonary infections (five or more spells of bronchitis and/or pneumonia) recorded in the follow-up significantly correlated in a dose-response manner with the prenatal PM2.5 level (OR=2.44, 95%CI: 1.12-5.36). In conclusion, the study suggests that prenatal exposure to PM2.5 increases susceptibility to respiratory infections and may program respiratory morbidity in early childhood. The study also provides evidence that the target value of 20μg/m(3) for the 24-h mean level of PM2.5 protects unborn babies better than earlier established EPA guidelines.

  5. 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…

  6. 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

  7. 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

  8. Single dose rasburicase in the management of tumor lysis syndrome in childhood acute lymphoblastic leukemia: A case series.

    PubMed

    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

  9. 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

  10. Reduced-Intensity Conditioning Before Donor Stem Cell Transplant in Treating Patients With High-Risk Hematologic Malignancies

    ClinicalTrials.gov

    2016-10-19

    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

  11. 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

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

    PubMed

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

    2014-01-01

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

  13. 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.

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

    PubMed Central

    Wesołowska-Andersen, A; Borst, L; Dalgaard, M D; Yadav, R; Rasmussen, K K; Wehner, P S; Rasmussen, M; Ørntoft, T F; Nordentoft, I; Koehler, R; Bartram, C R; Schrappe, M; Sicheritz-Ponten, T; Gautier, L; Marquart, H; Madsen, H O; Brunak, S; Stanulla, M; Gupta, R; Schmiegelow, K

    2015-01-01

    Childhood acute lymphoblastic leukemia survival approaches 90%. New strategies are needed to identify the 10–15% who evade cure. We applied targeted, sequencing-based genotyping of 25 000 to 34 000 preselected potentially clinically relevant single-nucleotide polymorphisms (SNPs) to identify host genome profiles associated with relapse risk in 352 patients from the Nordic ALL92/2000 protocols and 426 patients from the German Berlin–Frankfurt–Munster (BFM) ALL2000 protocol. Patients were enrolled between 1992 and 2008 (median follow-up: 7.6 years). Eleven cross-validated SNPs were significantly associated with risk of relapse across protocols. SNP and biologic pathway level analyses associated relapse risk with leukemia aggressiveness, glucocorticosteroid pharmacology/response and drug transport/metabolism pathways. Classification and regression tree analysis identified three distinct risk groups defined by end of induction residual leukemia, white blood cell count and variants in myeloperoxidase (MPO), estrogen receptor 1 (ESR1), lamin B1 (LMNB1) and matrix metalloproteinase-7 (MMP7) genes, ATP-binding cassette transporters and glucocorticosteroid transcription regulation pathways. Relapse rates ranged from 4% (95% confidence interval (CI): 1.6–6.3%) for the best group (72% of patients) to 76% (95% CI: 41–90%) for the worst group (5% of patients, P<0.001). Validation of these findings and similar approaches to identify SNPs associated with toxicities may allow future individualized relapse and toxicity risk-based treatments adaptation. PMID:24990611

  15. 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

  16. 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.

  17. 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

  18. 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.

  19. Secondary histiocytic sarcoma may cause apparent persistence or recurrence of minimal residual disease in childhood acute lymphoblastic leukemia.

    PubMed

    Alten, Julia; Klapper, Wolfram; Leuschner, Ivo; Eckert, Cornelia; Beier, Rita; Vallo, Elisabeth; Krause, Martin; Claviez, Alexander; Vieth, Simon; Bleckmann, Kirsten; Möricke, Anja; Schrappe, Martin; Cario, Gunnar

    2015-09-01

    Histiocytic sarcoma (HS) is a rare disease with poor prognosis which may develop subsequent to acute lymphoblastic leukemia (ALL). Here we report two children treated within the AIEOP-BFM ALL 2009 trial: one patient succumbed to fulminant hemophagocytic lymphohistiocytosis triggered by HS during ALL maintenance therapy, the other patient had a smoldering course of HS for over 2 years, and subsequently died after allogeneic stem cell transplantation. In both cases, HS and ALL were clonally related and apparent return of minimal residual disease (MRD) was detected by qPCR in bone marrow. Thus, HS should be considered in ALL when MRD appears to persist or reappear.

  20. [Complications in the central nervous system during chemotherapy for childhood acute lymphoblastic leukemia: JACLS ALL-02 study].

    PubMed

    Umeda, Katsutsugu; Yoshida, Makoto; Suzuki, Nobuhiro; Endo, Mikiya; Sato, Atsushi; Hori, Hiroki; Isogai, Mitsuharu; Matsumoto, Kimikazu; Hara, Jun-iIchi; Hasegawa, Daiichiro; Hashii, Yoshiko; Chayama, Kosuke; Miyaji, Ryousuke; Nishimura, Shin-ichiro; Tanizawa, Akihiko; Uami, Ikuya; Horibe, Keizo; Wakazono, Yoshihiro; Yagi, Keiko

    2007-03-01

    We evaluated central nervous system (CNS) complications treated under the ALL-02 protocol of the Japan Association of Childhood Leukemia Study (JACLS) from April 2002 to March 2005. According to NCI Toxicity Criteria, 17 events of grade 3 and 4 CNS complications were reported in 15 out of 541 patients. Out of these CNS complications, leukoencephalopathy was seen in 5 patients; seizure in 5; cerebrovascular disease in 3; conscious disturbance in 2; and hypertensive encephalopathy and reversible posterior leukoencephalopathy syndrome in one patient each. The complications were intensively observed during induction therapy and the last of the early phase chemotherapy. The protocol treatment was stopped or modified in most patients after CNS complications. MRI imaging demonstrated no improvement in one patient with leukoencephalopathy who developed an isolated CNS relapse, while other patients were alive and remain in their first complete remission without any neurological sequelae. Further studies will be required to analyze risk factors for CNS complications during chemotherapy not accompanied by irradiation and to establish alternative treatments after the appearance of such CNS complications.

  1. Real-Time PCR Threshold Cycle Cutoffs Help To Identify Agents Causing Acute Childhood Diarrhea in Zanzibar

    PubMed Central

    Andersson, Maria; Msellem, Mwinyi I.; Welinder-Olsson, Christina; Petzold, Max; Björkman, Anders; Trollfors, Birger; Mårtensson, Andreas

    2014-01-01

    Molecular assays might improve the identification of causes of acute diarrheal disease but might lead to more frequent detection of asymptomatic infections. In the present study, real-time PCR targeting 14 pathogens was applied to rectal swabs from 330 children aged 2 to 59 months in Zanzibar, including 165 patients with acute diarrhea and 165 asymptomatic control subjects. At least one pathogen was detected for 94% of the patients and 84% of the controls, with higher rates among patients for norovirus genogroup II (20% versus 2.4%; P < 0.0001), rotavirus (10% versus 1.8%; P = 0.003), and Cryptosporidium (30% versus 11%; P < 0.0001). Detection rates did not differ significantly for enterotoxigenic Escherichia coli (ETEC)-estA (33% versus 24%), ETEC-eltB (44% versus 46%), Shigella (35% versus 33%), and Campylobacter (35% versus 33%), but for these agents threshold cycle (CT) values were lower (pathogen loads were higher) in sick children than in controls. In a multivariate analysis, CT values for norovirus genogroup II, rotavirus, Cryptosporidium, ETEC-estA, and Shigella were independently associated with diarrhea. We conclude that this real-time PCR allows convenient detection of essentially all diarrheagenic agents and provides CT values that may be critical for the interpretation of results for pathogens with similar detection rates in patients and controls. The results indicate that the assessment of pathogen loads may improve the identification of agents causing gastroenteritis in children. PMID:24403298

  2. 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.

  3. 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

  4. Counseling the high-risk adolescent.

    PubMed

    Busen, N H

    1992-01-01

    Interviewing and counseling high-risk adolescents provides a challenge to nurse practitioners. The problems of poverty, substance abuse, mental illness, and low self-esteem overlay other characteristics of risk, making assessment and management of the adolescent's problems complex and difficult. Survey data, obtained in this study on adolescent risk-taking, suggest that violence, aggression, and thrill-seeking behaviors are increasingly common. The finding is supported by current national statistics on adolescents. A case study is used to show the process of gathering information on home and educational settings that can provide insight into family dysfunction and specific problem behaviors.

  5. 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) ...

  6. Minimal Residual Disease-Based Risk Stratification in Chinese Childhood Acute Lymphoblastic Leukemia by Flow Cytometry and Plasma DNA Quantitative Polymerase Chain Reaction

    PubMed Central

    Cheng, Suk Hang; Lau, Kin Mang; Li, Chi Kong; Chan, Natalie P. H.; Ip, Rosalina K. L.; Cheng, Chi Keung; Lee, Vincent; Shing, Matthew M. K.; Leung, Alex W. K.; Ha, Shau Yin; Cheuk, Daniel K. L.; Lee, Anselm C. W.; Li, Chak Ho; Luk, Chung Wing; Ling, Siu Cheung; Hrusak, Ondrej; Mejstrikova, Ester; Leung, Yonna; Ng, Margaret H. L.

    2013-01-01

    Minimal residual disease, or MRD, is an important prognostic indicator in childhood acute lymphoblastic leukemia. In ALL-IC-BFM 2002 study, we employed a standardized method of flow cytometry MRD monitoring for multiple centers internationally using uniformed gating, and determined the relevant MRD-based risk stratification strategies in our local patient cohort. We also evaluated a novel method of PCR MRD quantitation using peripheral blood plasma. For the bone marrow flow MRD study, patients could be stratified into 3 risk groups according to MRD level using a single time-point at day-15 (Model I) (I-A: <0.1%, I-B: 0.1–10%, I-C: >10%), or using two time-points at day-15 and day-33 (Model II) (II-A: day-15<10% and day-33<0.01%, II-B: day-15≥10% or day-33≥0.01% but not both, II-C: day-15≥10% and day-33≥0.01%), which showed significantly superior prediction of relapse (p = .00047 and <0.0001 respectively). Importantly, patients with good outcome (frequency: 56.0%, event-free survival: 90.1%) could be more accurately predicted by Model II. In peripheral blood plasma PCR MRD investigation, patients with day-15-MRD≥10−4 were at a significantly higher risk of relapse (p = 0.0117). By multivariate analysis, MRD results from both methods could independently predict patients’ prognosis, with 20–35-fold increase in risk of relapse for flow MRD I-C and II-C respectively, and 5.8-fold for patients having plasma MRD of ≥10−4. We confirmed that MRD detection by flow cytometry is useful for prognostic evaluation in our Chinese cohort of childhood ALL after treatment. Moreover, peripheral blood plasma DNA MRD can be an alternative where bone marrow specimen is unavailable and as a less invasive method, which allows close monitoring. PMID:23936021

  7. Treatment of high-risk neuroblastoma.

    PubMed

    Sung, Ki Woong

    2012-04-01

    Although high-dose chemotherapy and autologous stem cell transplantation (HDCT/autoSCT) have improved the prognosis for patients with high-risk neuroblastoma (NB), event-free survival rates remain in the range of 30 to 40%, which is unsatisfactory. To further improve outcomes, several clinical trials, including tandem HDCT/autoSCT, high-dose (131)I-metaiodobenzylguanidine treatment, and immunotherapy with NB specific antibody, have been undertaken and pilot studies have reported encouraging results. Nonetheless, about half of high-risk NB patients still experience treatment failure and have no realistic chance for cure with conventional treatment options alone after relapse. Therefore, a new modality of treatment is warranted for these patients. In recent years, several groups of investigators have examined the feasibility and effectiveness of reduced-intensity allogeneic stem cell transplantation (RI alloSCT) for the treatment of relapsed/progressed NB. Although a graft-versus-tumor effect has not yet been convincingly demonstrated in the setting of relapsed NB, the strategy of employing RI alloSCT has provided hope that treatment-related mortality will be reduced and a therapeutic benefit will emerge. However, alloSCT for NB is still investigational and there remain many issues to be elucidated in many areas. At present, alloSCT is reserved for specific clinical trials testing the immunomodulatory effect against NB.

  8. 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

    2016-11-02

    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

  9. 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

  10. Overt testicular disease at diagnosis of childhood acute lymphoblastic leukemia: lack of therapeutic role of local irradiation.

    PubMed

    Hijiya, N; Liu, W; Sandlund, J T; Jeha, S; Razzouk, B I; Ribeiro, R C; Rubnitz, J E; Howard, S C; Kyzer, E P; Redd, D S; Cheng, C; Rivera, G K; Hudson, M M; Relling, M V; Pui, C-H

    2005-08-01

    To assess the prognosis of overt testicular disease at diagnosis of acute lymphoblastic leukemia, and any therapeutic role of irradiation for this involvement, we reviewed the data of 811 boys treated on St Jude studies Total X--XI (early period) and Total XII-XIV (recent period). In all, 19 boys (2.3%) had testicular disease at diagnosis. In the early period, patients with testicular leukemia had a poorer overall survival (OS) (P=0.003), event-free survival (EFS) (P=0.064), and higher cumulative incidence of relapse (P=0.041) than did other patients. During the recent period, patients with and without overt testicular leukemia did not differ in OS (P=0.257), EFS (P=0.102), or cumulative incidence of relapse (P=0.51). In a multivariate analysis, OS was lower for patients with testicular disease than for those without the involvement in the early period (P=0.047) but not in the recent one (P=0.75). Both patients who received irradiation for residual testicular disease at the end of induction subsequently died of leukemia. Of the other 17 patients who did not receive irradiation, only one developed testicular relapse in combination with bone marrow relapse. In conclusion, the prognostic impact of overt testicular disease has diminished. Irradiation appears to provide no survival advantage to this patient population. PMID:15973454

  11. Outcome after cessation of therapy in childhood acute lymphoblastic leukaemia. The Associazione Italiana Ematologia ed Oncologia Pediatrica (AIEOP).

    PubMed

    Jankovic, M; Fraschini, D; Amici, A; Aricò, M; Arrighini, A; Basso, G; Colella, R; DiTullio, M T; Haupt, R; Macchia, P

    1993-01-01

    A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P < 0.0001). Thirteen patients died in continuous complete remission, 5 because of non-neoplastic central nervous system complications. There were 11 second solid malignancies, 8 of them in the central nervous system; 9 subjects presented an haematopoietic malignancy after ALL. The projected event-free survival at 8 years is 73%. Twenty-two of the 171 young adults (age > 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

  12. 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.

  13. 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

  14. 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

  15. 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

  16. 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

  17. The 12;21 translocation involving TEL and deletion of the other TEL allele: two frequently associated alterations found in childhood acute lymphoblastic leukemia.

    PubMed

    Raynaud, S; Cave, H; Baens, M; Bastard, C; Cacheux, V; Grosgeorge, J; Guidal-Giroux, C; Guo, C; Vilmer, E; Marynen, P; Grandchamp, B

    1996-04-01

    A recurrent t(12;21)(p13;q22) has recently been described in human acute lymphoblastic leukemias (ALLs). This translocation fuses TEL and AML1, two genes previously cloned from translocation breakpoints in myeloid leukemias. In addition, allelic loss of the TEL gene can be detected in 15% to 22% of childhood ALLs. In the present study, we have sought allelic deletions of TEL and the presence of the t(12;21) in 50 children with B-lineage ALL, using a combination of microsatellite typing, fluorescent in situ hybridization (FISH), and analysis of the fusion transcripts resulting from the TEL-AML1 gene fusion. Our results indicate that the association between the t(12;21) and the deletion of the nontranslocated allele of TEL is among the most frequent abnormalities observed in B-lineage ALLs. FISH analysis using several cosmid probes showed that, in one patient with a t(12;21) translocation involving TEL, the second allele had an intragenic deletion. This observation points to TEL as the actual target of 12p12-13 deletions in patients that associate a t(12;21) with a deletion. The TEL-AML1 fusion RNA was found in all patients with the t(12;21) whereas the reciprocal AML1-TEL transcript was only found in a subset of patients, suggesting that only the protein product encoded by TEL-AML1 is likely to play a role in leukemogenesis. The observation that, in two patients with the t(12;21), a deletion of TEL was only present in a subclone indicates that this deletion was a secondary event that occurred after the translocation. The frequent occurrence of TEL deletions in patients with t(12;21) suggests that the deletion of the normal TEL allele subsequent to the t(12;21) provides a further proliferative advantage to leukemic cells.

  18. Body composition and bone health in long-term survivors of acute lymphoblastic leukaemia in childhood and adolescence: the protocol for a cross-sectional cohort study

    PubMed Central

    Barr, Ronald; Nayiager, Trishana; Gordon, Christopher; Marriott, Christopher; Athale, Uma

    2015-01-01

    Introduction Success in the treatment of young people with cancer, as measured conventionally by survival rates, is mitigated by late effects of therapy that impose a burden of morbidity and limit life expectancy. Among these adverse sequelae are altered body composition, especially obesity, and compromised bone health in the form of osteoporosis and increased fragility. These outcomes are potentially reversible and even preventable. This study will examine measures of body composition and bone health in long-term survivors of acute lymphoblastic leukaemia (ALL) in childhood and adolescence. These measures will be complemented by measures of physical activity and health-related quality of life (HRQL). Methods and analysis Survivors of ALL who are at least 10 years from diagnosis, following treatment on uniform protocols, will undergo measurements of body mass index; triceps skin fold thickness and mid-upper arm circumference; fat mass, lean body mass, skeletal muscle mass and bone mineral density by dual energy X-ray absorptiometry; trabecular and cortical bone indices and muscle density by peripheral quantitative CT; physical activity by the Habitual Activity Estimation Scale; and HRQL by Health Utilities Index instruments. Descriptive measures will be used for continuous variables and number (percent) for categorical variables. Associations between variables will be assessed using Fisher's exact t test and the χ2 test; correlations will be tested by the Pearson correlation coefficient. Ethics and dissemination The study is approved by the institutional research ethics board and is supported by a competitive funding award. Dissemination of the results will occur by presentations to scientific meetings and publications in peer-reviewed journals, and by posting summaries of the results on websites accessed by adolescent and young adult survivors of cancer. PMID:25603918

  19. Frequent and sex-biased deletion of SLX4IP by illegitimate V(D)J-mediated recombination in childhood acute lymphoblastic leukemia.

    PubMed

    Meissner, Barbara; Bartram, Thies; Eckert, Cornelia; Trka, Jan; Panzer-Grümayer, Renate; Hermanova, Ivana; Ellinghaus, Eva; Franke, Andre; Möricke, Anja; Schrauder, André; Teigler-Schlegel, Andrea; Dörge, Petra; von Stackelberg, Arend; Basso, Giuseppe; Bartram, Claus R; Kirschner-Schwabe, Renate; Bornhäuser, Beat; Bourquin, Jean-Pierre; Cazzaniga, Giovanni; Hauer, Julia; Attarbaschi, Andishe; Izraeli, Shai; Zaliova, Marketa; Cario, Gunnar; Zimmermann, Martin; Avigad, Smadar; Sokalska-Duhme, Magdalena; Metzler, Markus; Schrappe, Martin; Koehler, Rolf; Te Kronnie, Geertruy; Stanulla, Martin

    2014-02-01

    Acute lymphoblastic leukemia (ALL) accounts for ∼25% of pediatric malignancies. Of interest, the incidence of ALL is observed ∼20% higher in males relative to females. The mechanism behind the phenomenon of sex-specific differences is presently not understood. Employing genome-wide genetic aberration screening in 19 ALL samples, one of the most recurrent lesions identified was monoallelic deletion of the 5' region of SLX4IP. We characterized this deletion by conventional molecular genetic techniques and analyzed its interrelationships with biological and clinical characteristics using specimens and data from 993 pediatric patients enrolled into trial AIEOP-BFM ALL 2000. Deletion of SLX4IP was detected in ∼30% of patients. Breakpoints within SLX4IP were defined to recurrent positions and revealed junctions with typical characteristics of illegitimate V(D)J-mediated recombination. In initial and validation analyses, SLX4IP deletions were significantly associated with male gender and ETV6/RUNX1-rearranged ALL (both overall P < 0.0001). For mechanistic validation, a second recurrent deletion affecting TAL1 and caused by the same molecular mechanism was analyzed in 1149 T-cell ALL patients. Validating a differential role by sex of illegitimate V(D)J-mediated recombination at the TAL1 locus, 128 out of 1149 T-cell ALL samples bore a deletion and males were significantly more often affected (P = 0.002). The repeatedly detected association of SLX4IP deletion with male sex and the extension of the sex bias to deletion of the TAL1 locus suggest that differential illegitimate V(D)J-mediated recombination events at specific loci may contribute to the consistent observation of higher incidence rates of childhood ALL in boys compared with girls. PMID:24045615

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

    PubMed Central

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

    2013-01-01

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

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

    PubMed

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

    1990-04-01

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

  2. 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

  3. [The West-Berlin therapy study of acute lymphoblastic leukemia in childhood--report after 6 years].

    PubMed

    Riehm, H; Gadner, H; Welte, K

    2013-05-01

    During the last 6 years 73 previously untreated children and adolescents with acute lymphoblastic leukemia were enrolled on a non-randomized therapy protocol. In this longitudinal study the specific accent was put on the intensified induction treatment of 8 weeks' duration which was thought to achieve a higher remission quality. In this phase 8 effective drugs were applied up to the patient's tolerance limits; in addition prophylactic irradiation to the central nervous system was given in two modifications. After 4 weeks all patients were in complete remission. During the first 4 months 6 children died due to complications for which therapy must be at least partially responsible. 17 out of 67 patients relapsed between 4 and 59 months after diagnosis, which corresponds to a remission rate according to the life table analysis of 62% (50 out of 67 patients in first remission). The majority of patients with relapse is characterized at diagnosis by a specific pattern of clinical findings. 2 therapy groups, differently treated in respect to central nervous system irradiation and duration of continuation therapy, do not at present statistically differ from each other. According to statistics 8 more children may be expected to suffer from relapse. The improved results are due to a lower incidence of bone marrow relapses; it seems that there is a direct relation between intensity of treatment during the induction phase and the occurrence of bone marrow relapses. The specific problems of the presented study take place during the induction phase, which, due to toxicity, regularly results in a number of side effects and severe complications. In order to realize the induction therapy, the use of prophylactic and supportive procedures is of utmost importance. Profound knowledge of possible side effects and complications is most essential as well as the knowledge of how to cope with these problems. It is the authors' opinion that the induction phase can only be performed in

  4. 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

  5. Immunization of high-risk paediatric populations: Central European Vaccination Awareness Group recommendations.

    PubMed

    Richter, Darko; Anca, Ioana; André, Francis E; Bakir, Mustafa; Chlibek, Roman; Čižman, Milan; Mangarov, Atanas; Mészner, Zsófia; Pokorn, Marko; Prymula, Roman; Salman, Nuran; Simurka, Pavol; Tamm, Eda; Tešović, Goran; Urbančíková, Ingrid; Usonis, Vytautas; Wysocki, Jacek; Zavadska, Dace; Central European Vaccination Awareness Group

    2014-06-01

    Over the last decade, childhood immunization has substantially reduced morbidity and mortality from vaccine-preventable diseases. However, particular paediatric risk groups, such as those with comorbidities, may not be adequately vaccinated despite being more susceptible to complications and death from certain infectious diseases. This may be due to lack of immunization recommendations, lack of awareness, or incomplete adherence to existing guidelines. Furthermore, recommendations for immunization can be inconsistent across Europe. An expanded initiative from the Central European Vaccination Awareness Group aims to raise awareness of the different high-risk paediatric groups, differentiate them according to their specific risk, and formalise a guidance statement for the immunization of each population.

  6. 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.

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

    ClinicalTrials.gov

    2016-07-26

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

  8. Risk-Adapted Chemotherapy in Treating Younger Patients With Newly Diagnosed Standard-Risk Acute Lymphoblastic Leukemia or Localized B-Lineage Lymphoblastic Lymphoma

    ClinicalTrials.gov

    2016-09-23

    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

  9. 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

  10. 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.

  11. 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.

  12. 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

  13. 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

  14. Alteration of the SETBP1 Gene and Splicing Pathway Genes SF3B1, U2AF1, and SRSF2 in Childhood Acute Myeloid Leukemia

    PubMed Central

    Choi, Hyun-Woo; Kim, Hye-Ran; Baek, Hee-Jo; Kook, Hoon; Cho, Duck; Shin, Jong-Hee; Suh, Soon-Pal; Ryang, Dong-Wook

    2015-01-01

    Background Recurrent somatic SET-binding protein 1 (SETBP1) and splicing pathway gene mutations have recently been found in atypical chronic myeloid leukemia and other hematologic malignancies. These mutations have been comprehensively analyzed in adult AML, but not in childhood AML. We investigated possible alteration of the SETBP1, splicing factor 3B subunit 1 (SF3B1), U2 small nuclear RNA auxiliary factor 1 (U2AF1), and serine/arginine-rich splicing factor 2 (SRSF2) genes in childhood AML. Methods Cytogenetic and molecular analyses were performed to reveal chromosomal and genetic alterations. Sequence alterations in the SETBP1, SF3B1, U2AF1, and SRSF2 genes were examined by using direct sequencing in a cohort of 53 childhood AML patients. Results Childhood AML patients did not harbor any recurrent SETBP1 gene mutations, although our study did identify a synonymous mutation in one patient. None of the previously reported aberrations in the mutational hotspot of SF3B1, U2AF1, and SRSF2 were identified in any of the 53 patients. Conclusions Alterations of the SETBP1 gene or SF3B1, U2AF1, and SRSF2 genes are not common genetic events in childhood AML, implying that the mutations are unlikely to exert a driver effect in myeloid leukemogenesis during childhood. PMID:25553291

  15. 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.

  16. 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

  17. Immune-based therapies for childhood cancer.

    PubMed

    Mackall, Crystal L; Merchant, Melinda S; Fry, Terry J

    2014-12-01

    After decades of research, immunotherapies for cancer are demonstrating increasing success. These agents can amplify existent antitumour immunity or induce durable antitumour immune responses in a wide array of cancers. The spectrum of immunotherapeutics is broad, spanning monoclonal antibodies and their derivatives, tumour vaccines, and adoptive therapies using T cells and natural killer cells. Only a small number of immunotherapies have been tested in paediatric cancers, but impressive antitumour effects have already been observed. Mononclonal antibodies targeting GD2 that induce antibody-dependent cell-mediated cytotoxicity improve survival in high-risk neuroblastoma. Bi-specific monoclonal antibodies that simultaneously target CD19 and activate T cells can induce remission in acute B-cell lymphoblastic leukaemia (B-ALL) and adoptive immunotherapy using T cells genetically engineered to express chimeric antigen receptors targeting CD19 induce impressive responses in B-ALL. Efforts are underway to generate and test new immunotherapies in a wider array of paediatric cancers. Major challenges include a need to identify immunotherapy targets on the most lethal childhood cancers, to expand availability of technology-intense platforms, such as adoptive cell therapy, to optimize management of novel toxicities associated with this new class of cancer therapies and to determine how best to incorporate these therapies into standard treatment paradigms.

  18. 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

  19. 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…

  20. Effectiveness of Palivizumab in Preventing RSV Hospitalization in High Risk Children: A Real-World Perspective

    PubMed Central

    Rawlinson, William; Snelling, Thomas L.; Jaffe, Adam

    2014-01-01

    Infection with respiratory syncytial virus (RSV) is one of the major causes globally of childhood respiratory morbidity and hospitalization. Palivizumab, a humanized monoclonal antibody, has been recommended for high risk infants to prevent severe RSV-associated respiratory illness. This recommendation is based on evidence of efficacy when used under clinical trial conditions. However the real-world effectiveness of palivizumab outside of clinical trials among different patient populations is not well established. We performed a systematic review focusing on postlicensure observational studies of the protective effect of palivizumab prophylaxis for reducing RSV-associated hospitalizations in infants and children at high risk of severe infection. We searched studies published in English between 1 January 1999 and August 2013 and identified 420 articles, of which 20 met the inclusion criteria. This review supports the recommended use of palivizumab for reducing RSV-associated hospitalization rates in premature infants born at gestational age < 33 weeks and in children with chronic lung and heart diseases. Data are limited to allow commenting on the protective effect of palivizumab among other high risk children, including those with Down syndrome, cystic fibrosis, and haematological malignancy, indicating further research is warranted in these groups. PMID:25548575

  1. Prevalence of High-Risk Human Papillomavirus Among Older Women

    PubMed Central

    Lindau, Stacy Tessler; Drum, Melinda L.; Gaumer, Elyzabeth; Surawska, Hanna; Jordan, Jeanne A.

    2009-01-01

    Objective To estimate the prevalence, genotypes, and individual-level correlates of high-risk human papillomavirus (HPV) among women aged 57–85. Methods Community-residing women (n=1550), aged 57–85, were drawn from a nationally-representative probability sample. In-home interviews and biomeasures, including a self-collected vaginal specimen, were obtained between 2005 and 2006. Specimens were analyzed for high-risk HPV DNA using probe hybridization and signal amplification (hc2); of 1,028 specimens provided, 1,010 were adequate for analysis. All samples testing positive were analyzed for HPV DNA by L1 consensus polymerase chain reaction followed by type-specific hybridization. Results The overall population-based weighted estimate of high-risk HPV prevalence by hc2 was 6.0% (95% confidence interval [CI] = 4.5 to 7.9). Current marital and smoking status, frequency of sexual activity, history of cancer, and hysterectomy were associated with high-risk HPV positivity. Among high-risk HPV+ women, 63% had multiple type infections. HPV 16 or 18 was present in 17.4% of all high-risk HPV+ women. The most common high-risk genotypes among high-risk HPV+ women were HPV 61 (19.1%), 31 (13.1%), 52 (12.9%), 58 (12.5%), 83 (12.3%), 66(12.0%), 51 (11.7%), 45 (11.2%), 56 (10.3%), 53 (10.2%), 16 (9.7%), and 62 (9.2%). Being married and having an intact uterus were independently associated with lower prevalence of high-risk HPV. Among unmarried women, current sexual activity and smoking were independently and positively associated with high-risk HPV infection. Conclusions In this nationally representative population, nearly 1 in 16 women aged 57–85 were found to have high-risk HPV and prevalence was stable across older age groups. PMID:18978096

  2. [Infant acute leukemia].

    PubMed

    Brethon, Benoît; Cavé, Hélène; Fahd, Mony; Baruchel, André

    2016-03-01

    If acute leukemia is the most frequent cancer in childhood (33%), it remains a very rare diagnosis in infants less than one year old, e.g. less than 5% of cases. At this age, the frequency of acute lymphoblastic leukemia (ALL) (almost all of B-lineage) is quite similar to the one of myeloblastic forms (AML). Infant leukemia frequently presents with high hyperleucocytosis, major tumoral burden and numerous extra-hematological features, especially in central nervous system and skin. Whatever the lineage, the leukemic cell is often very immature cytologically and immunologically. Rearrangements of the Mixed Lineage Leukemia (MLL) gene, located on band 11q23, are the hallmark of these immature leukemias and confer a particular resistance to conventional approaches, corticosteroids and chemotherapy. The immaturity of infants less than 1-year-old is associated to a decrease of the tolerable dose-intensity of some drugs (anthracyclines, alkylating agents) or asks questions about some procedures like radiotherapy or high dose conditioning regimen, responsible of inacceptable acute and late toxicities. The high level of severe infectious diseases and other high-grade side effects limits also the capacity to cure these infants. The survival of infants less than 1-year-old with AML is only 50% but similar to older children. On the other hand, survival of those with ALL is the same, then quite limited comparing the 80% survival in children over one year. Allogeneic stem cell transplantations are indicated in high-risk subgroups of infant ALL (age below 6 months, high hyperleucocytosis >300.10(9)/L, MLL-rearrangement, initial poor prednisone response). However, morbidity and mortality remain very important and these approaches cannot be extended to all cases. During the neonatal period, the dismal prognosis linked to the high number of primary failures or very early relapses and uncertainties about the late toxicities question physicians about ethics. It is an emergency to

  3. Language Deficits in Children at High Risk for Drug Abuse.

    ERIC Educational Resources Information Center

    Najam, Najma; Tarter, Ralph E.; Kirisci, Levent

    1997-01-01

    Compared the language capacities of children at high risk for substance abuse to low-risk children to uncover focal areas of deficit. Results indicate that high-risk subjects' performance was significantly poorer on several measures of language ability. Findings suggest that poor language mediation increases the risk for substance abuse. (RJM)

  4. Identify and Assist the Development of High Risk Preschool Children.

    ERIC Educational Resources Information Center

    Mann, Marlis

    This speech offers a guide to identifying and teaching high-risk children, those who exhibit a lag in development severe enough to be a handicap in learning. The high-risk children focused on are those whose developmental lag is frequently not recognized until they fail in school. The two major areas of neurodevelopmental learning disorders are in…

  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. 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 ...

  8. 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 ...

  9. 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 ...

  10. Thiazolidinediones and Cardiovascular Events In High-Risk Patients with Type-2 Diabetes Mellitus

    PubMed Central

    Shaya, Fadia T.; Lu, Zhiqiang; Sohn, Kyongsei; Weir, Matthew R.

    2009-01-01

    Context. The use of thiazolidinediones (TZDs) in patients with type-2 diabetes mellitus appears to be associated with an increased risk of myocardial infarction (MI) compared with placebo or other oral antidiabetic drug regimens. Objective. We conducted a study to investigate whether there was a difference in the risk of acute MI and hemorrhagic and non-hemorrhagic stroke between specific TZDs, namely rosiglitazone maleate (Avandia) and pioglitazone (Actos), and other oral antidiabetic agents in a high-risk, largely underrepresented and largely minority Medicaid population. Study Design, Setting, and Patients. We analyzed patient encounter data using propensity-scoring methods and logistic regression to compare the risk of cardiovascular (CV) events in patients with type-2 diabetes in a high-risk population. Main Outcome Measures. Outcomes were identified through International Classification of Disease (ICD-9) codes 410–411 for acute MI; 430–438 for stroke; and revenue (emergency department) codes 450–459 in the case of MI. Results. Using retrospective medical encounter and prescription data analyses, we found that rosiglitazone, compared with other oral antidiabetic agents, was associated with an increased rate of CV events by 20% in a high-risk cohort of diabetic patients. Neither pioglitazone nor the TZD drug class as a whole was associated with an increased CV risk. Conclusion. Rosiglitazone was associated with a significant increase in CV events (MI and stroke) among high-risk patients with type-2 diabetes, whereas pioglitazone was not. We recommend further research to capture risk factors that were not observed in our encounter data. PMID:20140111

  11. [Migraine variants and unusual types of migraine in childhood].

    PubMed

    Gaul, C; Kraya, T; Holle, D; Benkel-Herrenbrück, I; Schara, U; Ebinger, F

    2011-04-01

    Migraine is a frequent primary headache disorder in children and adolescents. Most of the young sufferers of migraine describe typical migraine symptoms but sometimes rare forms of migraine variants and unusual types of migraine occur in children and adolescents. These childhood periodic syndromes are common precursors of migraine. Phenotypes are alternating hemiplegia of childhood, benign paroxysmal torticollis, benign paroxysmal vertigo of childhood, alternating hemiplegia in childhood, Alice in Wonderland syndrome, cyclic vomiting syndrome, acute confusional migraine and abdominal migraine. PMID:21431964

  12. Vulnerable Blood in High Risk Vascular Patients: Study Design and Methods

    PubMed Central

    McDermott, Mary M.; Greenland, Philip; Liu, Kiang; Tian, Lu; Green, David; Shah, Sanjiv J.; Huffman, Mark; Wilkins, John; Kibbe, Melina; Liao, Yihua; Huang, Chiang-Ching; Skelly, Christopher; Jacobs, Chad; McCarthy, Walter; Auerbach, Amanda; Lloyd-Jones, Donald

    2014-01-01

    BACKGROUND Basic research suggests that rapid increases in circulating inflammatory and hemostatic blood markers may trigger or indicate impending plaque rupture and coronary thrombosis, resulting in acute ischemic heart disease (IHD) events. However, these associations are not established in humans. METHODS AND RESULTS The Biomarker Risk Assessment in Vulnerable Outpatients (BRAVO) Study will determine whether levels of inflammatory and hemostatic biomarkers rapidly increase during the weeks prior to an acute IHD event in people with lower extremity peripheral artery disease (PAD). The BRAVO Study will determine whether biomarker levels measured immediately prior to an IHD event are higher than levels not preceding an IHD event; whether participants who experience an IHD event (cases) have higher biomarker levels immediately prior to the event and higher biomarker levels at each time point leading up to the IHD event than participants without an IHD event (controls); and whether case participants have greater increases in biomarkers during the months leading up to the event than controls. BRAVO enrolled 595 patients with PAD, a population at high risk for acute IHD events. After a baseline visit, participants returned every two months for blood collection, underwent an electrocardiogram to identify new silent myocardial infarctions, and were queried about new hospitalizations since their prior study visit. Mortality data were also collected. Participants were followed prospectively for up to three years. CONCLUSIONS BRAVO results will provide important information about the pathophysiology of IHD events and may lead to improved therapies for preventing IHD events in high-risk patients. PMID:24721480

  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. 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.

  15. 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

  16. 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

  17. 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.

  18. 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

  19. 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.

  20. [Anesthesiological management of the high-risk surgical patient].

    PubMed

    Bertoldi, G; Avalle, M

    1980-03-01

    Evaluation of the anaesthesiological risk in surgical patients is described and an account is given of results obtained with an association of ketamin and NLA II in 57 high-risk patients subjected to general surgical management.

  1. Contemporary therapeutic options for children with high risk neuroblastoma.

    PubMed

    Sterba, J

    2002-01-01

    Despite the use of aggressive chemotherapy, stage 4 high risk neuroblastoma still has a very poor prognosis, which is estimated at 25%. Therefore, novel treatment approaches are needed. Increasing number of reports has been concerned with the use of novel treatment modalities. Literature regarding intensive induction, local therapy, myeloablative therapy and immunotherapy and biotherapy was reviewed in order to draw conclusions and recommendations for the management of children with high risk neuroblastic tumors.

  2. Lenalidomide Maintenance for High Risk Multiple Myeloma after Allogeneic Hematopoietic Cell Transplantation

    PubMed Central

    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.

    2016-01-01

    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 1–21 of 28 days cycles, with intra-patient 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 2009–2012. The median time from alloHCT to LEN initiation was 96 days (66–171 days). Eleven patients (37%) completed maintenance and 10 mg daily was the most commonly delivered dose (44%).Most common reasons for discontinuation were aGVHD (37%) and disease progression (37%). Cumulative incidence of grades III–IV acute GVHD from time of initiation of Len was 17%. Outcomes at 18 months after initiation of maintenance were MM progression, 28%; transplant related mortality, 11%; and progression-free and overall survival, 63% and 78%, respectively. The use of LEN post alloHCT is feasible at lower doses, although associated with a 38% incidence of aGVHD. Survival outcomes observed in this high risk MM population warrant further study of this approach. PMID:24769014

  3. Childhood Leukemia

    MedlinePlus

    ... leukemia, having certain genetic disorders and having had radiation or chemotherapy. Treatment often cures childhood leukemia. Treatment options include chemotherapy, other drug therapy and radiation. In some cases bone marrow and blood stem ...

  4. Childhood mortality after a high dose of vitamin A in a high risk population.

    PubMed Central

    Daulaire, N. M.; Starbuck, E. S.; Houston, R. M.; Church, M. S.; Stukel, T. A.; Pandey, M. R.

    1992-01-01

    OBJECTIVES--To determine whether a single high dose of vitamin A given to all children in communities with high mortality and malnutrition could affect mortality and to assess whether periodic community wide supplementation could be readily incorporated into an ongoing primary health programme. DESIGN--Opportunistic controlled trial. SETTING--Jumla district, Nepal. SUBJECTS--All children aged under 5 years; 3786 in eight subdistricts given single dose of vitamin A and 3411 in remaining eight subdistricts given no supplementation. MAIN OUTCOME MEASURES--Mortality and cause of death in the five months after supplementation. RESULTS--Risk of death for children aged 1-59 months in supplemented communities was 26% lower (relative risk 0.74, 95% confidence interval 0.55 to 0.99) than in unsupplemented communities. The reduction in mortality was greatest among children aged 6-11 months: death rate (deaths/1000 child years at risk) was 133.8 in supplemented children and 260.8 in unsupplemented children (relative risk 0.51, 0.30 to 0.89). The death rate from diarrhoea was also reduced (63.5 supplemented v 97.5 unsupplemented; relative risk 0.65, 0.44 to 0.95). The extra cost per death averted was about $11. CONCLUSION--The results support a role for Vitamin A in increasing child survival. The supplementation programme was readily integrated with the ongoing community health programme at little extra cost. PMID:1739794

  5. Treatment of high-risk neuroblastoma with anti-GD2 antibodies.

    PubMed

    Castel, Victoria; Segura, Vanessa; Cañete, Adela

    2010-12-01

    Anticancer monoclonal antibodies (mAbs) targeting specific antigens on the tumour surface are increasingly being applied in cancer treatment. Potential advantages include long half-life, low toxicity, high affinity and specificity. In order to develop novel immune therapies for high-risk cancers, finding tumour targets that are not widely shared by normal cells is a goal. GD2-disialoganglioside is one of them. It is expressed on the surface of a variety of tumours with no curative therapies for patients with advanced disease. In childhood, neuroblastoma is the most common GD2-expressing tumour. Because of this tumour-selective expression, it is an attractive target for tumour-specific therapies such as antibody therapy. Over the last two decades, several anti-GD2 antibodies have been developed. To reduce both toxicity and development of human anti-mouse antibodies (HAMA), research efforts have primarily focused on exploring anti-GD2 antibodies that substitute mouse components by human ones. This review will examine antibodies currently undergoing clinical testing as well as the most recent advances to improve antibody therapy for patients with high-risk neuroblastoma.

  6. Innovation of High-risk Infants Follow-up Surveillance System in Iran

    PubMed Central

    Jodeiry, Behzad; Heidarzadeh, Mohammad; Mirnia, Kayvan; Akrami, Forouzan; Heidarabadi, Seifoallah; Ebadi, Ali

    2015-01-01

    Background: Early childhood development is one of the most social determinants of health that must be notified in order to reducing social gap and inequity. In spite of increasingly developing intensive neonatal care wards and decreasing neonatal mortality rate, there is no follow-up surveillance system to identify high-risk infants (HRI) and their health problems for timely intervention after discharge. This study was carried out to design and pilot high-risk infant follow-ups (HRIFs) surveillance system, in Alzahra Hospital, a tertiary level center of Tabriz University of Medical Sciences (TUOMS), in 2012–2013. Methods: In this qualitative research after studying international documents, consensus about criteria of HRIs accomplished by focus group discussion. Then, Delphi agreement technique was used to finalizing assessment timetable. In the second phase, we piloted the designed surveillance system in Alzahra Hospital, a tertiary level center of TUOMS. Pilot study was implemented by follow-up team organized in designed model at the first phase of the study. Then, the findings of the pilot study were being assessed by an expert panel. If the members agreed on made decisions, they were being placed on the agenda of the national committee of development care of newborns for final approval. Results: High-risk infants follow-up surveillance system was designed in following steps: Defining of evidence-based criteria of HRIs, organizing the follow-up team, regulating the organs and neurodevelopment assessment timetable, publishing a health certificate notebook for HRIs, and designing Access database software for data collection, report and evaluation. Conclusions: We designed and piloted HRIFs surveillance system, so this system was institutionalized in Alzahra Hospital, finally. It can be prepared to apply in the whole country, after detecting the quantitative outcomes and developing the program in East Azarbijan. PMID:25969705

  7. 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…

  8. 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

  9. 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

  10. Dasatinib and Combination Chemotherapy in Treating Young Patients With Newly Diagnosed Acute Lymphoblastic Leukemia

    ClinicalTrials.gov

    2016-09-08

    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

  11. High-risk neuroblastoma: a therapy in evolution.

    PubMed

    Fong, Abraham; Park, Julie R

    2009-11-01

    High-risk neuroblastoma remains a therapeutic challenge for pediatric oncologists. It is becoming increasingly evident that conventional chemotherapeutics are approaching or perhaps have already attained their maximum therapeutic potential. The focus of this review is to summarize current therapies and bring to light some of the novel strategies for treating high-risk neuroblastoma. These rationally designed therapies include molecular- and immune-targeted agents in an attempt to exploit the biology of the neuroblastoma cell. These novel therapies are likely to pose a whole new set of challenges and questions and emphasize the need for continued enrollment of patients in therapeutic studies.

  12. 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

  13. 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.

  14. 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…

  15. 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.…

  16. Early Identification of Educationally High Potential and High Risk Children.

    ERIC Educational Resources Information Center

    Keogh, Barbara K.; Smith, Carol E.

    Early identification of educationally high potential and high risk children was investigated by following the same 49 children from kindergarten entrance through grade five of a regular school program. Kindergarten predictive measures were the Bender Gestalt Test and teachers' evaluations; follow-up measures were yearly standard achievement test…

  17. Genomic analysis of high-risk smoldering multiple myeloma

    PubMed Central

    López-Corral, Lucía; Mateos, María Victoria; Corchete, Luis A.; Sarasquete, María Eugenia; de la Rubia, Javier; de Arriba, Felipe; Lahuerta, Juan-José; García-Sanz, Ramón; San Miguel, Jesús F.; Gutiérrez, Norma C.

    2012-01-01

    Smoldering myeloma is an asymptomatic plasma cell dyscrasia with a heterogeneous propensity to progress to active myeloma. In order to investigate the biology of smoldering myeloma patients with high risk of progression, we analyzed the genomic characteristics by FISH, SNP-arrays and gene expression profile of a group of patients with high-risk smoldering myeloma included in a multicenter randomized trial. Chromosomal abnormalities detected by FISH and SNP-arrays at diagnosis were not associated to risk of progression to symptomatic myeloma. However, the overexpression of four SNORD genes (SNORD25, SNORD27, SNORD30 and SNORD31) was correlated with shorter time to progression (P<0.03). When plasma cells from high-risk smoldering patients who progressed to symptomatic myeloma were sequentially analyzed, newly acquired lesions together with an increase in the proportion of plasma cells carrying a given abnormality were observed. These findings suggest that gene expression profiling is a valuable technique to identify smoldering myeloma patients with high risk of progression. (Clinical Trials NCT00443235) PMID:22331267

  18. 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.

  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. Intervening with High-Risk Families via Infant Daycare.

    ERIC Educational Resources Information Center

    Ramey, Craig T.; Farran, Dale C.

    A longitudinal study was conducted at the Frank Porter Graham Center NC to explore the use of educational day care and related services as a mechanism for preparing socially disadvantaged children for success in later public schooling. Infant children of mothers who met a criterion score on a high risk index were randomly assigned to either an…

  1. Identification of High Risk Students from Matriculation Information.

    ERIC Educational Resources Information Center

    Sandusky, Sam T.

    A study was conducted at Sacramento City College (California) to determine the possibility of identifying high-risk students from information available from applications, assessment results, transcripts, and college enrollment data. Fall 1985 grade point averages (GPA) and progress percentages were used for high or low risk determination. Study…

  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. Diagnosis and Management of High Risk Group for Gastric Cancer

    PubMed Central

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval. PMID:25547086

  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. Prospective screening for deep vein thrombosis in high risk patients.

    PubMed

    Barnes, R W

    1977-08-01

    In 257 patients undergoing total hip replacement, gastric bypass for morbid obesity, major abdominal surgery, and major leg amputation, Doppler ultrasonic screening revealed only five instances of deep vein thrombosis. The present study suggests that Doppler screening of high risk patients is a useful alternative to routine anticoagulant prophylaxis of venous thromboembolic disease.

  7. [USA approval of high-risk medical device].

    PubMed

    Chang, Yongheng

    2013-03-01

    During the practice of supervision and management of medical device in different countries, the strict regulatory and needs of the program by the regulations is to be determined by the risk level of the medical equipment. This paper briefly describes the regulatory requirements of the United States to enter the market for high-risk medical device. PMID:23777072

  8. Diagnosis and management of high risk group for gastric cancer.

    PubMed

    Yoon, Hyuk; Kim, Nayoung

    2015-01-01

    Gastric cancer is associated with high morbidity and mortality worldwide. To reduce the socioeconomic burden related to gastric cancer, it is very important to identify and manage high risk group for gastric cancer. In this review, we describe the general risk factors for gastric cancer and define high risk group for gastric cancer. We discuss strategies for the effective management of patients for the prevention and early detection of gastric cancer. Atrophic gastritis (AG) and intestinal metaplasia (IM) are the most significant risk factors for gastric cancer. Therefore, the accurate selection of individuals with AG and IM may be a key strategy for the prevention and/or early detection of gastric cancer. Although endoscopic evaluation using enhanced technologies such as narrow band imaging-magnification, the serum pepsinogen test, Helicobacter pylori serology, and trefoil factor 3 have been evaluated, a gold standard method to accurately select individuals with AG and IM has not emerged. In terms of managing patients at high risk of gastric cancer, it remains uncertain whether H. pylori eradication reverses and/or prevents the progression of AG and IM. Although endoscopic surveillance in high risk patients is expected to be beneficial, further prospective studies in large populations are needed to determine the optimal surveillance interval.

  9. Biochemical profile and outcome in normal and high risk subjects.

    PubMed

    Vijayalaxmi, K G; Urooj, Asna

    2009-07-01

    The present study was carried out to assess the biochemical profile and outcome of pregnancy and study the adverse consequences if any, among normal and high risk pregnant women. The study group included 182 normal and 168 high risk cases attending to private and Government Hospitals in Bangalore. The high risk groups were: Pregnancy induced hypertension (PIH), gestational diabetes mellitus (GDM), Adolescents and anemic cases. Lipid peroxidation was enhanced in PIH and GDM groups (5.56 nmol/ml and 3.98 nmol/ml) MDA values as compared to other groups. Vitamin E levels were significantly (p< 0.05) lower in PIH group (0.38 mg/dl) as compared to other groups. Caesarean as a mode of delivery indicating more number of complications were higher among GDM (61.9%) followed by PIH group. Incidences of low birth weight were observed more in PIH group. The study revealed occurrence of oxidative stress and adverse outcome among high risk pregnancy groups. PMID:23105848

  10. 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

  11. Female seafarers adopt the high risk lifestyle of male seafarers

    PubMed Central

    Hansen, H. L.; Jensen, J.

    1998-01-01

    OBJECTIVE: To study the mortality of women in an occupation known to have a high mortality among men. METHODS: A total of 6788 female seafarers of all job categories who had been employed on Danish merchant ships, passenger ships, and privately owned ferries between 1986 and 1993, were followed up until the end of 1993. RESULTS: Standardised mortality ratio (SMR) was 1.20 (95% confidence interval (95% CI) 0.89 to 1.58) for all causes of death and job categories together. For women in traditionally male jobs, SMR was 2.82 (1.41- 5.05), whereas galley and catering staff had SMRs close to the general female population. The high mortality among women in traditional male jobs could be explained by a high risk of fatal accidents including occupational accidents. In the whole cohort, there were fewer deaths from natural causes than expected but an excess risk of death due to lung cancer, heart diseases, and non-natural deaths. CONCLUSION: The increased mortality could primarily be explained by an excess risk of fatal accidents and suicide. Especially, female seafarers entering traditional male jobs had a high risk of fatal accidents, not only at sea but also ashore. An excess risk of dying of lung cancer and heart diseases probably reflects a high tobacco consumption. Female seafarers are probably influenced by their occupation towards hazardous behaviour and a high risk lifestyle but people with a high risk lifestyle may also be attracted by or forced into high risk jobs such as traditional male jobs at sea.   PMID:9536163

  12. 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

  13. Appalachian Childhood.

    ERIC Educational Resources Information Center

    Arnow, Pat, Ed.; Cheek, Pauline, Ed.

    1987-01-01

    This magazine offers interviews, short stories and articles with a general focus on childhood in Appalachia. Two interviews include: "Creative Response to Life-Pauline Cheek," by Jane Harris Woodside, and "Insights and Experience: A Talk with Eliot Wigginton," by Pauline Binkley Cheek. Short stories include: "Thief in the Night," by Jan Barnett;…

  14. Childhood Obesity

    ERIC Educational Resources Information Center

    Yuca, Sevil Ari, Ed.

    2012-01-01

    This book aims to provide readers with a general as well as an advanced overview of the key trends in childhood obesity. Obesity is an illness that occurs due to a combination of genetic, environmental, psychosocial, metabolic and hormonal factors. The prevalence of obesity has shown a great rise both in adults and children in the last 30 years.…

  15. Childhood obesity.

    PubMed

    Strauss, R

    1999-01-01

    Approximately 10% of children are obese. Twin and adoption studies demonstrate a large genetic component to obesity, especially in adults. However, the increasing prevalence of obesity over the last 20 years can only be explained by environmental factors. In most obese individuals, no measurable differences in metabolism can be detected. Few children engage in regular physical activity. Obese children and adults uniformly underreport the amount of food they eat. Obesity is particularly related to increased consumption of high-fat foods. BMI is a quick and easy way to screen for childhood obesity. Treating childhood obesity relies on positive family support and lifestyle changes involving the whole family. Food preferences are influenced early by parental eating habits, and when developed in childhood, they tend to remain fairly constant into adulthood. Children learn to be active or inactive from their parents. In addition, physical activity (or more commonly, physical inactivity) habits that are established in childhood tend to persist into adulthood. Weight loss is usually followed by changes in appetite and metabolism, predisposing individuals to regain their weight. However, when the right family dynamics exist--a motivated child with supportive parents--long-term success is possible.

  16. Second Childhood.

    ERIC Educational Resources Information Center

    Arluke, Arnold; Levin, Jack

    1982-01-01

    Ageism (unfair stereotyping of older adults), deeply embedded in the culture of 20th-century America, is reinforced by television and newspapers. The media depict old people as rigid, meddlesome, sexless, conservative, unhealthy, and forgetful. Most pernicious of all old age stereotypes is that of second childhood. Popular culture portrays…

  17. 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.

  18. Outcome in 146 patients with paediatric acute myeloid leukaemia treated according to the AML99 protocol in the period 2003-06 from the Japan Association of Childhood Leukaemia Study.

    PubMed

    Imamura, Toshihiko; Iwamoto, Shotaro; Kanai, Rie; Shimada, Akira; Terui, Kiminori; Osugi, Yuko; Kobayashi, Ryoji; Tawa, Akio; Kosaka, Yoshiyuki; Kato, Koji; Hori, Hiroki; Horibe, Keizo; Oda, Megumi; Adachi, Souichi

    2012-10-01

    The acute myeloid leukaemia (AML) 99 trial conducted previously in Japan for the treatment of de novo paediatric AML showed excellent results, with a 5-year overall survival (OS) and event-free survival (EFS) of 75·6% and 61·6%, respectively. To examine reproducibility of these results in another cohort, the outcome of 146 newly diagnosed AML paediatric patients prospectively registered in the Japan Association of Childhood Leukaemia Study (JACLS) from 2003 to 2006 was compared to that of 240 patients in the original AML 99 clinical trial. The 5-year EFS and OS achieved in the new cohort was 66·7 ± 4·0% and 77·7 ± 8·0% respectively, which were comparable to those obtained in the original AML 99 clinical trial, although less frequent core-binding factor (CBF) AML (29·5% vs. 37%) and an almost equal frequency of allogeneic haematopoietic stem cell transplantation (allo-HSCT) during first complete remission (16·5% vs. 19%) were observed. The 5-year EFS in patients with a normal karyotype (NK) (n = 35, 54·9 ± 15·1%) was inferior in the present cohort when compared to the original AML99 trial. This study confirmed the excellent outcome of the original AML99 protocol.

  19. Outcome of TCF3-PBX1 positive pediatric acute lymphoblastic leukemia patients in Japan: a collaborative study of Japan Association of Childhood Leukemia Study (JACLS) and Children's Cancer and Leukemia Study Group (CCLSG).

    PubMed

    Asai, Daisuke; Imamura, Toshihiko; Yamashita, Yuka; Suenobu, So-ichi; Moriya-Saito, Akiko; Hasegawa, Daiichiro; Deguchi, Takao; Hashii, Yoshiko; Endo, Mikiya; Hatakeyama, Naoki; Kawasaki, Hirohide; Hori, Hiroki; Horibe, Keizo; Yumura-Yagi, Keiko; Hara, Junichi; Watanabe, Arata; Kikuta, Atsushi; Oda, Megumi; Sato, Atsushi

    2014-06-01

    This study reviewed the clinical characteristics of 112 pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL) patients with TCF3-PBX1 fusion treated according to the Japan Association of Childhood Leukemia Study (JACLS) ALL02 protocol (n = 82) and Children's Cancer and Leukemia Study Group (CCLSG) ALL 2004 protocol (n = 30). The 3-year event-free survival (EFS) and overall survival (OS) rates were 85.4 ± 3.9% and 89.0 ± 3.5% in JACLS cohort, and the 5-year EFS and OS were 82.8 ± 7.0% and 86.3 ± 6.4% in CCLSG cohort, respectively, which are comparable to those reported in western countries. Conventional prognostic factors such as age at onset, initial white blood cell count, and National Cancer Institute risk have also no impact on OS in both cohorts. Surprisingly, the pattern of relapse in JACLS cohort, 9 of 82 patients, was unique: eight of nine patients relapsed during the maintenance phase and one patient had primary induction failure. However, bone marrow status and assessment of minimal residual disease on days 15 and 33 did not identify those patients. Interestingly, the two patients with IKZF1 deletion eventually relapsed in JACLS cohort, as did one patient in CCLSG cohort. International collaborative study of larger cohort is warranted to clarify the impact of the IKZF1 deletion on the poor outcome of TCF3-PBX1 positive BCP-ALL.

  20. 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

  1. Parenthood and Childhood in the Scandinavian Countries: Challenges of Responsibility.

    ERIC Educational Resources Information Center

    Jensen, An-Magritt

    1998-01-01

    Examines the impact of fertility, family changes, and employment trends on parenthood in Scandinavia. Maintains that the most vulnerable aspect of responsible parenthood is the privatization of the family and feminization of childhood. Parenthood as private choice may encourage societal nonresponsibility for children. The high risk of parental…

  2. A phase II trial of partially incompatible bone marrow transplantation for high-risk acute lymphoblastic leukaemia in children: prevention of graft rejection with anti-LFA-1 and anti-CD2 antibodies. Société Française de Greffe de Moelle Osseuse.

    PubMed

    Cavazzana-Calvo, M; Bordigoni, P; Michel, G; Esperou, H; Souillet, G; Leblanc, T; Stephan, J L; Vannier, J P; Mechinaud, F; Reiffers, J; Vilmer, E; Landman-Parker, J; Benkerrou, M; Baruchel, A; Pico, J; Bernaudin, F; Bergeron, C; Plouvier, E; Thomas, C; Wijdenes, J; Lacour, B; Blanche, S; Fischer, A

    1996-04-01

    Bone marrow transplantation (BMT) from matched sibling donors has been useful for the treatment of acute lymphoblastic leukaemia in children with a poor prognosis but is not available to more than two-thirds of patients who do not have a matched allogeneic donor. This study was undertaken to assess one strategy of marrow graft rejection prevention when alternative marrow sources such as HLA-phenoidentical unrelated volunteers and HLA-partially incompatible relatives were used. Results have been compared with two matched groups of children with the same risks factors and disease status who underwent HLA-genoidentical or autologous BMT. The conditioning regimen was the same for the three groups of patients; in the study group anti-LFA-1 and anti-CD2 monoclonal antibodies combined with T-cell depletion of the marrow was added to prevent graft rejection and graft-versus-host disease. Nineteen patients were included and followed for a median of 25 months (14 months to 3 years). Bone marrow engraftment occurred in 83% of the evaluable patients. Post-transplantation infectious diseases were the most frequent causes of death in the study group, occurring in 31% of patients. No fatal infections occurred in the two control groups. Post-transplantation relapse of leukaemia occurred in 26% of study group's patients, in 58% of autologous BMT control group's patients and 5% of HLA-genoidentical allogeneic group's patients. The event-free survival was 83% in the HLA-genoidentical control group, and 30% and 24% in the study group and in the autologous control group, respectively. In conclusion, a high rate of engraftment was achieved by the use of anti-LFA-1 and anti CD2 antibodies. Occurrence of a long-lasting immunodeficiency, however, led to a high incidence of lethal infections and relapses. Combined approaches are therefore to be investigated accelerating immune reconstitution after transplantations of T-depleted HLA partially incompatible marrow.

  3. 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 February and June of 2014. HRPSS was "forward-backward" translated from English to Greek. Principal axis factoring with promax rotation was used to test the factor structure of the HRPSS. Measures of state anxiety (STAI) and depressive symptoms (EPDS) were used to assess the convergent validity of the HRPSS. Exploratory factor analysis suggested three factors: concerns of pregnancy, movement restriction, and isolation and restriction of external activities. Construct validity was confirmed by computing correlations between the HRPSS and constructions of anxiety and depressive symptoms. Internal consistency reliability was satisfactory (α = 0.813). The original factor structure of the HRPSS was only partly replicated. The results of the exploratory factor analysis suggested that a three-factor solution instead of a two-factor solution would be the most adequate. The HRPSS is an appropriate measure for assessing the levels of concerns regarding pregnancy outcome, movement restriction, isolation, and external activity restrictions in Greek high-risk pregnant women.

  4. Treating childhood acute lymphoblastic leukaemia (ALL): summary of ten years' experience in Italy. ALL Steering Committee of the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP).

    PubMed

    Paolucci, G; Masera, G; Vecchi, V; Marsoni, S; Pession, A; Zurlo, M G

    1989-01-01

    Between 1976 and 1986, 2,093 children with ALL were enrolled in three consecutive generations of trials conducted by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP). A 50% event-free survival at 5 years was achieved overall in this population, approximately accounting for more than 50% of the entire childhood ALL population in Italy. Participation in the group protocols increased from the original seven founding centers to the current 37 institutions. Results in the standard population (non-T immunophenotype, non-FAB L3, and less than 50,000 white blood cells (WBC/ml) were considerably better with more recent, more aggressive protocols. The two major results in this population (N = 540) were a relatively low incidence (8% at 5 years) of central nervous system (CNS) relapse in the "good"-risk population (less than 10,000 WBC, ages 3-6 years, and FAB L1), without the use of cranial irradiation, and a projected 4-year disease-free interval for bone-marrow relapse of 80% in the "average"-risk group, where a three-drug reinduction program was adopted after consolidation. Overall, the event-free survival of the most recent generation (protocol 82, median follow-up time of 38 months) is 66% at 4 years (95% confidence limits [CL] 61-71). Based on these 10 years of experience, the general strategy of the group for the 90s is outlined and discussed.

  5. Planned Two-Fraction Proton Beam Stereotactic Radiosurgery for High-Risk Inoperable Cerebral Arteriovenous Malformations

    SciTech Connect

    Hattangadi, Jona A.; Chapman, Paul H.; Bussiere, Marc R.; Niemierko, Andrzej; Ogilvy, Christopher S.; Rowell, Alison; Daartz, Juliane; Loeffler, Jay S.; Shih, Helen A.

    2012-06-01

    Purpose: To evaluate patients with high-risk cerebral arteriovenous malformations (AVMs), based on eloquent brain location or large size, who underwent planned two-fraction proton stereotactic radiosurgery (PSRS). Methods and Materials: From 1991 to 2009, 59 patients with high-risk cerebral AVMs received two-fraction PSRS. Median nidus volume was 23 cc (range, 1.4-58.1 cc), 70% of cases had nidus volume {>=}14 cc, and 34% were in critical locations (brainstem, basal ganglia). Median AVM score based on age, AVM size, and location was 3.19 (range, 0.9-6.9). Many patients had prior surgery or embolization (40%) or prior PSRS (12%). The most common prescription was 16 Gy radiobiologic equivalent (RBE) in two fractions, prescribed to the 90% isodose. Results: At a median follow-up of 56.1 months, 9 patients (15%) had total and 20 patients (34%) had partial obliteration. Patients with total obliteration received higher total dose than those with partial or no obliteration (mean dose, 17.6 vs. 15.5 Gy (RBE), p = 0.01). Median time to total obliteration was 62 months (range, 23-109 months), and 5-year actuarial rate of partial or total obliteration was 33%. Five-year actuarial rate of hemorrhage was 22% (95% confidence interval, 12.5%-36.8%) and 14% (n = 8) suffered fatal hemorrhage. Lesions with higher AVM scores were more likely to hemorrhage (p = 0.024) and less responsive to radiation (p = 0.026). The most common complication was Grade 1 headache acutely (14%) and long term (12%). One patient developed a Grade 2 generalized seizure disorder, and two had mild neurologic deficits. Conclusions: High-risk AVMs can be safely treated with two-fraction PSRS, although total obliteration rate is low and patients remain at risk for future hemorrhage. Future studies should include higher doses or a multistaged PSRS approach for lesions more resistant to obliteration with radiation.

  6. Influence of Serum Leptin on Weight and Body Fat Growth in Children at High Risk for Adult Obesity

    PubMed Central

    Fleisch, Abby F.; Agarwal, Neha; Roberts, Mary D.; Han, Joan C.; Theim, Kelly R.; Vexler, Albert; Troendle, James; Yanovski, Susan Z.; Yanovski, Jack A.

    2007-01-01

    Objective Our objective was to examine serum leptin prospectively as a predictor of weight and body fat growth in children at high risk for adult obesity. We hypothesized that leptin measurements would be positively associated with increased growth of adipose tissue because children with high baseline leptin for their body fat mass have greater leptin resistance and thus would have greater susceptibility to weight gain. Methods Children ages 6–12 yr at high risk for adult obesity because of early-onset childhood overweight and/or parental overweight were recruited from 1996–2004. Growth in body mass index (BMI) was studied in 197 children, and growth in total body fat mass was examined in 149 children over an average follow-up interval of 4.4 yr (range, 1–8 yr). Longitudinal analyses accounted for sex, race, socioeconomic status, initial body composition, age, skeletal age, and physical activity and included all available interim visits for each individual so that a total of 982 subject visits were included in the analysis. Results At baseline, 43% of children studied were overweight (BMI ≥ 95th percentile); during follow-up, an additional 14% became overweight. Independent of initial body composition, baseline leptin was a statistically significant positive predictor of increased BMI (P = 0.0147) and increased total body fat mass (P < 0.007). Conclusions High serum leptin, independent of body fat, may be an indicator of increased leptin resistance, which predisposes children at high risk for adult obesity to somewhat greater growth in weight and body fat during childhood. PMID:17179198

  7. Aetiology of childhood leukaemia.

    PubMed

    Eden, Tim

    2010-06-01

    The acute leukaemias account for about 30% of all malignancy seen in childhood across the Western world. A peak incidence of precursor B cell ALL has emerged as socio-economic conditions have improved in countries worldwide. From twin studies and the use of neonatal blood spots it has been possible to back track the first initiating genetic events within critical haemopoietic cells to foetal development in utero for most precursor B cell ALL and some cases of AML. These events may occur as part of normal foetal development. Whether other factors (environmental or constitutional) are involved to increase the chance of these first genetic changes happening is unclear. For some leukaemias (e.g. infant MLL positive ALL) the first event appears adequate to create a malignant clone but for the majority of ALL and AML further 'genetic' changes are required, probably postnatal. Many environmental factors have been proposed as causative for leukaemia but only ionising irradiation and certain chemicals, e.g. benzene and cytotoxics (alkylators and topoisomerase II inhibitors) have been confirmed and then principally for acute myeloid leukaemia. It appears increasingly likely that delayed, dysregulated responses to 'common' infectious agents play a major part in the conversion of pre-leukaemic clones into overt precursor B cell ALL, the most common form of childhood leukaemia. Constitutional polymorphic alleleic variants in immune response genes (especially the HLA Class II proteins) and cytokines may play a role in determining the type of immune response. High penetrance germ-line mutations are involved in only about 5% of childhood leukaemias (more in AML than ALL). There is little evidence to support any role of viral transformation in causation, unlike in animals. Other environmental factors for which some evidence exists include non-ionising electromagnetic radiation and electric fields, although their mode of action in leukaemogenesis remains unclear. There is no single

  8. 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

  9. Pragmatic fluid optimization in high-risk surgery patients: when pragmatism dilutes the benefits.

    PubMed

    Reuter, Daniel A

    2012-01-31

    There is increasing evidence that hemodynamic optimization by fluid loading, particularly when performed in the early phase of surgery, is beneficial in high-risk surgery patients: it leads to a reduction in postoperative complications and even to improved long-term outcome. However, it is also true that goal- directed strategies of fluid optimization focusing on cardiac output optimization have not been applied in the clinical routine of many institutions. Reasons are manifold: disbelief in the level of evidence and on the accuracy and practicability of the required monitoring systems, and economics. The FOCCUS trial examined perioperative fluid optimization with a very basic approach: a standardized volume load with 25 ml/kg crystalloids over 6 hours immediately prior to scheduled surgery in high-risk patients. The hypothesis was that this intervention would lead to a compensation of preoperative fluid deficit caused by overnight fasting, and would result in improved perioperative fluid homeostasis with less postoperative complications and earlier hospital discharge. However, the primary study endpoints did not improve significantly. This observation points towards the facts that: firstly, the differentiation between interstitial fluid deficit caused by fasting and intravascular volume loss due to acute blood loss must be recognized in treatment strategies; secondly, the type of fluid replacement may play an important role; and thirdly, protocolized treatment strategies should also always be tailored to suit the patients' individual needs in every individual clinical situation.

  10. Identifying high-risk areas of bacillary dysentery and associated meteorological factors in Wuhan, China.

    PubMed

    Li, Zhenjun; Wang, Ligui; Sun, Weige; Hou, Xuexin; Yang, Haiyan; Sun, Lina; Xu, Shuai; Sun, Qiangzheng; Zhang, Jingshan; Song, Hongbin; Lin, Hualiang

    2013-11-21

    Spatial distribution of bacillary dysentery incidence was mapped at the district level in Wuhan, China. And a generalized additive time series model was used to examine the effect of daily weather factors on bacillary dysentery in the high-risk areas, after controlling for potential confounding factors. Central districts were found to be the high-risk areas. The time series analysis found an acute effect of meteorological factors on bacillary dysentery occurrence. A positive association was found for mean temperature (excess risk (ER) for 1°C increase being 0.94% (95% confidence interval (CI): 0.46% to 1.43% on the lag day 2), while a negative effect was observed for relative humidity and rainfall, the ER for 1% increase in relative humidity was -0.21% (95% CI: -0.34% to -0.08%), and the ER for 1 mm increase in rainfall was -0.23% (95% CI: -0.37% to -0.09%). This study suggests that bacillary dysentery prevention and control strategy should consider local weather variations.

  11. Overcoming the Odds: High Risk Children from Birth to Adulthood.

    ERIC Educational Resources Information Center

    Werner, Emmy E.; Smith, Ruth S.

    The lives of 505 individuals born in 1955 on the island of Kauai (Hawaii) were followed from the prenatal period to adulthood to elucidate their resilience in the face of childhood adversity or their recovery in later years. The Kauai Longitudinal Study monitored the impact of a variety of biological and psychosocial risk factors, stressful life…

  12. Applying the lessons of high risk industries to health care.

    PubMed

    Hudson, P

    2003-12-01

    High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks. PMID:14645741

  13. Applying the lessons of high risk industries to health care

    PubMed Central

    Hudson, P

    2003-01-01

    High risk industries such as commercial aviation and the oil and gas industry have achieved exemplary safety performance. This paper reviews how they have managed to do that. The primary reasons are the positive attitudes towards safety and the operation of effective formal safety management systems. The safety culture provides an important explanation of why such organisations perform well. An evolutionary model of safety culture is provided in which there is a range of cultures from the pathological through the reactive to the calculative. Later, the proactive culture can evolve towards the generative organisation, an alternative description of the high reliability organisation. The current status of health care is reviewed, arguing that it has a much higher level of accidents and has a reactive culture, lagging behind both high risk industries studied in both attitude and systematic management of patient risks. PMID:14645741

  14. [Artificial circulation in high-risk percutaneous coronary interventions].

    PubMed

    Bazylev, V V; Evdokimov, M E; Pantiukhina, M A; Morozov, Z A

    2016-01-01

    In their everyday practical clinical work cardiovascular surgeons sometimes have to deal with patients at extremely high risk of both percutaneous coronary interventions (PCIs) and direct myocardial revascularization. A method of choice in such situations may become a PCI supported by artificial circulation (AC), for which foreign and Russian authors propose using systems of prolonged extracorporeal membrane oxygenation (ECMO). The present work was aimed at sharing our experience with using standard systems of AC and their modifications (mini-circuit systems) for performing high-risk PCIs. Between October 2011 and November 2014, PCIs supported by artificial circulation were performed in a total of ten patients. All had extremely high risk of PCI due to coronary artery lesions [subocclusion of the trunk of the left coronary artery (LCA) combined with occlusion or significant stenosis of the right coronary artery (RCA)], concomitant pathology (obesity, diabetes mellitus, age, etc.) or critical state (circulatory arrest, resuscitating measures). Three patients during PCI developed ventricular fibrillation and one patient suffered an episode of asystole. All cardiac arrhythmias after restoration of the coronary blood flow disappeared spontaneously on the background of extracorporeal support. The only lethal outcome was registered during emergency PCI in a female patient admitted to the roentgen-operating room in the state of clinical death, on the background of continuing resuscitation measures. The presented methods of assisted circulation based on the standard AC systems and modification thereof (mini-circuit system) proved efficient. They make it possible to perform high-risk PCIs, including in clinics having neither appropriate equipment nor experience in ECMO. PMID:27626258

  15. High-risk energy plans yield low rewards

    NASA Astrophysics Data System (ADS)

    Gwynne, Peter

    2009-10-01

    Scientists have complained that a new research body run by the US Department of Energy (DOE) is suffering from management problems and is rejecting funding proposals without stating why. The DOE's Advanced Research Projects Agency-Energy (ARPA-E) - created in 2007 - is designed to fund high-risk, high-payoff research and development projects in energy. However, the agency, which received its first budget in April, has so far turned down almost 95% of proposals after the first round.

  16. Next-generation personalised medicine for high-risk paediatric cancer patients - The INFORM pilot study.

    PubMed

    Worst, Barbara C; van Tilburg, Cornelis M; Balasubramanian, Gnana Prakash; Fiesel, Petra; Witt, Ruth; Freitag, Angelika; Boudalil, Miream; Previti, Christopher; Wolf, Stephan; Schmidt, Sabine; Chotewutmontri, Sasithorn; Bewerunge-Hudler, Melanie; Schick, Matthias; Schlesner, Matthias; Hutter, Barbara; Taylor, Lenka; Borst, Tobias; Sutter, Christian; Bartram, Claus R; Milde, Till; Pfaff, Elke; Kulozik, Andreas E; von Stackelberg, Arend; Meisel, Roland; Borkhardt, Arndt; Reinhardt, Dirk; Klusmann, Jan-Henning; Fleischhack, Gudrun; Tippelt, Stephan; Dirksen, Uta; Jürgens, Heribert; Kramm, Christof M; von Bueren, Andre O; Westermann, Frank; Fischer, Matthias; Burkhardt, Birgit; Wößmann, Wilhelm; Nathrath, Michaela; Bielack, Stefan S; Frühwald, Michael C; Fulda, Simone; Klingebiel, Thomas; Koscielniak, Ewa; Schwab, Matthias; Tremmel, Roman; Driever, Pablo Hernáiz; Schulte, Johannes H; Brors, Benedikt; von Deimling, Andreas; Lichter, Peter; Eggert, Angelika; Capper, David; Pfister, Stefan M; Jones, David T W; Witt, Olaf

    2016-09-01

    The 'Individualized Therapy for Relapsed Malignancies in Childhood' (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of 'intermediate' or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase-mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors

  17. Next-generation personalised medicine for high-risk paediatric cancer patients - The INFORM pilot study.

    PubMed

    Worst, Barbara C; van Tilburg, Cornelis M; Balasubramanian, Gnana Prakash; Fiesel, Petra; Witt, Ruth; Freitag, Angelika; Boudalil, Miream; Previti, Christopher; Wolf, Stephan; Schmidt, Sabine; Chotewutmontri, Sasithorn; Bewerunge-Hudler, Melanie; Schick, Matthias; Schlesner, Matthias; Hutter, Barbara; Taylor, Lenka; Borst, Tobias; Sutter, Christian; Bartram, Claus R; Milde, Till; Pfaff, Elke; Kulozik, Andreas E; von Stackelberg, Arend; Meisel, Roland; Borkhardt, Arndt; Reinhardt, Dirk; Klusmann, Jan-Henning; Fleischhack, Gudrun; Tippelt, Stephan; Dirksen, Uta; Jürgens, Heribert; Kramm, Christof M; von Bueren, Andre O; Westermann, Frank; Fischer, Matthias; Burkhardt, Birgit; Wößmann, Wilhelm; Nathrath, Michaela; Bielack, Stefan S; Frühwald, Michael C; Fulda, Simone; Klingebiel, Thomas; Koscielniak, Ewa; Schwab, Matthias; Tremmel, Roman; Driever, Pablo Hernáiz; Schulte, Johannes H; Brors, Benedikt; von Deimling, Andreas; Lichter, Peter; Eggert, Angelika; Capper, David; Pfister, Stefan M; Jones, David T W; Witt, Olaf

    2016-09-01

    The 'Individualized Therapy for Relapsed Malignancies in Childhood' (INFORM) precision medicine study is a nationwide German program for children with high-risk relapsed/refractory malignancies, which aims to identify therapeutic targets on an individualised basis. In a pilot phase, reported here, we developed the logistical and analytical pipelines necessary for rapid and comprehensive molecular profiling in a clinical setting. Fifty-seven patients from 20 centers were prospectively recruited. Malignancies investigated included sarcomas (n = 25), brain tumours (n = 23), and others (n = 9). Whole-exome, low-coverage whole-genome, and RNA sequencing were complemented with methylation and expression microarray analyses. Alterations were assessed for potential targetability according to a customised prioritisation algorithm and subsequently discussed in an interdisciplinary molecular tumour board. Next-generation sequencing data were generated for 52 patients, with the full analysis possible in 46 of 52. Turnaround time from sample receipt until first report averaged 28 d. Twenty-six patients (50%) harbored a potentially druggable alteration with a prioritisation score of 'intermediate' or higher (level 4 of 7). Common targets included receptor tyrosine kinases, phosphoinositide 3-kinase-mammalian target of rapamycin pathway, mitogen-activated protein kinase pathway, and cell cycle control. Ten patients received a targeted therapy based on these findings, with responses observed in some previously treatment-refractory tumours. Comparative primary relapse analysis revealed substantial tumour evolution as well as one case of unsuspected secondary malignancy, highlighting the importance of re-biopsy at relapse. This study demonstrates the feasibility of comprehensive, real-time molecular profiling for high-risk paediatric cancer patients. This extended proof-of-concept, with examples of treatment consequences, expands upon previous personalised oncology endeavors

  18. Cyclophosphamide and Busulfan Followed by Donor Stem Cell Transplant in Treating Patients With Myelofibrosis, Acute Myeloid Leukemia, or Myelodysplastic Syndrome

    ClinicalTrials.gov

    2014-04-03

    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); Childhood Acute Myeloid Leukemia in Remission; Childhood Myelodysplastic Syndromes; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Myelodysplastic Syndrome With Isolated Del(5q); Polycythemia Vera; Previously Treated Myelodysplastic Syndromes; Primary Myelofibrosis; Recurrent Adult Acute Myeloid Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Secondary Acute Myeloid Leukemia; Secondary Myelodysplastic Syndromes; Secondary Myelofibrosis; Untreated Adult Acute Myeloid Leukemia; Untreated Childhood Acute Myeloid Leukemia and Other Myeloid Malignancies

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

    PubMed Central

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

    2010-01-01

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

  20. Long-term Results Of the Pediatric Oncology Group Studies For Childhood Acute Lymphoblastic Leukemia 1984-2001: A Report From The Children’s Oncology Group

    PubMed Central

    Salzer, Wanda L.; Devidas, Meenakshi; Carroll, William L.; Winick, Naomi; Pullen, Jeanette; Hunger, Stephen P.; Camitta, Bruce A.

    2015-01-01

    From 1984-2001, the Pediatric Oncology Group (POG) conducted 12 acute lymphoblastic leukemia (ALL) studies. 10-year event free survival (EFS) for patients >12 months of age with B-precursor ALL on Acute Leukemia in Children 14, 15, and 16 series were 66.7 ± 1.2%, 68.1 ± 1.4% and 73.2 ± 2.1%, respectively. Intermediate dose methotrexate (ID MTX; 1 g/m2) improved outcomes for standard risk patients (10-year EFS 77.5 ± 2.7% vs. 66.3 ± 3.1% for oral MTX). Neither MTX intensification (2.5 g/m2) nor addition of cytosine arabinoside/daunomycin/teniposide improved outcomes for higher risk patients. Intermediate dose mercaptopurine (1 g/m2) failed to improve outcomes for either group. 10-year EFS for patients with T-cell ALL, POG 8704 and 9404, were 49.1 ± 3.1% and 72.2 ± 4.7%, respectively. Intensive asparaginase (10-year EFS 61.8% vs 42.7%) and high dose MTX (5 g/m2) (10-year EFS 78.0% vs. 65.8%) improved outcomes. There was a non-significant improvement in EFS for infants (10-year EFS 17.7 ± 7.2% to 31.9 ± 8.3%). Prognostic indicators for B-precursor ALL were age and WBC at diagnosis, gender, central nervous system disease, DNA index, and cytogenetic abnormalities. Only gender was prognostic in T-cell ALL. In infants, WBC and MLL translocation were linked to inferior outcome. PMID:20016527

  1. IKZF1 deletion is an independent prognostic marker in childhood B-cell precursor acute lymphoblastic leukemia, and distinguishes patients benefiting from pulses during maintenance therapy: results of the EORTC Children's Leukemia Group study 58951.

    PubMed

    Clappier, E; Grardel, N; Bakkus, M; Rapion, J; De Moerloose, B; Kastner, P; Caye, A; Vivent, J; Costa, V; Ferster, A; Lutz, P; Mazingue, F; Millot, F; Plantaz, D; Plat, G; Plouvier, E; Poirée, M; Sirvent, N; Uyttebroeck, A; Yakouben, K; Girard, S; Dastugue, N; Suciu, S; Benoit, Y; Bertrand, Y; Cavé, H

    2015-11-01

    The added value of IKZF1 gene deletion (IKZF1(del)) as a stratifying criterion in B-cell precursor acute lymphoblastic leukemia (BCP-ALL) is still debated. We performed a comprehensive analysis of the impact of IKZF1(del) in a large cohort of children (n=1223) with BCR-ABL1-negative BCP-ALL treated in the EORTC-CLG trial 58951. Patients with IKZF1(del) had a lower 8-year event-free survival (EFS, 67.7% versus 86.5%; hazard ratio (HR)=2.41; 95% confidence interval (CI)=1.75-3.32; P<0.001). Importantly, despite association with high-risk features such as high minimal residual disease, IKZF1(del) remained significantly predictive in multivariate analyses. Analysis by genetic subtype showed that IKZF1(del) increased risk only in the high hyperdiploid ALLs (HR=2.57; 95% CI=1.19-5.55; P=0.013) and in 'B-other' ALLs, that is, lacking classifying genetic lesions (HR=2.22; 95% CI=1.45-3.39; P<0.001), the latter having then a dramatically low 8-year EFS (56.4; 95% CI=44.6-66.7). Among IKZF1(del)-positive patients randomized for vincristine-steroid pulses during maintenance, those receiving pulses had a significantly higher 8-year EFS (93.3; 95% CI=61.3-99.0 versus 42.1; 95% CI=20.4-62.5). Thus, IKZF1(del) retains independent prognostic significance in the context of current risk-adapted protocols, and is associated with a dismal outcome in 'B-other' ALL. Addition of vincristine-steroid pulses during maintenance may specifically benefit to IKZF1(del) patients in preventing relapses.

  2. Postoperative Chemotherapy Followed by Conformal Concomitant Chemoradiotherapy in High-Risk Gastric Cancer

    SciTech Connect

    Quero, Laurent; Bouchbika, Zineb; Kouto, Honorine; Baruch-Hennequin, Valerie; Gornet, Jean-Marc; Munoz, Nicolas; Cojean-Zelek, Isabelle; Houdart, Remi; Panis, Yves; Valleur, Patrice; Aparicio, Thomas; Maylin, Claude; Hennequin, Christophe

    2012-06-01

    Purpose: To analyze the efficacy, toxicity, and pattern of relapse after adjuvant cisplatin-based chemotherapy followed by three-dimensional irradiation and concomitant LV5FU2 chemotherapy (high-dose leucovorin and 5-fluorouracil bolus plus continuous infusion) in the treatment of completely resected high-risk gastric cancer. Methods and Materials: This was a retrospective analysis of 52 patients with high-risk gastric cancer initially treated by total/partial gastrectomy and lymphadenectomy between January 2002 and June 2007. Median age was 54 years (range, 36-75 years). Postoperative treatment consisted of 5-fluorouracil and cisplatin chemotherapy. Adjuvant chemotherapy was followed by three-dimensional conformal radiotherapy in the tumor bed and regional lymph nodes at 4500 cGy/25 fractions in association with concomitant chemotherapy. Concomitant chemotherapy consisted of a 2-h infusion of leucovorin (200 mg/m Superscript-Two ) followed by a bolus of 5-fluorouracil (400 mg/m Superscript-Two ) and then a 44-h continuous infusion of 5-fluorouracil (2400-3600 mg/m Superscript-Two ) given every 14 days, for three cycles (LV5FU2 protocol). Results: Five-year overall and disease-free survival were 50% and 48%, respectively. Distant metastases and peritoneal spread were the most frequent sites of relapse (37% each). After multivariate analysis, only pathologic nodal status was significantly associated with disease-free and overall survival. Acute toxicities were essentially gastrointestinal and hematologic. One myocardial infarction and one pulmonary embolism were also reported. Eighteen patients had a radiotherapy program interruption because of acute toxicity. All patients but 2 have completed radiotherapy. Conclusion: Postoperative cisplatin-based chemotherapy followed by conformal radiotherapy in association with concurrent 5-fluorouracil seemed to be feasible and resulted in successful locoregional control.

  3. [Childhood hypertension].

    PubMed

    Takemura, Tsukasa

    2015-11-01

    For accurate diagnosis of childhood hypertension, selection of appropriate manchette size according to the child age and the circumstantial size of upper limb is essentially important. In addition, except for the emergency case of hypertension, repeated measurement of blood pressure would be desirable in several weeks interval. Recently, childhood hypertension might be closely related to the abnormality of maternal gestational period caused by the strict diet and the maternal smoking. Developmental Origins of Health and Disease(DOHaD) theory is now highlighted in the pathogenesis of adulthood hypertension. To prevent hypertension of small-for-date baby in later phase of life, maternal education for child nursing should be conducted. In children, secondary hypertension caused by renal, endocrinologic, or malignant disease is predominant rather than idiopathic hypertension. PMID:26619664

  4. Estimating the risk for late effects of therapy in children newly diagnosed with standard risk acute lymphoblastic leukemia using an historical cohort: A report from the Childhood Cancer Survivor Study

    PubMed Central

    Essig, Stefan; Li, Qiaozhi; Chen, Yan; Hitzler, Johann; Leisenring, Wendy; Greenberg, Mark; Sklar, Charles; Hudson, Melissa M; Armstrong, Gregory T; Krull, Kevin R; Neglia, Joseph P; Oeffinger, Kevin C; Robison, Leslie L; Kuehni, Claudia E; Yasui, Yutaka; Nathan, Paul C

    2014-01-01

    Summary Background Pediatric acute lymphoblastic leukemia (ALL) therapy has evolved such that the risk for late effects in ALL survivors treated on contemporary protocols is likely different from that observed in survivors treated in prior eras. We estimated the risk for late effects in children with standard-risk ALL treated in the current era using data from similarly treated members of the Childhood Cancer Survivor Study (CCSS) cohort. Methods The CCSS is a multi-centre North American study of five-year survivors of childhood cancer diagnosed between 1970 and1986. Cohort members were eligible for this analysis if they were aged 1·0–9·9 years at the time of ALL diagnosis and received therapy consistent with contemporary standard-risk ALL protocols. Outcomes were compared to a sibling cohort (n=2788) and the general United States population. Findings 556/5980 cohort members treated for ALL met the inclusion criteria. After a median follow up of 18·4 years (range 0·0–33·0) from cohort entry, 28/556 (5%) had died (standardized mortality ratio, 3·5; 95% CI, 2·3–5·0). Sixteen deaths were due to causes other than ALL recurrence. Among 556 survivors, six (1%) developed a subsequent malignant neoplasm (standardized incidence ratio, 2·6; 95% CI, 1·0–5·7). 107 subjects in each group would need to be followed for one year in order to observe one extra chronic health condition in the ALL group compared to the sibling group (95% CI, 81–193). 415 subjects in each group would need to be followed for one year to observe one extra severe, life-threatening or fatal condition in the ALL group (95% CI, 376–939) Survivors did not differ from siblings in their educational attainment, rate of marriage or independent living. Interpretation Overall, the expected prevalence of adverse long-term outcomes among children treated for standard risk ALL on contemporary protocols is low, but regular care from a knowledgeable primary care practitioner is warranted. Funding

  5. Donor Atorvastatin Treatment in Preventing Severe Acute GVHD After Nonmyeloablative Peripheral Blood Stem Cell Transplant in Patients With Hematological Malignancies

    ClinicalTrials.gov

    2016-04-28

    Aggressive Non-Hodgkin Lymphoma; Myelodysplastic/Myeloproliferative Neoplasm; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Aggressive Adult Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Myeloid Leukemia; Recurrent Chronic Lymphocytic Leukemia; Recurrent Diffuse Large B-Cell Lymphoma; Recurrent Hodgkin Lymphoma; Recurrent Mantle Cell Lymphoma; Recurrent Plasma Cell Myeloma; Waldenstrom Macroglobulinemia

  6. Blockade of BCL-2 proteins efficiently induces apoptosis in progenitor cells of high-risk myelodysplastic syndromes patients.

    PubMed

    Jilg, S; Reidel, V; Müller-Thomas, C; König, J; Schauwecker, J; Höckendorf, U; Huberle, C; Gorka, O; Schmidt, B; Burgkart, R; Ruland, J; Kolb, H-J; Peschel, C; Oostendorp, R A J; Götze, K S; Jost, P J

    2016-01-01

    Deregulated apoptosis is an identifying feature of myelodysplastic syndromes (MDS). Whereas apoptosis is increased in the bone marrow (BM) of low-risk MDS patients, progression to high-risk MDS correlates with an acquired resistance to apoptosis and an aberrant expression of BCL-2 proteins. To overcome the acquired apoptotic resistance in high-risk MDS, we investigated the induction of apoptosis by inhibition of pro-survival BCL-2 proteins using the BCL-2/-XL/-W inhibitor ABT-737 or the BCL-2-selective inhibitor ABT-199. We characterized a cohort of 124 primary human BM samples from MDS/secondary acute myeloid leukemia (sAML) patients and 57 healthy, age-matched controls. Inhibition of anti-apoptotic BCL-2 proteins was specifically toxic for BM cells from high-risk MDS and sAML patients, whereas low-risk MDS or healthy controls remained unaffected. Notably, ABT-737 or ABT-199 treatment was capable of targeting the MDS stem/progenitor compartment in high-risk MDS/sAML samples as shown by the reduction in CD34(+) cells and the decreased colony-forming capacity. Elevated expression of MCL-1 conveyed resistance against both compounds. Protection by stromal cells only partially inhibited induction of apoptosis. Collectively, our data show that the apoptotic resistance observed in high-risk MDS/sAML cells can be overcome by the ABT-737 or ABT-199 treatment and implies that BH3 mimetics might delay disease progression in higher-risk MDS or sAML patients.

  7. Autonomic dysfunction in subjects at high risk for Parkinson's disease.

    PubMed

    Liepelt-Scarfone, Inga; Pilotto, Andrea; Müller, Katharina; Bormann, Christian; Gauss, Katharina; Wurster, Isabel; Streffer, Johannes; Berg, Daniela

    2015-12-01

    Aim of this project was to evaluate autonomic dysfunction in subjects proposed to be at high risk to develop Parkinson's disease (PD) compared to control subjects and PD patients at different disease stages. Combinations of substantia nigra hyperechogenicity (SN+) assessed by transcranial ultrasound (TCS), hyposmia, lifetime prevalence of depression and mild PD-specific motor signs were used to identify subjects at high risk for motor Parkinson's disease (HR-PD). Supine and standing blood pressure (BP), hearth rate (HR), orthostatic, urinary, sexual and bowel symptoms were evaluated in HR-PD, healthy control subjects and PD patients, divided into mild and advanced stages. The study group consisted of 113 PD patients (mild PD n = 71, advanced PD, n = 42), 40 HR-PD individuals and 50 controls. Compared to controls, HR-PD subjects complained more often about urinary (p = 0.002) and bowel dysfunction (p = 0.001) and had a higher diastolic BP drop after standing (p = 0.01). The cumulative number of autonomic symptoms differentiated PD as well as HR-PD significantly from controls (p < 0.001). Advanced PD patients presented often and severe orthostatic symptoms, not significantly different from mild PD after concomitant medication correction. Our results support the presence of urinary and bowel dysfunction in subjects at high risk for motor PD. Presence and severity of orthostatic symptoms was higher during stages and increase in advanced stages, at least partly due to increase in dopaminergic and conflicting medication. Understanding the progression of non-motor aspects in PD might offer the possibility to use them as targets for disease-modifying therapies.

  8. New dimensions in the care of high risk pregnancy.

    PubMed

    Sanchez, P

    1989-01-01

    In June 1989, the past president of the Philippine Nurses Association spoke at the annual convention of the Maternal Child Nurses Association at the Children's Medical Center in Quezon City. She addressed maternal health and high risk pregnancies in the Philippines. The maternal mortality rate was 90/100,000 live births each year. It was 4-5 times higher among remote tribes such as the Muslims of Sulu than the national rate. 54% of maternal deaths were attributed to pregnancy complications especially eclampsia (28%). About 2 million women experienced pregnancy annually and almost 1 million had anemia or were malnourished. 20% of these 1 million women gave birth to low birth weight infants who were at high risk of death from infections. About 574,000 out of 1.4 million infants born annually were unwanted. 63% of pregnant women each year did not want any children. Nurses can play an important role to reduce suffering and death among mothers and infants if they practice good health teaching. For example, they can inform mothers about child spacing and birth limiting. They can also identify high risk pregnancies and refer them to other health professionals to manage them. In September 1987, the Philippines Department of Health sponsored a conference on maternal health. Participants made 6 resolutions. The 1st resolution was to consider maternal mortality an indicator of Health for All by year 2000. They also resolved to declare 1988-97 the Decade of Safe Motherhood which included the creation of a multisectoral task force under the Department of Health. The speaker concluded by encouraging Philippine nurses to resist the temptation to work abroad to make more money and instead stay in the Philippines to care for their own people.

  9. Air pollution exposure: Who is at high risk?

    NASA Astrophysics Data System (ADS)

    Peled, Ronit

    2011-04-01

    This article reviews the sub-population groups who are at high risk and first to be harmed by air pollution coming from anthropogenic combustions. Epidemiological studies from the last few decades contributed to the understanding of the different levels of susceptibility to air pollution. Older people and young infants, people who suffer from allergies, pulmonary and heart diseases, pregnant women and newborn babies, and deprived populations that suffer from low socio-economic status have all been described as populations at risk. A better understanding of the role of air pollution on large as well as specific populations' health, will promote a better protection policy.

  10. Teamwork in high-risk environments analogous to space

    NASA Technical Reports Server (NTRS)

    Kanki, Barbara G.

    1990-01-01

    Mountaineering expeditions combine a number of factors which make them potentially good analogs to the planetary exploration facet of long-duration space missions. A study of mountain climbing teams was conducted in order to evaluate the usefulness of the environment as a space analog and to specifically identify the factors and issues surrounding teamwork and 'successful' team performance in two mountaineering environments. This paper focuses on social/organizational factors, including team size and structure, leadership styles and authority structure which were found in the sample of 22 climb teams (122 individuals). The second major issue discussed is the construction of a valid performance measure in this high-risk environment.

  11. Embedded CMs work with high-risk patients.

    PubMed

    2014-01-01

    Care managers embedded in primary care clinics work with patients with high-risk diagnoses and multiple visits to the emergency department or hospital. Patients are identified though risk assessments, suggestions from inpatient case management, and requests from primary care clinicians. Care managers call patients before their clinic visits, look for gaps in care and find out patients' questions and concerns, sharing the information with the treating clinicians. Care managers follow patients for four weeks after their visit, helping them meet their health care goals and follow their treatment plan.

  12. [Acute Chest Pain].

    PubMed

    Gmür, Christian

    2016-02-17

    Acute chest pain is a frequent consultation reason in general practice as well as in emergency departments. With the help of history, physical examination, ECG, laboratory and newly developed risk scores, potentially life-threatening diseases and high-risk patients may be detected and treated early, quickly and cost-effectively. New biomarkers and their combination with risk scores can increase the negative predictive value to exclude certain diseases. PMID:26886697

  13. Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.

    PubMed

    Mora, Jaume

    2016-01-01

    Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy.

  14. Dinutuximab for the treatment of pediatric patients with high-risk neuroblastoma.

    PubMed

    Mora, Jaume

    2016-01-01

    Neuroblastoma (NB) is the most common extra cranial solid tumor of childhood, with 60% of patients presenting with high risk (HR) NB by means of clinical, pathological and biological features. The 5-year survival rate for HR-NB remains below 40%, with the majority of patients suffering relapse from chemorefractory tumor. Immunotherapy is the main strategy against minimal residual disease and clinical experience has mostly focused on monoclonal antibodies (MoAb) against the glycolipid disialoganglioside GD2. Three anti-GD2 antibodies have been tested in the clinic including murine 14G2a, human-mouse chimeric ch14.18 and 3F8. Anti-GD2 MoAb induces cellular cytoxicity against NB and is most effective when effector cells like natural killer cells, granulocytes and macrophages are amplified by cytokines. The combination of cytokines IL-2 and GM-CSF with the anti-GD2 MoAb ch14.18 (Dinutuximab) has shown a significant improvement in outcome for HR-NB. The FDA and EMA approved dinutuximab (Unituxin(R)) in 2015 for the treatment of patients with HR-NB who achieved at least a partial response after multimodality therapy. PMID:26934530

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

    ClinicalTrials.gov

    2016-07-08

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

  16. Progress in the management of childhood asthma

    PubMed Central

    Pensrichon, Rattana; Kurasirikul, Suruthai

    2012-01-01

    Asthma has become the most common chronic disease in childhood. Significant advances in epidemiological research as well as in therapy of pediatric asthma have been made over the past 2 decades. In this review, we look at certain aspects therapy of childhood asthma, both in the past and present. Literature review on allergen avoidance (including mites, cockroach and cat), intensive therapy with β2-agonists in acute asthma (administering via continuous nebulization and intravenous routes), a revisit of theophylline use and its action, the use of inhaled corticosteroids in various phases of childhood asthma and sublingual immunotherapy in asthma are examined. Recent facts and dilemmas of these treatments are identified along with expression of our opinions, particularly on points of childhood asthma in the Asia-Pacific, are made in this review. PMID:22348203

  17. Hyperparathyroidism After Irradiation for Childhood Malignancy

    SciTech Connect

    McMullen, Todd; Bodie, Greg; Gill, Anthony; Ihre-Lundgren, Catharina; Shun, Albert; Bergin, Mary; Stevens, Graham; Delbridge, Leigh

    2009-03-15

    Purpose: To examine the occurrence of hyperparathyroidism in a cohort of patients undergoing combined parathyroid and thyroid surgery after previous head-and-neck irradiation for childhood malignancy. Methods and Materials: This is a retrospective cohort study for the years 1996 to 2007. The study group comprised patients undergoing surgery in University of Sydney Endocrine Surgical Unit who had received previous head-and-neck irradiation in childhood and who were identified as having pathologic thyroid and parathyroid characteristics. Results: A total of 53 patients were identified in whom head-and-neck irradiation for the treatment of childhood malignancy had been documented. In each of the cases, thyroid disease was the primary reason for referral for surgery. Five of these patients (10%) were found to exhibit coexisting hyperparathyroidism. The latency period for hyperparathyroidism was less than 20 years in 4 of the 5 cases. There were four conventional parathyroid adenomas and one parathyroid lipoadenoma. All patients exhibited a significant decrease in postoperative calcium levels after surgery. Conclusions: To our knowledge, this is the first study to document the significant risk of hyperparathyroidism after radiation exposure for childhood malignancy. The timeframe for development of disease is much shorter than that published for individuals who have undergone irradiation for benign diseases. High doses of therapeutic radiation at a young age make childhood survivors of malignancy at especially high risk for developing hyperparathyroidism.

  18. Acute Intraoperative Pulmonary Aspiration

    PubMed Central

    Nason, Katie S.

    2015-01-01

    Synopsis Acute intraoperative aspiration is a potentially fatal complication with significant associated morbidity. Patients undergoing thoracic surgery are at increased risk for anesthesia-related aspiration, largely due to the predisposing conditions associated with this complication. Awareness of the risk factors, predisposing conditions, maneuvers to decrease risk and immediate management options by both the thoracic surgeon and the anesthesia team is imperative to reducing risk and optimizing patient outcomes associated with acute intraoperative pulmonary aspiration. Based on the root-cause analyses that many of the aspiration events can be traced back to provider factors, having an experienced anesthesiologist present for high-risk cases is also critical. PMID:26210926

  19. Evaluation of the NOD/SCID xenograft model for glucocorticoid-regulated gene expression in childhood B-cell precursor acute lymphoblastic leukemia

    PubMed Central

    2011-01-01

    Background Glucocorticoids such as prednisolone and dexamethasone are critical drugs used in multi-agent chemotherapy protocols used to treat acute lymphoblastic leukemia (ALL), and response to glucocorticoids is highly predictive of outcome. The NOD/SCID xenograft mouse model of ALL is a clinically relevant model in which the mice develop a systemic leukemia which retains the fundamental biological characteristics of the original disease. Here we report a study evaluating the NOD/SCID xenograft mouse model to investigate glucocorticoid-induced gene expression. Cells from a glucocorticoid-sensitive xenograft derived from a child with B-cell precursor ALL were inoculated into NOD/SCID mice. When highly eng