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Sample records for acute leukaemia undergoing

  1. The effect of scheduling in children undergoing prophylactic cranial irradiation for acute lymphoblastic leukaemia

    Costello, A.S.; Jones, R.D.; Barrett, A. (Western Infirmary, Glasgow (United Kingdom). Beatson Oncology Centre, Department of Radiation Oncology)

    1991-09-01

    Control of central nervous system disease and overall survival have been analysed in a group of 829 children with leukaemia entered into the UKALL VIII trial to determine whether scheduling of the cranial irradiation is of prognostic significance. It is shown that short gaps in treatment do not influence prognosis and that current radiotherapy practice need not be modified. (author). 20 refs., 1 fig., 2 tabs.

  2. Oral manifestations of acute leukaemia

    Ivanović Mirjana

    2011-01-01

    Full Text Available Acute leukaemia is the most common form of chilhood cancer. The aim of this paper was to underline the importance of oral manifestations in children with acute leukaemia. The disease and its treatment can directly or indirectly affect oral health. Oral manifestations are gingival inflammation and enlargement. Leukaemic cells are capable of infiltrating the gingiva and the deeper periodontal tissues which leads to ulceration and infection of oral tissues. Gingival bleeding is a common sign in patients with leukaemia. Symptoms include local lymphadenopathy, mucous membrane Petechiae and ecchymoses. Cytotoxic drugs have direct effects like mucositis, involving atrophy, desquamation and ulceration of the mucosa, with increasing the risk for local and systemic infections. Leukaemia can directly influence dental care and dental treatment, while oral lesions may have life-threatening consequences. Knowledge and skills among dentists may also not be adequate to treat children with acute leukaemia. It is therefore imperative that all stomatologists be aware of dental problems that occur in leukaemia in order to be able to effectively carry out appropriate measures to mitigate these problems.

  3. Significance of Phi bodies in acute leukaemia.

    Cardullo, L de S; Morilla, R; Catovsky, D

    1981-01-01

    Material from 39 patients with acute leukaemia was investigated with the peroxidase cytochemical reaction using 3,3'diaminobenzidine (DAB) and other substrates in order to test their sensitivity in detecting myeloid differentiation. The proportion of positive blasts and of cases with Auer rods in acute myeloid leukaemia (AML) was significantly greater with DAB than with benzidine. In addition, Phi bodies were demonstrated in AML blasts only when DAB was used; Phi bodies were also observed in two out of seven cases of chronic granulocytic leukaemia in "myeloid" blast crisis but were not seen in any case of acute lymphoblastic leukaemia. Phi bodies were more numerous when the reaction was carried out at pH 9.7, and their number was significantly reduced in the presence of 3-amino 1,2,4-triazole. Both findings suggest that the Phi bodies derive from catalase-containing granules (microperoxisomes) and are distinct from Auer rods, which derive from peroxidase-containing (primary) granules. Like Auer rods, Phi bodies appear to be characteristics of immature myeloid cells in leukaemia but are seen with a higher frequency than Auer rods in acute myeloid leukemia. Images p154-a PMID:6262384

  4. Acute leukaemia: making sense of a complex blood cancer.

    Meenaghan, Teresa

    2012-01-01

    Acute leukaemia represents a diverse group of blood cancers that affect both children and adults. Treatment schedules for these haematology cancers are often prolonged, with many associated side effects and complications. Nurses caring for patients with acute leukaemia require an anticipatory approach, where care is aimed at minimizing the side effects of treatment and being constantly vigilant for any impending adverse effects. Moreover, patients require support for the psychosocial issues that can arise for patients during their illness. This article provides an overview of acute lymphoblastic leukaemia and acute myeloid leukaemia. Nursing considerations in the care of patients being treated for acute leukaemia are also explored.

  5. Biphenotypic acute leukaemia: Case reports of two paediatric patients

    Vujić Dragana

    2010-01-01

    Full Text Available Introduction. Biphenotypic acute leukaemia is an uncommon type of leukaemia whose blasts co-express myeloid and B-or T-lymphoid antigens. Case report. We describe two cases of paediatric patients with biphenotypic acute leukaemia. A four-year-old female patient was found to have myeloid and B-lymphoid associated antigens in the same blast cells. Cytogenetic analysis showed a Philadelphia (Ph positivity t (9;22 (q34;q11 with rearrangements of M.bcr-Abl (p210. She was treated with combined acute myeloid leukaemia/acute lymphoblastic leukaemia induction therapy followed by autologous stem cell transplantation. The patient died due to the complications of stem cell transplantation procedure. Another patient was a 20-month-old girl with myeloid and T-lymphoid associated antigens in the blast cells and with normal karyotype. She received acute myeloid leukaemia induction therapy. She has never achieved remission. Discussion. Immunophenotype is essential to establish the diagnosis of biphenotypic acute leukaemia according to the scoring system adopted by the European Group of Immunological Classification of Leukaemia. There is no agreement about uniformity in treatment for the patients with this type of leukaemia. Biphenotypic acute leukaemia is a high risk leukaemia which requires a more intensive treatment. Conclusion. Therapy for every patient with biphenotypic acute leukaemia should depend on their immunophenotype and gene rearrangement profiles.

  6. Giant Molluscum Contagiosum In Acute Lymphoblastic Leukaemia

    Venkatesan Sivaraman

    2001-01-01

    Full Text Available A 14 year old female with acute lymphoblastic leukaemia had a tumoral lesion over the face of 3 months duration. Excision biopsy of the lesion confirmed it to be molluscum contagiosum. Giant molluscum contagiosum attaining polypoidal character as seen in our patient is an uncommon presentation and hence being reported for its rarity.

  7. Aberrant Gene Expression in Acute Myeloid Leukaemia

    Bagger, Frederik Otzen

    Summary Acute Myeloid Leukaemia (AML) is an aggressive cancer of the bone marrow, affecting formation of blood cells during haematopoiesis. This thesis presents investigation of AML using mRNA gene expression profiles (GEP) of samples extracted from the bone marrow of healthy and diseased subjects...

  8. Acute Myeloid Leukaemia of Donor Cell Origin Developing 17 Years after Allogenic Hematopoietic Cell Transplantation for Acute Promyelocytic Leukaemia

    Jiménez, Pilar; Alvarez, J. Carlos; Garrido, Pilar; Lorente, J. Antonio; Palacios, Jorge; Ruiz-Cabello, Francisco

    2012-01-01

    Donor cell leukaemia (DCL) is a rare complication of allogenic hematopoietic cell transplantation (HCT). We report the case of a female patient with acute promyelocytic leukaemia (APL), FAB type M3, who developed acute myeloid leukaemia (AML) type M5 of donor origin 17 years after allogenic bone marrow transplantation (BMT) from her HLA-matched sister. Morphology and immunophenotyping showed differences with the initial leukaemia, and short tandem repeat (STR) analysis confirmed donor-type ha...

  9. Acute lymphoblastic leukaemia presenting with arthritis in an adult patient

    Usalan, C.; Ozarslan, E; Zengin, N.; Buyukayk, Y.; Gullu, Y.

    1999-01-01

    The earliest manifestations of leukaemia often include rheumatic signs and symptoms. Arthritis is a well recognised complication of leukaemia in children, but acute and chronic leukaemia may also cause arthritis in adults. Leukaemic arthritis may occur at any time during the course of leukaemia and may be the presenting manifestation. It should therefore be considered in the differential diagnosis of both childhood and adult rheumatic disease. We present an adult patient presenting with arthr...

  10. Rhinocerebral zygomycosis in acute lymphoblastic leukaemia.

    Sica, S; Morace, G; La Rocca, L M; Etuk, B; Di Mario, A; Pagano, L; Zini, G; Rutella, S; Leone, G

    1993-01-01

    We describe a patient with acute lymphoblastic leukaemia who developed rhinocerebral zygomycosis during the aplastic phase induced by antineoplastic chemotherapy. The patient was treated with fluconazole intravenously (400 mg daily) for 30 days and underwent surgical debridement. As a result of this treatment a complete remission of the zygomycosis-associated symptoms was observed. The possibility of treating zygomycosis with fluconazole is discussed. PMID:8015558

  11. Analysis of images of acute human and animal leukaemia

    This research thesis first proposes a review of the development of stereology: historical backgrounds, basic principles. It discusses the choices regarding instrumentation: Coulter counter (principle and theory), quantitative analysis of particles, image analyser (optical microscope, epidiascope, scanners, detection, electronic pencil, computers, programming and data processing system), and stereo-logical parameters. The author then reports the stereo-logical study of acute human leukaemia: definition, classification, determination of spherical particle size distribution, lympho-blast size distributions. He reports the comparative study of rat L 5222 leukaemia and Brown Norway rat acute myelocytic leukaemia, and discusses their relationship with acute human leukaemia

  12. Acute lymphocytic leukaemia in children in the Netherlands

    Some features, present at diagnosis in children with acute lymphocytic leukaemia, investigated during the period 1973-1975, and the results of treatment according to protocol AL II of the Dutch Childhood Leukaemia Study Group (SNWLK), are described. This report concerns the results of induction treatment, elective treatment of the central nervous system, and also of the prospective comparative study on the influence of the addition of cyclophosphamide to maintenance treatment with 6-mercaptopurine and methotrextate. In the context of the investigation of long-term side effects of disease and treatment, the immunocompetence of children with acute lymphocytic leukaemia in continuous remission after cessation of therapy was studied. (Auth.)

  13. The eye in acute leukaemia. 1

    The dose to the ocular lens during standard cranial irradiation prophylaxis in childhood acute lymphoblastic leukaemia (ALL) has been studied both in patients and in an anthropomorphic phantom. Doses to the lens depend on patient set-up and in order that this is minimised, a simple immobilisation technique is recommended. Surface thermoluminescent dosimeter (TLD) measurements seriously underestimate the dose received by the ocular lens. Previous measurements made in a phantom have used a large volume ionisation chamber and therefore the minimum cataractogenic dose of 400 cGy for a fractionated treatment is an underestimate. The exact position of the anterior orbital field margin and thus its distance behind the surface of the eye is also important as regards lens dose. Data from the phantom demonstrate accurately the dose gradient through the eye during standard cranial prophylaxis and may explain the lower incidence of leukaemic relapse in the posterior segment of the eye, and yet explain the persistence of isolated anterior chamber relapses. 17 refs.; 5 figs.; 2 tabs

  14. Molecular therapy for acute myeloid leukaemia.

    Coombs, Catherine C; Tallman, Martin S; Levine, Ross L

    2016-05-01

    Acute myeloid leukaemia (AML) is a heterogeneous disease that is, in general, associated with a very poor prognosis. Multiple cytogenetic and molecular abnormalities that characterize different forms of AML have been used to better prognosticate patients and inform treatment decisions. Indeed, risk status in patients with this disease has classically been based on cytogenetic findings; however, additional molecular characteristics have been shown to inform risk assessment, including FLT3, NPM1, KIT, and CEBPA mutation status. Advances in sequencing technology have led to the discovery of novel somatic mutations in tissue samples from patients with AML, providing deeper insight into the mutational landscape of the disease. The majority of patients with AML (>97%) are found to have a clonal somatic abnormality on mutational profiling. Nevertheless, our understanding of the utility of mutation profiling in clinical practice remains incomplete and is continually evolving, and evidence-based approaches to application of these data are needed. In this Review, we discuss the evidence-base for integrating mutational data into treatment decisions for patients with AML, and propose novel therapeutic algorithms in the era of molecular medicine. PMID:26620272

  15. Aetiology of childhood acute leukaemias: Current status of knowledge

    Acute leukaemia is a consequence of malignant transformation of a haematopoietic progenitor cell. Molecular studies have revealed a prenatal origin of many childhood leukaemias. According to current models, a pre-leukaemic stem cell clone is generated by a first mutation in utero which, in a minority of children, progresses to leukaemia after receiving further postnatal genetic hits. The nature of pre- and postnatal events involved in leukemogenesis in children is not well understood. Although genetic predisposition and specific environmental exposures may account for individual cases, the bulk of childhood leukaemia cannot be explained by any of these factors. The higher incidence of the most common leukaemia subtype in affluent societies, as well as the age peak between 2-5 y, suggest a contributory role of socioeconomic factors. An abnormal immune response during delayed exposure to common infections provides a plausible mechanism for malignant progression of pre-leukaemic clones in a subgroup of children. As highlighted in this review, a common cause for all types and subtypes of childhood leukaemia is highly unlikely. Deeper insights into the pathogenesis of childhood leukaemia will rely on large-scale and combined epidemiological and bio-molecular studies. (authors)

  16. Myeloid sarcoma in a child with acute myeloblastic leukaemia

    We report a rare occurrence of myeloid sarcoma in a 7 years old child with acute myeloblastic leukaemia (AML - FAB type M2). He presented with fever, generalized weakness, bilateral proptosis and left parotid swelling. CT scan revealed a mass in paranasal sinuses extending into brain and retro-orbital region. Diagnosis of AML M2 was made on bone marrow aspiration and special stains. Induction therapy for AML was given according to standard protocol. The extramedullary lesion as well as the acute leukaemia went into complete remission. (author)

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

    Hjalmars, U; G. Gustafsson; . .

    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 t...

  18. T-cell acute lymphoblastic leukaemia : recent molecular biology findings

    Kraszewska, Monika D.; Dawidowska, Malgorzata; Szczepanski, Tomasz; Witt, Michal

    2012-01-01

    For many years, T-cell acute lymphoblastic leukaemia (T-ALL) has been considered and treated as a single malignancy, but divergent outcomes in T-ALL patients receiving uniform treatment protocols encouraged intensive research on the molecular biology of this disease. Recent findings in the field dem

  19. Academic career after treatment for acute lymphoblastic leukaemia

    Kingma, A; Rammeloo, LAJ; van der Does-van den Berg, A; Rekers-Mombarg, L; Postma, A

    2000-01-01

    Aim-To evaluate academic career in long term survivors of childhood acute lymphoblastic leukaemia (ALL), in comparison to their healthy siblings. Patients-Ninety four children treated for ALL with cranial irradiation 18 or 25 Gy and intrathecal methotrexate as CNS prophylaxis. Median age at evaluati

  20. Improved outcome after relapse in children with acute myeloid leukaemia

    Abrahamsson, Jonas; Clausen, Niels; Gustafsson, Göran;

    2007-01-01

    In the Nordic Society for Paediatric Haematology and Oncology paediatric study acute myeloid leukaemia (AML) 93, event-free survival was 50% and overall survival was 66%, indicating that many patients were cured following relapse. Factors influencing outcome in children with relapsed AML were...

  1. Reduced activity of TAFI (thrombin-activatable fibrinolysis inhibitor) in acute promyelocytic leukaemia

    Meijers, JCM; Oudijk, EJD; Mosnier, LO; Nieuwenhuis, HK; Fijnheer, R; Bouma, Bonno N.; Bos, R

    2000-01-01

    Acute promyelocytic leukaemia (APL) is a disease that is distinguished from other leukaemias by the high potential for early haemorrhagic death. Several processes are involved, such as disseminated intravascular coagulation and hyperfibrinolysis. Recently, TAFI (thrombin-activatable fibrinolysis inh

  2. A Hypothetical-Mathematical Model of Acute Myeloid Leukaemia Pathogenesis

    Andrei Cucuianu

    2010-01-01

    Full Text Available Acute myeloid leukaemia is defined by the expansion of a mutated haematopoietic stem cell clone, with the inhibition of surrounding normal clones. Haematopoiesis can be seen as an evolutionary tree, starting with one cell that undergoes several divisions during the expansion phase, afterwards losing functional cells during the aging-related contraction phase. During divisions, offspring cells acquire ‘variations’, which can be either normal or abnormal. If an abnormal variation is present in more than 25% of the final cells, a monoclonal, leukemic pattern occurs. Such a pattern develops if: (A1 The abnormal variation occurs early, during the first or second divisions; (A2 The variation confers exceptional proliferative capacity; (B A sizable proportion of the normal clones are destroyed and a previously non-significant abnormal clone gains relative dominance over a depleted environment; (C The abnormal variation confers relative ‘immortality’, rendering it significant during the contraction phase. Combinations of these pathways further enhance the leukemic risk of the system. A simple mathematical model is used in order to characterize normal and leukemic states and to explain the above cellular processes generating monoclonal leukemic patterns.

  3. L-asparaginase induced hyperlipidaemia in acute lymphoblastic leukaemia

    Objective: To evaluate hyperlipidaemia in patients with acute lymphoblastic leukaemia (ALL) receiving L-asparaginase. Methods: A case-control study carried out between October 2007 and October 2010 with 77 patients undergoing chemotherapy at a teaching children hospital in Babol, Iran. Patients were treated with anti-leukaemic agents according to the protocols for standard-risk and high-risk ALL. Those patients who received asparaginase represented the cases and those who did not receive it were the controls. Biochemical markers were checked during the induction phase chemotherapy. Lipid profile of patients was recorded. Data was analysed using SPSS 16. Results: Of the 77 patients, 37 (48.05%) received asparaginase therapy and 40 (51.94%) patients did not. The mean peak triglyceride and cholesterol levels during asparaginase therapy in the first group were significantly higher than the levels in the second group. Conclusion: Severe hyperlipidaemia may be the cause of some morbidity in children receiving asparaginase. Asparaginase-induced hyperlipidaemia should be monitored in ALL patients during the induction phase of treatment. (author)

  4. What Role for Angiogenesis in Childhood Acute Lymphoblastic Leukaemia?

    P. Schneider

    2011-01-01

    Full Text Available The role of angiogenesis in acute leukaemia has been discussed since the cloning of the gene of vascular endothelial growth factor (VEGF from the acute myelogenous leukemia cell line (HL60 and, thereafter, when the first studies reported increased bone marrow vascularity and elevation of angiogenic cytokines in acute lymphoblastic leukaemia (ALL. VEGF and basic fibroblast growth factor (bFGF are the major proangiogenic cytokines that have been studied, and evaluation of their prognostic impact in childhood ALL has been reported in several studies, though with controversial results. The antiangiogenic response, contributing to the angiogenic balance, has scarcely been reported. The origin of the factors, their prognostic value, and their relevance as good markers of what really happens in the bone marrow are discussed in this paper. The place of antiangiogenic drugs in ALL has to be defined in the global treatment strategy.

  5. Immunological and ultrastructural studies in acute biphenotypic leukaemia.

    Shetty, V; Chitale, A; Matutes, E; Buccheri, V; Morilla, R; Catovsky, D

    1993-01-01

    AIMS--To compare the sensitivity of the ultrastructural method to detect myeloperoxidase (MPO) with light microscopy and immunocytochemistry using an anti-MPO antibody; to examine the expression of lymphoid antigens in relation to MPO activity in blast cells from cases of biphenotypic leukaemia. METHODS--Blast cells from 14 cases of biphenotypic acute leukaemia were analysed. Immunological markers were performed by single or double immunofluorescence staining on a flow cytometer. The presence of MPO was determined by light microscopy, electron microscopy on fixed and unfixed cells, and by immunoalkaline phosphatase with an anti-MPO antibody. The immunogold method was applied at the ultrastructural level to assess the expression of lymphoid and myeloid antigens at the same time as the MPO activity. RESULTS--Six of the 14 cases were initially classified as acute lymphoblastic leukaemia (ALL) and eight as acute myeloid leukaemia (AML). MPO activity was shown at the ultrastructural level in 4-99% blasts from all cases. Six of the 14 were MPO negative by light microscopy and three of these were negative with the antibody anti-MPO. Coexpression of lymphoid antigens (CD19, CD10, or CD2) and MPO was shown by the immunogold method in four out of 11 cases; in seven cases the blasts coexpressed myeloid antigens (CD13, CD33) and MPO. CONCLUSIONS--Electron microscopy is more sensitive for showing MPO than light microscopy and immunocytochemistry; the immunogold method combined with MPO used at the ultrastructural level can help to define the cell lineage involved in biphenotypic leukaemia by highlighting the myeloid component defined by MPO. Images PMID:8227405

  6. High-flow priapism in acute lymphatic leukaemia

    Mentzel, Hans-Joachim; Vogt, Susanna; Kaiser, Werner A. [Institute of Diagnostic and Interventional Radiology, Department of Pediatric Radiology, Friedrich-Schiller-Universitaet Jena, Bachstrasse 18, 07740, Jena (Germany); Kentouche, Karim; Doerfel, Claus; Zintl, Felix [Department of Paediatrics, University of Jena (Germany)

    2004-07-01

    Priapism is defined as prolonged and persistent erection of the penis without sexual stimulation. It is associated with excessive hyperleukocytosis (e.g. in acute or chronic leukaemia); however, this complication is rarely seen in the pediatric population. We report a 12-year-old boy suffering from acute leukaemia presenting with, at first intermittent, but increasingly persistent erection. Doppler US revealed signs of high-flow priapism. MRI excluded intrapelvic tumour masses, and three-dimensional contrast-enhanced MR angiography could not demonstrate an arteriovenous fistula or thrombosis. Cavernosal blood-gas measurement was in agreement with high-flow priapism. On the basis of the imaging findings, invasive therapeutic management was avoided in our patient with a successful outcome. (orig.)

  7. Value of monoclonal anti-myeloperoxidase (MPO7) for diagnosing acute leukaemia.

    Storr, J; Dolan, G.; Coustan-Smith, E; Barnett, D.; Reilly, J. T.

    1990-01-01

    The expression of myeloperoxidase (MPO) was studied in 100 cases of acute leukaemia (83 with acute myeloid leukaemia (AML) and 17 acute lymphoblastic leukaemia (ALL) by both a conventional cytochemical method and the immunocytochemical antiperoxidase (APAAP) technique using the monoclonal antibody MPO7. In each case the staining was evaluated by light microscopical examination (percentage of positive cells). Of the 83 cases of AML, 78 (93.9%) were positive for MPO7 compared with 70 (84.3%) by...

  8. Acute Myeloid Leukaemia: Optimal Management and Recent Developments

    Villela, Luis; Bolaños-Meade, Javier

    2011-01-01

    The current treatment of patients with acute myeloid leukaemia yields poor results, with expected cure rates in the order of 30–40% depending on the biological characteristics of the leukaemic clone. Therefore, new agents and schemas are intensively studied in order to improve patients’ outcomes. This review summarizes some of these new paradigms, including new questions such as which anthracycline is most effective and at what dose. High doses of daunorubicin have shown better responses in y...

  9. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    Pels, Elżbieta

    2012-01-01

    Aim of the study Oral mucositis is the most commonly reported side effect observed in neoplastic patients treated with chemotherapy and radiotherapy of the head and neck region as well as in patients who have received a haematopoietic stem cell transplant. The aim of the study was to assess the oral mucosa status in children with acute lymphoblastic leukaemia (ALL) during antineoplastic therapy. Material and methods The clinical examination included 78 children aged 2-18 with ALL. The clinica...

  10. Variable detection of myeloid antigens in childhood acute lymphoblastic leukaemia.

    Howard, M R; Thomas, L; Reid, M. M.

    1994-01-01

    AIMS--To determine whether the use of different sources of anti-CD13 and anti-CD33 monoclonal antibodies leads to discrepant results in childhood acute lymphoblastic leukaemia (ALL), which might contribute to the wide variation in the reported incidence of myeloid antigen expressing ALL in childhood. METHODS--Stored leukaemic cells from 10 children with previously defined myeloid positive ALL were examined. A range of commercially available anti-CD13 and anti-CD33 monoclonal antibodies, direc...

  11. Minor changes on cranial MRI during treatment in children with acute lymphoblastic leukaemia

    Paeaekkoe, E. [Dept. of Diagnostic Radiology, Univ. of Oulu (Finland); Vainionpaeae, L. [Dept. of Paediatrics, Univ. of Oulu (Finland); Pyhtinen, J. [Dept. of Diagnostic Radiology, Univ. of Oulu (Finland); Lanning, M. [Dept. of Paediatrics, Univ. of Oulu (Finland)

    1996-04-01

    Cranial MRI was used to study treatment-related changes in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or lymphoma. Nineteen children (18 with ALL, 1 with lymphoma) underwent MRI at the beginning of treatment and at intervals during it, to a total of 105 imaging studies and a minimum of 3 per case. Nine patients had finished all therapy, all received consolidation treatment. No patient had central nervous system (CNS) leukaemia at diagnosis or developed a CNS relapse. Mild treatment-related white matter changes were observed in only 2 patients after consolidation therapy with three 5 g/m{sup 2} pulses of intravenous methotrexate. Transient enlargement of the ventricles and cortical sulci was observed in 13 patients, always temporally related to steroid treatment. These preliminary data suggest that treatment-related white matter changes are rare and no routine MRI follow-up is needed during treatment in asymptomatic children after a baseline assessment. (orig.)

  12. Minor changes on cranial MRI during treatment in children with acute lymphoblastic leukaemia

    Cranial MRI was used to study treatment-related changes in children undergoing therapy for acute lymphoblastic leukaemia (ALL) or lymphoma. Nineteen children (18 with ALL, 1 with lymphoma) underwent MRI at the beginning of treatment and at intervals during it, to a total of 105 imaging studies and a minimum of 3 per case. Nine patients had finished all therapy, all received consolidation treatment. No patient had central nervous system (CNS) leukaemia at diagnosis or developed a CNS relapse. Mild treatment-related white matter changes were observed in only 2 patients after consolidation therapy with three 5 g/m2 pulses of intravenous methotrexate. Transient enlargement of the ventricles and cortical sulci was observed in 13 patients, always temporally related to steroid treatment. These preliminary data suggest that treatment-related white matter changes are rare and no routine MRI follow-up is needed during treatment in asymptomatic children after a baseline assessment. (orig.)

  13. Survival in France after childhood acute leukaemia and non-Hodgkin's lymphoma (1990-2000).

    Goubin, Aurélie; Auclerc, Marie-Françoise; Auvrignon, Anne; Patte, Catherine; Bergeron, Christophe; Hémon, Denis; Clavel, Jacqueline

    2006-01-01

    This article describes the survival after childhood acute leukaemia (AL) and non-Hodgkin's lymphoma (NHL) of French population aged less than 15 years. The French National Registry of Childhood Leukaemia and Lymphoma recorded 3995 cases of acute lymphoblastic leukaemia (ALL), 812 of acute myeloid leukaemia (AML) and 1137 of NHL over the period from 1990 to 2000. Overall survival rates at 5 years were 82% (95% CI 80-83), 58% (95% CI 54-61) and 87% (95% CI 85-89) for ALL, AML and NHL, respectiv...

  14. Acute leukaemia after exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid.

    Timonen, T T; Palva, I P

    1980-01-01

    Acute leukaemia is known to develop in many cases of benzene-induced pancytopenia [1]. This is a report of the development of acute leukaemia in a patient who had apparently recovered from pancytopenia after chronic exposure to a weed killer, 2-methyl-4-chlorphenoxyacetic acid. PMID:6769284

  15. Molecular mechanisms involved in chemoresistance in paediatric acute lymphoblastic leukaemia

    Stanković Tatjana

    2008-01-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common paediatric cancer. Despite cure rates approaching 80%, resistance to treatment and disease relapse remain a significant clinical problem. Identification of the genes and biological pathways responsible for chemoresistance is therefore crucial for the design of novel therapeutic approaches aiming to improve patient survival. Mutations in the membrane transporter P-glycoprotein genes, genetic variations in drug-metabolising enzymes and defects in apoptotic pathways are mechanisms of chemoresistance common to a wide spectrum of cancers and also play a role in paediatric ALL. In addition, several recent microarray studies have identified transcriptional profiles specifically associated with chemoresistance and pointed to a number of potentially novel therapeutic targets. These microarray studies have shown that genes discriminating between clinically responsive and resistant leukaemias tend to be involved in cellular processes such as regulation of cell cycle, proliferation, and DNA repair. Here we review the outcomes of these microarray studies and also present our own investigations into apoptotic resistance to DNA double strand breaks (DSBs in paediatric ALL. We present stratification of paediatric ALL by the profile of DNA damage response following ionising radiation (IR in vitro. This approach allows classification of ALL tumours at presentation into IR-apoptotic sensitive and IR-apoptotic resistant. Furthermore, apoptotic resistant leukaemias exhibit abnormal response of NFkB pathway following irradiation and inhibition of this pathway can sensitise leukaemic cells to IR-induced DSBs.

  16. Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

    With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs

  17. Oral squamous cell carcinoma following treatment of acute lymphoblastic leukaemia

    Waal, R.I.F. van der; Waal, I. van der [Univ. Hospital Vrije Univ., Dept. of Oral and Maxillofacial Surgery/Oral Pathology, Amsterdam (Netherlands); Veerman, A.J.P. [Univ. Hospital Vrije Univ., Dept. of Paediatric Oncology, Amsterdam (Netherlands); Snow, G.B. [Univ. Hospital Vrije Univ., Dept. of Otorhinolaryngology, Amsterdam (Netherlands)

    1997-02-01

    With substantially increased survival after most paediatric cancers over the past decades have come the late sequelae of treatment. Of all late complications of treatment, second malignancies are generally considered to be the most serious. We report on a 20-year-old man with an oral squamous cell carcinoma 17 years after initial chemotherapy and irradiation for acute lymphoblastic leukaemia. Although occurrence of the oral malignancy in this patient could have been treatment-related, one should keep in mind that the occurrence of second tumours may also be based on a shared genetic aetiology. (au) 9 refs.

  18. [Disseminated fusariosis in a patient with acute lymphoblastic leukaemia

    Hermansen, N.E.; Ralfkiaer, E.M.; Kjeldsen, L.

    2008-01-01

    Invasive mould infections are a major cause of infectious mortality in highly immunosuppressed patients. Incidence in this high risk group is 10-20% with a death rate in excess of 50%. Most invasive moulds are Aspergillus spp. We present a case of a 74-year-old woman with acute lymphoblastic...... leukaemia who developed a rare disseminated mould infection with Fusarium solani during induction chemotherapy. We present the case story and discuss the pathogenesis, clinical characteristics and treatment of invasive fusariosis Udgivelsesdato: 2008/9/8...

  19. Effect of age on 6-mercaptopurine metabolic profile during the maintenance phase in children with acute lymphoblastic leukaemia

    DZHANGt; AGILBER; KYAKOUBEN; YMEDARD; EVILMER; EJACQZ-AIGRAIN

    2004-01-01

    INTRODUCTION: 6-Mercaptopurine (6-MP) is a thiopurine analogue administered for the treatment of acute lymphoblastic leukaemia (ALL). It is an inactive pro-drug that undergoes extensive metabolism resulting in the formation of active metabolites 6-thioguanine nucleotides (6-TGN) and inactive 6-mercaptopurine methylated metabolites (6-MMP) under the genetic control of the enzyme thiopurine methyltransferase (TPMT). 6-MP metabolic profile (6-MMP/6-TGN) was proposed as a tool to

  20. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Imilia Ismail

    2014-01-01

    Full Text Available Acute promyelocytic leukaemia (APL is an M3 subtype of acute myeloid leukaemia (AML. This classification is based on the morphology of promyelocytic cell. The clinical characteristics of APL can be recognized by haemorrhagic episodes, a differentiation block at the promyelocytic stage, and sensitivity to the differentiation response to all-trans-retinoic acid (ATRA. Cytogenetically, APL is characterized by a balanced reciprocal translocation between chromosomes 15 and 17, which results in the production of PML/RARα fusion protein. Recent studies reported that microRNAs (miRNAs have also been proposed to contribute to the pathogenesis of APL. miRNAs have been associated with the pathogenesis of cancer and their involvement as oncogenic and tumour suppressor activities have been identified. They are involved in various biological processes including the cell proliferation, differentiation, growth and development, metabolism, apoptosis, and haematopoiesis. The new discovery of miRNAs as possible therapeutic markers will provide new insight for the diagnosis and therapeutic entries for the treatment of APL. This review highlights the potential of miRNAs as biomarkers in APL.

  1. Cerebrospinal fluid asparagine depletion during pegylated asparaginase therapy in children with acute lymphoblastic leukaemia

    Henriksen, Louise T; Nersting, Jacob; Raja, Raheel A;

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Cerebrospinal fluid (CSF) asparagine depletion is considered a marker of asparaginase effect in the central nervous system (CNS) and may play a role in CNS-directed anti-leukaemia therapy. The...

  2. CBL mutations do not frequently occur in paediatric acute myeloid leukaemia

    Coenen, Eva A.; Driessen, Emma M. C.; Zwaan, C. Michel; Stary, Jan; Baruchel, Andre; de Haas, Valerie; de Bont, Eveline S. J. M.; Reinhardt, Dirk; Kaspers, Gertjan J. L.; Arentsen-Peters, Susan T. C. J. M.; Meyer, Claus; Marschalek, Rolf; Pieters, Rob; Stam, Ronald W.; van den Heuvel-Eibrink, Marry M.

    2012-01-01

    RAS-pathway mutations, causing a proliferative advantage, occur in acute myeloid leukaemia (AML) and MLL-rearranged leukaemia. Recently, mutations in the Casitas B lineage lymphoma (CBL) gene were reported to be involved in RAS-pathway activation in various myeloid malignancies, but their role in pa

  3. Current standard treatment of adult acute promyelocytic leukaemia.

    Lo-Coco, Francesco; Cicconi, Laura; Breccia, Massimo

    2016-03-01

    The outcome of patients with acute promyelocytic leukaemia (APL) has dramatically improved over the last two decades, due to the introduction of combined all-trans retinoic acid (ATRA) and chemotherapy regimens and, more recently, to the advent of arsenic trioxide (ATO). ATRA and anthracycline-based chemotherapy remains a widely used strategy, providing cure rates above 80%, but it is associated with risk of severe infections and occurrence of secondary leukaemias. ATO is the most effective single agent in APL and, used alone or in combination with ATRA or ATRA and reduced-intensity chemotherapy, results in greater efficacy with considerably less haematological toxicity. The toxic profile of ATO includes frequent, but manageable, QTc prolongation and increase of liver enzymes. Two large randomized studies have shown that ATRA + ATO is superior to ATRA + chemotherapy for newly diagnosed low-risk APL resulting in 2-4 year event-free survival rates above 90% and very few relapses. According to real world data, the spectacular progress in APL outcomes reported in clinical trials has not been paralleled by a significant improvement in early death rates, this remains the most challenging issue for the final cure of the disease. PMID:26687281

  4. Orbital mass secondary to infantile acute lymphoblastic leukaemia.

    Hossain, Ibtesham Tausif; Moosajee, Mariya; Abou-Rayyah, Yassir; Pavasovic, Vesna

    2016-01-01

    An 8-month-old Asian infant girl was referred with a 1-week history of left periorbital swelling on a background of a narrowed left palpebral aperture over the preceding 8 weeks. There was no history of chronic illness, fever or other systemic features. Examination revealed a tender and fluctuant medial canthal swelling with associated periorbital haematoma. There were no other ophthalmic findings and neurological examination was normal. A MRI scan of the brain and orbit demonstrated abnormal soft tissue with features of an aggressive tumour in the left orbital region with no globe invasion. Peripheral blood smear revealed blast cells, confirmed by bone marrow aspirate. A diagnosis of infant acute lymphoblastic leukaemia was made. The patient was started on risk-stratified chemotherapy according to the Interfant-06 Protocol The periorbital swelling resolved by day eight following a course of prednisolone, the patient continues on chemotherapy and is currently in molecular remission. PMID:27143162

  5. Harnessing the immune system in acute myeloid leukaemia.

    Austin, Rebecca; Smyth, Mark J; Lane, Steven W

    2016-07-01

    Acute myeloid leukaemia (AML) is an aggressive blood cancer caused by the proliferation of immature myeloid cells. The genetic abnormalities underlying AML affect signal transduction pathways, transcription factors and epigenetic modifiers. In solid tumours, it is emerging that the genetic landscape of the tumour has a direct effect on the anti-tumour immune responses and response to immunotherapeutic treatment. However, there remains little information as to whether genetic abnormalities affect anti-leukemic immune responses. This review discusses current knowledge of AML antigens and immune responses to AML with a particular focus on the role of T cells and natural killer cells. Understanding immune responses to AML has implications for the development and use of immunotherapies to treat AML patients with distinct genetic abnormalities. PMID:27247119

  6. Effect of azole antifungal therapy on vincristine toxicity in childhood acute lymphoblastic leukaemia

    Schie, R.M. van; Bruggemann, R.J.M.; Hoogerbrugge, P.M.; Loo, D.M. te

    2011-01-01

    BACKGROUND: Vincristine is one of the cornerstones of the treatment of children with acute lymphoblastic leukaemia (ALL). Constipation, and peripheral and central neurotoxicities are the most common side effects. A comparative study exploring vincristine toxicity in individual patients receiving vin

  7. CD19-Chimeric Antigen Receptor T Cells for Treatment of Chronic Lymphocytic Leukaemia and Acute Lymphoblastic Leukaemia

    Lorentzen, C L; thor Straten, Per

    2015-01-01

    Adoptive cell therapy (ACT) for cancer represents a promising new treatment modality. ACT based on the administration of cytotoxic T cells genetically engineered to express a chimeric antigen receptor (CAR) recognizing CD19 expressed by B cell malignancies has been shown to induce complete lasting...... responses in patients with chronic lymphocytic leukaemia (CLL) and acute lymphoblastic leukaemia (ALL). So far, eleven clinical trials including 99 CLL and ALL patients treated with CAR T cells targeting CD19 have been published, and the results from these trials are promising with impressive clinical...... responses in heavily pretreated patients. Thus, CAR T cell therapy has induced complete responses in both CLL and ALL, and surprisingly, current results indicate that patients with ALL are more prone to respond than are CLL patients. Importantly, the majority of CAR cell studies have observed severe therapy...

  8. Oral methotrexate is as effective as intramuscular in maintenance therapy of acute lymphoblastic leukaemia.

    Chessells, J M; Leiper, A D; Tiedemann, K.; Hardisty, R. M.; Richards, S.

    1987-01-01

    It has been postulated that variations in methotrexate absorption may influence the outcome of treatment in lymphoblastic leukaemia. One hundred and forty four children with acute lymphoblastic leukaemia not of the T cell type were randomised to receive continuing treatment with daily 6-mercaptopurine, vincristine, and prednisolone six weekly and methotrexate once weekly, either as a single oral dose or an intramuscular injection. Analysis of results with a minimum follow up of three and a ha...

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

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

    2016-04-01

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

  10. Clofarabine in the treatment of poor risk acute myeloid leukaemia.

    Krawczyk, Janusz

    2010-09-01

    Clofarabine is a second generation nucleoside analogue. It inhibits DNA repair and activates the mitochondrial apoptotic pathway leading to cell death. In vitro clofarabine has demonstrated synergy with daunorubicin and Ara-C and in phase II clinical trials has shown promising activity in poor risk Acute myeloid leukaemia (AML) patients. In our institution over a 24 month period 22 AML patients (11 M, 11 F) with poor risk features, deemed unsuitable for standard therapy, were treated with clofarabine, alone (eight patients) or in combination (14 patients) for up to three cycles of treatment. The median age was 67.5 years (24-76) with 16 patients > 60 years. At the time of treatment 18 patients had active AML. Four patients intolerant of standard induction received clofarabine as consolidation. The overall response rate (ORR) for the 18 patients with active AML was 61%, nine patients (50%) achieving a complete response (CR). Induction and consolidation were well tolerated with no unexpected toxicities. Predictably, all patients developed grade 4 neutropenia but the median duration was only 20 days (17-120). Induction mortality was acceptable at 17%. In conclusion, clofarabine (alone or in combination) is active in poor risk AML with an acceptable safety profile and should be considered a potential option in poor risk AML patients.

  11. Consensus definitions of 14 severe acute toxic effects for childhood lymphoblastic leukaemia treatment

    Schmiegelow, Kjeld; Attarbaschi, Andishe; Barzilai, Shlomit;

    2016-01-01

    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......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...

  12. Expression of partial tandem duplication of mixed lineage leukaemia in patients with acute leukaemia and their relatives

    He Yi; Wang Dongning; Li Xudong; Hu Yuan; Wang Wenwen; Huang Renwei

    2014-01-01

    Background Partial tandem duplication of mixed lineage leukaemia (MLL-PTD) is detected both in patients with acute leukemia and in healthy people.However,MLL-PTD in relatives of patients with MLL-PTD has not been reported.The objective of this study was to investigate the expression of MLL-PTD in patients with acute leukemia and in their relatives.Methods The bone marrow or peripheral blood was collected from patients with acute leukaemia and their relatives.Nested reverse transcription-polymerase chain reaction (RT-PCR) was applied to detect the mRNA expression of the MLL-PTD fused gene,and further confirm in genomic DNA level.Results Analysing MLL-PTD in case 1,the patient's older brother and his younger brother were positive,while his mother and his son were negative.The exon type in case 1 was e9/3 fusion,but in his older brother,it was e9/3 and e11/3 fusion,and in his younger brother,it was e9/3,e10/3,and e11/3 fusion.MLL-PTD in case 2 was negative,but in the patient's older sister was positive,and the exon type was e9/3,e10/3,and e11/3.Conclusions The expression of MLL-PTD was present in cases with acute leukaemia with a single expression type.However,various expression types were detected in their healthy relatives.MLL-PTD can couple with other chromosome aberrations,and its impact on disease prognosis remains to be studied further.

  13. Late effects of treatment in survivors of childhood acute lymphoblastic leukaemia

    The overall aim of this study was a comprehensive assessment of the nature and severity of the late effects of treatment in a group of children surviving acute lymphoblastic leukaemia. In the absence of damage preceding treatment, late effects could be ascribed to treatment. Cranial irradiation, methotrexate, L-asparaginase and cytosine arabinoside are therapeutic modalities most likely to cause injury to the central nervous system. Survivors of childhood leukaemia also showed an increase in weight-for-height during and after therapy which appeared to be the consequence of a loss in statural growth as well as increasing weight-for-age. Assessment of endocrine function in leukaemia survivors indicated abnormalities in the regulation of growth hormone and thyroid stimulating hormone in some patients. Survivors of childhood leukaemia were shown to have an intellectual deficit compared with their siblings and a high incidence of visual-perceptual defects. The intellectual effects of lower doses of cranial irradiation are as yet unknown. A variety of minor neurological abnormalities were detected among leukaemia survivors and thought to be related to preceding central nervous system 'prophylactic' chemotherapy and irradiation. A new instrument, the functional deficit score, was derived to reflect overall outcome in survivors of childhood leukaemia. With few exceptions, leukaemia survivors in this study had received 2400 rads of deep x-ray therapy as cranial irradiation. This dosage has since been reduced world-wide. Current cranial irradiation 'prophylaxis' consists of 1800 rad of megavoltage radiotherapy

  14. Response rate of Pakistani children with acute lymphoblastic leukaemia to medical research council acute lymphoblastic leukaemia 97 chemotherapy protocol

    Background: Acute lymphoblastic leukaemia (ALL), a malignancy of lymphoid lineage cells, has excellent prognosis in children. In Pakistan, a few studies highlighted the response of ALL to chemotherapy. The Present study was planned to see the response rate of Pakistani children with ALL to Medical Research Council ALL 97 (MRCALL97) chemotherapy protocol. This descriptive case series was conducted at the Department of Haematology, Armed Forces Institute of Pathology and the Department of Paediatric Oncology, Combined Military Hospital, Rawalpindi from February 16, 2007 to August 16, 2007. Methods: Diagnosed children with ALL fulfilling the inclusion criteria were interviewed regarding history of the present, past illnesses, and family history. Physical examination was performed. Presenting clinical features, blood counts and blood and bone marrow blasts percentage were used to see the response on day 29 post chemotherapy. The data was recorded on a structured proforma for statistical analysis. Results: A total of 33 patients were studied including 26 males and 7 females. Twenty-five patients belonged to age group 2-9 years, and 8 to 9 years, median age being 4.5 years. Presenting WBC count was 50 X 10/sup 9/L in 3 patients. At the end of induction, complete remission was achieved in 31 out of 33 (94%) patients while two patients did not achieve remission. Conclusion: Response rate of Pakistani children with ALL to chemotherapy was superior to the previously reported figures from Pakistan. (author)

  15. Radiation-induced acute myeloid leukaemia in mice

    Ample epidemiological studies of human populations implicate ionizing radiation as a carcinogen and these quantitative studies provide the foundation for the core estimates of radiation cancer risk. The majority of the epidemiological data originate from situations of radiation exposure at high dose and high dose rate. The relevance of risk estimates based on such exposures to the more commonly encountered low dose and dose rate situation has been questioned frequently. Thus, there is a need to investigate and quantitate low dose and dose rate effects. A number of approaches may be considered, for example, very large scale epidemiology, very large scale animal experimentation; however, both of these present problems of a practical and/or ethical nature. A further possible approach is that of mechanistic modelling. This requires a fairly detailed understanding of neoplastic disease and how it develops post-irradiation. Many factors and variables have to be taken into consideration in mechanistic modelling approaches. Testing of mechanistic modelling schemes is best carried out using animal model systems. Acute myeloid leukaemia (AML) is a radiogenic cancer of significance in man and several good mouse models of the disease are available. Here, recent studies conducted at NRPB with the aim of elucidating the post-irradiation development of AML will be discussed. In particular three areas critical for developing a sound mechanistic model will be covered, definition of the initiating event; study of disease progression, this addresses the question of the frequency of conversion of initiated cells into the neoplastic state and the influence of genetic background on leukaemogenesis. (author)

  16. A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia.

    Lum, S H; How, S J; Ariffin, H; Krishnan, S

    2016-02-01

    Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage. PMID:27130741

  17. Aplastic anaemia preceding acute lymphoblastic leukaemia in an adult with isolated deletion of chromosome 9q.

    Kelly, Kevin

    2008-12-01

    Aplastic anaemia (AA) can precede acute lymphoblastic leukaemia (ALL) in 2% of children but this is rarely reported to occur in adults. A 21-year-old male presented with bone marrow failure and bone marrow biopsy showed a profoundly hypocellular marrow. He recovered spontaneously but represented 2 months later when he was diagnosed with pre-B acute lymphoblastic leukaemia. Chromosomal examination revealed 46,XY,del(9)(q13q34). To the best of our knowledge this is the first case to be reported of aplasia preceding ALL with 9q minus as the sole chromosomal abnormality.

  18. Granulocytic sarcoma of the femur in a patient with acute megakaryoblastic leukaemia

    Čolović Milica

    2011-01-01

    Full Text Available Introduction. Granulocytic sarcoma, chloroma or myeloblastoma are observed in 3% to7% of acute myeloid leukaemia and represents localized tumour composed of collection of immature leukaemic cells. It appears most frequently in patients with M2, M4 and M5 subtypes of acute myeloid leukaemia Case Outline. A 58-year-old female presented with pain and oedema of the right upper limb in November 2009. After two months the patinet had fracture dislocation and numerous osteolytic lesions of the right femur. Immunohistochemistry of tumour biopsy showed megakaryoblastic granulocytic sarcoma which was CD31++, F-XIII++, CD34-, FVIII+++, S100-, aktin-, EMA++, Bcl2++, CD43++, with positive proliferative marker measured with Ki-67 positivity in more of 50% of cells. Aspirate of bone marrow and immunophenotyping with flowcytometry revealed diagnosis of acute megakaryoblastic leukaemia. The course of the disease was rapid and the patient died before commencing chemotherapy, five months after first complaints. Conclusion. Granulocytic sarcoma is extramedullary localization of collection of leukaemia cells which can proceed, to arise concomitantly with leukaemia, or may be the only manifestation of the disease. The diagnosis can be established only with immunohystochemistry.

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

    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

  20. Effect of glutathione S-transferases on the survival of patients with acute myeloid leukaemia

    Autrup, Judith; Hokland, Peter; Pedersen, Lars;

    2002-01-01

    The objective of the study was to investigate the effect of genetic polymorphisms in glutathione S-transferases (GST) on the survival of acute myeloid leukaemia patients receiving adriamycin induction therapy. A total of 89 patients were included in the study. Patients who carried at least one GSTM...

  1. Two consecutive immunophenotypic switches in a child with immunogenotypically stable acute leukaemia

    Bierings, M; Szczepanski, T; van Wering, ER; Willemse, MJ; Langerak, AW; Revesz, T; van Dongen, JJM

    2001-01-01

    A 12-year-old girl presented with a CD33(+) precursor B-acute lymphoblastic leukaemia (ALL) and seemed to respond well to ALL treatment. However. 2 weeks after diagnosis her leucocyte count rose rapidly with a predominance of myeloid blasts with M5b morphology and CD19(+) myeloid immunophenotype. Ac

  2. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

    Lund, Bendik; Åsberg, Ann; Heyman, Mats;

    2011-01-01

    BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 and...

  3. Prognosis in childhood and adult acute lymphoblastic leukaemia : a question of maturation?

    Plasschaert, SLA; Kamps, WA; Vellenga, E; de Vries, EGE; de Bont, ESJM

    2004-01-01

    Acute lymphoblastic leukaemia (ALL) is a disease diagnosed in children as well as adults. Progress in the treatment of ALL has led to better survival rates, however, children have benefited more from improved treatment modalities than adults. Recent evidence has underscored that the difference in ch

  4. Clinical relevance of molecular aberrations in paediatric acute myeloid leukaemia at first relapse

    Bachas, Costa; Schuurhuis, Gerrit Jan; Reinhardt, Dirk; Creutzig, Ursula; Kwidama, Zinia J.; Zwaan, C. Michel; van den Heuvel-Eibrink, Marry M.; De Bont, Evelina S. J. M.; Elitzur, Sarah; Rizzari, Carmelo; de Haas, Valerie; Zimmermann, Martin; Cloos, Jacqueline; Kaspers, Gertjan J. L.

    2014-01-01

    Outcome for relapsed paediatric acute myeloid leukaemia (AML) remains poor. Strong prognostic factors at first relapse are lacking, which hampers optimization of therapy. We assessed the frequency of molecular aberrations (FLT3, NRAS, KRAS, KIT, WT1 and NPM1 genes) at first relapse in a large set (n

  5. Risk factors for treatment related mortality in childhood acute lymphoblastic leukaemia

    Lund, Bendik; Åsberg, Ann; Heyman, Mats;

    2011-01-01

    BACKGROUND: In spite of major improvements in the cure rate of childhood acute lymphoblastic leukaemia (ALL), 2-4% of patients still die from treatment related complications. PROCEDURE: We investigated the pattern of treatment related deaths (TRDs) and possible risk factors in the NOPHO ALL-92 and...... towards patients at risk. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc....

  6. Changing bone marrow micro-environment during development of acute myeloid leukaemia in rats

    Mortensen, B T; Jensen, P O; Helledie, N;

    1998-01-01

    bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction of......The Brown Norwegian rat transplanted with promyelocytic leukaemic cells (BNML) has been used as a model for human acute myeloid leukaemia. We have previously shown that both the blood supply to the bone marrow and the metabolic rate decrease in relation to the leukaemic development in these rats...

  7. Low dose-rate irradiation in the treatment of acute myelogenous leukaemia in first remission

    Thirty-six patients with acute myelogenous leukaemia (AML) in first remission received sibling bone marrow transplants following cyclophosphamide and a single dose of 1000 rad total body irradiation (TBI). The preparation programme for a patient undergoing a bone marrow transplant is described. The aim of the cyclophosphamide and TBI is to eradicate all active bone marrow present in the patient and to reduce the immune response of the patient to the graft, thus preventing rejection. The cobalt unit and treatment box used for the TBI is described together with details of the planning for TBI including test doses on the patient. The procedure on the day of the 8 hour TBI treatment is then given. The likely reactions following the TBI and the graft are described. Of these transplanted patients, 64% remain alive, well and disease-free, nine of them for more than one year and one surviving more than three years. These results are a significant improvement on the results of AML treated with chemotherapy and immunotherapy. (U.K.)

  8. Epidural spinal cord compression as initial clinical presentation of an acute myeloid leukaemia: case report and literature review

    Dominique N'Dri Oka; Alpha Boubacar Bah; André Valentin Tokpa; Louis Derou

    2016-01-01

    Epidural localization of myeloid leukaemia is rarely reported.Spinal cord compression as an initial presentation of acute myeloid leukaemia is extremely rare.This is a report of a 17-year-old black boy who presented to emergency department with neurological symptoms of spinal cord compression.Imaging modalities showed multiple soft tissue masses in the epidural space.After surgical treatment,histopathological examination of the epidural mass showed myeloid leukaemia cells infiltration.Literature review on Medline and "scholar Google" database was done.The characteristics and management of extra-medullary leukaemia are discussed.Granulocytic sarcoma,myeloid sarcoma or chloroma with acute myeloid leukaemia should be considered as part of epidural spinal cord compression.Therefore surgery is indicated on an emergent basis.

  9. Treatment-related toxicities in children with acute lymphoblastic leukaemia predisposition syndromes

    Schmiegelow, Kjeld

    2016-01-01

    Although most children with acute lymphoblastic leukaemia (ALL) do not harbor germline mutations that strongly predispose them to development of this malignancy, large syndrome registries and detailed mapping of exomes or whole genomes of familial leukaemia kindreds have revealed that 3-5% of all...... anticancer agents, while others are not. This review summarises our current knowledge on the risk of acute toxicities for these ALL patients and provides guidance for treatment adjustments....... patients is important in order to adjust therapy and offer genetic counseling and cancer surveillance to mutation carriers in the family. In the coming years large genomic screening projects are expected to reveal further hitherto unrecognised familial ALL syndromes. The treatment of ALL cases harboring...

  10. Unusual fungal sepsis of Alternaria alternata in acute lymphoblastic leukaemia in an adult patient

    S Jain

    2015-01-01

    Full Text Available We report a case of unusual fungal sepsis of Alternaria alternata in a patient of acute lymphoblastic leukaemia in 62-year-old male who presented with complaints of 'off and on' fever with decreased oral intake. On evaluation, haemogram showed low platelet count and 68% blast cells in peripheral blood. On flow cytometry of peripheral blood, the gated blasts (approximately 55% highly express CD45, CD10, CD19, CD22 and condition was diagnosed as acute lymphoblastic leukaemia. He was started on standard induction treatment along with supportive therapies. During the course of treatment, two sets of paired blood cultures were sent 48 h apart. All of blood cultures were done on Bac-T alert 3D system. All of them yielded fungus. The fungus was then grown on Sabouraud's Dextrose agar media. It was identified as A. alternata. The patient condition worsened and later had cardiac arrest in ICU and could not be revived.

  11. The pharmacokinetics of subcutaneous cytosine arabinoside in patients with acute myelogenous leukaemia.

    Slevin, M L; Piall, E M; Aherne, G.W.; Johnston, A.; Sweatman, M C; Lister, T. A.

    1981-01-01

    1 The pharmacokinetics of subcutaneous cytosine arabinoside were compared with bolus intravenous injection and intravenous infusion in five patients with acute myelogenous leukaemia. 2 Subcutaneous cytosine arabinoside was rapidly absorbed and then declined biexponentially with initial and terminal half-lives similar to intravenous bolus injection. 3 Cytosine arabinoside levels declined rapidly after intravenous bolus and subcutaneous bolus injection, and fell below steady state infusion leve...

  12. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Gulhadiye Avcu

    2016-03-01

    Full Text Available Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immunocompromised patients.

  13. Competitive PCR for quantification of minimal residual disease in acute lymphoblastic leukaemia

    Nyvold, C; Madsen, H O; Ryder, L P;

    2000-01-01

    A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical to...... at least one malignant cell in 10(5) normal cells. This method may be used for treatment stratification based on the early response to antileukaemic therapy. Udgivelsesdato: 2000-Jan-13...

  14. Difficult diagnosis of invasive fungal infection predominantly involving the lower gastrointestinal tract in acute lymphoblastic leukaemia

    Avcu, Gulhadiye; Karapinar, Deniz Yilmaz; Yazici, Pinar; Duyu, Muhterem; Polat, Suleyha Hilmioglu; Atabay, Berna; Doganavsargil, Basak; Karapinar, Bulent

    2016-01-01

    Invasive fungal infections are most commonly seen in immunocompromised patients and usually affect the respiratory system. Gastrointestinal system involvement of mucormycosis and invasive aspergillosis is rarely reported in childhood. Here we describe a 5 year old boy with acute lymphoblastic leukaemia who developed invasive fungal infection particularly affecting the lower gastrointestinal system to emphasise the difficulties in diagnosis and management of invasive fungal infections in immun...

  15. Acute lymphoblastic leukaemia among Spanish children and mothers' occupation: a case-control study.

    Infante-Rivard, C; Mur, P.; Armstrong, B; ALVAREZ-DARDET, C.; Bolumar, F

    1991-01-01

    STUDY OBJECTIVE: The aim was to investigate the association between mothers' occupational exposure during pregnancy and the incidence of acute lymphoblastic leukaemia in children. DESIGN: The study was a case-control investigation. A face to face interview was used to assess exposures at work and relevant confounding variables. SETTING: The study was community based and was carried out in five provinces of Spain. SUBJECTS: 128 cases less than 15 years of age were interviewed (91% of those eli...

  16. Cognitive outcome in children and adolescents treated for acute lymphoblastic leukaemia with chemotherapy only

    Lofstad, G Elisabeth; Reinfjell, Trude; Hestad, Knut; Diseth, Trond H

    2009-01-01

    Objective: To examine cognitive outcome in children and adolescents with acute lymphoblastic leukaemia (ALL) in remission, treated with central nervous system prophylactic chemotherapy only. Method: Thirty-five children and adolescents, age 8.4–15.3 years in long-term remission from ALL, 4.2–12.4 years post diagnosis, without relapse and no prediagnosis history of neurodevelopmental disorder were compared with 35 healthy controls matched for gender and age, on measures of intellectual functio...

  17. Early molecular diagnosis of aspergillosis in a patient with acute myeloid leukaemia

    Greco, R; Mancini, N.; Peccatori, J.; Cieri, N.; Vago, L.; F. Giglio; Morelli, M; Ghidoli, N; Carletti, S; Levati, G; Crucitti, L; E. Sala; Lupo Stanghellini, M T; Lorentino, F; Forcina, A

    2014-01-01

    Diagnosis of invasive fungal infection remains challenging. Here we report a case of early diagnosis of invasive aspergillosis in a neutropenic patient affected by acute myeloid leukaemia, achieved through the detection of Aspergillus fumigatus species-specific ribonucleic acid sequences by a sensitive multiplex real-time polymerase chain reaction-based molecular assay. Thanks to the early diagnosis, targeted therapy was promptly established and the severe fungal infection controlled, allowin...

  18. PLZF/RARalpha binding partners and their influence on the induction of acute promyelocytic leukaemia

    Frech, Miriam

    2014-01-01

    The acute promyelocytic leukaemia (APL) accounts for 10% of the adult AML patients. APL patients carry chromosomal translocations involving the rarα gene on chromosome 17. The most frequent translocations lead to the expression of the fusion proteins PML/RARα (98%; t(15;17)) and PLZF/RARα (1%; t(11;17)) (X-RARα). The APL is characterised by a differentiation block at the promyelocytic stage and leads to an increased amount of myel...

  19. Combined Bezafibrate and Medroxyprogesterone Acetate: Potential Novel Therapy for Acute Myeloid Leukaemia

    Khanim, Farhat L.; Hayden, Rachel E.; Jane Birtwistle; Alessia Lodi; Stefano Tiziani; Davies, Nicholas J; Ride, Jon P.; Viant, Mark R.; Gunther, Ulrich L.; Mountford, Joanne C; Heinrich Schrewe; Green, Richard M.; Murray, Jim A.; Drayson, Mark T; Chris M Bunce

    2009-01-01

    BACKGROUND: The majority of acute myeloid leukaemia (AML) patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. PRINCIPAL FINDINGS: Here we demonstrate the potent anti-leukaemic activity of the combination of t...

  20. The effect of game-based exercise on infant acute lymphocytic leukaemia patients

    Édgar Cortés-Reyes; Paola Escobar-Zabala; Laura González-García

    2013-01-01

    Objective. To establish the effect of a game-based exercise programme on Physical Deconditioning Syndrome (PDS) in 5 to 12 year-old children suffering Acute Lymphocytic Leukaemia (ALL). Materials and methods. This was a quasi-experimental study involving seven children being treated for ALL at the National Cancer Institute (NCI) in Bogotá, Colombia. Fitness determinants (aerobic capacity, muscle strength, flexibility, motor skills and proprioception) were initially assessed to establish their...

  1. Host genome variations and risk of infections during induction treatment for childhood acute lymphoblastic leukaemia

    Lund, Bendik; Wesolowska-Andersen, Agata; Lausen, Birgitte;

    2014-01-01

    Objectives: To investigate association of host genomic variation and risk of infections during treatment for childhood acute lymphoblastic leukaemia (ALL). Methods: We explored association of 34 000 singlenucleotide polymorphisms (SNPs) related primarily to pharmacogenomics and immune function...... to risk of infections among 69 ALL patients on induction therapy. Results: Forty-eight (70%) patients experienced infectious events including 23 with positive blood cultures. Infectious events and positive blood cultures were associated significantly with 24 and 21 SNPs, respectively (P

  2. Feedback mechanisms control coexistence in a stem cell model of acute myeloid leukaemia.

    Crowell, Helena L; MacLean, Adam L; Stumpf, Michael P H

    2016-07-21

    Haematopoietic stem cell dynamics regulate healthy blood cell production and are disrupted during leukaemia. Competition models of cellular species help to elucidate stem cell dynamics in the bone marrow microenvironment (or niche), and to determine how these dynamics impact leukaemia progression. Here we develop two models that target acute myeloid leukaemia with particular focus on the mechanisms that control proliferation via feedback signalling. It is within regions of parameter space permissive of coexistence that the effects of competition are most subtle and the clinical outcome least certain. Steady state and linear stability analyses identify parameter regions that allow for coexistence to occur, and allow us to characterise behaviour near critical points. Where analytical expressions are no longer informative, we proceed statistically and sample parameter space over a coexistence region. We find that the rates of proliferation and differentiation of healthy progenitors exert key control over coexistence. We also show that inclusion of a regulatory feedback onto progenitor cells promotes healthy haematopoiesis at the expense of leukaemia, and that - somewhat paradoxically - within the coexistence region feedback increases the sensitivity of the system to dominance by one lineage over another. PMID:27130539

  3. Clinical effectiveness of palifermin in prevention and treatment of oral mucositis in children with acute lymphoblastic leukaemia:a case-control study

    Dorina Lauritano; Massimo Petruzzi; Dario Di Stasio; Alberta Lucchese

    2014-01-01

    The aim of this study was to evaluate the efficacy of palifermin, an N-terminal truncated version of endogenous keratinocyte growth factor, in the control of oral mucositis during antiblastic therapy. Twenty patients undergoing allogeneic stem-cell transplantation for acute lymphoblastic leukaemia were treated with palifermin, and compared to a control group with the same number of subjects and similar inclusion criteria. Statistical analysis were performed to compare the outcomes in the treatment vs. control groups. In the treatment group, we found a statistically significant reduction in the duration of parenteral nutrition (P50.002), duration of mucositis (P50.003) and the average grade of mucositis (P50.03). The statistical analysis showed that the drug was able to decrease the severity of mucositis. These data, although preliminary, suggest that palifermin could be a valid therapeutic adjuvant to improve the quality of life of patients suffering from leukaemia.

  4. Demonstration of cytoplasmic and nuclear antigens in acute leukaemia using flow cytometry.

    Farahat, N; van der Plas, D; Praxedes, M; Morilla, R; Matutes, E; Catovsky, D

    1994-01-01

    AIMS--To detect cytoplasmic and nuclear antigens using flow cytometry in acute leukaemia and to use this technique for double marker combinations. METHODS--Cytoplasmic staining was carried out in samples from 40 cases of acute leukaemia with monoclonal antibodies against the myeloid antigen CD13, the lymphoid antigens CD3, CD22, mu chain and the enzymes terminal deoxynucleotidyl transferase (TdT) and myeloperoxidase (MPO). The cells were fixed with paraformaldehyde and permeabilised with Tween 20 and Becton Dickinson's FACS lysing solution. Flow cytometry results were compared in the same cases with immunocytochemistry results using the alkaline phosphatase anti-alkaline phosphatase method. RESULTS--The gentle permeabilisation induced by this method permitted preservation of the membrane antigens and the size and morphology of the cells. The results using flow cytometry were comparable with those obtained using immunocytochemistry, with nearly complete concordance in most cases. CONCLUSIONS--This technique is simple, rapid, sensitive and reproducible and it is suitable for double staining procedures, such as nuclear and cytoplasmic, nuclear and membrane, or cytoplasmic and membrane. It therefore provides a powerful tool for extending the use of immunophenotyping for the diagnosis and follow up of acute leukaemia. It could also be used for the investigation of minimal residual disease. PMID:7962655

  5. A Clinicopathological Correlation of Acute Leukaemias in relation to Immunophenotyping and Cytogenetics

    Sunil Pazhayanur Venkateswaran

    2012-10-01

    Full Text Available Introduction: Leukemia accounts for 0.15 – 0.6% of the total medical admissions in many general hospitals in India. Frequency of leukemia seen in India of Acute Myeloid leukaemia (AML is 20 - 25% and Acute Lymphoblastic leukaemia (ALL is 15-25%. The Annual incidence rate of AML and ALL are 5.6 and 30.9 per million population respectively. Aims: To study the clinicopathological correlation in Acute myeloid and Acute Lymphoblastic leukaemias in relation to immunophenotyping and cytogenetics. Materials & Methods: All newly diagnosed cases of acute myeloid leukaemia that presented to our hospital from January 2007 to July 2009 were included in this study. The peripheral blood and bone marrow were tested for surface membrane, cytoplasmic and nuclear antigens and were classified by the French-American- British (FAB Cooperative Group Classification by using Romanowsky (Leishman and May Grunwald Giemsa[MGG] stained smears and cytochemical stains. Results & Summary: A series of available 100 cases of Acute Leukemia diagnosed during a period of 30 months (January 2007 to July 2009 were reviewed and various clinical, biochemical, immunophenotypic and cytogenetic parameters were assessed. 88 cases were subject to immunophenotyping and 60 cases were subject to cytogenetic analysis either by conventional Karyotyping, FISH (fluorescence in situ hybridization and RT-PCR (Reverse transcriptase polymerase chain reaction. The antigen expressions by immunophenotype in acute myeloid and lymphoblastic leukemias were compared with age, Haemoglobin, Total WBC count, Platelet counts, Lactate dehydrogenase levels and abnormal karyotypes. Analytical statistics showed a significant correlation in the expressions of CD13, CD33, CD117 and CD64 in Acute Myeloid Leukemia and CD10, CD19, CD20 and CD22 in Acute Lymphoblastic leukemia and the expressions of CD13/CD117, CD3/CD10/CD22,CD3/CD5/CD2 and CD117/CD11c were related to the age, Haemoglobin, WBC count and Lactate

  6. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol

    Raja, Raheel A; Schmiegelow, Kjeld; Albertsen, BK;

    2014-01-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis...... within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO...

  7. French “real life” experience of clofarabine in children with refractory or relapsed acute lymphoblastic leukaemia

    Trioche, Pascale; Nelken, Brigitte; Michel, Gérard; Pellier, Isabelle; Petit, Arnaud; Bertrand, Yves; Rohrlich, Pierre; Schmitt, Claudine; Sirvent, Nicolas; Boutard, Patrick; Margueritte, Geneviève; Pautard, Brigitte; Ducassou, Stéphane; Plantaz, Dominique; Robert, Alain

    2012-01-01

    Background Clofarabine alone or in combination with cyclophosphamide and etoposide has shown a good efficacy and a tolerable toxicity profile in previous studies of children with relapsed or refractory leukaemia. This report describes a retrospective study of 38 French patients who received clofarabine as a monotherapy or in combination for relapsed or refractory acute lymphoblastic leukaemia (ALL) outside of clinical trials after marketing authorization. Methods We retrospectively analysed d...

  8. Distinctive patterns of microRNA expression associated with karyotype in acute myeloid leukaemia.

    Amanda Dixon-McIver

    Full Text Available Acute myeloid leukaemia (AML is the most common acute leukaemia in adults; however, the genetic aetiology of the disease is not yet fully understood. A quantitative expression profile analysis of 157 mature miRNAs was performed on 100 AML patients representing the spectrum of known karyotypes common in AML. The principle observation reported here is that AMLs bearing a t(15;17 translocation had a distinctive signature throughout the whole set of genes, including the up regulation of a subset of miRNAs located in the human 14q32 imprinted domain. The set included miR-127, miR-154, miR-154*, miR-299, miR-323, miR-368, and miR-370. Furthermore, specific subsets of miRNAs were identified that provided molecular signatures characteristic of the major translocation-mediated gene fusion events in AML. Analysis of variance showed the significant deregulation of 33 miRNAs across the leukaemic set with respect to bone marrow from healthy donors. Fluorescent in situ hybridisation analysis using miRNA-specific locked nucleic acid (LNA probes on cryopreserved patient cells confirmed the results obtained by real-time PCR. This study, conducted on about a fifth of the miRNAs currently reported in the Sanger database (microrna.sanger.ac.uk, demonstrates the potential for using miRNA expression to sub-classify cancer and suggests a role in the aetiology of leukaemia.

  9. Femoral diaphyseal stress fracture as the initial presentation of acute leukaemia in an adolescent.

    Chase, Helen Emily; Pang, Joe Hwong; Sanghrajka, Anish Pradip

    2016-01-01

    A 14-year-old boy was referred to the orthopaedic clinic by his general practitioner, reporting of a 6-week history of left thigh pain. Clinical examination was unremarkable. Radiographs demonstrated a periosteal reaction at the proximal femur. MRI scans demonstrated a stress fracture of the femur, with no associated sinister features and no evidence of a pathological lesion. As the fracture healed and symptoms improved, the patient became unwell with weight loss, lethargy, chest and jaw pain and fevers. After multiple blood tests over a 25-day period, including five full blood counts and two normal blood films, a third blood film finally demonstrated blasts in keeping with acute leukaemia. We discuss a literature review of musculoskeletal manifestations of leukaemia and the often atypical presentations found. PMID:27353177

  10. Adult acute lymphoblastic leukaemia in Denmark. A national population-based retrospective study on acute lymphoblastic leukaemia in Denmark 1998-2008

    Toft, Nina; Schmiegelow, Kjeld; Klausen, Tobias W;

    2012-01-01

    Since July 2008, children and adults 1-45 years, diagnosed with acute lymphoblastic leukaemia (ALL) in Denmark have been treated according to the common Nordic Society for Paediatric Haematology and Oncology ALL2008 protocol. To explore whether this strategy will improve survival compared with...... intended treatment, the pEFS(5y) and pOS(5y) were 36·6% and 44·1%, respectively, with a significantly higher pOS(5y) for patients 15-35 years compared with patients 36-65 years (50·7% vs. 38·9%, P = 0·006). Cox multiple regression analysis identified age (Hazard Ratio = 1·7, P ...

  11. Obstructive Jaundice Due to a Pancreatic Mass: A Rare Presentation of Acute Lymphoblastic Leukaemia in an Adult

    Sudin Varghese Daniel

    2010-01-01

    Full Text Available Context To highlight a rare presentation of acute lymphoblastic leukaemia. Case report A 39-year-old man presented with a 4 month history of weight loss and a 6 week history of upper abdominal pain radiating to the back with nausea and vomiting. Liver function tests showed an obstructive picture, full blood count was normal and on computerised tomography there was diffuse enlargement of the pancreas, with dilatation of the common bile duct and intra hepatic biliary radicles. Four weeks after presenting, the white cell count became elevated with blasts on the blood film and bone marrow biopsy revealed a precursor B cell acute lymphoblastic leukaemia. After induction chemotherapy his jaundice resolved, the pancreatic mass reduced in size and he is now in a complete remission. Conclusion Acute lymphoblastic leukaemia may mimic common causes of a pancreatic mass such as adenocarcinoma and should be considered as part of the differential diagnosis when atypical features are present.

  12. Height and weight pattern up to 20 years after treatment for acute lymphoblastic leukaemia

    Birkebak, N; Clausen, N

    1998-01-01

    OBJECTIVE—To assess height and body mass index standard deviation scores up to 20 years after treatment for acute lymphoblastic leukaemia (ALL).
SUBJECTS AND METHODS—Height and body mass index standard deviation scores were measured in 33 patients (14 boys and 19 girls) with childhood ALL at diagnosis, after the end of treatment, at final height, and at follow up 10-20 years (median, 16.2) after diagnosis. Eleven patients were treated with chemotherapy only and 22 patient...

  13. A rare case of acute lymphoblastic leukaemia with hemophilia A

    John Biju

    2009-12-01

    Full Text Available Abstract A rare case of Acute lymphoblastic leukemia with hemophillia in a 12 year old boy is presented in the article. Patient was known case of hemophillia (factor VIII deficiency. He was diagnosed as a case of ALL based on bone marrow examination and immunophenotypic study. Patient was treated as per Children Cancer group guidelines. The main aim of reporting this rare association lies in developing treatment strategies in preventing life threatening bleeding due to this rare association which though may be accidental but need further research.

  14. MLL-rearranged acute lymphoblastic leukaemia stem cell interactions with bone marrow stroma promote survival and therapeutic resistance that can be overcome with CXCR4 antagonism

    Sison, Edward Allan R; Rau, Rachel E.; McIntyre, Emily; LI Li; Small, Donald; Brown, Patrick

    2013-01-01

    Infants with MLL-rearranged (MLL-R) acute lymphoblastic leukaemia (ALL) have a dismal prognosis. While most patients achieve remission, approximately half of patients recur with a short latency to relapse. This suggests that chemotherapy-resistant leukaemia stem cells (LSCs) survive and can recapitulate the leukaemia. We hypothesized that interactions between LSCs and the bone marrow microenvironment mediate survival and chemotherapy resistance in MLL-R ALL. Using primary samples of infant ML...

  15. Early related or unrelated haematopoietic cell transplantation results in higher overall survival and leukaemia-free survival compared with conventional chemotherapy in high-risk acute myeloid leukaemia patients in first complete remission.

    Basara, N; Schulze, A; Wedding, U; Mohren, M; Gerhardt, A; Junghanss, C; Peter, N; Dölken, G; Becker, C; Heyn, S; Kliem, C; Lange, T; Krahl, R; Pönisch, W; Fricke, H-J; Sayer, H G; Al-Ali, H; Kamprad, F; Niederwieser, D

    2009-04-01

    Between 1996 and 2004, a total of 708 patients were enrolled in the acute myeloid leukaemia (AML) '96 and '02 studies of the East German Study Group (OSHO). Of these, 138 patients (19.5%) had unfavourable cytogenetics defined as complex karyotype, del (5q)/-5, del (7q)/-7, abn (3q26) and abn (11q23). In all, 77 (56%) achieved complete remission 1 (CR1) after induction chemotherapy and were eligible for haematopoietic cell transplantation (HCT). HCT was performed after a median of two cycles of consolidation chemotherapy (CT) in the AML '96 and one cycle in the AML '02 study (P=0.03). After a median follow-up of 19 months, overall survival (OS) at two years was significantly better in the donor group (52+/-9%) versus the no-donor group (24+/-8%; P=0.005). Differences in outcomes were mainly because of a lower relapse incidence in patients after HCT (39+/-11%) compared with a higher relapse incidence in patients undergoing CT (77+/-10%; P=0.0005). Treatment-related mortality was low and not statistically significantly different between the two treatment groups (15+/-7 and 5+/-5% for HCT and chemotherapy, respectively; P=0.49).We conclude that early HCT from related or unrelated donors led to significantly better OS and leukaemia-free survival compared with chemotherapy in patients with unfavourable karyotype. PMID:19151786

  16. Genome-wide analysis of transcriptional reprogramming in mouse models of acute myeloid leukaemia.

    Nicolas Bonadies

    Full Text Available Acute leukaemias are commonly caused by mutations that corrupt the transcriptional circuitry of haematopoietic stem/progenitor cells. However, the mechanisms underlying large-scale transcriptional reprogramming remain largely unknown. Here we investigated transcriptional reprogramming at genome-scale in mouse retroviral transplant models of acute myeloid leukaemia (AML using both gene-expression profiling and ChIP-sequencing. We identified several thousand candidate regulatory regions with altered levels of histone acetylation that were characterised by differential distribution of consensus motifs for key haematopoietic transcription factors including Gata2, Gfi1 and Sfpi1/Pu.1. In particular, downregulation of Gata2 expression was mirrored by abundant GATA motifs in regions of reduced histone acetylation suggesting an important role in leukaemogenic transcriptional reprogramming. Forced re-expression of Gata2 was not compatible with sustained growth of leukaemic cells thus suggesting a previously unrecognised role for Gata2 in downregulation during the development of AML. Additionally, large scale human AML datasets revealed significantly higher expression of GATA2 in CD34+ cells from healthy controls compared with AML blast cells. The integrated genome-scale analysis applied in this study represents a valuable and widely applicable approach to study the transcriptional control of both normal and aberrant haematopoiesis and to identify critical factors responsible for transcriptional reprogramming in human cancer.

  17. Splenic artery pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase

    Larsen, Cæcilie Crawley; Laursen, Christian B; Dalby, Kasper;

    2014-01-01

    Acute pancreatitis is a rare phenomenon in children but its incidence seems to be increasing. In children, it is generally caused due to systemic illness, biliary disease, trauma, idiopathy and side effects of medicines like L-aspariginase. Acute pancreatitis is difficult to diagnose in children...... pseudoaneurysm due to acute pancreatitis in a 6-year-old boy with acute lymphoblastic leukaemia treated with L-aspariginase. He presented with fever, irritability and pain in his left groin region....

  18. Prolonged bone marrow T1-relaxation in acute leukaemia. In vivo tissue characterization by magnetic resonance imaging

    Thomsen, C; Sørensen, P G; Karle, H;

    1987-01-01

    osseous tissue. Nine patients with acute leukaemia, one patient with myelodysplastic syndrome, and ten normal volunteers were included in the study. The T1- and T2-relaxation processes were measured in the lumbar spine bone marrow using a wholebody superconductive MR-scanner operating at 1.5 Tesla. In the...

  19. Vincristine-induced apoptosis in vivo in peripheral blood mononuclear cells of children with acute lymphoblastic leukaemia (ALL)

    Groninger, E; Meeuwsen-de Boer, GJ; Sluiter, WJ; Poppema, S

    2000-01-01

    We conducted a study to demonstrate vincristine-induced apoptosis in vivo in peripheral blood mononuclear cells of children with newly diagnosed acute lymphoblastic leukaemia (ALL). In five children, apoptosis was detected by terminal deoxynucleotide transferase-mediated dUTP-digoxigenin nick-end la

  20. Dexamethasone in the maintenance phase of acute lymphoblastic leukaemia treatment: is the risk of lethal infections too high?

    Poele, E.M. Te; Bont, E.S. de; Boezen, H.M.; Revesz, T.; Bokkerink, J.P.M.; Beishuizen, A.; Nijhuis, I.J.M.; Oude Nijhuis, C.S.; Veerman, A.J.P.; Kamps, W.A.

    2007-01-01

    We report an increased incidence of infectious deaths during maintenance treatment of the ninth protocol for acute lymphoblastic leukaemia of the Dutch Childhood Oncology Group (DCOG-ALL-9). The main difference in maintenance treatment between DCOG-ALL-9 and the DCOG-ALL-7 and DCOG-ALL-8 protocols i

  1. Dexamethasone in the maintenance phase of acute lymphoblastic leukaemia treatment : Is the risk of lethal infections too high?

    Te Poele, Esther M; de Bont, Eveline S J M; Boezen, Hendrika; Revesz, Tom; Bökkerink, Jos P M; Beishuizen, Auke; Nijhuis, Ilse J M; Oude Nijhuis, Claudi S M; Veerman, Anjo J P; Kamps, Willem A

    2007-01-01

    We report an increased incidence of infectious deaths during maintenance treatment of the ninth protocol for acute lymphoblastic leukaemia of the Dutch Childhood Oncology Group (DCOG-ALL-9). The main difference in maintenance treatment between DCCG-ALL-9 and the DCOG-ALL-7 and DCOG-ALL-8 protocols i

  2. Outcome of treatment in childhood acute lymphoblastic leukaemia with rearrangements of the 11q23 chromosomal region

    Pui, CH; Gaynon, PS; Boyett, JM; Chessells, JM; Baruchel, A; Kamps, W; Silverman, LB; Biondi, A; Harms, DO; Vilmer, E; Schrappe, M; Camitta, B

    2002-01-01

    Background The prognosis and optimum treatment of childhood acute lymphoblastic leukaemia (ALL) with abnormalities of chromosomal band 11q23 are controversial. We aimed to identify prognostic factors that might help in planning future therapy, and to assess the effectiveness of haemopoietic stem-cel

  3. Vincristine induced apoptosis in acute lymphoblastic leukaemia cells: A mitochondrial controlled pathway regulated by reactive oxygen species?

    Groninger, E.; Boer, A.W. de; Graaf, S.S.N. de; Kamps, W.A.; Bont, E.S. de

    2002-01-01

    Vincristine (VCR), a microtubule interfering anti-cancer agent, plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL). The route of VCR induced apoptosis in ALL cells is not well defined. In this study we demonstrated caspase-9 and -3 activation in vivo in bone marrow le

  4. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas;

    2015-01-01

    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

  5. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  6. Cytochemical studies in leukaemias

    Batra Neelam

    1978-01-01

    Full Text Available One hundred cases of acute leukaemia were studied, by Romanowsky stains and by cytochemical stains such as Sudan Black B, Periodic Acid Schiff, Alkaline phosphatase and Peroxidase stains. Cases difficult to diagnose by Romanowsky stained smears were easily classified by these supplementary stains. Their importance as supplements to the routine Romanowsky staining in the diagnosis of leukaemia is emphasized and the division of acute lymphoblastic leukaemia based on these patterns is suggested.

  7. Regenerating normal B-cell precursors during and after treatment of acute lymphoblastic leukaemia : implications for monitoring of minimal residual disease

    van Wering, ER; Van der Linden-Schrever, BEM; Szczepanski, T; Willemse, MJ; Baars, EA; Van Wijngaarde-Schmitz, HM; Kamps, WA; Van Dongen, JJM

    2000-01-01

    We studied 57 childhood acute lymphoblastic leukaemia (ALL) patients who remained in continuous complete remission after treatment according to the Dutch Childhood Leukaemia Study Group ALL-8 protocols. The patients were monitored at 18 time points during and after treatment [640 bone marrow (BM) an

  8. Phase 1 Dose- Escalation Trial of Clofarabine Followed by Escalating Dose of Fractionated Cyclophosphamide in Adults with Relapsed or Refractory Acute Leukaemias

    Zeidan, Amer M.; Ricklis, Rebecca M.; Carraway, Hetty E.; Yun, Hyun D.; Greer, Jacqueline M.; Smith, B. Douglas; Levis, Mark J.; McDevitt, Michael A.; Pratz, Keith W.; Showel, Margaret M.; Gladstone, Douglas E; Gore, Steven D.; Judith E Karp

    2012-01-01

    The prognosis of patients with relapsed and refractory acute leukaemia (RRAL) is very poor. Forty patients with RRAL were enrolled (28 acute myeloid leukaemia [AML], 12 acute lymphoblastic leukaemia [ALL]) in this Phase 1 dose-escalation trial of daily-infused clofarabine (CLO) followed by cyclophosphamide (CY) for 4 consecutive days (CLO-CYx4). The median age was 48.5 years. The median number of prior regimens was 2 (range 1–5), and 6/40 patients (15%) had prior allogeneic haematopoietic ste...

  9. ZBTB7A mutations in acute myeloid leukaemia with t(8;21) translocation.

    Hartmann, Luise; Dutta, Sayantanee; Opatz, Sabrina; Vosberg, Sebastian; Reiter, Katrin; Leubolt, Georg; Metzeler, Klaus H; Herold, Tobias; Bamopoulos, Stefanos A; Bräundl, Kathrin; Zellmeier, Evelyn; Ksienzyk, Bianka; Konstandin, Nikola P; Schneider, Stephanie; Hopfner, Karl-Peter; Graf, Alexander; Krebs, Stefan; Blum, Helmut; Middeke, Jan Moritz; Stölzel, Friedrich; Thiede, Christian; Wolf, Stephan; Bohlander, Stefan K; Preiss, Caroline; Chen-Wichmann, Linping; Wichmann, Christian; Sauerland, Maria Cristina; Büchner, Thomas; Berdel, Wolfgang E; Wörmann, Bernhard J; Braess, Jan; Hiddemann, Wolfgang; Spiekermann, Karsten; Greif, Philipp A

    2016-01-01

    The t(8;21) translocation is one of the most frequent cytogenetic abnormalities in acute myeloid leukaemia (AML) and results in the RUNX1/RUNX1T1 rearrangement. Despite the causative role of the RUNX1/RUNX1T1 fusion gene in leukaemia initiation, additional genetic lesions are required for disease development. Here we identify recurring ZBTB7A mutations in 23% (13/56) of AML t(8;21) patients, including missense and truncating mutations resulting in alteration or loss of the C-terminal zinc-finger domain of ZBTB7A. The transcription factor ZBTB7A is important for haematopoietic lineage fate decisions and for regulation of glycolysis. On a functional level, we show that ZBTB7A mutations disrupt the transcriptional repressor potential and the anti-proliferative effect of ZBTB7A. The specific association of ZBTB7A mutations with t(8;21) rearranged AML points towards leukaemogenic cooperativity between mutant ZBTB7A and the RUNX1/RUNX1T1 fusion. PMID:27252013

  10. Acute myeloid leukaemia: a paradigm for the clonal evolution of cancer?

    Carolyn S. Grove

    2014-08-01

    Full Text Available Acute myeloid leukaemia (AML is an uncontrolled clonal proliferation of abnormal myeloid progenitor cells in the bone marrow and blood. Advances in cancer genomics have revealed the spectrum of somatic mutations that give rise to human AML and drawn our attention to its molecular evolution and clonal architecture. It is now evident that most AML genomes harbour small numbers of mutations, which are acquired in a stepwise manner. This characteristic, combined with our ability to identify mutations in individual leukaemic cells and our detailed understanding of normal human and murine haematopoiesis, makes AML an excellent model for understanding the principles of cancer evolution. Furthermore, a better understanding of how AML evolves can help us devise strategies to improve the therapy and prognosis of AML patients. Here, we draw from recent advances in genomics, clinical studies and experimental models to describe the current knowledge of the clonal evolution of AML and its implications for the biology and treatment of leukaemias and other cancers.

  11. Mutations affecting both the rearranged and the unrearranged PML alleles in refractory acute promyelocytic leukaemia.

    Iaccarino, Licia; Ottone, Tiziana; Divona, Mariadomenica; Cicconi, Laura; Cairoli, Roberto; Voso, Maria Teresa; Lo-Coco, Francesco

    2016-03-01

    Acute promyelocytic leukaemia (APL) is characterized by the PML/RARA fusion transcript. PML and RARA mutations have been shown to directly respond to arsenic trioxide (ATO) and all-trans retinoic (ATRA). We analysed the prevalence of PML mutations in 32 patients with de novo or therapy-related APL (t-APL; n = 5), treated with ATO. We identified one ATO-resistant t-APL patient, who presented a PML A216T mutation in both the rearranged and unrearranged PML alleles, and two mutations in the rearranged RARA gene. In this patient, subclones with different PML and RARA mutations acquired clonal dominance during the disease course, probably leading to treatment resistance. PMID:26728337

  12. Initial presentation of CNS-restricted acute lymphoblastic B cell leukaemia as peripheral polyneuropathy.

    Piovezani Ramos, Guilherme; Villasboas Bisneto, Jose C; Chen, Dong; Pardanani, Animesh

    2016-01-01

    We report a case of a 58-year-old woman who presented with a 1-month course of progressive lower and upper extremity weakness in addition to binocular diplopia. Diagnostic lumbar puncture revealed atypical lymphoid cells with 28% blasts. Immunophenotype was consistent with B cell acute lymphoblastic leukaemia (B-ALL). Further work up showed no systemic involvement but extensive thoracolumbar-sacral leptomeningeal disease. The patient was treated with several courses of intrathecal and systemic chemotherapy followed by craniospinal irradiation for consolidation. There was initial steady improvement in neurological symptoms and leptomeningeal disease, the latter being ascertained through radiological studies and cerebrospinal fluid examination. After 10 months of response, the patient relapsed with central nervous system (CNS) and systemic disease. B-ALL is a rare precursor lymphoid neoplasm that generally presents with systemic disease. While CNS involvement is not uncommon, isolated involvement of this compartment without systemic disease is exceedingly rare. PMID:27095809

  13. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia

    Vaitkeviciene, Goda; Forestier, Erik; Hellebostad, Marit;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1-15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland......, Iceland, Norway and Sweden). Ten-year event-free (pEFS(10 y)) survival and overall (pOS(10 y)) survival were 0.75 ± 0.01 and 0.85 ± 0.01, respectively. Although treatment intensity was determined by WBC, non-remission and relapsed patients still had significantly higher WBC than those in remission for B-cell...

  14. A comparative assessment of the curative potential of reduced intensity allografts in acute myeloid leukaemia

    Russell, N H; Kjeldsen, L; Craddock, C;

    2015-01-01

    Allogeneic stem cell transplantation (SCT) provides the best mechanism of preventing relapse in acute myeloid leukaemia (AML). However non-relapse mortality (NRM) negates this benefit in older patients. Reduced intensity conditioning (RIC) permits SCT with reduced NRM, but its contribution to cure...... is uncertain. In the MRC AML15 Trial, patients in remission without favourable risk disease could receive SCT from a matched sibling or unrelated donor (MUD). If aged >45 years, a RIC was recommended and in patients aged 35-44 years, either RIC or myeloablative conditioning was permitted. The aim...... was to determine which approach improved survival and within which prespecified cytogenetic groups. RIC transplants significantly reduced relapse (adjusted hazard ratio (HR) 0.66 (0.50-0.85), P=0.002) compared to chemotherapy The 5-year overall survival from a sibling RIC (61%) was superior to a MUD RIC (37...

  15. Isolation of Rhodotorula. A Case Report in a patient with acute myeloid leukaemia

    Idalmis Reyes Martínez

    2013-10-01

    Full Text Available Rhodotorula species are fungi that are part of the commensal microflora of the skin, nails and mucous membranes. They are playing a significant role as human pathogen in immunocompromised and permanently catheterized patients. In addition, they are included among the emerging infectious agents. We report the case of a 38-year-old female patient suffering from acute myeloid leukaemia, admitted to the Dr. Gustavo Aldereguía Lima Hospital in Cienfuegos for usual treatment and who started presenting fever and general malaise. Yeast of the genus Rhodotorula was isolated in the analysis of the catheter culture. The antifungal amphotericin B was used as treatment since it is effective against species of this genus, helping the patient progress satisfactorily. This case is reported given the rarity of the isolation in our area and the fact that this organism is emerging as an infectious agent.

  16. Unilateral parotid gland swelling as the sole presenting symptom of acute lymphoblastic leukaemia in children

    Yatiee Swany Lahuri

    2015-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL in infants below 1 year of age contributed 2.5–5% of childhood ALL incidence. Children with ALL commonly presented with fever, bruising, mucosal bleeding, bone pain, pallor, hepatosplenomegaly, and lymphadenopathy. Common extra medullary leukaemic infiltration has also been reported at diagnosis of ALL to sites such as the liver, spleen, lymph nodes, brain, testes and even nephromegaly. However ALL presented with parotid infiltration is exceedingly rare. We herein present a case of unilateral parotid enlargement in a child with newly diagnosed ALL. This unusual presentation focuses on the importance of considering ALL in the differential diagnosis of parotid enlargement especially when associated with abnormal blood counts.

  17. Comparison of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia

    A retrospective comparison was made of three methods of central-nervous-system prophylaxis in childhood acute lymphoblastic leukaemia; (1) intrathecal methotrexate only; (2) intermediate-dose methotrexate infusion and intrathecal methotrexate and; (3) 2400 rads cranial irradiation and intrathecal methotrexate. The incidence of primary meningeal relapse was statistically significantly lower in both standard-risk patients (age > 24 months and 120 months and/or white-cell count > 20 000) whose central-nervous-system prophylaxis included cranial irradiation. The disease-free and overall survival of irradiated increased-risk patients was significantly better than that of unirradiated increased-risk patients. The disease-free survival of standard-risk patients who received intermediate-dose methotrexate was statistically superior to that of the remaining standard-risk patients. There were no significant differences in overall survival between the three groups of standard-risk patients. (author)

  18. Hospitalisation for infection prior to diagnosis of acute lymphoblastic leukaemia in children

    Vestergaard, Therese Risom; Rostgaard, Klaus; Grau, Katrine;

    2013-01-01

    BACKGROUND: It has been proposed that infections in infancy and early childhood are associated with a reduced risk of childhood acute lymphoblastic leukaemia (ALL). We tested this hypothesis in a register-based study of hospitalisations for infectious diseases prior to diagnosis of childhood ALL....... PROCEDURE: A nation-wide cohort encompassing all Danish children aged 0-14 years and born between 1977 and 2008 (N = 1,778,129) was established and followed for hospitalisations for infectious diseases and risk of childhood ALL. The exposure was lagged 1 year to limit reverse causality. In the statistical...... hospitalisations for infectious diseases before (incidence rate ratio = 0.92, 95% confidence interval 0.78-1.07) nor at/after 2 years of age (incidence rate ratio = 1.04, 95% confidence interval 0.81-1.32). This also applied to subsets of ALL supposedly initiated prenatally. CONCLUSION: The absence of association...

  19. Human Parvovirus B19 in childhood acute lymphoblastic leukaemia in basrah

    Objective: To investigate the association of human parvovirus B19 infection with the onset of acute lymphoblastic leukaemia and its effect on TEL-AML-1 fusion gene and the presence of mutant P53. Methods: The case-control study was conducted at Basrah Hospital for Paediatrics and Gynaecology, Basrah, Iraq, from May 2009 to April 2010. A total of 100 blood samples were collected from 40 newly diagnosed cases and 60 healthy children to serve as control matched by age and gender. Human parvovirus B19-IgG and anti-P53 antibody were detected by enzyme-linked immunosorbent assay and TEL-AML-1 fusion gene was detected by reverse transcriptase-polymerase chain reaction on extracted ribonucleic acid from fresh blood samples using specified primers. SPSS 15 was used for statistical analysis. Results: A higher proportion of human parvovirus B19-positive cases was found in leukaemic patients (n=19; 47.5%) compared to 12 (20%) in the control group (p<0.05). There was significant association between Tel-Amyl-1 translocation and human parvovirus-B19 infection as 10 (71.4%) of TEL-AML-1 translocation-positive cases had human parvovirus-B19 IgG. On the other hand, there was no association between such infections and P53 gene mutation in the patients. Conclusion: Human parvovirus-B19 infection is common in the population, with higher prevalence among leukaemic patients with significant association between human parvovirus-B19 and TEL-AML-1 fusion gene in patients of acute lymphoblastic leukaemia. (author)

  20. Membrane and Soluble Apo-1 as a Marker of Apoptosis in Patients with Acute Leukaemia

    We have planned this work to evaluate the significance and prognostic values of both membrane and soluble APO- 1 as markers of apoptosis in patients with acute leukaemia before and after chemotherapy. Methods and Materials: For that, 30 patients suffering from acute leukaemia (15 patients with ALL and 15 patients with AML) and 10 apparently healthy individuals serving as control group, were selected and subjected to the following: thorough history and clinical examination, routine investigations including: complete blood picture, bone marrow examination, cytochemistry, immuno phenotyping of the blast cells and specific investigations including: detection of mAPO-1 (CD95) on surface of blast cells by flow cytometry, detection of DNA fragmentation by agarose gel electrophoresis and measurement of soluble APO- 1 by ELISA technique before and after chemotherapy. Results: Surface membrane CD95 was found to be expressed on the majority of ALL blast cells (86.6%) and in only 60% of AML blast cells. The degree of surface membrane expression was variable ranging from 23-86% in ALL and from 43-89% in AML. In both ALL and AML patients, a significant relationship was detected between surface CD95 expression and response to initial induction chemotherapy. Ninety-one percent of ALL patients and 84% of AML patients who had surface CD95 expression> 20% on their blast cells showed complete hematological remission after initial induction chemotherapy. This was confirmed by finding that DNA extracted from patients under chemotherapy, whose blast cells CD95 expression was > 20%, showed DNA fragmentation (DNA laddering) by agarose gel electrophoresis (characteristic of apoptosis). As regards soluble CD95 (SCD95) before starting chemotherapy, no statistically significant difference was observed between the level of soluble CD95 in both ALL and AML patients and the control group ((ρ > 0.05). But, in AML patients, the level of soluble CD95 tended to be elevated (not significantly) in

  1. Activity of Bruton's tyrosine-kinase inhibitor ibrutinib in patients with CD117-positive acute myeloid leukaemia: a mechanistic study using patient-derived blast cells

    Rushworth, Stuart; Pillinger, Genevra; Abdul-Aziz, Amina; Piddock, Rachel; Shafat, Manar S.; Murray, Megan Y; Zaitseva, Lyubov; Lawes, Matthew J.; MacEwan, David J.; Bowles, Kristian M.

    2015-01-01

    Summary Background Roughly 80% of patients with acute myeloid leukaemia have high activity of Bruton's tyrosine-kinase (BTK) in their blast cells compared with normal haemopoietic cells, rendering the cells sensitive to the oral BTK inhibitor ibrutinib in vitro. We aimed to develop the biological understanding of the BTK pathway in acute myeloid leukaemia to identify clinically relevant diagnostic information that might define a subset of patients that should respond to ibrutinib treatment. M...

  2. Primary Cytomegalovirus-Related Eosinophilic Pneumonia in a Three-year-old Child with Acute Lymphoblastic Leukaemia: Case report and literature review

    Mohammed Al Reesi

    2014-10-01

    Full Text Available A diagnosis of eosinophilic pneumonia (EP is rare in patients with acute lymphoblastic leukaemia (ALL. We report a case of EP in association with a primary cytomegalovirus (CMV infection in a three-yearold Omani child with ALL. The patient presented with fever while undergoing maintenance chemotherapy. He was admitted to the Child Health Department of Royal Hospital, in Muscat, Oman, in November 2011. He was initially thought to have sepsis but failed to respond to antibiotics. Chest computed tomography showed diffuse ground glass lung opacification. Bronchoalveolar lavage (BAL cytology was consistent with the diagnosis of EP. Polymerase chain reaction tests for CMV were performed on the BAL and blood samples and were both markedly elevated. The patient made a full recovery after treatment with prednisolone and ganciclovir. The association between CMV infection and EP as well as the management of this combination in immunocompromised patients has never been reported in the English literature.

  3. A randomized study to compare oral fluconazole to amphotericin B in the prevention of fungal infections in patients with acute leukaemia.

    Rozenberg-Arska, M; Dekker, A W; Branger, J; Verhoef, J

    1991-03-01

    In a prospective randomized study the efficacy of fluconazole (50 mg in one single daily dose) was compared with oral amphotericin B in suspension and tablets (each 200 mg four times daily) for prevention of colonization and subsequent infection by yeasts in 50 patients undergoing remission induction treatment for acute leukaemia. All patients received ciprofloxacin for prevention of bacterial infections. Fluconazole was as effective as amphotericin B in preventing severe local and disseminated fungal disease (one documented and one highly suspected infection in each group of patients). Fluconazole effectively prevented yeast colonization of the oropharynx but was less effective than amphotericin B in preventing colonization of the lower alimentary tract. Fifty-two percent of patients receiving fluconazole had persistent positive stool cultures as compared to 4% in the amphotericin B group (P less than 0.01). Fluconazole was better tolerated than amphotericin B. One patient developed an extended rash leading to the termination of fluconazole. PMID:2037541

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

    Robert J Weeks

    Full Text Available 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.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.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.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.

  5. Case report: hydroquinone and/or glutaraldehyde induced acute myeloid leukaemia?

    Alexopoulos Evangelos C

    2006-07-01

    Full Text Available Abstract Background Exposures to high doses of irradiation, to chemotherapy, benzene, petroleum products, paints, embalming fluids, ethylene oxide, herbicides, pesticides, and smoking have been associated with an increased risk of acute myelogenous leukemia (AML. Although there in no epidemiological evidence of relation between X-ray developer, fixer and replenisher liquids and AML, these included glutaraldehyde which has weakly associated with lymphocytic leukemia in rats and hydroquinone has been increasingly implicated in producing leukemia, causing DNA and chromosomal damage, inhibits topo-isomerase II, alter hematopoiesis and inhibit apoptosis of neoplastic cells. Case presentation Two white females (A and B hired in 1985 as medical radiation technologists in a primary care center, in Greece. In July 2001, woman A, 38-years-old, was diagnosed as having acute monocytic leukaemia (FAB M5. The patient did not respond to therapy and died threeweeks later. In August 2001, woman B, 35-year-old, was diagnosed with acute promyelocytic leukaemia (FAB M3. Since discharge, she is in continuous complete remission. Both women were non smokers without any medical history. Shortly after these incidents official inspectors and experts inspected workplace, examined equipment, archives of repairs, notes, interviewed and monitored employees. They concluded that shielding was inadequate for balcony's door but personal monitoring did not show any exceeding of TLV of 20 mSv yearly and cytogenetics analysis did not reveal findings considered to be characteristics of ionizing exposure. Equipment for developing photos had a long list of repairs, mainly leakages of liquids and increases of temperature. On several occasions the floor has been flooded especially during 1987–1993 and 1997–2001. Inspection confirmed a complete lack of ventilation and many spoiled medical x-ray films. Employees reported that an "osmic" level was continuously evident and frequently

  6. ROS & Energy Production Pathways in the Determination of Resistance/ Sensitivity to Glucocorticoids-Induced Apoptosis in 11Acute Lymphoblastic Leukaemia

    Berrou, Ilhem

    2012-01-01

    ABSTRACTGlucocorticoids have long been used in the treatment of acute lymphoblastic leukaemia due to their ability to cause cell cycle arrest and apoptosis of lymphoid cells. However, some patients do not respond to glucocorticoid treatment and the majority, who initially respond, may relapse upon prolonged hormone treatment. The inefficiency of the treatment is mainly attributed to the gradual loss of the cellular sensitivity to glucocorticoid-induced apoptosis. Therefore, the need to unders...

  7. SWOG S0910: A Phase 2 Trial of Clofarabine/Cytarabine/Epratuzumab for Relapsed/Refractory Acute Lymphocytic Leukaemia

    Advani, Anjali S; McDonough, Shannon; Coutre, Steven; Wood, Brent; Radich, Jerald; Mims, Martha; O’Donnell, Margaret; Elkins, Stephanie; Becker, Michael; Othus, Megan; Appelbaum, Frederick R.

    2014-01-01

    Precursor B-acute lymphoblastic leukaemias (pre-B ALLs) comprise the majority of ALLs and virtually all blasts express CD22 in the cytoplasm and on the cell surface. In the present study (Southwestern Oncology Group S0910), we evaluated the addition of epratuzumab, a humanized monoclonal antibody against CD22, to the combination of clofarabine and cytarabine in adults with relapsed/refractory pre-B ALL. The response rate [complete remission and complete remission with incomplete count recover...

  8. DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma

    Hedeland, Rikke L; Hvidt, Kristian; Nersting, Jacob;

    2010-01-01

    To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), met......), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT)....

  9. Obstructive Jaundice Due to a Pancreatic Mass: A Rare Presentation of Acute Lymphoblastic Leukaemia in an Adult

    Sudin Varghese Daniel; Andrew Melvin Smith; Quentin Antony Hill; Krishna Viswanath Menon; Deven Harshad Vani

    2010-01-01

    Context To highlight a rare presentation of acute lymphoblastic leukaemia. Case report A 39-year-old man presented with a 4 month history of weight loss and a 6 week history of upper abdominal pain radiating to the back with nausea and vomiting. Liver function tests showed an obstructive picture, full blood count was normal and on computerised tomography there was diffuse enlargement of the pancreas, with dilatation of the common bile duct and intra hepatic biliary radicles. Four weeks after ...

  10. DNA incorporation of 6-thioguanine nucleotides during maintenance therapy of childhood acute lymphoblastic leukaemia and non-Hodgkin lymphoma

    Hedeland, Rikke L.; Hvidt, Kristian; Nersting, Jacob; Rosthøj, Susanne; Dalhoff, Kim; Lausen, Birgitte; Schmiegelow, Kjeld

    2009-01-01

    Abstract Purpose To explore the DNA incorporation of 6-thioguanine nucleotide levels (DNA-6TGN) during 6-mercaptopurine (6MP) therapy of childhood acute lymphoblastic leukaemia (ALL) and non-Hodgkin lymphoma (NHL) and its relation to erythrocyte levels of their metabolites: 6-thioguanine-nucleotides (E-6TGN), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT). ...

  11. Long-term therapy related side effect on endocrine system among survivor with paediatric brain tumour and acute lymphoblastic leukaemia

    Chan, Shu-wing, Sophia; 陳舒穎

    2015-01-01

    Background: Acute lymphoblastic leukaemia (ALL) and brain tumours are frequently seen in childhood malignancies. With the improved effectiveness of treatments, approximately 70–80% patients can be cured of their primary illness. However, therapy-related long-term sequelae among survivors are becoming a major concern. Traditional treatments include surgery, radiation and chemotherapy, and these have been shown to have prolonged side effects on the endocrine system, and symptoms may develop mon...

  12. Asparaginase-associated pancreatitis in children with acute lymphoblastic leukaemia in the NOPHO ALL2008 protocol.

    Raja, Raheel A; Schmiegelow, Kjeld; Albertsen, Birgitte K; Prunsild, Kaie; Zeller, Bernward; Vaitkeviciene, Goda; Abrahamsson, Jonas; Heyman, Mats; Taskinen, Mervi; Harila-Saari, Arja; Kanerva, Jukka; Frandsen, Thomas L

    2014-04-01

    L-asparaginase is an important drug in the treatment of childhood acute lymphoblastic leukaemia (ALL). Treatment is associated with several toxicities, including acute pancreatitis. Clinical course, presentation, re-exposure to L-asparginase after pancreatitis and risk of recurrent pancreatitis within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO ALL toxicity registry. NOPHO ALL2008 includes eight or 15 doses of intramuscular pegylated L-asparginase (PEG-asparaginase) 1000 iu/m(2) /dose at 2-6 weeks intervals, with a total of 30 weeks of exposure to PEG-asparaginase (clinicaltrials.gov no: NCT00819351). Of 786 children, 45 were diagnosed with AAP with a cumulative risk of AAP of 5·9%. AAP occurred after a median of five doses (range 1-13), and 11 d (median) from the latest administration of PEG-Asparaginase. Thirteen patients developed pseudocysts (30%) and 11 patients developed necrosis (25%). One patient died from pancreatitis. Twelve AAP patients were re-exposed to L-asparginase, two of whom developed mild AAP once more, after four and six doses respectively. In conclusion, re-exposure to PEG-asparaginase in ALL patients with mild AAP seems safe. PMID:24428625

  13. Radioimmunotherapy for treatment of acute myeloid leukaemia and myelodysplastic syndrome. Conceptual chances

    The prognosis of patients with acute myeloid leukaemia (AML) has improved considerably by introduction of aggressive consolidation chemotherapy and haematopoietic stem cell transplantation (SCT). Nevertheless, only 20-30% of patients with AML achieve long-term disease-free survival after SCT. The most common cause of treatment failure is relapse. Additionally, mortality rates are significantly increased by therapy-related causes such as toxicity of chemotherapy and complications of SCT. Including radioimmunotherapies in the treatment of AML and myelodyplastic syndrome (MDS) allows for the achievement of a pronounced antileukaemic effect for the reduction of relapse rates on the one hand. On the other hand, no increase of acute toxicity and later complications should be induced. These effects are important for the primary reduction of tumour cells as well as for the myelblative conditioning before SCT. This paper provides a systematic and critical review of the currently used radionuclides and immunoconjugates for the treatment of AML and MDS and summarizes the literature on primary tumour cell reductive radioimmunotherapies on the one hand and conditioning radioimmunotherapies before SCT on the other hand. (orig.)

  14. Risk-adapted stratification and treatment of childhood acute lymphoblastic leukaemia

    Systematic enrolment of children and adolescents with acute lymphoblastic leukaemia (ALL) into clinical trials has allowed the establishment of prognostic parameters derived from initial diagnostic findings. More important, these trials have significantly contributed to the reduction of disease recurrence as much as to the reduction of acute and late side effects. Some problems that are related to the specificity of the parameters used for risk assessment were not overcome: high tumour load by white blood cell count (WBC), age and (rare) cytogenetic subtypes (e.g. t9;22) may characterise a significant proportion of children and adolescents with high-risk ALL. Most patients who will eventually relapse do not present with characteristic features at initial diagnosis. It appears feasible through careful response assessment to identify these patients at risk of relapse, who present initially without specific features. Earlier trials of the ALL-BFM (Berlin/Frankfurt/Muenster) study group and others have demonstrated that inadequate leukaemic blast reduction in the peripheral blood or bone marrow after the first few days of therapy is highly predictive of treatment failure. Using clone-specific polymerase chain reaction-based detection of minimal residual disease (MRD) as done in trial AIEOP-BFM ALL 2000 allowed a close surveillance of specific treatment elements when applied in MRD positive patients. This may facilitate innovative chemotherapy approaches and a more rational use of allogeneic haematopoietic stem cell transplantation. In addition, genetic signatures of treatment response or failure have been identified. (authors)

  15. Neurotoxicity during induction treatment of childhood acute lymphoblastic leukaemia: Two case reports

    Kostić Gordana

    2009-01-01

    Full Text Available Introduction. During chemotherapy of acute lymphoblastic leukaemia (ALL, children sometimes exhibit neurological disturbances. Chemiotherapeutic regimens include methotrexate, administered either intravenously or via intrathecal route. Although multiple drugs are used in addition to methotrexate, the acute neurotoxicity reported in patients is usually attributed to methotrexate. The acute neurotoxicity usually results in stroke-like symptoms such as aphasia, weakness, sensory deficits, ataxia and seizures. Outline of Cases. From 2002 until January 2008, 32 children with ALL were diagnosed and treated at the Children's Hospital in Niš. The patients' age ranged from 1.5 to 16 years. They were treated in accordance with the protocol ALL IC-BFM 2002 (ALL Intercontinental Berlin Frankfurt M'nster 2002. Two of the patients (6.25% exhibited neurotoxicity. After the occurrence of neurological symptoms, the patients were ophthalmologically and neurologically examined. In addition, the magnetic resonance (MR imaging, computerized tomography and electroencephalography were applied. The paper presents two patients, aged 9 and 15 years respectively, who exhibited acute neurotoxicity - methotrexate encephalopathy during ALL treatment. Both patients had tonic-clonic seizures and neurological symptoms in the course of the induction therapy. Neurotoxicity occurred 7 days after the third, and 3 days after the fourth intrathecal methotrexate therapy. MR images confirmed multi-focal morphological changes of brain density in one of the patients, while the other patient had normal CT reading. Even though the development significantly differed, the changes were reversible in both patients. Conclusion. The neurotoxicity in patients with ALL can be combined with significant structural changes of the brain, but also morphological changes can be absent. Several questions concerning aetiology and treatment of neurological events are raised.

  16. Fludarabine and cytarabine combined chemotherapy followed by transfusion of donor blood stem cells for treating relapse of acute leukaemia after allogeneic haematopoietic stem cell transplantation

    YOU Yong; LI Qiu-bai; CHEN Zhi-chao; LI Wei-ming; XIA Ling-hui; ZHOU Hao; ZOU Ping

    2008-01-01

    Background Relapse remains an obstacle to successful allogeneic haematopoietic stem cell transplantation (alIo-HSCT) for patients with acute leukaemia and no standard treatment is available. We assessed fludarabine and cytarabine with transfusion of donor haematopoietic stem cell in treating the relapse of acute leukaemia after alIo-HSCT.Methods Seven patients, median age 34 years, with relapse of acute leukaemia after alIo-HSCT received combination chemotherapy of fludarabine with cytarabine for 5 days. Five patients suffered from acute myeloid leukaemia (2 refractory) and 2 refractory acute lymphoblastic leukaemia. After the transplantation, the median relapse time was 110 days (range,38-185 days). Two days after chemotherapy, 5 patients received infusion of donor's peripheral blood stem cells, mobilized by granulocyte colony stimulating factor. No prophylactic agents of graft versus host diseases were administered.Results Six patients achieved haematopoietic reconstitution. DNA sequence analysis at day 30 after treatment identified all as full donor chimera type. The median observation time was 189 days. After the treatment, the median time for neutrophilic granulocyte value ≥0.5x109/L and for platelet value >20x109/L were 13 days (range, 10-18 days) and 15 days (range, 11-24 days), respectively. Graft versus host disease occurred in 2 patients (acute) and 3 (chronic). Five patients suffered from pulmonary fungal infection (2 died), 3 haemorrhagic cystitis and 2 cytomegalovirus viraemia. The other patients died of leukaemia related deaths. Three patients with chronic graft versus host disease who had received donor peripheral blood stem cells reinfusion have survived for 375 days, 232 days and 195 days, respectively.Conclusions Fludarabine with cytarabine plus the donor haematopoietic stem cell should be considered as an effective therapeutic regimen for relapse of acute leukaemia after alIo-HSCT. The disease free state of patients may increase, thou.gh with

  17. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed;

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  18. A Case Report on the Progression of Myeloid Sarcoma to Form Multiple Metastatic Deposits without Developing Acute Myeloid Leukaemia

    Sunita Kohli

    2015-01-01

    Full Text Available Introduction. Myeloid sarcomas (MS are rare tumours occurring at extramedullary sites. They are usually associated with other haematology disorders such as acute myeloid leukaemia, myelodysplastic syndrome, and chronic myeloproliferative neoplasms. They frequently occur with a diagnosis of acute myeloid leukaemia (AML or with relapse of preexisting disease. Patients with myeloid sarcomas without history or evidence of myeloid leukaemia typically progress to form AML. Case Presentation. A case report of a patient diagnosed with an isolated myeloid sarcoma that rarely did not transform to AML but instead spread to form multiple myeloid sarcomas throughout the body. Discussion. This case identifies the risk of metastatic spread of these tumours rather than the development of AML which is poorly documented in the literature, due to the rarity of cases, and may be significant in the investigation and management of isolated myeloid sarcomas. This case highlights the need for clinicians to consider repeat cross-sectional imaging to investigate unexplained clinical decline or symptoms, when there is no sign of AML progression and to consider radiotherapy treatment early.

  19. Noma in a child with acute leukaemia: when the 'face of poverty' finds an ally.

    Singh, Amitabh; Mandal, Anirban; Seth, Rachna; Kabra, Sushil Kumar

    2016-01-01

    A 2-year-6-month old, appropriately immunised, well-thriving boy, symptomatic for the past 6 months, presented with recurrent fever, progressive pallor, lymphadenopathy and a raw area on the right cheek, with discharging sinus. The necrotising infection of the face developed after one and half months of febrile illness. This febrile illness with bicytopaenia was diagnosed as enteric fever and treated with antibiotics. Skin grafting was performed for the full-thickness defect of the face. The patient continued to have a non-healing oral ulcer with progressive pallor and was finally diagnosed as having acute lymphoblastic leukaemia. Immunodeficiency was ruled out by appropriate investigations. Noma is an indirect measure of extreme poverty, but malignancy is known to predispose to this debilitating condition. The worldwide incidence of Noma is reported to be 30,000-140,000, with a preponderance in sub-Saharan Africa. This case emphasises the need for a thorough search for the underlying illness predisposing to a rare opportunistic infection such as Noma in a well-thriving child. PMID:26740267

  20. The potential of clofarabine in MLL-rearranged infant acute lymphoblastic leukaemia.

    Stumpel, Dominique J P M; Schneider, Pauline; Pieters, Rob; Stam, Ronald W

    2015-09-01

    MLL-rearranged acute lymphoblastic leukaemia (ALL) in infants is the most difficult-to-treat type of childhood ALL, displaying a chemotherapy-resistant phenotype, and unique histone modifications, gene expression signatures and DNA methylation patterns. MLL-rearranged infant ALL responds remarkably well to nucleoside analogue drugs in vitro, such as cytarabine and cladribine, and to the demethylating agents decitabine and zebularine as measured by cytotoxicity assays. These observations led to the inclusion of cytarabine into the treatment regimens currently used for infants with ALL. However, survival chances for infants with MLL-rearranged ALL do still not exceed 30-40%. Here we explored the in vitro potential of the novel nucleoside analogue clofarabine for MLL-rearranged infant ALL. Therefore we used both cell line models as well as primary patient cells. Compared with other nucleoside analogues, clofarabine effectively targeted primary MLL-rearranged infant ALL cells at the lowest concentrations, with median LC50 values of ∼25 nM. Interestingly, clofarabine displayed synergistic cytotoxic effects in combination with cytarabine. Furthermore, at concentrations of 5-10nM clofarabine induced demethylation of the promoter region of the tumour suppressor gene FHIT (Fragile Histidine Triad), a gene typically hypermethylated in MLL-rearranged ALL. Demethylation of the FHIT promoter region was accompanied by subtle re-expression of this gene both at the mRNA and protein level. We conclude that clofarabine is an interesting candidate for further studies in MLL-rearranged ALL in infants. PMID:26188848

  1. Developing "Care Assistant": A smartphone application to support caregivers of children with acute lymphoblastic leukaemia.

    Wang, Jingting; Yao, Nengliang; Wang, Yuanyuan; Zhou, Fen; Liu, Yanyan; Geng, Zhaohui; Yuan, Changrong

    2016-04-01

    Acute lymphoblastic leukaemia (ALL) is the most common childhood malignancy. Caring for children with ALL is an uncommon experience for parents without medical training. They urgently need professional assistance when their children are recovering at home. This paper documents the process of developing an Android application (app) "Care Assistant" for family caregivers of children with ALL. Key informant interviews and focus group studies were used before programming the app. The key informants and focus group members included: caregivers of children with ALL, cancer care physicians and nurses, and software engineers. We found several major challenges faced by caregivers: limited access to evidence-based clinic information, lack of financial and social assistance, deficient communications with doctors or nurses, lack of disease-related knowledge, and inconvenience of tracking treatments and testing results. This feedback was used to develop "Care Assistant". This app has eight modules: personal information, treatment tracking, family care, financial and social assistance, knowledge centre, self-assessment questionnaires, interactive platform, and reminders. We have also developed a web-based administration portal to manage the app. The usability and effectiveness of "Care Assistant" will be evaluated in future studies. PMID:26271029

  2. Subgroups of Paediatric Acute Lymphoblastic Leukaemia Might Differ Significantly in Genetic Predisposition to Asparaginase Hypersensitivity.

    Nóra Kutszegi

    Full Text Available L-asparaginase (ASP is a key element in the treatment of paediatric acute lymphoblastic leukaemia (ALL. However, hypersensitivity reactions (HSRs to ASP are major challenges in paediatric patients. Our aim was to investigate genetic variants that may influence the risk to Escherichia coli-derived ASP hypersensitivity. Sample and clinical data collection was carried out from 576 paediatric ALL patients who were treated according to protocols from the Berlin-Frankfurt-Münster Study Group. A total of 20 single nucleotide polymorphisms (SNPs in GRIA1 and GALNT10 genes were genotyped. Patients with GRIA1 rs4958351 AA/AG genotype showed significantly reduced risk to ASP hypersensitivity compared to patients with GG genotype in the T-cell ALL subgroup (OR = 0.05 (0.01-0.26; p = 4.70E-04, while no such association was found in pre-B-cell ALL. In the medium risk group two SNPs of GRIA1 (rs2055083 and rs707176 were associated significantly with the occurrence of ASP hypersensitivity (OR = 0.21 (0.09-0.53; p = 8.48E-04 and OR = 3.02 (1.36-6.73; p = 6.76E-03, respectively. Evaluating the genders separately, however, the association of rs707176 with ASP HSRs was confined only to females. Our results suggest that genetic variants of GRIA1 might influence the risk to ASP hypersensitivity, but subgroups of patients can differ significantly in this respect.

  3. Modelling the mechanism of GR/c-Jun/Erg crosstalk in apoptosis of acute lymphoblastic leukaemia

    Daphne eChen

    2012-11-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is one of the most common forms of malignancy that occurs in lymphoid progenitor cells, particularly in children. Synthetic steroid hormones glucocorticoids (GCs are widely used as part of the ALL treatment regimens due to their apoptotic function, but their use also brings about various side effects and drug resistance. The identification of the molecular differences between the GCs responsive and resistant cells therefore are essential to decipher such complexity and can be used to improve therapy. However, the emerging picture is complicated as the activities of genes and proteins involved are controlled by multiple factors. By adapting the systems biology framework to address this issue, we here integrated the available knowledge together with experimental data via the building of a series of mathematical models. This rationale enabled us to unravel molecular interactions involving c-Jun in GC induced apoptosis and identify Erg as determinant for GC resistance. The results revealed an alternative potential mechanism where c-Jun may be an indirect GR target that is controlled via an upstream repressor protein. The models also highlight the importance of Erg for GR function, particularly in GC sensitive C7 cells where Erg directly regulates GR in agreement with our previous experimental results. Our models describe potential GR-controlled molecular mechanisms of c-Jun/Bim and Erg regulation. We also demonstrate the importance of using a systematic approach to translate human disease processes into computational models in order to derive information-driven new hypotheses.

  4. Fractional model for pharmacokinetics of high dose methotrexate in children with acute lymphoblastic leukaemia

    Popović, Jovan K.; Spasić, Dragan T.; Tošić, Jela; Kolarović, Jovanka L.; Malti, Rachid; Mitić, Igor M.; Pilipović, Stevan; Atanacković, Teodor M.

    2015-05-01

    The aim of this study is to promote a model based on the fractional differential calculus related to the pharmacokinetic individualization of high dose methotrexate treatment in children with acute lymphoblastic leukaemia, especially in high risk patients. We applied two-compartment fractional model on 8 selected cases with the largest number (4-19) of measured concentrations, among 43 pediatric patients received 24-h methotrexate 2-5 g/m2 infusions. The plasma concentrations were determined by fluorescence polarization immunoassay. Our mathematical procedure, designed by combining Post's and Newton's method, was coded in Mathematica 8.0 and performed on Fujicu Celsius M470-2 PC. Experimental data show that most of the measured values of methotrexate were in decreasing order. However, in certain treatments local maximums were detected. On the other hand, integer order compartmental models do not give values which fit well with the observed data. By the use of our model, we obtained better results, since it gives more accurate behavior of the transmission, as well as the local maximums which were recognized in methotrexate monitoring. It follows from our method that an additional test with a small methotrexate dose can be suggested for the fractional system parameter identification and the prediction of a possible pattern with a full dose in the case of high risk patients. A special feature of the fractional model is that it can also recognize and better fit an observed non-monotonic behavior. A new parameter determination procedure can be successfully used.

  5. Identification of Arsenic Direct-Binding Proteins in Acute Promyelocytic Leukaemia Cells

    Tao Zhang

    2015-11-01

    Full Text Available The identification of arsenic direct-binding proteins is essential for determining the mechanism by which arsenic trioxide achieves its chemotherapeutic effects. At least two cysteines close together in the amino acid sequence are crucial to the binding of arsenic and essential to the identification of arsenic-binding proteins. In the present study, arsenic binding proteins were pulled down with streptavidin and identified using a liquid chromatograph-mass spectrometer (LC-MS/MS. More than 40 arsenic-binding proteins were separated, and redox-related proteins, glutathione S-transferase P1 (GSTP1, heat shock 70 kDa protein 9 (HSPA9 and pyruvate kinase M2 (PKM2, were further studied using binding assays in vitro. Notably, PKM2 has a high affinity for arsenic. In contrast to PKM2, GSTP1and HSPA9 did not combine with arsenic directly in vitro. These observations suggest that arsenic-mediated acute promyelocytic leukaemia (APL suppressive effects involve PKM2. In summary, we identified several arsenic binding proteins in APL cells and investigated the therapeutic mechanisms of arsenic trioxide for APL. Further investigation into specific signal pathways by which PKM2 mediates APL developments may lead to a better understanding of arsenic effects on APL.

  6. Immunoglobulin genes and T-cell receptors as molecular markers in children with acute lymphoblastic leukaemia

    Lazić Jelena

    2009-01-01

    Full Text Available Introduction. Acute lymphoblastic leukaemia (ALL is a malignant clonal disease, one of the most common malignancies in childhood. Contemporary protocols ensure high remission rate and long term free survival. The ability of molecular genetic methods help to establish submicroscopic classification and minimal residual disease (MRD follow up, in major percent responsible for relapse. Objective. The aim of the study was to detect the frequency of IgH and TCR gene rearrangements and their correlation with clinical parameters. Methods. Forty-one children with ALL were enrolled in the study group, with initial diagnosis of IgH and TCR gene rearrangements by polimerase chain reaction ( PCR. MRD follow-up was performed in induction phase when morphological remission was expected, and after intensive chemiotherapy. Results. In the study group IgH rearrangement was detected in 82.9% of children at the diagnosis, while TCR rearrangement was seen in 56.1%. On induction day 33, clonal IgH rearrangements persisted in 39% and TCR rearrangements in 36.5% of children. Conclusion. Molecular analysis of genetic alterations and their correlation with standard prognostic parameters show the importance of risk stratification revision which leads to new therapy intensification approach. MRD stands out as a precise predictive factor for the relapse of disease.

  7. The effect of game-based exercise on infant acute lymphocytic leukaemia patients

    Édgar Cortés-Reyes

    2013-12-01

    Full Text Available Objective. To establish the effect of a game-based exercise programme on Physical Deconditioning Syndrome (PDS in 5 to 12 year-old children suffering Acute Lymphocytic Leukaemia (ALL. Materials and methods. This was a quasi-experimental study involving seven children being treated for ALL at the National Cancer Institute (NCI in Bogotá, Colombia. Fitness determinants (aerobic capacity, muscle strength, flexibility, motor skills and proprioception were initially assessed to establish their exercise regime category, classifying subjects into three levels. Post-intervention assessment at the end of the programme verified changes in such determinants. Results. Seven children aged 5 to 12 years-old (9±2.13 years suffering from ALL (4 girls and 3 boys met the inclusion criteria. Most determinants underwent changes leading to an increase in patients' evaluation scores (except for muscle strength, which remained constant. Whilst determinant variation was important, a greater difference was found when the overall score was analysed (p=0.05, signifying that the intervention had changed these children's health status. Conclusion. Game-based exercise was useful for managing PDS in 5 to12 year-old ALL patients and suggested new ways of providing an intervention concerning physical therapy. However, studies involving a larger target population and longer intervention time are needed to identify new findings in this field.

  8. Awareness of acute myeloid leukaemia risk induced by diagnosis of a myelodysplastic syndrome.

    Ousseine, Youssoufa M; Butow, Phyllis N; Julian-Reynier, Claire; Dring, Rebecca; Festy, Patrick; Fenaux, Pierre; Vey, Norbert; Mancini, Julien

    2016-07-01

    Myelodysplastic syndromes (MDS) can evolve to acute myeloid leukaemia (AML) in approximately 30% of cases. Knowing their AML risk is important for patients because it might impact adherence to care and psychological health. The aim of this study was to evaluate the awareness of AML risk among MDS patients and to study the factors associated with this awareness. A self-administered questionnaire was mailed to all members of French and Australian patients' national MDS associations. Data of 301 patients were analysed. Patients were satisfied with the information they had received, but 33.2% did not know that they had an increased risk of developing AML. Younger age, higher-risk MDS treatment, preferences for health-related information and satisfaction with information provided about treatment were the factors independently associated with awareness of AML risk. Compared to unaware patients, patients knowing their risk were more likely to participate in a hypothetical clinical trial (83.0% vs 72.4%, p=0.043). More efforts are needed to provide more systematic information about AML risk to patients wishing to know it. More research is needed to study if increasing awareness can lead to more active engagement of MDS patients in their care and can increase the rate of clinical trial participation. PMID:27173089

  9. A Fatal Case of Acute Myeloid Leukaemia-Methotrexate Related or Primary Autoimmune Disease Related: A Rare Case Report.

    Agarwal, Saurabh; Kaeley, Nidhi; Gupta, Priyanka; Gupta, Vibha; Bhatia, Rohan

    2016-03-01

    Methotrexate is being used for many years in the treatment of chronic medical disorders e.g. rheumatoid arthritis since 1951. It has been associated with various systemic toxicities and complications including bone marrow suppression and lymphomas. The development of leukaemia in a patient of chronic rheumatoid arthritis is either related with the primary disease or due to the drugs which are used in the treatment like cyclophosphamide. In our present case, a 70-year-old female who was a known case of Rheumatoid Arthritis (RA) and was on methotrexate once a week orally for the past 20 years presented with complaints of loss of appetite, loss of weight and anaemia since 2 months. After thorough examination and investigation, she was diagnosed with acute myeloid leukaemia (AML-M4) with bilateral chest consolidation. PMID:27134915

  10. Childhood acute lymphoblastic leukaemia: experience from a single tertiary care facility of Pakistan

    Objective: To evaluate the demographic features, outcome and prognostic factors seen in children with acute lymphoplastic leukaemia at a tertiary care hospital. Methods: The retrospective descriptive study was conducted at Aga Khan University Hospital, Karachi, comprising data related to children below 15 years of age and treated between January 1997 and December 2006. Kaplan Meir survival curves were used to describe overall and event-free survival rates. Cox Proportional Hazards model was used to describe factors associated with death and relapse. SPSS 16 was the main statistical tool. Results: Of the total 121 children diagnosed with the condition, 79 (65.3%) were males; 86 (71.1%) patients were between 1-9 years of age; Immunophenotyping was done in 99 (81.81%) patients: 86 (87%) cases had precursor B and 13 (13.13%) had precursor T. Of the total, 106(87.6%) patients opted for treatment, while 15 (11.6%) were lost to follow-up. Besides, 26(21.7%) patients had at least one relapse; the most common site being bone marrow in 13 (50%) followed by central nervous system in 9 (36.6%). There were 20(16.5%) deaths in the sample. Infection was the most frequent cause of death. The event-free survival and overall survival was 63% (n=76) and 65% (n=79) respectively. Conclusion: Through the clinical characteristics of children with acute lymphoblastic leukamia were similar to those reported in literature, the outcomes were inferior. The high rate of infections and relapse warrant better supportive care and risk-based approach. (author)

  11. Cell-targeted 114Inm and drug (BCNU) combination therapy in a rat acute lymphoblastic leukaemia

    A proportion of syngeneic female rats inoculated intramuscularly with a lethal T-cell lymphoblastic (Roser) leukaemia are cured by a single intraperitoneal injection of bischloroethylnitrosourea (BCNU) (Carmustine)(10 mg kg-1) given towards the end of the preleukaemic phase (day 7). Additional therapy on day 4, using intravenous leukaemia cells lethally labelled with the radionuclide 114Inm, enhanced the overall cure rate by 30%. The spleen is a major site of indium concentration from the targeting cells so that the continuous local radiation field appears to result in a substantial reduction of the body load of leukaemia cells in the enlarged spleen particularly, thus enhancing the curative potential of the drug. The results demonstrate in principle that in patients in remission a single dose of targeted radiotherapy in the spleen combined sequentially with an appropriate drug might provide considerable aid in eliminating a residual population of leukaemia cells. (author)

  12. Induction of apoptosis and bcl-2 expression in acute lymphoblastic leukaemia and non-Hodgkin's lymphoma in children.

    Pituch-Noworolska, A; Hajto, B; Balwierz, W; Klus, K

    2001-01-01

    bcl-2 expression is associated with the expression of the multidrug resistance molecule (p-gp) and the resistance of leukaemia cells to the induction of apoptosis. The activity of p-gp is the main mechanism of resistance of leukaemia cells to chemotherapy. This study assessed the induction of apoptosis of acute lymphoblastic leukaemia (ALL) and non-Hodgkin's lymphoma (NHL) blastic cells following in vitro treatment with dexamethasone (DXM), vincristine (VCR), and tumour necrosis factor (TNF) in relation to the expression of bcl-2 and p-gp. Common ALL (cALL; n = 24 patients), common ALL with co-expression of myeloid antigens (cALL + My; n = 9), ALL-T (n = 9), and NHL [n = 6 (T type, n = 2; B type, n = 4)] were included. The expression of bcl-2 and p-gp and apoptosis were assayed by flow cytometry. Spontaneous apoptosis was low ( 8%) in NHL and cALL + My. A high frequency of bcl-2 expression was noted in cALL and cALL + My. A high frequency of p-gp expression was observed in cALL + My, ALL-T, and NHL. There was a reverse association between bcl-2 expression and spontaneous apoptosis. DXM-induced apoptosis was observed in 52.63%, TNF-induced in 42.85%, VCR-induced in 36.36%, and GM-CSF-induced in 33.3% of leukaemia and lymphoma cases. DXM and GM-CSF-driven apoptosis was reversibly associated with bcl-2-expression (bcl-2-dependent mechanism). VCR and TNF-driven apoptosis was not associated with bcl-2 expression, suggesting a different, bcl-2-independent, mechanism(s) of its induction. The in vitro induction of apoptosis was not associated with expression of p-gp. PMID:11855781

  13. Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin

    The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion–solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide. (paper)

  14. Targeting etoposide to acute myelogenous leukaemia cells using nanostructured lipid carriers coated with transferrin

    Khajavinia, Amir; Varshosaz, Jaleh; Jafarian Dehkordi, Abbas

    2012-10-01

    The aim of the present study was to evaluate the diverse properties of transferrin (Tf)-conjugated nanostructured lipid carriers (NLCs) prepared using three different fatty amines, including stearylamine (SA), dodecylamine (DA) and spermine (SP), and two different methods for Tf coupling. Etoposide-loaded NLCs were prepared by an emulsion-solvent evaporation method followed by probe sonication. Chemical coupling of NLCs with Tf was mediated by an amide linkage between the surface-exposed amino group of the fatty amine and the carboxyl group of the protein. The physical coating was performed in a Ringer-Hepes buffer medium. NLCs were characterized by their particle size, zeta potential, polydispersity index, drug entrapment percentage, drug release profiles and Tf-coupling efficiency. The cytotoxicity of NLCs on K562 acute myelogenous leukaemia cells was studied by MTT assay, and their cellular uptake was studied by a flow cytometry method. SA-containing NLCs showed the lowest particle size, the highest zeta potential and the largest coupling efficiency values. The drug entrapment percentage and the zeta potential decreased after Tf coupling, but the average particle size increased. SP-containing formulations released their drug contents comparatively slower than SA- or DA-containing NLCs. Unconjugated NLCs released moderately more drug than Tf-NLCs. Flow cytometry studies revealed enhanced cellular uptake of Tf-NLCs compared to unconjugated ones. Blocking Tf receptors resulted in a significantly higher cell survival rate for Tf-NLCs. The highest cytotoxic activity was observed in the chemically coupled SA-containing nanoparticles, with an IC50 value of 15-fold lower than free etoposide.

  15. Extreme hyperferritinemia in the setting of acute myeloid leukaemia: a case report of hemophagocytic lymphohistiocytosis

    Denimal, Damien; Ménégaut, Louise; Rossi, Cédric; Duvillard, Laurence; Masson, David

    2016-01-01

    Introduction Major hyperferritinemia is a rare feature in clinical laboratories associated with a wide variety of disorders, including hemophagocytic lymphohistiocytosis (HLH). The diagnosis of HLH is based on clinical and biological criteria, such as those proposed by the Histiocyte Society. However, several of these criteria are not relevant in the specific setting of hematologic malignancies. Materials and methods A 69-year-old male was treated for an acute myeloid leukaemia. On day 15 after the start of chemotherapy, he developed severe sepsis with high fever, low blood pressure and hepatosplenomegaly. Results Blood tests were marked by extreme hyperferritinemia (191,000 µg/L, reference range: 26-388 µg/L) with increased C-reactive protein (87.0 mg/L) and procalcitonin (1.94 µg/L) and aspartate aminotransferase (499 U/L 37 °C) in the setting of chemotherapy-induced aplasia. This unusual extreme ferritinemia led to suspect HLH triggered by an invasive infection. Under intensive treatment, the clinical status improved and ferritin levels significantly decreased. Conclusions The diagnosis of HLH is usually based on clinical and biological criteria, mainly fever, splenomegaly, cytopenias, hypertriglyceridemia, hypofibrinogenemia, hemophagocytosis and hyperferritinemia. In this patient, the diagnosis of HLH was challenging because several criteria, such as hypertriglyceridemia, hemophagocytosis and hypofibrinogenemia, were absent. In addition, some criteria of HLH are not relevant in the setting of hematologic malignancy, in which fever, splenomegaly, cytopenias and elevated lactate dehydrogenase are commonly observed independently of HLH. This unusual case of extremely high ferritinemia emphasizes the important weight of the ferritin level for the diagnosis of HLH in adult patients in the setting of hematologic malignancies.

  16. Validation of a mouse xenograft model system for gene expression analysis of human acute lymphoblastic leukaemia

    Francis Richard W

    2010-04-01

    Full Text Available Abstract Background Pre-clinical models that effectively recapitulate human disease are critical for expanding our knowledge of cancer biology and drug resistance mechanisms. For haematological malignancies, the non-obese diabetic/severe combined immunodeficient (NOD/SCID mouse is one of the most successful models to study paediatric acute lymphoblastic leukaemia (ALL. However, for this model to be effective for studying engraftment and therapy responses at the whole genome level, careful molecular characterisation is essential. Results Here, we sought to validate species-specific gene expression profiling in the high engraftment continuous ALL NOD/SCID xenograft. Using the human Affymetrix whole transcript platform we analysed transcriptional profiles from engrafted tissues without prior cell separation of mouse cells and found it to return highly reproducible profiles in xenografts from individual mice. The model was further tested with experimental mixtures of human and mouse cells, demonstrating that the presence of mouse cells does not significantly skew expression profiles when xenografts contain 90% or more human cells. In addition, we present a novel in silico and experimental masking approach to identify probes and transcript clusters susceptible to cross-species hybridisation. Conclusions We demonstrate species-specific transcriptional profiles can be obtained from xenografts when high levels of engraftment are achieved or with the application of transcript cluster masks. Importantly, this masking approach can be applied and adapted to other xenograft models where human tissue infiltration is lower. This model provides a powerful platform for identifying genes and pathways associated with ALL disease progression and response to therapy in vivo.

  17. Association between single nucleotide polymorphisms in deoxycytidine kinase and treatment response among acute myeloid leukaemia patients

    JYShi; ZZZhang; SJZhu; YMGu; BWLi; GBai; XTGao; XDHu; JJin; WHuang; WChen; ZChen

    2005-01-01

    Development of resistance to 1-beta-arabinofuranosylcytosine (AraC) is a major obstacle in the treatment of patients with acute myeloid leukaemia (AML). Deficiency of functional deoxycytidine kinase (dCK) plays an important role in AraC resistance in vitro. We screened 5378 bp sequences of the dCK gene, including all exons and the 5' flanking region, and identified two single nucleotide polymorphisms (SNPs) in the regulatory region (rSNPs) with high allele frequencies. These two rSNPs (-201 C>T and -360C>G) formed two major haplotypes. Genotyping with sequencing and MassARRAY system among 122 AML patients showed that those with -360CG/-201CT and -360GG/-201TT compound genotypes (n = 41) displayed a favourable response to chemotherapy whereas those with -360CC/-201CC (n= 81) tended to have a poor response (P = 0.025). Moreover, real-time quantitative reverse transcriptase-polymerase chain reaction showed that patients with -360CG/-201CT and -360GG/-201TT genotypes expressed higher level of dCK mRNA compared to those with the -360CC/-201CC genotype (P = 0.0034). Luciferase-reporter assay showed that dCK 5' regulatory region bearing -360G/-201T genotype alone had an eight-fold greater transcriptional activation activity compared to that with -360C/-201C genotype, whereas co-transfection of both -360G/-201T and -360C/-201C constructs mimicked the heterozygous genotype, which exhibited a four-fold greater activity compared to that with -360C/-201C. These results indicate that rSNP haplotypes of dCK gene may serve as a genetic marker for predicting drug responsiveness, which will be beneficial in establishing more effective AML chemotherapeutic regimens.

  18. Combined bezafibrate and medroxyprogesterone acetate: potential novel therapy for acute myeloid leukaemia.

    Farhat L Khanim

    Full Text Available BACKGROUND: The majority of acute myeloid leukaemia (AML patients are over sixty years of age. With current treatment regimens, survival rates amongst these, and also those younger patients who relapse, remain dismal and novel therapies are urgently required. In particular, therapies that have anti-leukaemic activity but that, unlike conventional chemotherapy, do not impair normal haemopoiesis. PRINCIPAL FINDINGS: Here we demonstrate the potent anti-leukaemic activity of the combination of the lipid-regulating drug bezafibrate (BEZ and the sex hormone medroxyprogesterone acetate (MPA against AML cell lines and primary AML cells. The combined activity of BEZ and MPA (B/M converged upon the increased synthesis and reduced metabolism of prostaglandin D(2 (PGD(2 resulting in elevated levels of the downstream highly bioactive, anti-neoplastic prostaglandin 15-deoxy Delta(12,14 PGJ(2 (15d-PGJ(2. BEZ increased PGD(2 synthesis via the generation of reactive oxygen species (ROS and activation of the lipid peroxidation pathway. MPA directed prostaglandin synthesis towards 15d-PGJ(2 by inhibiting the PGD(2 11beta -ketoreductase activity of the aldo-keto reductase AKR1C3, which metabolises PGD(2 to 9alpha11beta-PGF(2alpha. B/M treatment resulted in growth arrest, apoptosis and cell differentiation in both AML cell lines and primary AML cells and these actions were recapitulated by treatment with 15d-PGJ(2. Importantly, the actions of B/M had little effect on the survival of normal adult myeloid progenitors. SIGNIFICANCE: Collectively our data demonstrate that B/M treatment of AML cells elevated ROS and delivered the anti-neoplastic actions of 15d-PGJ(2. These observations provide the mechanistic rationale for the redeployment of B/M in elderly and relapsed AML.

  19. Metabolomic profiling of drug responses in acute myeloid leukaemia cell lines.

    Stefano Tiziani

    Full Text Available Combined bezafibrate (BEZ and medroxyprogesterone acetate (MPA exert unexpected antileukaemic activities against acute myeloid leukaemia (AML and these activities are associated with the generation of reactive oxygen species (ROS within the tumor cells. Although the generation of ROS by these drugs is supported by preceding studies including our own, the interrelationship between the cellular effects of the drugs and ROS generation is not well understood. Here we report the use of NMR metabolomic profiling to further study the effect of BEZ and MPA on three AML cell lines and to shed light on the underlying mechanism of action. For this we focused on drug effects induced during the initial 24 hours of treatment prior to the onset of overt cellular responses and examined these in the context of basal differences in metabolic profiles between the cell lines. Despite their ultimately profound cellular effects, the early changes in metabolic profiles engendered by these drugs were less pronounced than the constitutive metabolic differences between cell types. Nonetheless, drug treatments engendered common metabolic changes, most markedly in the response to the combination of BEZ and MPA. These responses included changes to TCA cycle intermediates consistent with recently identified chemical actions of ROS. Notable amongst these was the conversion of alpha-ketoglutarate to succinate which was recapitulated by the treatment of cell extracts with exogenous hydrogen peroxide. These findings indicate that the actions of combined BEZ and MPA against AML cells are indeed mediated downstream of the generation of ROS rather than some hitherto unsuspected mechanism. Moreover, our findings demonstrate that metabolite profiles represent highly sensitive markers for genomic differences between cells and their responses to external stimuli. This opens new perspectives to use metabolic profiling as a tool to study the rational redeployment of drugs in new disease

  20. In vitro toxicity assay of cisplatin on mouse acute lymphoblastic leukaemia and spermatogonial stem cells.

    Shabani, R; Ashtari, K; Behnam, B; Izadyar, F; Asgari, H; Asghari Jafarabadi, M; Ashjari, M; Asadi, E; Koruji, M

    2016-06-01

    Testicular cancer is the most common cancer affecting men in reproductive age, and cisplatin is one of the major helpful chemotherapeutic agents for treatment of this cancer. In addition, exposure of testes cancer cells to cisplatin could potentially eliminate tumour cells from germ cells in patients. The aim of this study was to evaluate the effect of cisplatin on viability of mouse acute lymphoblastic leukaemia cell line (EL-4) and neonatal mouse spermatogonial cells in vitro. In this study, the isolated spermatogonial stem cells (SSC) and EL-4 were divided into six groups including control (received medium), sham (received DMSO in medium) and experimental groups which received different doses of cisplatin (0.5, 5, 10 and 15 μg ml(-1) ). Cells viability was evaluated with MTT assay. The identity of the cultured cells was confirmed by the expression of specific markers. Our finding showed that viability of both SSC and EL-4 cells was reduced with the dose of 15 μg/ml when compared to the control group (P ≤ 0.05). Also, the differences between the IC50 in doses 10 and 15 μg/ml at different time were significant (P ≤ 0.05). The number of TUNEL-positive cells was increased, and the BAX and caspase-3 expressions were upregulated in EL4 cells for group that received an effective dose of cisplatin). In conclusion, despite the dramatic effects of cisplatin on both cells, spermatogonial stem cells could form colony in culture. PMID:26428408

  1. Clofarabine and high-dose cytosine arabinoside in the treatment of refractory or relapsed acute myeloid leukaemia

    Tse, Eric; Anskar Y. H. Leung; Sim, Joycelyn; Lee, Harold K.K.; Liu, Herman S. Y.; Yip, Sze-Fai; Kwong, Yok-Lam

    2011-01-01

    Clofarabine (40 mg/m 2/day×5) and high-dose cytosine arabinoside (Ara-C, 1-2 g/m 2/day×5) were used in 10 men and 11 women, at a median age of 45 (22-62) years, with refractory (N=4) and relapsed (N=17) acute myeloid leukaemia, after a median of 3 (2-5) prior regimens. Grade 4 myelosuppression was observed in all cases, with two patients dying of bacterial sepsis. Nine patients achieved a complete remission. Disease status, number of prior therapies, and cytogenetic aberrations were not assoc...

  2. Targeting CD13 (aminopeptidase-N) in turn downregulates ADAM17 by internalization in acute myeloid leukaemia cells

    Bouchet, Sandrine; TANG, RUOPING; Fava, Fanny; Legrand, Ollivier; Bauvois, Brigitte

    2014-01-01

    Secreted matrix metalloproteinases (MMP)-2 and MMP-9 and membrane-anchored aminopeptidase-N/CD13 are abnormally expressed in human acute myeloid leukaemia (AML). We previously showed that CD13 ligation by anti-CD13 monoclonal antibodies can induce apoptosis in AML cells. Here, we assessed ADAM17 expression in primary blood blasts CD13+CD33+ from patients with AML. Primary AML cells expressed ADAM17 transcript and its surface expression was higher in subtype M4 (myelomonocytic) and M5 (monocyt...

  3. Amino-acid substitutions at codon 13 of the N-ras oncogene in human acute myeloid leukaemia

    Bos, Johannes L.; Toksoz, Deniz; Marshall, Christopher J.; Verlaan-de Vries, Matty; Veeneman, Gerrit H.; van der Eb, Alex J.; van Boom, Jacques H.; Janssen, Johannes W. G.; Steenvoorden, Ada C. M.

    1985-06-01

    DNAs from four out of five patients with acute myeloid leukaemia (AML) tested by an in vivo selection assay in nude mice using transfected mouse NIH 3T3 cells were found to contain an activated N-ras oncogene. Using a set of synthetic oligonucleotide probes, we have detected a mutation at codon 13 in all four genes. The same codon is mutated in an additional AML DNA that is positive in the focus-formation assay on 3T3 cells. DNA from the peripheral blood of one patient in remission does not contain a codon 13 mutation.

  4. Haemostatic function and biomarkers of endothelial damage before and after platelet transfusion in patients with acute myeloid leukaemia

    Larsen, A M; Leinøe, E B; Johansson, P I; Larsen, R; Wantzin, P; Birgens, H; Ostrowski, S R

    2015-01-01

    and after platelet transfusion in patients with acute myeloid leukaemia. MATERIALS AND METHODS: Blood was sampled before, 1 and 24 h after platelet transfusion. Primary and secondary haemostasis was evaluated by whole blood aggregometry (Multiplate) and thromboelastography (TEG). Endothelial...... values of most TEG parameters and slightly increased platelet aggregation (all P < 0·05). Endothelial biomarkers were not significantly affected by transfusion. The 1 h sCD40L level correlated positively with Syndecan-1 and soluble thrombomodulin delta values, biomarkers of endothelial damage (both P = 0...

  5. The implications of re-analysing radiation-induced leukaemia in atomic bomb survivors: risks for acute and chronic exposures are different

    Implications of risk estimates, as required for practical radiation protection purposes, were explored through a preliminary re-analysis of leukaemia in the Japanese atomic bomb survivors using a biologically based cancer model. The calculations for the risks posed for contracting leukaemia pointed to important differences between low-dose-rate ('chronic') and high-dose-rate ('acute') exposures. For example, the risks caused by long-term ('chronic') exposures are calculated to be substantially lower than those for 'acute' exposures. In view of these model predictions the results of epidemiological studies are discussed. (author)

  6. Acute myeloid leukaemia induced by mitoxantrone: case report Leucemia mielóide aguda induzida por mitoxantrone: relato de caso

    Walter Oleschko Arruda

    2005-06-01

    Full Text Available Mitoxantrone (MX is an immunosupressant drug used in secondarily progressive multiple sclerosis (SPMS and in relapsing-remitting multiple sclerosis (RRMS. It has a leukemogenesis potential induced by cytogenetic abnormalities, though with a low incidence. Promyelocitic leukaemia (type M3 and other forms of acute myeloblastic leukaemias (M4 and M5 have been described in a few MS patients who received MX during their treatment. We describe a white female patient, 47 year-old, with SPMS (EDSS = 4 with 14 years of disease. She received MX during her disease and developed acute promyelocytic leukaemia (M3, with severe thrombocytopenia 30 months later. She ultimately died due to intracerebral hemorrhage. Other cases of treatment related to AML are reviewed and discussed.Mitoxantrone (MX é uma agente imunossupressor utilizado nas formas progressivas secundárias de esclerose múltipla (EM ou formas surto-remissão sem resposta com outras formas de tratamento (p.ex. beta-interferon, acetato de glatirâmer. Com o uso desta medicação, ocorre uma incidência maior, embora pequena, de desenvolvimento de leucemia mielóide aguda induzida por quimioterápicos. Descrevemos o caso de uma paciente com forma progressiva secundária de EM, submetida a uma dose única de MX de 15mg e que 30 meses após desenvolveu quadro fulminante de leucemia promieloblástica aguda (M3, com trombocitopenia grave. A paciente faleceu por hemorragia intracerebral maciça. É feita revisão de outros casos relatados na literatura e os possíveis mecanismos de desenvolvimento desta complicação grave secundária ao uso do MX.

  7. A comparison of busulphan versus total body irradiation combined with cyclophosphamide as conditioning for autograft or allograft bone marrow transplantation in patients with acute leukaemia

    We retrospectively compared the outcome in patients in the EBMT database transplanted for acute leukaemia from January 1987 to January 1994 who received busulphan and cyclophosphamide (BU/CY) as a pretransplant regimen versus those who received cyclophosphamide and total-body irradiation (CY-TBI). The patients were matched for type of transplant (autologous bone marrow transplantation (ABMT) versus allogenic (BMT)), diagnosis (acute lymphoblast leukaemia (ALL) ora cute myeloid leukaemia (AML)), status (early first complete remission, CR-1) versus intermediate (second or later remission, first relapse)), age, FAB classification for AML, prevention of graft-versus-host disease and year of transplantation. BU/CY and CY/TBI as pretransplant regimens gave similar results in all situations, except ABMT for ALL intermediate stages with more than 2 years from diagnosis to transplantation, where a lower RI and a higher LFS were associated with CY/TBI. (author)

  8. MR features of isolated uterine relapse in an adolescent with acute lymphoblastic leukaemia

    Novellas, Sebastien; Fournol, Maude; Geoffray, Anne; Chevallier, Patrick [Regional Hospital Centre and University of Nice, Medical Imaging Service, Archet 2 Hospital, 151 route de Saint Antoine de Ginestiere, B.P. 3079, Nice Cedex 3 (France); Deville, Anne [Regional Hospital Centre and University of Nice, Paediatric Service, Archet 2 Hospital, Nice (France); Kurzenne, Jean-Yves [Regional Hospital Centre and University of Nice, Paediatric Surgery Service, Archet 2 Hospital, Nice (France)

    2008-03-15

    Relapses of lymphoblastic leukaemia traditionally involve the central nervous system and testes in boys. Involvement of the female pelvic organs is frequently found at autopsy; however, involvement of the cervical uterus is rare and even less commonly symptomatic. A 13-cm uterine mass was discovered in a 15-year-old adolescent with a history of lymphoblastic leukaemia during childhood. Pelvic MRI was the best tool to assess the size, characteristics and invasive nature of this lesion of the uterine cervix. To our knowledge, this is a unique case in that we describe the MRI appearance of a relapsing lymphoblastic leukaemic mass both before and after treatment. (orig.)

  9. Guidelines for the diagnosis and management of acute myeloid leukaemia in pregnancy.

    Ali, Sahra; Jones, Gail L; Culligan, Dominic J; Marsden, Philippa J; Russell, Nigel; Embleton, Nicholas D; Craddock, Charles

    2015-08-01

    Pregnant women should be managed by a multidisciplinary team that includes haematologists, obstetricians, neonatologists and anaesthetists (Grade 1C) As for non-pregnant patients, acute myeloid leukaemia (AML) should be diagnosed using the World Health Organization (WHO) classification (Grade 1A) Women diagnosed with AML in pregnancy should be treated without delay (Grade 1B) When the diagnosis of AML is made in the first trimester, a successful pregnancy outcome is unlikely and spontaneous pregnancy loss in this situation carries considerable risks for the mother. The reasons for and against elective termination should be discussed with the patient (Grade 2C) In the case of presentation beyond 32 weeks gestation, it may be reasonable to deliver the foetus prior to commencement of chemotherapy (Grade 2C) Between 24 and 32 weeks, risks of foetal chemotherapy exposure must be balanced against risks of prematurity following elective delivery at that stage of gestation (Grade 1C) The risk-benefit ratio must be carefully considered before using any drugs in pregnancy (Grade 1C) Where AML induction chemotherapy is delivered, a standard daunorubicin, cytarabine 3 + 10 schedule should be used (Grade 1B) Chemotherapy should be dosed according to actual body weight and adjustments made for weight changes during treatment (Grade 1C) Quinolones, tetracyclines and sulphonamide use should be avoided in pregnancy (Grade 1B) Amphotericin B or lipid derivatives are the antifungal of choice in pregnancy (Grade 2C) Cytomegalovirus (CMV)-negative blood products should be administered during pregnancy regardless of CMV serostatus (Grade 1B) A course of corticosteroids should be considered if delivery is anticipated between 24 and 35 weeks gestation, given over a 48-h period during the week prior to delivery (Grade 1A) Use of magnesium sulphate should be considered in the 24 h prior to delivery if this is before 30 weeks gestation (Grade 1A) Where possible, delivery should be

  10. Allergic complications of L-asparaginase therapy in children with acute lymphoblastic leukaemia

    Konstantinidis Georgios

    2011-01-01

    Full Text Available Introduction. L-asparaginase (L-ASP is one of the most effective medications for the treatment of acute lymphoblastic leukaemia (ALL in children, and allergic reactions to the therapy are considered the most significant side effects. Objective. The aim of this study was to determine the prevalence and type of allergic reactions, as well as to identify potential risk factors for the development of allergic reactions during L-ASP therapy in children with ALL. Methods. The study encompassed 70 patients under 18 years of age, who were treated at the Institute for Child and Youth Healthcare of Vojvodina, Novi Sad in the period January 2000 - June 2009. We analyzed the frequency and type of allergic reactions during the administration of L-ASP, the onset of allergic reaction in relation to the phase of therapy of underlying disease, as well as the prevalence of allergic reactions in relation to drug administration method. Results. Allergic reaction manifested in 17 patients (24%. In 14 patients (82% allergic reaction to L-ASP manifested as urticaria, bronchospasm or anaphylaxis, whereas a mild local reaction was observed in only three patients (18%. In a group treated, according to the high-risk protocol, the prevalence of allergic reactions was statistically significantly higher in the intermediate-risk group of patients (p<0.01, i.e. statistically significantly more frequent, as compared to the standard-risk group of patients (p<0.05. The majority of patients (11; 65% developed allergic reactions to the 9th dose of L-ASP, i.e. the first dose during the reinduction phase. The time interval between the last L-ASP dose in the induction phase and the 1st dose in the reinduction phase was at least four weeks. With respect to administration method, the majority of patients (16; 94% developed allergic reaction after intravenous application of L-ASP. Conclusion. Potential risk factors for the development of allergic reaction to L-ASP are a high-risk therapy

  11. Promoter hypermethylation of the retinoic acid receptor beta2 gene is frequent in acute myeloid leukaemia and associated with the presence of CBFβ-MYH11 fusion transcripts

    Rethmeier, Anita; Aggerholm, Anni; Olesen, Lene Hyldahl;

    2006-01-01

    Silencing of the putative tumour suppressor gene retinoic acid receptor beta2 (RARbeta2) caused by aberrant promoter hypermethylation has been identified in several solid tumours. In order to evaluate the extent of RARbeta2 hypermethylation and transcription in acute myeloid leukaemia (AML) at...

  12. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival

    Forestier, Erik; Heyman, Mats; Andersen, Mette K; Autio, Kirsi; Blennow, Elisabeth; Borgström, Georg; Golovleva, Irina; Heim, Sverre; Heinonen, Kristina; Hovland, Randi; Johannsson, Johann H; Kerndrup, Gitte; Nordgren, Ann; Rosenquist, Richard; Swolin, Birgitta; Johansson, Bertil

    2008-01-01

    The prognostic impact of t(12;21)(p13;q22) [ETV6/RUNX1 fusion] in paediatric acute lymphoblastic leukaemia (ALL) has been extensively debated, particularly with regard to the frequency of late relapses and appropriate treatment regimens. We have retrospectively collected 679 ALLs with known ETV6/...

  13. In vitro drug resistance and prognostic impact of p16(INK4A)/p15(INK4B) deletions in childhood T-cell acute lymphoblastic leukaemia

    Ramakers-van Woerden, NL; Pieters, R; Slater, RM; Loonen, A.H.; Beverloo, HB; van Drunen, E; Heyman, M; Moreno, TC; Rots, MG; van Wering, ER; Kamps, WA; Janka-Schaub, GE; Veerman, AJP

    2001-01-01

    p16 gene deletions are present in about 70% of primary paediatric T-cell acute lymphoblastic leukaemia (T-ALL) and 20% of common/precursor B-cell ALL cases. It is not clear what the impact of the frequent p16 deletions is within the subgroup of T-lineage ALL. We studied the relationship between p16/

  14. Post-treatment intellectual functioning in children treated for acute lymphoblastic leukaemia (ALL) with chemotherapy-only : A prospective, sibling-controlled study

    Jansen, Nathalie C.; Kingma, Annette; Schuitema, Arnout; Bourma, Anke; Huisman, Jaap; Veerman, Anjo J.; Kamps, Willem A.; Bouma, A

    2006-01-01

    intellectual functioning (verbal, performance and full-scale IQ) in 43 children treated for acute lymphoblastic leukaemia (ALL) with chemotherapy-only was evaluated in a nationwide, prospective, sibling-controlled study. Intellectual assessment was performed at diagnosis and repeated shortly after c

  15. Cerebral sinus venous thromboses in children with acute lymphoblastic leukaemia - a multicentre study from the Nordic Society of Paediatric Haematology and Oncology

    Ranta, Susanna; Tuckuviene, Ruta; Mäkipernaa, Anne;

    2014-01-01

    We present a prospective multicentre cohort of 20 children with acute lymphoblastic leukaemia (ALL) and cerebral sinus venous thrombosis (CSVT). The study covers a period of 5 years and comprises 1038 children treated according to the Nordic Society of Paediatric Haematology and Oncology (NOPHO...

  16. Improved outcome of adult acute lymphoblastic leukaemia by moderately intensified chemotherapy which includes a 'pre-induction' course for rapid tumour reduction : preliminary results on 66 patients

    Daenen, S; Van Imhoff, GW; Van den Berg, E; De Kam, PJ; Haaxma-Reiche, H; Vellenga, E; Smit, JW; Halie, RM

    1998-01-01

    Sixty-six consecutive adult patients with acute lymphoblastic leukaemia (ALL) were treated with intensified chemotherapy which included a 'pre-induction' course of cytarabine (AraC) and etoposide (VP16) when the white blood cell count (WBC) was greater than or equal to 30x10(9)/l (18 patients), and

  17. P-gp activity is a critical resistance factor against AVE9633 and DM4 cytotoxicity in leukaemia cell lines, but not a major mechanism of chemoresistance in cells from acute myeloid leukaemia patients

    AVE9633 is a new immunoconjugate comprising a humanized monoclonal antibody, anti-CD33 antigen, linked through a disulfide bond to the maytansine derivative DM4, a cytotoxic agent and potent tubulin inhibitor. It is undergoing a phase I clinical trial. Chemoresistance to anti-mitotic agents has been shown to be related, in part, to overexpression of ABC proteins. The aim of the present study was to investigate the potential roles of P-gp, MRP1 and BCRP in cytotoxicity in AVE9633-induced acute myeloid leukaemia (AML). This study used AML cell lines expressing different levels of P-gp, MRP1 or BCRP proteins and twenty-five samples from AML patients. Expression and functionality of the transporter protein were analyzed by flow cytometry. The cytotoxicity of the drug was evaluated by MTT and apoptosis assays. P-gp activity, but not MRP1 and BCRP, attenuated AVE9633 and DM4 cytotoxicity in myeloid cell lines. Zosuquidar, a potent specific P-gp inhibitor, restored the sensitivity of cells expressing P-gp to both AVE9633 and DM4. However, the data from AML patients show that 10/25 samples of AML cells (40%) were resistant to AVE9633 or DM4 (IC50 > 500 nM), and this was not related to P-gp activity (p-Value: 0.7). Zosuquidar also failed to re-establish drug sensitivity. Furthermore, this resistance was not correlated with CD33 expression (p-Value: 0.6) in those cells. P-gp activity is not a crucial mechanism of chemoresistance to AVE9633. For patients whose resistance to conventional anthracycline AML regimens is related to ABC protein expression, a combination with AVE9633 could be beneficial. Other mechanisms such as microtubule alteration could play an important role in chemoresistance to AVE9633

  18. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor, E-mail: manzoork@aims.amrita.edu, E-mail: ullasmony@aims.amrita.edu [Amrita Centre for Nanoscience and Molecular Medicine, Amrita Institute of Medical Science, Cochin 682 041 (India)

    2011-07-15

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with {approx} 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of {approx} 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in {approx} 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of {approx} 12 nm retained bright fluorescence over an extended duration of {approx} a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of {approx} 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of {approx} 8.2% in human peripheral blood cells (PBMCs) which are CD33{sup low}. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  19. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Retnakumari, Archana; Jayasimhan, Jasusri; Chandran, Parwathy; Menon, Deepthy; Nair, Shantikumar; Mony, Ullas; Koyakutty, Manzoor

    2011-07-01

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with ~ 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of ~ 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in ~ 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of ~ 12 nm retained bright fluorescence over an extended duration of ~ a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of ~ 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of ~ 8.2% in human peripheral blood cells (PBMCs) which are CD33low. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  20. CD33 monoclonal antibody conjugated Au cluster nano-bioprobe for targeted flow-cytometric detection of acute myeloid leukaemia

    Protein stabilized gold nanoclusters (Au-NCs) are biocompatible, near-infrared (NIR) emitting nanosystems having a wide range of biomedical applications. Here, we report the development of a Au-NC based targeted fluorescent nano-bioprobe for the flow-cytometric detection of acute myeloid leukaemia (AML) cells. Au-NCs with ∼ 25-28 atoms showing bright red-NIR fluorescence (600-750 nm) and average size of ∼ 0.8 nm were prepared by bovine serum albumin assisted reduction-cum-stabilization in aqueous phase. The protein protected clusters were conjugated with monoclonal antibody against CD33 myeloid antigen, which is overexpressed in ∼ 99.2% of the primitive population of AML cells, as confirmed by immunophenotyping using flow cytometry. Au-NC-CD33 conjugates having average size of ∼ 12 nm retained bright fluorescence over an extended duration of ∼ a year, as the albumin protein protects Au-NCs against degradation. Nanotoxicity studies revealed excellent biocompatibility of Au-NC conjugates, as they showed no adverse effect on the cell viability and inflammatory response. Target specificity of the conjugates for detecting CD33 expressing AML cells (KG1a) in flow cytometry showed specific staining of ∼ 95.4% of leukaemia cells within 1-2 h compared to a non-specific uptake of ∼ 8.2% in human peripheral blood cells (PBMCs) which are CD33low. The confocal imaging also demonstrated the targeted uptake of CD33 conjugated Au-NCs by leukaemia cells, thus confirming the flow cytometry results. This study demonstrates that novel nano-bioprobes can be developed using protein protected fluorescent nanoclusters of Au for the molecular receptor targeted flow cytometry based detection and imaging of cancer cells.

  1. Fatal veno-occlusive disease of the liver after chemotherapy, whole-body irradiation and bone marrow transplantation for refractory acute leukaemia

    Rapid onset of liver failure with fatal outcome occured in a young woman after successful bone marrow transplantation undertaken for refractory acute leukaemia. Centrilobular necrosis was demonstrated at autopsy and was attributed to prior cytotoxic chemotherapy, possibly potentiated by the total-body irradiation that was used in preparation for the transplant. This association between liver damage and prolonged drug therapy, coupled with the short median survival currently achieved within these chemotherapy regimens, has initiated an evaluation of bone marrow transplantation in patients with leukaemia during the first complete remission, rather than at a later stage when cumulative drug toxicity to the liver may have taken place

  2. Sinonasal Lymphoma Presenting as a Probable Sanctuary Site for Relapsed B Acute Lymphoblastic Leukaemia: A Case Report and Review of the Literature

    W. Y. Lim

    2015-01-01

    Full Text Available Sinonasal lymphoma is a non-Hodgkin lymphoma (NHL representing 1.5% of all lymphomas. It presents as an unremitting ulceration with progressive destruction of midline sinonasal and surrounding structures. Poor prognosis warrants early treatment although diagnosis is challenging and frequently delayed. It is usually primary in origin and to our knowledge the sinonasal region has never been reported as a sanctuary site in leukaemia/lymphoma relapse. We present a unique case of B-cell ALL (acute lymphoblastic leukaemia with late relapse to the nasal septum as a sinonasal lymphoblastic lymphoma and with genetic support for this as a sanctuary site.

  3. Effects of pharmacological and genetic disruption of CXCR4 chemokine receptor function in B-cell acute lymphoblastic leukaemia.

    Randhawa, Shubhchintan; Cho, Byung S; Ghosh, Dipanjan; Sivina, Mariela; Koehrer, Stefan; Müschen, Markus; Peled, Amnon; Davis, Richard E; Konopleva, Marina; Burger, Jan A

    2016-08-01

    B cell acute lymphoblastic leukaemia (B-ALL) cells express high levels of CXCR4 chemokine receptors for homing and retention within the marrow microenvironment. Bone marrow stromal cells (BMSC) secrete CXCL12, the ligand for CXCR4, and protect B-ALL cells from cytotoxic drugs. Therefore, the therapeutic use of CXCR4 antagonists has been proposed to disrupt cross talk between B-ALL cells and the protective stroma. Because CXCR4 antagonists can have activating agonistic function, we compared the genetic and pharmacological deletion of CXCR4 in B-ALL cells, using CRISPR-Cas9 gene editing and CXCR4 antagonists that are in clinical use (plerixafor, BKT140). Both genetic and pharmacological CXCR4 inhibition significantly reduced B-ALL cell migration to CXCL12 gradients and beneath BMSC, and restored drug sensitivity to dexamethasone, vincristine and cyclophosphamide. NOD/SCID/IL-2rγnull mice injected with CXCR4 gene-deleted B-ALL cells had significant delay in disease progression and superior survival when compared to control mice injected with CXCR4 wild-type B-ALL cells. These findings indicate that anti-leukaemia activity of CXCR4 antagonists is primarily due to CXCR4 inhibition, rather than agonistic activity, and corroborate that CXCR4 is an important target to overcome stroma-mediated drug resistance in B-ALL. PMID:27071778

  4. Immunohistochemical distinction of haematogones from B lymphoblastic leukaemia/lymphoma or B-cell acute lymphoblastic leukaemia (B-ALL) on bone marrow trephine biopsies: a study on 62 patients.

    Al-Shieban, Saeed; Byrne, Elizabeth; Trivedi, Pritesh; Morilla, Ricardo; Matutes, Estella; Naresh, Kikkeri N

    2011-08-01

    Haematogones are normal, maturing B-cell precursors. They can be confused with neoplastic immature lymphoid cells of B lymphoblastic leukaemia/lymphoma or B-cell acute lymphoblastic leukaemia (B-ALL). Though multi-colour flow-cytometry strategies for distinguishing haematogones from cells of B-ALL are well-described, similar strategies have not been determined for bone marrow trephine biopsies (BMTB). We revisited the morphological and immunohistochemical features (CD20, CD34, TdT and PAX5 expression) in 69 BMTB from 62 patients - 27 with excess haematogones; seven with residual B-ALL after therapy; 18 with no reported excess of haematogones or residual acute leukaemia on BMTB; and 17 diagnostic samples of B-ALL. The distinctive immunophenotypic pattern of BMTB with excess haematogones was of CD34, TdT, CD20 and PAX5 accounting for increasing proportions of cells in the order mentioned, whereas among B-ALL, the immunohistochemical pattern was of CD20, PAX5 and TdT accounting for an equal proportion of cells. Furthermore, among haematogones, the intensity of CD20 expression was extremely heterogeneous as compared to the neoplastic cells in CD20-positive B-ALL. The TdT-positive haematogones were generally small and uniform, while a certain degree of heterogeneity was noticed among neoplastic B-ALL cells. This study provides a practical strategy to distinguish haematogones from B-ALL cells in BMTB. PMID:21722099

  5. Haematological manifestations and frequency of fab subtypes in patients of acute myeloid leukaemia: a single center study

    To determine the clinical/haematological manifestations and frequency of different subtypes of Acute Myeloid Leukaemia (AML) according to the French-American-British (FAB) classification. Study Design: Descriptive study. Place and Duration of Study: The study was carried out at haematology department of Armed Forces Institute of Pathology (AFIP), Rawalpindi from January 2011 to September 2012. Material and Methods: Retrospective review of documents of patient diagnosed to have acute myeloid leukaemia on bone marrow aspiration was done. Patient's age, gender, major signs and symptoms at time of presentation and haematological parameters of peripheral blood and bone marrow were noted. The subtype of AML according to FAB classification was also documented. Data was entered and analyzed in SPSS 16.0. Results: During the selected study duration acute myeloid leukaemia was diagnosed in 173 patients on bone marrow examination. Out of these 123 (71.1%) were males and 50 (28.9%) were females. Thirty (17.3%) of the patients fell in paediatric age group (< 15 years) while the remaining 143 (82.7%) were in adult age category (> 15 years). The mean age of presentation was 9 years among paediatric patients and 44.5 years among adults. The overall mean age of both these two groups was 38.4 years (3-84 years). Fever (71.6%), generalized weakness (34.1%) and pallor (23.7%) were the three main complaints of the patients, followed by splenomegaly and lymphadenopathy. The mean total leukocyte count, haemoglobin and platelet count were 57.4 * 109/L, 7.9 g/dL and 54 * 109/L respectively. AML-M2 was found to be the most frequent FAB AML subtype among 72 (41.6%) paediatric and adult patients. Conclusion: The main signs and symptoms of the patients of AML presenting to our centre were fever, generalized weakness and pallor. AML-M2 was found to be the most common FAB subtype among AML in children and adults. (author)

  6. Chilblain-like leukaemia cutis.

    Tran, Chi; McEwen, Gary; Fraga, Garth Robert

    2016-01-01

    Chilblain, also known as pernio, is an abnormal inflammatory response to cold, moist environmental conditions. Persistent or atypical lesions should prompt investigation to exclude underlying systemic illness. We describe a case of acute myeloid leukaemia that presented with chilblain-like leukaemia cutis. PMID:27095810

  7. SWOG S0910: a phase 2 trial of clofarabine/cytarabine/epratuzumab for relapsed/refractory acute lymphocytic leukaemia.

    Advani, Anjali S; McDonough, Shannon; Coutre, Steven; Wood, Brent; Radich, Jerald; Mims, Martha; O'Donnell, Margaret; Elkins, Stephanie; Becker, Michael; Othus, Megan; Appelbaum, Frederick R

    2014-05-01

    Precursor B-acute lymphoblastic leukaemias (pre-B ALLs) comprise the majority of ALLs and virtually all blasts express CD22 in the cytoplasm and on the cell surface. In the present study (Southwestern Oncology Group S0910), we evaluated the addition of epratuzumab, a humanized monoclonal antibody against CD22, to the combination of clofarabine and cytarabine in adults with relapsed/refractory pre-B ALL. The response rate [complete remission and complete remission with incomplete count recovery] was 52%, significantly higher than our previous trial with clofarabine/cytarabine alone, where the response rate was 17%. This result is encouraging and suggests a potential benefit to adding epratuzumab to chemotherapy for ALL; however, a randomized trial will be needed to answer this question. PMID:24579885

  8. Pseudozyma aphidis fungaemia with invasive fungal pneumonia in a patient with acute myeloid leukaemia: case report and literature review.

    Joo, Hyonsoo; Choi, Yeon-Geun; Cho, Sung-Yeon; Choi, Jae-Ki; Lee, Dong-Gun; Kim, Hee-Je; Jo, Irene; Park, Yeon-Joon; Lee, Kyo-Young

    2016-01-01

    Pseudozyma species rarely cause invasive diseases in humans, which are usually isolated from plants. There have been anecdotal reports regarding Pseudozyma species infections in patients with underlying diseases or in neonates. However, clinical data and the pathogenicity in humans are still insufficient. We experienced a case of Pseudozyma aphidis fungaemia with invasive fungal pneumonia that developed during reinduction chemotherapy in a 51-year-old male with acute myeloid leukaemia (AML). P. aphidis was suspected based on the morphology of the yeast isolated from the blood and was confirmed via rDNA gene sequencing analysis. The patient successfully underwent stem cell transplantation with continuing antifungal treatment and finally completely recovered from both the AML and infectious complications. Here, we report a case of P. aphidis infection that developed during neutropenia in an AML patient and review the global literature. PMID:26608844

  9. Incidence and significance of FLT3-ITD and NPM1 mutations in patients with normal karyotype acute myeloid leukaemia.

    Haslam, K

    2012-02-01

    BACKGROUND: Acute myeloid leukaemia (AML) is a heterogeneous clonal disorder of haematopoietic progenitor cells. Approximately half of all adult AML patients have a normal karyotype (NK-AML) and an intermediate risk prognosis. AIMS: To determine the incidence and prognostic significance of NPM1 and FLT3-ITD mutations in a population of patients with NK-AML. METHODS: FLT3-ITD and NPM1 mutation status was retrospectively sought in presentation samples from 44 NK-AML patients. RESULTS: FLT3-ITD and NPM1 mutations were detected in 45.5 and 54.5% of patients, respectively, allowing stratification according to genotype. CONCLUSIONS: FLT3-ITD and NPM1 mutation status can be defined in NK-AML. Prospective screening for these mutations is advocated in all NK-AML patients, as the genotype is of clinical importance when considering treatment options including stem cell transplantation.

  10. Association of 1800 cGy cranial irradiation with intellectual function in children with acute lymphoblastic leukaemia

    Cranial radiation therapy in childhood acute lymphoblastic leukaemia has been associated with adverse neuropsychological effects, such as low intelligence. We evaluated 203 children for six years in a multi-centre European study. The patients were divided into two groups: 129 children treated with 1800 cGy of cranial radiation therapy and 74 children who received high-dose methotrexate but no radiation therapy. We found a significant decline in full scale intelligence quotient in the irradiated group that increased with the length of time from diagnosis. Younger age at diagnosis was associated with lower full scale intelligence quotient in the radiated group. Our results indicate that a radiation dose of 1800 cGy can have negative effects on neurocognitive function and we continue to question the benefit of low-dose cranial radiation therapy. (author)

  11. Minimal residual disease evaluation by flow cytometry is a complementary tool to cytogenetics for treatment decisions in acute myeloid leukaemia.

    Vidriales, María-Belén; Pérez-López, Estefanía; Pegenaute, Carlota; Castellanos, Marta; Pérez, José-Juan; Chandía, Mauricio; Díaz-Mediavilla, Joaquín; Rayón, Consuelo; de Las Heras, Natalia; Fernández-Abellán, Pascual; Cabezudo, Miguel; de Coca, Alfonso García; Alonso, Jose M; Olivier, Carmen; Hernández-Rivas, Jesús M; Montesinos, Pau; Fernández, Rosa; García-Suárez, Julio; García, Magdalena; Sayas, María-José; Paiva, Bruno; González, Marcos; Orfao, Alberto; San Miguel, Jesús F

    2016-01-01

    The clinical utility of minimal residual disease (MRD) analysis in acute myeloid leukaemia (AML) is not yet defined. We analysed the prognostic impact of MRD level at complete remision after induction therapy using multiparameter flow cytometry in 306 non-APL AML patients. First, we validated the prognostic value of MRD-thresholds we have previously proposed (≥ 0.1%; ≥ 0.01-0.1%; and information on favourable and adverse cytogenetics, since patients with favourable cytogenetics and high MRD levels have poor prognosis and patients with adverse cytogenetics but undetectable MRD overcomes the adverse prognosis. Interestingly, in patients with intermediate or high MRD levels, intensification with transplant improved the outcome as compared with chemotherapy, while the type of intensification therapy did not influenced the outcome of patients with low MRD levels. Multivariate analysis revealed age, MRD and cytogenetics as independent variables. Moreover, a scoring system, easy in clinical practice, was generated based on MRD level and cytogenetics. PMID:26598032

  12. SWOG S0910: A Phase 2 Trial of Clofarabine/Cytarabine/Epratuzumab for Relapsed/Refractory Acute Lymphocytic Leukaemia

    Advani, Anjali S.; McDonough, Shannon; Coutre, Steven; Wood, Brent; Radich, Jerald; Mims, Martha; O’Donnell, Margaret; Elkins, Stephanie; Becker, Michael; Othus, Megan; Appelbaum, Frederick R.

    2014-01-01

    Summary Precursor B-acute lymphoblastic leukaemias (pre-B ALLs) comprise the majority of ALLs and virtually all blasts express CD22 in the cytoplasm and on the cell surface. In the present study (Southwestern Oncology Group S0910), we evaluated the addition of epratuzumab, a humanized monoclonal antibody against CD22, to the combination of clofarabine and cytarabine in adults with relapsed/refractory pre-B ALL. The response rate [complete remission and complete remission with incomplete count recovery ] was 52%, significantly higher than our previous trial with clofarabine/cytarabine alone, where the response rate was 17%. This result is encouraging and suggests a potential benefit to adding epratuzumab to chemotherapy for ALL; however, a randomized trial will be needed to answer this question. PMID:24579885

  13. Results obtained from the treatment of the acute lymphoid leukaemia (ALL) to children from areas affected by the Chernobyl accident

    Since march 1990, 103 children with acute lymphoid leukaemia (ALL) have received medical treatment in Cuba. All the patients had arrived with a previous treatment, which had them go through different stages of the therapeutic scheme which was in force in our country, the 7-ALL-87. The statistical study by the Kaplan Meler method showed a complete remission period of a 64% at 24 months. The event-free survival was of a 64%, and the global survival was of an 89%. In 25 children (24,2%), a relapse in the bone marrow was produced, where as 4 children (3,8%) underwent a relapse in the central nervous system. Eleven patients died, mostly because of a progression in the disease; 73 (70,8%) are under remission for periods of 3-32 months. Bone marrow autologous transplant was performed in five children with high risk; 2 died and the other 3 are under remission

  14. Chemotherapy in a transplantable myeloid leukaemia in brown Norway rats : studies on BNML as a model for human acute myeloid leukaemia

    L.P. Colly

    1980-01-01

    textabstractLeukaemia accounts for less than 5% of the total number of malignant diseases in the USA {McCredie et al., 1976),· while about 9% of all neeplasros in the Netherlands originate in the lymphatic and blood forming organs. Because of the relatively easy accessibility of the turnoor cells in

  15. Childhood leukaemia

    The debate on whether there is any link between leukaemia clusters and nuclear installations has been raging since the early eighties. A Government Inquiry found no link between childhood leukaemia and residence near Seascale, an area near British Nuclear Fuels Sellafield plant. Research in the 1980s linked childhood leukaemia to fathers' occupations prior to conception in the Seascale plant but also to workers in the iron, steel, farming and chemical industries. This article reviews research findings to date. (UK)

  16. Chronic myeloid leukaemia occurring in a patient with hairy cell leukaemia

    Wandroo, F; Bareford, D; El-Jehani, F

    2000-01-01

    Occurrences of second malignancies in hairy cell leukaemia are well recognised. Most of these malignancies are either solid tumours or lymphoproliferative disorders. The association of myeloproliferative disorders with hairy cell leukaemia (HCL) is very rare. This report describes a case of a patient with HCL who after remaining in remission developed Philadelphia chromosome positive chronic myeloid leukaemia (CML), which rapidly transformed to acute lymphoblastic leukaemia with further cytog...

  17. Detection of prognostically relevant genetic abnormalities in childhood B-cell precursor acute lymphoblastic leukaemia: recommendations from the Biology and Diagnosis Committee of iBFM-SG

    Harrison, Christine J; Haas, Oskar A.; Harbott, W; Biondi, Andrea; Stanulla, Martin; Trka, Jan; Izraeli, Shai

    2010-01-01

    Abstract Treatment of childhood acute lymphoblastic leukaemia (ALL) has improved considerably in recent years. A contributing factor has been the improved stratification for treatment according to a number of factors including genetic determinants of outcome. Here we review the current diagnostic criteria of genetic abnormalities in precursor B-ALL (BCP-ALL), including the relevant technical approaches and the application of the most appropriate methods for the detection of each ab...

  18. Lack of structural rearrangement in c-kit and stem cell factor genes in Hong Kong Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia

    Chui, CH; Leung, PHM; Lau, FY; Wan, TSK; Cheng, G.; Chan, LC

    1998-01-01

    Stem cell factor is a haemopoietic growth factor that interacts with the c-kit--encoded transmembrane tyrosine kinase receptor during signal transduction in haemopoietic progenitor stem cells. We have screened 127 Chinese patients with myelodysplastic syndromes or acute myeloid leukaemia for structural rearrangements in the stem cell factor and c-kit genes using Southern blot analysis. No structural rearrangements were detected in any of the bone marrow samples that were tested. It seems that...

  19. Clofarabine with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming for relapsed and refractory acute myeloid leukaemia

    Becker, Pamela S.; Kantarjian, Hagop M.; Appelbaum, Frederick R.; Petersdorf, Stephen H.; Storer, Barry; Pierce, Sherry; Shan, Jianqin; Hendrie, Paul C.; Pagel, John M.; Shustov, Andrei R.; Stirewalt, Derek L.; Faderl, Stephan; Harrington, Elizabeth; Estey, Elihu H.

    2011-01-01

    This phase I/II study was conducted to determine the maximum tolerated dose, toxicity, and efficacy of clofarabine in combination with high dose cytarabine and granulocyte colony-stimulating factor (G-CSF) priming (GCLAC), in the treatment of patients with relapsed or refractory acute myeloid leukaemia (AML). Dose escalation of clofarabine occurred without dose-limiting toxicity, so most patients were treated at the maximum dose, 25 mg/m2/day with cytarabine 2 g/m2/day, each...

  20. The value of molecular stratification for CEBPA_DM and NPM1_MUT_FLT3_WT genotypes in older patients with acute myeloid leukaemia

    Dickson, G.J.; Bustraan, S.; Hills, R. K.; Ali, A; Goldstone, A. H.; Burnett, A K; Linch, D. C.; Gale, R. E.

    2015-01-01

    Older adult patients (≥60 years) with acute myeloid leukaemia (AML) are generally considered to be poor-risk and there is limited information available regarding risk stratification based on molecular characterization in this age group, particularly for the double-mutant CEBPA (CEBPADM) genotype. To investigate whether a molecular favourable-risk genotype can be identified, we investigated CEBPA, NPM1 and FLT3 status and prognostic impact in a cohort of 301 patients aged 60 years or more with...

  1. Azacitidine prolongs overall survival and reduces infections and hospitalizations in patients with WHO-defined acute myeloid leukaemia compared with conventional care regimens: an update

    Fenaux, P; Mufti, GJ; Hellström-Lindberg, E; Santini, V; Gattermann, N; G. Sanz; List, AF; Gore, SD; Seymour, JF; Backstrom, J; Zimmerman, L.; McKenzie, D; Beach, CL; Silverman, LB

    2008-01-01

    Azacitidine (AZA), as demonstrated in the phase III trial (AZA-001), is the first MDS treatment to significantly prolong overall survival (OS) in higher risk MDS pts ((2007) Blood 110 817). Approximately, one-third of the patients (pts) enrolled in AZA-001 were FAB RAEB-T (≥20–30% blasts) and now meet the WHO criteria for acute myeloid leukaemia (AML) ((1999) Blood 17 3835). Considering the poor prognosis (median survival

  2. AML1/ETO proteins control POU4F1/BRN3A expression and function in t(8;21) acute myeloid leukaemia

    Dunne, Jenny; Gascoyne, Duncan M.; Lister, T. Andrew; Brady, Hugh J.M.; Heidenreich, Olaf; Young, Bryan D.

    2010-01-01

    A variety of genetic lesions, including chromosomal translocations, internal tandem duplications and mutations have been described in acute myeloid leukaemia (AML). Expression profiling has shown that chromosomal translocations, in particular, are associated with distinctive patterns of gene expression. AML exhibiting the translocation t(8;21), which fuses the AML1 and ETO genes, has such a characteristic expression profile. One gene whose expression is highly correlated with the presence of ...

  3. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood

    Celena eScheede-Bergdahl; R Thomas Jagoe

    2013-01-01

    There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL), have increased rates of longterm skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strong...

  4. Genomic imbalances are confined to non-proliferating cells in paediatric patients with acute myeloid leukaemia and a normal or incomplete karyotype.

    Erica Ballabio

    Full Text Available Leukaemia is often associated with genetic alterations such as translocations, amplifications and deletions, and recurrent chromosome abnormalities are used as markers of diagnostic and prognostic relevance. However, a proportion of acute myeloid leukaemia (AML cases have an apparently normal karyotype despite comprehensive cytogenetic analysis. Based on conventional cytogenetic analysis of banded chromosomes, we selected a series of 23 paediatric patients with acute myeloid leukaemia and performed whole genome array comparative genome hybridization (aCGH using DNA samples derived from the same patients. Imbalances involving large chromosomal regions or entire chromosomes were detected by aCGH in seven of the patients studied. Results were validated by fluorescence in situ hybridization (FISH to both interphase nuclei and metaphase chromosomes using appropriate bacterial artificial chromosome (BAC probes. The majority of these copy number alterations (CNAs were confirmed by FISH and found to localize to the interphase rather than metaphase nuclei. Furthermore, the proliferative states of the cells analyzed by FISH were tested by immunofluorescence using an antibody against the proliferation marker pKi67. Interestingly, these experiments showed that, in the vast majority of cases, the changes appeared to be confined to interphase nuclei in a non-proliferative status.

  5. Seasonal variations in the onset of childhood leukaemia and lymphoma.

    Westerbeek, R. M.; Blair, V; Eden, O B; Kelsey, A M; Stevens, R. F.; Will, A. M.; Taylor, G M; Birch, J M

    1998-01-01

    Infection has long been suspected as a possible factor in the aetiology of leukaemia and lymphoma. If seasonal variation in the onset of disease could be shown in any of the diagnostic subgroups of leukaemia or lymphoma, this would provide supportive evidence of an aetiology linked to exposure to infection. All cases in the Manchester Children's Tumour Registry (aged 0-14 years at diagnosis) with acute lymphoblastic leukaemia (ALL), acute non-lymphocytic leukaemia (ANLL), Hodgkin's disease (H...

  6. [Evaluation of systolic and diastolic function of the left ventricle in children with acute lymphoblastic leukaemia before treatment].

    Jackowska, Teresa; Pleskot, Marek; Gołabek, Małgorzata; Rokicka-Milewska, Roma; Wróblewska-Kałuzewska, Maria; Wypych, Agnieszka; Matysiak, Michał; Klus, Kinga; Juraszewska, Ewa; Balwierz, Walentyna; Wójcik, Beata; Sadurska, Elzbieta; Kowalczyk, Jerzy; Stencel, Dariusz; Siwinska, Aldona; Wachowiak, Jacek; Szmyd, Krzysztof; Kukawczyńska, Ewa; Chybicka, Alicja; Płoszyńska, Anna; Aleszewicz-Baranowska, Janina; Balcerska, Anna; Ostański, Mariusz; Pobudejska, Agnieszka; Sońta-Jakimczyk, Danuta; Krenke, Katarzyna; Madry, Wojtek; Syczewska, Małgorzata; Rudziński, Andrzej

    2004-01-01

    Between 1995 and 2001 echo-cardiography was performed in 244 children (128 boys, 116 girls) with acute lymphoblastic leukaemia (ALL) before the beginning of therapy with anthracyclines (medium 5.4 days after the diagnosis). The mean age at diagnosis was 5.4 years (range 9 months to 17.7 years). 189 children (97 boys and 92 girls) were included into the standard and medium risk groups and 55 (31 boys and 24 girls) into the high risk group. 29% of ALL children had disturbances in ECG. Changes in the thickness of the intraventricular septum (%IVSTh) and left ventricular posterior wall (%LVPWTh) were statistically lower, especially in children under 7 years of age. Some children showed lowering of shortening fraction (%FS - 8.6%), ejection fraction (%EF - 10.2%) and corrected velocity of fibber-shortening (Vcfc - 25.8%). Children with decreased shortening fraction (%FS) had left ventricular posterior wall thickness (%LVPWTh) impairment. Changes in diastolic function indicate impaired relaxation and compliance of the left ventricle. Decreased peak early filling velocity (E) was found. There were also longer deceleration time (EDecT) and decreased deceleration from peak E velocity (E/Dec) and longer isovolumetric relaxation time in children in standard and medium risk groups. Shorter acceleration time (EAccT) was seen in the high risk group. Evaluation of cardiac function before anthracycline chemotherapy will allow to select patients with pre-existing cardiac impairment for whom cardioprotective treatment is absolutely necessary. PMID:15686051

  7. Pulmonary fungal infections in patients with acute myeloid leukaemia: is it the time to revise the radiological diagnostic criteria?

    Maccioni, Francesca; Vetere, Simone; De Felice, Carlo; Al Ansari, Najwa; Micozzi, Alessandra; Gentile, Giuseppe; Foà, Robin; Girmenia, Corrado

    2016-06-01

    The definition of pulmonary fungal infections (PFI) according to the EORTC-MSG criteria may lack diagnostic sensitivity due to the possible presentation of PFI with different radiological pictures. We evaluated the hypothesis to apply less restrictive radiological criteria to define PFI in patients with acute myeloid leukaemia (AML) submitted to chemotherapy. Overall, 73 consecutive episodes of pulmonary infiltrates associated to positive serum galactomannan test or fungal isolation or galactomannan detection from respiratory specimens were considered. CT scans acquired at the onset of symptoms (time-0) and within 4 weeks (time-1) were analysed to identify specific (group A) or aspecific radiological signs (group B). Pulmonary infiltrates fulfilled the EORTC-MSG criteria in 49 patients (group A), whereas in 24 patients (group B) they did not reach the criteria due to aspecific CT findings at time-0. Eleven of 21 (52.4%) patients of the group B evaluable for the evolution of the radiological findings fulfilled EORTC-MSG criteria at time-1. All the analysed clinical and mycological characteristics, response to antifungal therapy and survival were comparable in the two groups. Our study seems to confirm the possibility to extend the radiological suspicion of PFI to less restrictive chest CT findings when supported by microbiological criteria in high-risk haematological patients. PMID:26865204

  8. The coagulopathy and thrombotic risk associated with L-asparaginase treatment in adults with acute lymphoblastic leukaemia.

    Truelove, E; Fielding, A K; Hunt, B J

    2013-03-01

    The dramatic improvements seen in the outcome of paediatric patients with acute lymphoblastic leukaemia (ALL) have led to increasing incorporation of L-asparaginase (L-Asp) in adult treatment protocols. However, its use is associated with a disruption in the physiological balance between haemostatic and anticoagulant pathways, with the predominant clinical manifestation being thrombosis. Although L-Asp therapy is known to be associated with an acquired deficiency of antithrombin (AT), the concurrent depletion of fibrinogen and other haemostatic proteins means that the precise mechanism of thrombosis remains to be defined. In vitro coagulation assays are often prolonged but thrombosis rather than haemorrhage is the primary concern. Management of thrombotic events in these patients is based around agents that rely on AT for their anticoagulant effect, even though it is usually depleted. There is currently only limited evidence supporting the use of AT concentrates in either primary prevention or management following an established event. Evidence-based guidelines for prevention and management strategies are lacking. PMID:23099335

  9. Single nucleotide polymorphism in IL1B is associated with infection risk in paediatric acute myeloid leukaemia.

    Sung, L; Dix, D; Cellot, S; Gillmeister, B; Ethier, M C; Roslin, N M; Johnston, D L; Feusner, J; Mitchell, D; Lewis, V; Aplenc, R; Yanofsky, R; Portwine, C; Price, V; Zelcer, S; Silva, M; Bowes, L; Michon, B; Stobart, K; Traubici, J; Allen, U; Beyene, J; den Hollander, N; Paterson, A D

    2016-06-01

    We evaluated single nucleotide polymorphisms (SNPs) associated with infection risk in children with newly diagnosed acute myeloid leukaemia (AML). We conducted a multicentre, prospective cohort study that included children aged ≤18 years with de novo AML. DNA was isolated from blood lymphocytes or buccal swabs, and candidate gene SNP analysis was conducted. Primary outcome was the occurrence of microbiologically documented sterile site infection during chemotherapy. Secondary outcomes were Gram-positive and -negative infections, viridans group streptococcal infection and proven/probable invasive fungal infection. Interpretation was guided by consistency in risk alleles and microbiologic agent with previous literature. Over the study period 254 children and adolescents with AML were enrolled. Overall, 190 (74.8%) had at least one sterile site microbiologically documented infection. Among the 172 with inferred European ancestry and DNA available, nine significant associations were observed; two were consistent with previous literature. Allele A at IL1B (rs16944) was associated with decreased microbiologically documented infection, and allele G at IL10 (rs1800896) was associated with increased risk of Gram-positive infection. We identified SNPs associated with infection risk in paediatric AML. Genotype may provide insight into mechanisms of infection risk that could be used for supportive-care novel treatments. PMID:26932518

  10. CD19 CAR immune pressure induces B-precursor acute lymphoblastic leukaemia lineage switch exposing inherent leukaemic plasticity.

    Jacoby, Elad; Nguyen, Sang M; Fountaine, Thomas J; Welp, Kathryn; Gryder, Berkley; Qin, Haiying; Yang, Yinmeng; Chien, Christopher D; Seif, Alix E; Lei, Haiyan; Song, Young K; Khan, Javed; Lee, Daniel W; Mackall, Crystal L; Gardner, Rebecca A; Jensen, Michael C; Shern, Jack F; Fry, Terry J

    2016-01-01

    Adoptive immunotherapy using chimeric antigen receptor (CAR) expressing T cells targeting the CD19 B lineage receptor has demonstrated marked success in relapsed pre-B-cell acute lymphoblastic leukaemia (ALL). Persisting CAR-T cells generate sustained pressure against CD19 that may drive unique mechanisms of resistance. Pre-B ALL originates from a committed pre-B cell or an earlier progenitor, with potential to reprogram into other hematopoietic lineages. Here we report changes in lineage markers including myeloid conversion in patients following CD19 CAR therapy. Using murine ALL models we study the long-term effects of CD19 CAR-T cells and demonstrate partial or complete lineage switch as a consistent mechanism of CAR resistance depending on the underlying genetic oncogenic driver. Deletion of Pax5 or Ebf1 recapitulates lineage reprogramming occurring during CD19 CAR pressure. Our findings establish lineage switch as a mechanism of CAR resistance exposing inherent plasticity in genetic subtypes of pre-B-cell ALL. PMID:27460500

  11. Permutation tests for centre effect on survival endpoints with application in an acute myeloid leukaemia multicentre study.

    Biard, L; Porcher, R; Resche-Rigon, M

    2014-07-30

    When analysing multicentre data, it may be of interest to test whether the distribution of the endpoint varies among centres. In a mixed-effect model, testing for such a centre effect consists in testing to zero a random centre effect variance component. It has been shown that the usual asymptotic χ(2) distribution of the likelihood ratio and score statistics under the null does not necessarily hold. In the case of censored data, mixed-effects Cox models have been used to account for random effects, but few works have concentrated on testing to zero the variance component of the random effects. We propose a permutation test, using random permutation of the cluster indices, to test for a centre effect in multilevel censored data. Results from a simulation study indicate that the permutation tests have correct type I error rates, contrary to standard likelihood ratio tests, and are more powerful. The proposed tests are illustrated using data of a multicentre clinical trial of induction therapy in acute myeloid leukaemia patients. PMID:24676752

  12. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed;

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction...... with CDKN2B methylation status or karyotype. Median overall survival was 20 months. Hypermethylation of CDH1 was significantly associated with low CR rate, early relapse, and short overall survival (P = 0.003). 5-azacytidine treatment, at a dose of 60 mg/m(2) was well tolerated. Grade III......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  13. Clinical analysis of biphenotypic acute leukaemia%急性双表型白血病临床研究

    陈心传; 勾红峰; 徐才刚

    2004-01-01

    目的探讨急性双表型白血病(biphenotypic acute leukaemia BAL)的临床与生物学特点、治疗及预后.方法本文总结报道了5例BAL的诊治资料,所有患者均结合细胞形态学、组织化学染色、免疫表型,参照急性白血病免疫学特征欧洲协作组(European Group for the Immunological Characterization of Acute Leukemias EGIL)评分系统诊断.结合相关文献复习.结果全部患者均有相应的肿瘤相关的症状.5例患者中,免疫表型为共同表达髓系和B淋巴系标志者2例,共同表达髓系和T淋巴系标志者2例,同时表达三个细胞系标志者1例.CD34阳性者2例.治疗宜采用兼顾急性髓细胞白血病(AML)及急性淋巴细胞白血病(ALL)的化疗方案,但患者对治疗反应差.结论 BAL具有独特的临床、生物学和预后特征.

  14. Childhood leukaemia in Wessex

    Following claims by an anti-nuclear group that there is an excess of acute lymphoblastic leukaemia in children in Dorset the incidence and geographical distribution of the disease was studied in Dorset, Hampshire and Wiltshire. In large urban centres there is a gradient of incidence from lowest in urban centres to highest in surrounding commuter communities and in the smaller towns the distribution tends to be peripheral. The widespread pattern makes it unlikely that the explanation lies with the presence of the Atomic Energy Establishment at Winfrith. Three cases of acute lymphoblastic leukaemia have occurred in the vicinity of Winfrith in the past 30 years: the expected number was 2.4. No abnormal levels of radiation were found in association with the occurrence of leukaemia, nor was there any association between leukaemia and water supplies. The temporal distribution of incidence in Dorset shows a peak of incidence in 1980/81 with a subsequent decline, and data for Wiltshire and Hampshire suggest a similar pattern there, with a peak of incidence in 1979. (author)

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

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

    2000-01-01

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

  16. SIRT2 activates G6PD to enhance NADPH production and promote leukaemia cell proliferation.

    Xu, Shuang-Nian; Wang, Tian-Shi; Li, Xi; Wang, Yi-Ping

    2016-01-01

    Like most other types of cancer cells, leukaemia cells undergo metabolic reprogramming to support rapid proliferation through enhancing biosynthetic processes. Pentose phosphate pathway (PPP) plays a pivotal role in meeting the anabolic demands for cancer cells. However, the molecular mechanism by which PPP contributes to leukaemia remains elusive. Here, we report that leukaemia cell proliferation is dependent on the oxidative branch of PPP, in particular the first and rate-limiting enzyme glucose-6-phosphate dehydrogenase (G6PD). Knockdown of G6PD reduces NADPH level in acute myeloid leukaemia (AML) cell lines. Exogenous lipid supplements partially restore the proliferation of G6PD-depleted cells. Deacetylase SIRT2 promotes NADPH production through deacetylating G6PD at lysine 403 (K403). Activation of G6PD by SIRT2 supports the proliferation and clonogenic activity of leukaemia cells. Chemical inhibitors against SIRT2 suppress G6PD activity, leading to reduced cell proliferation of leukaemia cells, but not normal hematopoietic stem and progenitor cells. Importantly, SIRT2 is overexpressed in clinical AML samples, while K403 acetylation is downregulated and G6PD catalytic activity is increased comparing to that of normal control. Together, our study reveals that acetylation regulation of G6PD is involved in the metabolic reprogramming of AML, and SIRT2 serves as a promising target for further therapeutic investigations. PMID:27586085

  17. Nicorandil in patients with acute coronary syndrome and stable angina undergoing Percutaneous Coronary Intervention: literature review

    Neda Partovi; Homa Falsoleiman

    2014-01-01

    Percutaneous coronary intervention is an option for the treatment of coronary artery disease such as acute coronary syndrome and stable angina.Acute coronary syndrome has two groups including acute myocardial infarction and unstable angina.Periprocedural myocardial infarction is a frequent and prognostically important complication of percutaneous coronary intervention and can be easily monitored by measuring myocardial enzymes. Coronary microvascular dysfunction in patients undergoing primary...

  18. Acute myeloid leukaemia-derived Langerhans-like cells enhance Th1 polarization upon TLR2 engagement.

    Bock, Stephanie; Murgueitio, Manuela S; Wolber, Gerhard; Weindl, Günther

    2016-03-01

    Langerhans cells (LCs) represent a highly specialized subset of epidermal dendritic cells (DCs), yet not fully understood in their function of balancing skin immunity. Here, we investigated in vitro generated Langerhans-like cells obtained from the human acute myeloid leukaemia cell line MUTZ-3 (MUTZ-LCs) to study TLR- and cytokine-dependent activation of epidermal DCs. MUTZ-LCs revealed high TLR2 expression and responded robustly to TLR2 engagement, confirmed by increased CD83, CD86, PD-L1 and IDO expression, upregulated IL-6, IL-12p40 and IL-23p19 mRNA levels IL-8 release. TLR2 activation reduced CCR6 and elevated CCR7 mRNA expression and induced migration of MUTZ-LCs towards CCL21. Similar results were obtained by stimulation with pro-inflammatory cytokines TNF-α and IL-1β whereas ligands of TLR3 and TLR4 failed to induce a fully mature phenotype. Despite limited cytokine gene expression and production for TLR2-activated MUTZ-LCs, co-culture with naive CD4(+) T cells led to significantly increased IFN-γ and IL-22 levels indicating Th1 differentiation independent of IL-12. TLR2-mediated effects were blocked by the putative TLR2/1 antagonist CU-CPT22, however, no selectivity for either TLR2/1 or TLR2/6 was observed. Computer-aided docking studies confirmed non-selective binding of the TLR2 antagonist. Taken together, our results indicate a critical role for TLR2 signalling in MUTZ-LCs considering the leukemic origin of the generated Langerhans-like cells. PMID:26794428

  19. The new low-toxic histone deacetylase inhibitor S-(2) induces apoptosis in various acute myeloid leukaemia cells.

    Cellai, C; Balliu, M; Laurenzana, A; Guandalini, L; Matucci, R; Miniati, D; Torre, E; Nebbioso, A; Carafa, V; Altucci, L; Romanelli, M N; Paoletti, F

    2012-08-01

    Histone deacetylase inhibitors (HDACi) induce tumour cell cycle arrest and/or apoptosis, and some of them are currently used in cancer therapy. Recently, we described a series of powerful HDACi characterized by a 1,4-benzodiazepine (BDZ) ring hybridized with a linear alkyl chain bearing a hydroxamate function as Zn(++)--chelating group. Here, we explored the anti-leukaemic properties of three novel hybrids, namely the chiral compounds (S)-2 and (R)-2, and their non-chiral analogue 4, which were first comparatively tested in promyelocytic NB4 cells. (S)-2 and partially 4--but not (R)-2--caused G0/G1 cell-cycle arrest by up-regulating cyclin G2 and p21 expression and down-regulating cyclin D2 expression, and also apoptosis as assessed by cell morphology and cytofluorimetric assay, histone H2AX phosphorylation and PARP cleavage. Notably, these events were partly prevented by an anti-oxidant. Moreover, novel HDACi prompted p53 and α-tubulin acetylation and, consistently, inhibited HDAC1 and 6 activity. The rank order of potency was (S)-2 > 4 > (R)-2, reflecting that of other biological assays and addressing (S)-2 as the most effective compound capable of triggering apoptosis in various acute myeloid leukaemia (AML) cell lines and blasts from patients with different AML subtypes. Importantly, (S)-2 was safe in mice (up to 150 mg/kg/week) as determined by liver, spleen, kidney and bone marrow histopathology; and displayed negligible affinity for peripheral/central BDZ-receptors. Overall, the BDZ-hydroxamate (S)-2 showed to be a low-toxic HDACi with powerful anti-proliferative and pro-apototic activities towards different cultured and primary AML cells, and therefore of clinical interest to support conventional anti-leukaemic therapy. PMID:22004558

  20. Detection of Telomerase Activity and the Expression of Telomerase Subunits in the Patients with Acute Myelogenous Leukaemia

    李一荣; 吴健民; 王琳; 陈凤花; 胡丽华

    2004-01-01

    Summary: Telomerase activity and the expression of telomerase subunits (for example, telomerase reverse transcriptase and telomerase associated protein 1 and telomerase RNA component) of peripheral white blood cells were detected in the patients with acute myelogenous leukaemia (AML)and the correlation between telomerase activity and the expression of telomerase subunits was observed. In 94 peripheral white blood cells from 18 healthy volunteers and 76 patients with AML,including 31 AML at initial presentation, 24 at relapse and 21 at complete remission, the telomerase activity and telomerase subunits mRNA or RNA were detected by PCR-ELISA and RT-PCR respectively. The results showed that the positive rate of telomerase from patients with AML at initial presentation, at relapse and at complete remission was 74.1 %, 79.2 % and 4.8 % respectively.The positive rate of telomerase reverse transcriptase mRNA from healthy volunteers, AML at initial presentation, AML at relapse and AML at complete remission was 5.6 %, 80. 6 %, 83.3 %and 9.5 % respectively. The positive rate of telomerase associated protein 1 mRNA and telomerase RNA component in all samples were 100 %. It was suggested that the up-regulation of telomerase activity and the expression of telomerase reverse transcriptase is correlated closely with the occurrence and relapse of AML, so telomerase activity and the expression of telomerase reverse transcriptase may be used to estimate the curative effect and predict relapse of AML. Moreover, the upregulation of telomerase activity is correlated with the expression of telomerase reverse transcriptase significantly.

  1. Effect of dexamethasone on quality of life in children with acute lymphoblastic leukaemia: a prospective observational study

    Kaspers Gert Jan L

    2008-11-01

    Full Text Available Abstract Background Glucocorticoids are important in the treatment of childhood acute lymphoblastic leukaemia (ALL. However, cyclic administration of high dose glucocorticoids may cause rapid and substantial changes in quality of life (QoL. The maintenance phase of the Dutch ALL-9 protocol consisted of alternating two weeks on and five weeks off dexamethasone (6 mg/m2/day. The present study was performed to assess the effect of dexamethasone on QoL during treatment for ALL according to this protocol. Methods In a multicentre prospective cohort study, QoL was assessed halfway (T1 and at the end of the two-year treatment (T2. A generic (Child Health Questionnaire and disease specific (PedsQL™ cancer version QoL questionnaire were used to assess QoL in two periods: on and off dexamethasone, respectively. Results 41 children (56% males were evaluated, mean age at diagnosis was 5.6 years. The CHQ physical and psychosocial summary scores were significantly lower than population norms. At T1 and T2, overall QoL showed no significant change. However, regarding specific domains (pain, cognitive functioning, emotion/behaviour and physical functioning QoL decreased over time. QoL was significantly more impaired during periods on dexamethasone. Conclusion Dexamethasone was associated with decreased QoL. At the end of treatment, reported QoL during dexamethasone deteriorated even more on certain scales (pain, cognitive functioning, emotion/behaviour and physical functioning. Knowledge of the specific aspects of QoL is essential to improve counselling and coping in paediatric oncology. Adverse effects of specific drugs on QoL should be taken into account when designing treatment protocols.

  2. The effect of the number of fractions of cranial irradiation on growth in children with acute lymphoblastic leukaemia

    Growth was documented over a period of 7 years in all long-term survivors treated for acute lymphoblastic leukaemia (ALL) with the DAL-70- and BFM-70-protocol. Normal growth was documented in patients of the DAL-70-protocol during and after therapy. In contrast, in children treated with the BFM-70-protocol the mean height standard deviation score (SDS) decreased significantly from 1.21 SDS prior to therapy to 0.80 SDS at the end of therapy and remained unchanged thereafter. Prophylatic cranial irradiation was given in total doses of 15 to 30 Gy. Ten children of the DAL-70- and 20 children of the BFM-70-protocol received 24 Gy of cranial irradiation. No significant change in height-SDS was observed in any patients of the DAL-70- and in 8 patients of the BFM-70-group, who received 24 Gy of cranial irradiation on 16-26 fractions. Adult height in 7 girls and 6 boys was normal and 3.15 cm and 5.06 cm above target height. In the remaining 12 patients of the BFM-70-protocol the total dose of 24 Gy of cranial irradiation was applied in 11-14 fractions. Their height-SDS had fallen significantly from 1.24 SDS before to 0.66 SDS at the end of therapy. Adult height in 4 girls and 6 boys was also normal, but the height increase was comparatively smaller, -2.20 cm below target height in the girls and 1.91 cm above in the boys. We conclude, that the loss of height-SDS in patients with ALL receiving 24 Gy of cranial irradiation is most probably due to the number of fractions of irradiation and not to the total radiation dose or the type of chemotherapy

  3. MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status

    Faraoni Isabella; Laterza Serena; Ardiri Davide; Ciardi Claudia; Fazi Francesco; Lo-Coco Francesco

    2012-01-01

    Abstract Background MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML). The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p) in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation. Findings We found that miR-424 was down-modulated in...

  4. Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial

    Pallis, M; Hills, R.; White, P.; Grundy, M.; Russell, N.; A Burnett

    2011-01-01

    Retrospective analyses in non-randomised cohorts suggest that regimens containing fludarabine/Ara C and/or idarubicin/ara C may be more effective than daunorubicin/AraC (DA)-containing regimens in cases of acute myeloid leukaemia (AML) overexpressing p-glycoprotein (Pgp). We prospectively measured Pgp protein and function by flow cytometry in CD45-gated blasts from 434 AML15 trial patients randomised to remission induction therapy with two courses of FLAG-Ida or DA±etoposide (DA/ADE). In all,...

  5. Elevated serum levels of IGFBP-2 found in children suffering from acute leukaemia is accompanied by the occurrence of IGFBP-2 mRNA in the tumour clone.

    H. Wex; Vorwerk, P.; Mohnike, K; Bretschneider, D.; Kluba, U.; Aumann, V.; Blum, W F; Mittler, U

    1998-01-01

    Insulin-like growth factor-binding proteins (IGFBPs) are important modulators of IGF action. In 50 children suffering from acute lymphoblastic leukaemia (ALL), we studied the serum levels of IGFBP-1,-2 and-3. The mean standard deviation score (SDS) values were estimated to be 0.7, 3.1 and -1.7 for the IGFBP-1,-2 and-3, respectively, compared with the normal range defined by a SDS from -2 to +2. IGFBP-1 and-3 were normal, but for IGFBP-2 we found a significantly elevated serum level compared w...

  6. Sepsis in acute myeloid leukaemia patients receiving high-dose chemotherapy: no impact of chitotriosidase and mannose-binding lectin polymorphisms

    Klostergaard, Anja; Steffensen, Rudi; Møller, Jens K;

    2010-01-01

    Infections after chemotherapy often cause significant morbidity in patients with acute myeloid leukaemia (AML). Chitotriosidase (CHIT) and mannose-binding lectin (MBL) are part of the innate immune system. Polymorphism in the CHIT-coding gene (CHIT1) may be associated with Gram-negative sepsis in...... observed. The severe and long-lasting neutropenia and mucositis after chemotherapy may explain why the MBL system does not protect against sepsis in patients with AML. Replacement therapy with recombinant MBL is not likely to decrease the risk of sepsis in patients with AML....

  7. Azacitidine prolongs overall survival and reduces infections and hospitalizations in patients with WHO-defined acute myeloid leukaemia compared with conventional care regimens: an update.

    Fenaux, P; Mufti, G J; Hellström-Lindberg, E; Santini, V; Gattermann, N; Sanz, G; List, A F; Gore, S D; Seymour, J F; Backstrom, J; Zimmerman, L; McKenzie, D; Beach, C L; Silverman, L B

    2008-01-01

    Azacitidine (AZA), as demonstrated in the phase III trial (AZA-001), is the first MDS treatment to significantly prolong overall survival (OS) in higher risk MDS pts ((2007) Blood 110 817). Approximately, one-third of the patients (pts) enrolled in AZA-001 were FAB RAEB-T (≥20-30% blasts) and now meet the WHO criteria for acute myeloid leukaemia (AML) ((1999) Blood 17 3835). Considering the poor prognosis (median survival <1 year) and the poor response to chemotherapy in these pts, this sub-group analysis evaluated the effects of AZA versus conventional care regimens (CCR) on OS and on response rates in pts with WHO AML. PMID:22275991

  8. Treatment on leukaemia in children

    McCann, S.R. (St. James' s Hospital, Dublin (Ireland))

    1984-06-01

    Since the late 1960s it has become clear that significant numbers of children may achieve long term remissions from acute leukaemia and that substantial numbers are probably cured of their disease. Results in most European countries and North America have failed to demonstrate any improvement on the early ''success'' rates and more than 50% of children will still ultimately die from their diseases. This review will attempt to outline the results of current approaches and treatment, to highlight prognostic factors and to examine the role of bone marrow transplantation in a onetime invariably fatal disease. For the purpose of this review, acute lymphoblastic leukaemia (ALL) only, will be dealt with in detail, as this accounts for 85% of cases of childhood acute leukaemia. 27 refs.

  9. Acute respiratory viral infections in pediatric cancer patients undergoing chemotherapy

    Eliana C.A. Benites

    2014-07-01

    Full Text Available OBJECTIVE: to estimate the prevalence of infection by respiratory viruses in pediatric patients with cancer and acute respiratory infection (ARI and/or fever. METHODS: cross-sectional study, from January 2011 to December 2012. The secretions of nasopharyngeal aspirates were analyzed in children younger than 21 years with acute respiratory infections. Patients were treated at the Grupo em Defesa da Criança Com Câncer (Grendacc and University Hospital (HU, Jundiaí, SP. The rapid test was used for detection of influenza virus (Kit Biotrin, Inc. Ireland, and real-time multiplex polymerase chain reaction (FTD, Respiratory pathogens, multiplex Fast Trade Kit, Malta for detection of influenza virus (H1N1, B, rhinovirus, parainfluenza virus, adenovirus, respiratory syncytial virus, human parechovirus, bocavirus, metapneumovirus, and human coronavirus. The prevalence of viral infection was estimated and association tests were used (χ2 or Fisher's exact test. RESULTS: 104 samples of nasopharyngeal aspirate and blood were analyzed. The median age was 12 ± 5.2 years, 51% males, 68% whites, 32% had repeated ARIs, 32% prior antibiotic use, 19.8% cough, and 8% contact with ARIs. A total of 94.3% were in good general status. Acute lymphocytic leukemia (42.3% was the most prevalent neoplasia. Respiratory viruses were detected in 50 samples: rhinoviruses (23.1%, respiratory syncytial virus AB (8.7%, and coronavirus (6.8%. Co-detection occurred in 19% of cases with 2 viruses and in 3% of those with 3 viruses, and was more frequent between rhinovirus and coronavirus 43. Fever in neutropenic patients was observed in 13%, of which four (30.7 were positive for viruses. There were no deaths. CONCLUSIONS: the prevalence of respiratory viruses was relevant in the infectious episode, with no increase in morbidity and mortality. Viral co-detection was frequent in patients with cancer and ARIs.

  10. Thymoquinone Induces Mitochondria-Mediated Apoptosis in Acute Lymphoblastic Leukaemia in Vitro

    Bassem Y. Sheikh

    2013-09-01

    Full Text Available There has been a growing interest in naturally occurring compounds from traditional medicine with anti-cancer potential. Nigella sativa (black seed is one of the most widely studied plants. This annual herb grows in countries bordering the Mediterranean Sea and India. Thymoquinone (TQ is an active ingredient isolated from Nigella sativa. The anti-cancer effect of TQ, via the induction of apoptosis resulting from mitochondrial dysfunction, was assessed in an acute lymphocyte leukemic cell line (CEMss with an IC50 of 1.5 µg/mL. A significant increase in chromatin condensation in the cell nucleus was observed using fluorescence analysis. The apoptosis was then confirmed by Annexin V and an increased number of cellular DNA breaks in treated cells were observed as a DNA ladder. Treatment of CEMss cells with TQ encouraged apoptosis with cell death-transducing signals by a down-regulation of Bcl-2 and up-regulation of Bax. Moreover, the significant generation of cellular ROS, HSP70 and activation of caspases 3 and 8 were also observed in the treated cells. The mitochondrial apoptosis was clearly associated with the S phase cell cycle arrest. In conclusion, the results from the current study indicated that TQ could be a promising agent for the treatment of leukemia.

  11. Importance of genotyping of Thiopurine S-methyltransferase in children with acute lymphoblastic leukaemia during maintenance therapy

    Dokmanović Lidija

    2008-01-01

    Full Text Available INTRODUCTION Thiopurine S-methyltransferase (TPMT is an enzyme that catalyses the inactivation of mercaptopurine (MP which is widely used in the treatment of acute lymphoblastic leukaemia (ALL of childhood. Potentially fatal myelotoxicity may develop after standard doses of MP in TPMT deficient patients. OBJECTIVES To establish if individually tailored doses of MP can reduce myelotoxicity in ALL patients carrying mutations in the TPMT gene. To establish if variable number of tandem repeats (VNTR genotype influences the treatment effects of MP. METHOD Fifty randomly selected patients treated according to ALL IC-BFM 2002 protocol were tested for most frequent TPMT gene mutations using PCR based methods. VNTR genotype was determined in 20 children by PCR methods. During the maintenance phase, we recorded the number of weeks when therapy was applied in either full doses, reduced doses or when patients were without any therapy. RESULTS Fifty children were examined, 29 boys (58% and 21 girls (42%; age ranged from 1.8-17.3 years (median 6.2 years. Four patients (8% were heterozygous for TPMT mutations, all of them carrying the TPMT*3A variant. After 12, 14, 16 and 19 weeks of therapy with reduced doses of MP, the patients switched to full doses due to good tolerance. There was no therapy omission. Cumulative dose of MP was reduced for 7.8%, 7.4%, 11.2% and 16.6%, respectively, in patients with TPMT mutations. No significant difference was found between children with no mutations and TPMT heterozygotes regarding full dose therapy (53.6 vs. 55.7 weeks, respectively and reduced dose therapy (19.9 vs. 15.2 weeks respectively. The number of detected VNTRs ranged from four to seven. The majority of patients had different number of VNTRs on homologous chromosomes. Most frequently detected polymorphism was VNTR*5. No correlation was found between TPMT and VNTR genotype inheritance. CONCLUSION Obeying pharmacogenetic principles in the treatment of childhood ALL

  12. Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols

    Andersen, Mette Klarskov; Autio, Kirsi; Barbany, Gisela;

    2011-01-01

    The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19)t(1;19)-positive BCP ALL treated on two successive Nordic...

  13. The genetic landscape of paediatric de novo acute myeloid leukaemia as defined by single nucleotide polymorphism array and exon sequencing of 100 candidate genes.

    Olsson, Linda; Zettermark, Sofia; Biloglav, Andrea; Castor, Anders; Behrendtz, Mikael; Forestier, Erik; Paulsson, Kajsa; Johansson, Bertil

    2016-07-01

    Cytogenetic analyses of a consecutive series of 67 paediatric (median age 8 years; range 0-17) de novo acute myeloid leukaemia (AML) patients revealed aberrations in 55 (82%) cases. The most common subgroups were KMT2A rearrangement (29%), normal karyotype (15%), RUNX1-RUNX1T1 (10%), deletions of 5q, 7q and/or 17p (9%), myeloid leukaemia associated with Down syndrome (7%), PML-RARA (7%) and CBFB-MYH11 (5%). Single nucleotide polymorphism array (SNP-A) analysis and exon sequencing of 100 genes, performed in 52 and 40 cases, respectively (39 overlapping), revealed ≥1 aberration in 89%; when adding cytogenetic data, this frequency increased to 98%. Uniparental isodisomies (UPIDs) were detected in 13% and copy number aberrations (CNAs) in 63% (median 2/case); three UPIDs and 22 CNAs were recurrent. Twenty-two genes were targeted by focal CNAs, including AEBP2 and PHF6 deletions and genes involved in AML-associated gene fusions. Deep sequencing identified mutations in 65% of cases (median 1/case). In total, 60 mutations were found in 30 genes, primarily those encoding signalling proteins (47%), transcription factors (25%), or epigenetic modifiers (13%). Twelve genes (BCOR, CEBPA, FLT3, GATA1, KIT, KRAS, NOTCH1, NPM1, NRAS, PTPN11, SMC3 and TP53) were recurrently mutated. We conclude that SNP-A and deep sequencing analyses complement the cytogenetic diagnosis of paediatric AML. PMID:27022003

  14. The Polo-Like Kinase 1 (PLK1 inhibitor NMS-P937 is effective in a new model of disseminated primary CD56+ acute monoblastic leukaemia.

    Alessia Casolaro

    Full Text Available CD56 is expressed in 15-20% of acute myeloid leukaemias (AML and is associated with extramedullary diffusion, multidrug resistance and poor prognosis. We describe the establishment and characterisation of a novel disseminated model of AML (AML-NS8, generated by injection into mice of leukaemic blasts freshly isolated from a patient with an aggressive CD56(+ monoblastic AML (M5a. The model reproduced typical manifestations of this leukaemia, including presence of extramedullary masses and central nervous system involvement, and the original phenotype, karyotype and genotype of leukaemic cells were retained in vivo. Recently Polo-Like Kinase 1 (PLK1 has emerged as a new candidate drug target in AML. We therefore tested our PLK1 inhibitor NMS-P937 in this model either in the engraftment or in the established disease settings. Both schedules showed good efficacy compared to standard therapies, with a significant increase in median survival time (MST expecially in the established disease setting (MST = 28, 36, 62 days for vehicle, cytarabine and NMS-P937, respectively. Importantly, we could also demonstrate that NMS-P937 induced specific biomarker modulation in extramedullary tissues. This new in vivo model of CD56(+ AML that recapitulates the human tumour lends support for the therapeutic use of PLK1 inhibitors in AML.

  15. Early T-cell Precursor Leukaemia:A Subtype of Very High-risk Acute Lymphoblastic Leukaemia%极高危急淋亚型早期前体T细胞白血病的研究进展

    王学文

    2011-01-01

    起源于早期前体T细胞(ETPs)的急性淋巴细胞白血病(ETP-ALL)造成大约20%罹患该病的儿童死亡,其生物学的异质性尚未认识.CD5低表达与CD1a和CD8表达阙如并存即符合ETP基因型,ETP-ALL致癌的转录因子与典型T-ALL病例表达无明显差异,不能以此来分开这两种白血病亚型.ETP-ALL患者对标准加强化疗反应差,预后不佳,缓解失败或血液学复发的累积发生率以ETP-ALL亚组显著为高.%About 20% of children with acute T cell-acute lymphoblastic leukaemia( T-ALL )originating from early T-cell precursors( ETPs )( ETP-ALL )succumb to the disease, suggesting an unrecognized biological heterogeneity.Weak CDs expression combined with lack of CD1 a and CD8 expression could be diagnosed as ETP-ALL, but no clear distinction between ETP-ALL and typical T-ALL cases could be made and used to identify subtypes of T-ALL on the basis of the expression of certain oncogenic transcription factors.Patients of ETP-ALL showed a poor prognosis with use of standard intensive chemotherapy, and the cumulative incidence of remission failure or hematologic relapse was significantly higher.

  16. Interphase fluorescent in situ hybridization deletion analysis of the 9p21 region and prognosis in childhood acute lymphoblastic leukaemia (ALL)

    Kuchinskaya, Ekaterina; Heyman, Mats; Nordgren, Ann;

    2011-01-01

    Interphase fluorescent in situ hybridization (FISH) was applied on diagnostic BM smears from 519 children with acute lymphoblastic leukaemia (ALL) in order to establish the frequency and prognostic importance of 9p21 deletion in children enrolled in the Nordic Society of Paediatric Haematology and...... Oncology (NOPHO) - 2000 treatment protocol. Among the patients, 452 were diagnosed with B-cell precursor (BCP)-ALL and 66 with T-ALL. A higher incidence of 9p21 deletions was found in T-ALL (38%) compared to BCP-ALL (15·7%). Homozygous deletions were found in 19·7% of T-ALL and 4·0% of BCP-ALL; hemizygous...

  17. Estimation of dynamic treatment strategies for maintenance therapy of children with acute lymphoblastic leukaemia: an application of history-adjusted marginal structural models

    Rosthøj, Susanne; Keiding, Niels; Schmiegelow, Kjeld

    2012-01-01

    Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment is...... therefore highly dynamic. In 1992-1996, the Nordic Society of Paediatric Haematology and Oncology (NOPHO) conducted a randomised study (NOPHO-ALL-92) to investigate the effect of a new and more sophisticated dynamic treatment strategy. Unexpectedly, the new strategy worsened the outcome for the girls......, whereas there were no treatment differences for the boys. There are as yet no general guidelines for optimising the treatment. On basis of the data from this study, our goal is to formulate an alternative dosing strategy. We use recently developed methods proposed by van der Laan et al. to obtain...

  18. Outcome of ETV6/RUNX1-positive childhood acute lymphoblastic leukaemia in the NOPHO-ALL-1992 protocol: frequent late relapses but good overall survival

    Forestier, E.; Heyman, M.; Andersen, Mette Klarskov;

    2008-01-01

    The prognostic impact of t(12;21)(p13;q22) [ETV6/RUNX1 fusion] in paediatric acute lymphoblastic leukaemia (ALL) has been extensively debated, particularly with regard to the frequency of late relapses and appropriate treatment regimens. We have retrospectively collected 679 ALLs with known ETV6....../RUNX1 status, as ascertained by fluorescence in situ hybridization or reverse-transcription polymerase chain reaction, treated according to the Nordic Society of Paediatric Haematology and Oncology -ALL-1992 protocol. The assigned risk groups/treatment modalities for the 171 (25%) patients with t(12...... almost 50% of all relapses occurring > or = 5 years after diagnosis. Of all relapses after 6 years, 80% occurred in the t(12;21)-positive group. The overall survival was 94% at 5 years and 88% at 10 years; thus, the treatment of patients in second or later remission is usually successful. As yet, there...

  19. Survival of Mexican Children with Acute Lymphoblastic Leukaemia under Treatment with the Protocol from the Dana-Farber Cancer Institute 00-01

    Elva Jiménez-Hernández

    2015-01-01

    Full Text Available Our aim in this paper is to describe the results of treatment of acute lymphoblastic leukaemia (ALL in Mexican children treated from 2006 to 2010 under the protocol from the Dana-Farber Cancer Institute (DFCI 00-01. The children were younger than 16 years of age and had a diagnosis of ALL de novo. The patients were classified as standard risk if they were 1–9.9 years old and had a leucocyte count 100 × 109/L. The poor outcomes were associated with toxic death during induction, complete remission, and relapse. These factors remain the main obstacles to the success of this treatment in our population.

  20. High white blood cell count at diagnosis of childhood acute lymphoblastic leukaemia: biological background and prognostic impact. Results from the NOPHO ALL-92 and ALL-2000 studies

    Vaitkeviciene, G; Forestier, E; Hellebostad, M;

    2011-01-01

    Prognostic impact of peripheral blood white blood cell count (WBC) at the diagnosis of childhood acute lymphoblastic leukaemia (ALL) was evaluated in a population-based consecutive series of 2666 children aged 1–15 treated for ALL between 1992 and 2008 in the five Nordic countries (Denmark, Finland......, Iceland, Norway and Sweden). Ten-year event-free (pEFS10y) survival and overall (pOS10y) survival were 0.75 ± 0.01 and 0.85 ± 0.01, respectively. Although treatment intensity was determined by WBC, nonremission and relapsed patients still had significantly higher WBC than those in remission for B-cell...

  1. Leukoencephalopathy after prophylactic radiation for leukaemia in ataxia telangiectasia.

    Eyre, J A; Gardner-Medwin, D; Summerfield, G P

    1988-01-01

    Children with ataxia telangiectasia have a high probability of developing acute lymphoblastic leukaemia, and have increased sensitivity to chemotherapy and irradiation. We report a 51/2 year old boy who had undiagnosed ataxia telangiectasia when he presented with acute lymphoblastic leukaemia. He subsequently developed a chemoradiation induced leukoencephalopathy after conventional central nervous system prophylaxis.

  2. Indoor radon and childhood leukaemia

    This paper summarises the epidemiological literature on domestic exposure to radon and risk for childhood leukaemia. The results of 12 ecological studies show a consistent pattern of higher incidence and mortality rates for childhood leukaemia in areas with higher average indoor radon concentrations. Although the results of such studies are useful to generate hypotheses, they must be interpreted with caution, as the data were aggregated and analysed for geographical areas and not for individuals. The seven available case - control studies of childhood leukaemia with measurement of radon concentrations in the residences of cases and controls gave mixed results, however, with some indication of a weak (relative risk < 2) association with acute lymphoblastic leukaemia. The epidemiological evidence to date suggests that an association between indoor exposure to radon and childhood leukaemia might exist, but is weak. More case - control studies are needed, with sufficient statistical power to detect weak associations and based on designs and methods that minimise misclassification of exposure and provide a high participation rate and low potential selection bias. (authors)

  3. Arsenic speciation in saliva of acute promyelocytic leukemia patients undergoing arsenic trioxide treatment

    Chen, Baowei; Cao, Fenglin; Yuan, Chungang; Lu, Xiufen; Shen, Shengwen; Zhou, Jin; Le, X Chris

    2013-01-01

    Arsenic trioxide has been successfully used as a therapeutic in the treatment of acute promyelocytic leukemia (APL). Detailed monitoring of the therapeutic arsenic and its metabolites in various accessible specimens of APL patients can contribute to improving treatment efficacy and minimizing arsenic-induced side effects. This article focuses on the determination of arsenic species in saliva samples from APL patients undergoing arsenic treatment. Saliva samples were collected from nine APL pa...

  4. High Bolus Tirofiban vs Abciximab in Acute STEMI Patients Undergoing Primary PCI – The Tamip Study

    Balghith, Mohammed A.

    2012-01-01

    Background: Primary percutaneous coronary intervention (PCI) has been shown to be an effective therapy for patients with acute myocardial infarction (MI). Glycoprotein (GP) IIb/IIIa receptor blockers reduce thrombotic complications in patients undergoing PCI. Most available data relate to Reopro, which has been registered for this indication. GP IIb/IIIa reduce unfavorable outcome in U/A and non ST-elevation myocardial infarction (STEMI) patients. Only few studies focused on high dose Aggrast...

  5. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    Zhu, Hong; Miao, Mei-hua; Ji, Xue-qiang; Xue, Jun; Shao, Xue-jun, E-mail: xuejunshao@hotmail.com

    2015-04-03

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells.

  6. miR-664 negatively regulates PLP2 and promotes cell proliferation and invasion in T-cell acute lymphoblastic leukaemia

    MicroRNAs (miRNAs) play important roles in the pathogenesis of many types of cancers by negatively regulating gene expression at posttranscriptional level. However, the role of microRNAs in leukaemia, particularly T-cell acute lymphoblastic leukaemia (T-ALL), has remained elusive. Here, we identified miR-664 and its predicted target gene PLP2 were differentially expressed in T-ALL using bioinformatics methods. In T-ALL cell lines, CCK-8 proliferation assay indicated that the cell proliferation was promoted by miR-664, while miR-664 inhibitor could significantly inhibited the proliferation. Moreover, migration and invasion assay showed that overexpression of miR-664 could significantly promoted the migration and invasion of T-ALL cells, whereas miR-664 inhibitor could reduce cell migration and invasion. luciferase assays confirmed that miR-664 directly bound to the 3'untranslated region of PLP2, and western blotting showed that miR-664 suppressed the expression of PLP2 at the protein levels. This study indicated that miR-664 negatively regulates PLP2 and promotes proliferation and invasion of T-ALL cell lines. Thus, miR-664 may represent a potential therapeutic target for T-ALL intervention. - Highlights: • miR-664 mimics promote the proliferation and invasion of T-ALL cells. • miR-664 inhibitors inhibit the proliferation and invasion of T-ALL cells. • miR-664 targets 3′ UTR of PLP2 in T-ALL cells. • miR-664 negatively regulates PLP2 in T-ALL cells

  7. Attentional ability among survivors of leukaemia

    Rodgers, J; Horrocks, J; Britton, P.; Kernahan, J

    1999-01-01

    Attentional ability in 19 survivors of acute lymphoblastic leukaemia and 19 sibling controls was assessed using a neuropsychological model of attention. Analysis revealed that children who had received treatment for leukaemia exhibited significantly poorer performance on measures of the "focus encode" and "focus execute" elements of attention and on measures of the ability to respond to external cues and feedback. No significant differences in performance were found for m...

  8. Myeloid Sarcoma of the Uterine Cervix as Presentation of Acute Myeloid Leukaemia after Treatment with Low-Dose Radioiodine for Thyroid Cancer: A Case Report and Review of the Literature

    Anne Sophie Weingertner

    2009-01-01

    Full Text Available The development of acute myeloid leukaemia after low-dose radioiodine therapy and its presentation as a myeloid sarcoma of the uterine cervix are both rare events. We report a case of acute myeloid leukaemia revealed by a myeloid sarcoma of the uterine cervix in a 48-year-old woman, 17 months after receiving a total dose of 100 mCi 131I for papillary thyroid cancer. A strict hematological follow-up of patients treated with any dose of 131I is recommended to accurately detect any hematological complications which might have been underestimated. Unusual presentations, such as chloroma of the uterine cervix, may reveal myeloid malignancy and should be kept in mind.

  9. Comparison of prasugrel and clopidogrel in patients with acute coronary syndrome undergoing percutaneous coronary intervention

    Nicholas B Norgard

    2009-10-01

    Full Text Available Nicholas B Norgard,1 Mazen Abu-Fadel21University at Buffalo, School of Pharmacy and Pharmaceutical Sciences, Buffalo, NY, USA; 2University of Oklahoma Health Sciences Center, Cardiovascular Section, Oklahoma City, OK, USAAbstract: Antiplatelet agents are the cornerstone of treatment for patients with acute coronary syndrome (ACS undergoing percutaneous coronary intervention (PCI. Clopidogrel, when added to aspirin, has demonstrated considerable success at reducing thrombotic complications of ACS and/or PCI compared to aspirin alone and is standard of care for the management of patients with ACS and in patients undergoing PCI. Prasugrel is a novel thienopyridine antiplatelet agent recently approved for the treatment of patients with ACS undergoing PCI. Prasugrel provides greater and more consistent platelet inhibition than clopidogrel due to earlier and more extensive formation of its active metabolite. The enhanced platelet inhibition with prasugrel led to a reduction in major adverse cardiovascular events in patients with moderate to high risk ACS scheduled for PCI in the phase 3 TRITON-TIMI 38 trial. This benefit was seen more in patients suffering a STEMI and those with diabetes. However, this reduction in events was met with a significant increase in the risk of bleeding which overcame prasugrel’s benefit in certain groups. Future studies with prasugrel are needed to determine its optimal utilization to minimize bleeding risks and evaluate its outcomes in ACS and safety profile in special patient populations.Keywords: clopidogrel, prasugrel, percutaneous coronary intervention, acute coronary syndrome

  10. Impact of Timing of Eptifibatide Administration on Preprocedural Infarct-Related Artery Patency in Acute STEMI Patients Undergoing Primary PCI

    Dharma, Surya; Firdaus, Isman; Danny, Siska Suridanda; Juzar, Dafsah A.; Wardeh, Alexander J.; Jukema, J Wouter; van der Laarse, Arnoud

    2014-01-01

    The appropriate timing of eptifibatide initiation for acute ST segment elevation myocardial infarction (STEMI) patients undergoing primary percutaneous coronary intervention (PCI) remains unclear. This study aimed to analyze the impact of timing of eptifibatide administration on infarct-related artery (IRA) patency in STEMI patients undergoing primary PCI. Acute STEMI patients who underwent primary PCI (n = 324) were enrolled in this retrospective study; 164 patients received eptifibatide bol...

  11. A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia

    D’Crus, Angel; Melville, Kathleen; Verrills, Nicole M.; Rowlings, Philip

    2016-01-01

    Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A activator that inhibits multiple signalling pathways and has been used extensively in patients with multiple sclerosis and other indications. The initial positive results of PP2A activators in vitro and mouse models of AML are promising; however, its safety for use in AML has not been assessed. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A literature review was carried out to assess safety before the commencement of Phase I trials of the PP2A activator Fingolimod in AML. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A systematic review of published literature in Medline, EMBASE and the Cochrane Library of critical reviews was carried out. International standards for the design and reporting of search strategies were followed. Search terms and medical subject headings used in trials involving PP2A activators as well as a specific search were performed for ‘adverse events’, ‘serious adverse events’, ‘delays in treatment’, ‘ side effects’ and ‘toxicity’ for primary objectives. Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been

  12. A systematic evaluation of the safety and toxicity of fingolimod for its potential use in the treatment of acute myeloid leukaemia.

    Enjeti, Anoop K; D'Crus, Angel; Melville, Kathleen; Verrills, Nicole M; Rowlings, Philip

    2016-07-01

    Treatment of acute myeloid leukaemia (AML) is challenging and emerging treatment options include protein phosphatase 2A (PP2A) activators. Fingolimod is a known PP2A activator that inhibits multiple signalling pathways and has been used extensively in patients with multiple sclerosis and other indications. The initial positive results of PP2A activators in vitro and mouse models of AML are promising; however, its safety for use in AML has not been assessed. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A literature review was carried out to assess safety before the commencement of Phase I trials of the PP2A activator Fingolimod in AML. From human studies of fingolimod in other indications, it is possible to evaluate whether the safety and toxicity profile of the PP2A activators will allow their use in treating AML. A systematic review of published literature in Medline, EMBASE and the Cochrane Library of critical reviews was carried out. International standards for the design and reporting of search strategies were followed. Search terms and medical subject headings used in trials involving PP2A activators as well as a specific search were performed for 'adverse events', 'serious adverse events', 'delays in treatment', ' side effects' and 'toxicity' for primary objectives. Database searches were limited to papers published in the last 12 years and available in English. The search yielded 677 articles. A total of 69 journal articles were identified as relevant and included 30 clinical trials, 24 review articles and 15 case reports. The most frequently reported adverse events were nausea, diarrhoea, fatigue, back pain, influenza viral infections, nasopharyngitis and bronchitis. Specific safety concerns include monitoring of the heart rate and conduction at commencement of treatment as cardiotoxicity has been reported. There is

  13. The chronic leukaemias

    Peter Jacobs

    1989-09-01

    Full Text Available The slow progression of both chronic granulocytic and lymphocytic leukaemia, when compared to their acute counterparts, has been used as an argument to support less aggressive therapy or even, in some instances, a watch-and-wait policy. This conservative approach is bolstered by a number of observations including the ease with which haematologic control can initially be achieved, the older age of patients with the lymphocytic variant and the paucity of controlled data showing that long disease-free survival or cure can result from the use of aggressive treatment. Given these circumstances, it is not surprising that many such individuals are managed outside specialised centres using a variety of agents and schedules, both of which may, on occasions, be inappropriate. Accumulating evidence suggests a need to reconsider these practices since cure is now possible in selected patients with chronic granulocytic leukaemia while the use of multi-drug regimens in the lymphatic form can significantly improve survival. These advances are the result of carefully conducted clinical trials involving many individuals the world over and constitute the basis fo r advocating early referral to those institutions where all the necessary expertise is available.

  14. Nuclear power and leukaemia

    This booklet describes the nature of leukaemia, disease incidence in the UK and the possible causes. Epidemiological studies observing rates of leukaemia near nuclear power stations in the UK and other parts of the world are discussed. Possible causes of leukaemia excesses near nuclear establishments include radioactive discharges into the environment, paternal radiation exposure and viral causes. (UK)

  15. Predictors of outcome in neck pain patients undergoing chiropractic care: comparison of acute and chronic patients

    Peterson Cynthia

    2012-08-01

    Full Text Available Abstract Background Neck pain is a common complaint in patients presenting for chiropractic treatment. The few studies on predictors for improvement in patients while undergoing treatment identify duration of symptoms, neck stiffness and number of previous episodes as the strong predictor variables. The purpose of this study is to continue the research for predictors of a positive outcome in neck pain patients undergoing chiropractic treatment. Methods Acute ( 3 months (n = 255 neck pain patients with no chiropractic or manual therapy in the prior 3 months were included. Patients completed the numerical pain rating scale (NRS and Bournemouth questionnaire (BQ at baseline prior to treatment. At 1 week, 1 month and 3 months after start of treatment the NRS and BQ were completed along with the Patient Global Impression of Change (PGIC scale. Demographic information was provided by the clinician. Improvement at each of the follow up points was categorized using the PGIC. Multivariate regression analyses were done to determine significant independent predictors of improvement. Results Baseline mean neck pain and total disability scores were significantly (p  Conclusions The most consistent predictor of clinically relevant improvement at both 1 and 3 months after the start of chiropractic treatment for both acute and chronic patients is if they report improvement early in the course of treatment. The co-existence of either radiculopathy or dizziness however do not imply poorer prognosis in these patients.

  16. A novel RT-qPCR assay for quantification of the MLL-MLLT3 fusion transcript in acute myeloid leukaemia

    Abildgaard, Lotte; Ommen, Hans Beier; Lausen, Birgitte Frederiksen;

    2013-01-01

    heterogeneity of translocation break points, the MLL-MLLT3 fusion gene is a challenging target. We hypothesised that MRD monitoring using MLL-MLLT3 as a RT-qPCR marker is feasible in the majority of patients with t(9;11)-positive AML. METHODS: Using a locked nucleic acid probe, we developed a sensitive RT......-qPCR assay for quantification of the most common break point region of the MLL-MLLT3 fusion gene. Five paediatric patients with t(9;11)-positive AML were monitored using the MLL-MLLT3 assay. RESULTS: A total of 43 bone marrow (BM) and 52 Peripheral blood (PB) samples were collected from diagnosis until......OBJECTIVES: Patients with acute myeloid leukaemia (AML) of the monocytic lineage often lack molecular markers for minimal residual disease (MRD) monitoring. The MLL-MLLT3 fusion transcript found in patients with AML harbouring t(9;11) is amenable to RT-qPCR quantification but because of the...

  17. The value of molecular stratification for CEBPA(DM) and NPM1(MUT) FLT3(WT) genotypes in older patients with acute myeloid leukaemia.

    Dickson, Glenda J; Bustraan, Sophia; Hills, Robert K; Ali, Akbar; Goldstone, Anthony H; Burnett, Alan K; Linch, David C; Gale, Rosemary E

    2016-02-01

    Older adult patients (≥60 years) with acute myeloid leukaemia (AML) are generally considered to be poor-risk and there is limited information available regarding risk stratification based on molecular characterization in this age group, particularly for the double-mutant CEBPA (CEBPA(DM) ) genotype. To investigate whether a molecular favourable-risk genotype can be identified, we investigated CEBPA, NPM1 and FLT3 status and prognostic impact in a cohort of 301 patients aged 60 years or more with intermediate-risk cytogenetics, all treated intensively. Overall survival (OS) at 1 year was highest in the 12 patients (4%) that were CEBPA(DM) compared to the 76 (28%) with a mutant NPM1 and wild-type FLT3 (NPM1(MUT) FLT3(WT) ) genotype or all other patients (75%, 54%, 33% respectively), with median survival 15·2, 13·6 and 6·6 months, although the benefit was short-term (OS at 3 years 17%, 29%, 12% respectively). Combination of the CEBPA(DM) and NPM1(MUT) FLT3(WT) genotype patients defined a molecular group with favourable prognosis (P < 0·0001 in multivariate analysis), with 57% of patients alive at 1 year compared to 33% for all other patients. Knowledge of genotype in older cytogenetically intermediate-risk patients might influence therapy decisions. PMID:26847745

  18. MiR-424 and miR-155 deregulated expression in cytogenetically normal acute myeloid leukaemia: correlation with NPM1 and FLT3 mutation status

    Faraoni Isabella

    2012-06-01

    Full Text Available Abstract Background MicroRNA have a central role in normal haematopoiesis and are deregulated in acute myeloid leukaemia (AML. The purpose of the study was to investigate by qRT-PCR the expression of miRNAs involved in myeloid differentiation (miR-424, miR-155, miR-223, miR-17-5p in 48 patients with cytogenetically normal AML well characterized for NPM1 and/or FLT3 mutations. Three types of normalization were used for the data validation. Findings We found that miR-424 was down-modulated in AMLs with NPM1mutA regardless of FLT3 status. On the contrary, miR-155 showed up-regulation in patients with FLT3 internal tandem duplications (ITD with or without NPM1 mutations. No significant associations were found by analyzing miR-223 and miR-17-5p in relation to FLT3 and NPM1 status. Conclusions This study supports the view that major genetic subsets of CN-AML are associated with distinct miRNA signatures and suggests that miR-424 and miR-155 deregulation is involved in the pathogenesis of CN-AML with NPM1 and FLT3-ITD mutations, respectively.

  19. Direct X-ray radiogrammetry versus dual-energy X-ray absorptiometry: assessment of bone density in children treated for acute lymphoblastic leukaemia and growth hormone deficiency

    Rijn, Rick R. van; Wittenberg, Rianne [Academic Medical Centre Amsterdam, Department of Radiology, Amsterdam Zuid-Oost (Netherlands); Boot, Annemieke; Sluis, Inge M. van der; MuinckKeizer-Schrama, Sabine M.P.F. de [Erasmus MC-Sophia Children' s Hospital, Department of Paediatric Endocrinology, Rotterdam (Netherlands); Heuvel-Eibrink, Marry M. van den [Erasmus MC-Sophia Children' s Hospital, Department of Paediatric Haematology/Oncology, Rotterdam (Netherlands); Lequin, Maarten H. [Erasmus MC-Sophia Children' s Hospital, Department of Paediatric Radiology, Rotterdam (Netherlands); Kuijk, Cornelis Van [University Medical Centre ' Radboud' , Department of Radiology, Nijmegen (Netherlands)

    2006-03-15

    In recent years interest in bone densitometry in children has increased. To evaluate the clinical application of digital X-ray radiogrammetry (DXR) and compare the results with those of dual-energy X-ray absorptiometry (DXA). A total of 41 children with acute lymphoblastic leukaemia (ALL) and 26 children with growth hormone deficiency (GHD) were included in this longitudinal study. Radiographs of the left hand were obtained and used for DXR. DXA of the total body and of the lumbar spine was performed. In both study populations significant correlations between DXR and DXA were found, and, with the exception of the correlation between DXR bone mineral density (DXR-BMD) and bone mineral apparent density in the GHD population, all correlations had a P-value of <0.001. During treatment a change in DXR-BMD was found in children with GHD. Our study showed that DXR in a paediatric population shows a strong correlation with DXA of the lumbar spine and total body and that it is able to detect a change in BMD during treatment. (orig.)

  20. Outcome of central nervous system relapses in childhood acute lymphoblastic leukaemia--prospective open cohort analyses of the ALLR3 trial.

    Ashish Narayan Masurekar

    Full Text Available The outcomes of Central Nervous System (CNS relapses in children with acute lymphoblastic leukaemia (ALL treated in the ALL R3 trial, between January 2003 and March 2011 were analysed. Patients were risk stratified, to receive a matched donor allogeneic transplant or fractionated cranial irradiation with continued treatment for two years. A randomisation of Idarubicin with Mitoxantrone closed in December 2007 in favour of Mitoxantrone. The estimated 3-year progression free survival for combined and isolated CNS disease were 40.6% (25·1, 55·6 and 38.0% (26.2, 49.7 respectively. Univariate analysis showed a significantly better survival for age <10 years, progenitor-B cell disease, good-risk cytogenetics and those receiving Mitoxantrone. Adjusting for these variables (age, time to relapse, cytogenetics, treatment drug and gender a multivariate analysis, showed a poorer outcome for those with combined CNS relapse (HR 2·64, 95% CI 1·32, 5·31, p = 0·006 for OS. ALL R3 showed an improvement in outcome for CNS relapses treated with Mitoxantrone compared to Idarubicin; a potential benefit for matched donor transplant for those with very early and early isolated-CNS relapses.Controlled-Trials.com ISRCTN45724312.

  1. Lower-limb MRI in the staging and re-staging of osteonecrosis in paediatric patients affected by acute lymphoblastic leukaemia after therapy

    Ippolito, D.; Masetto, A.; Franzesi, C.T.; Bonaffini, P.A.; Sironi, S. [University of Milano-Bicocca Milan, School of Medicine, Monza (Italy); Department of Diagnostic Radiology, H. San Gerardo, Monza (Italy); Sala, A.; Biondi, A. [University of Milano-Bicocca Milan, School of Medicine, Monza (Italy); H. San Gerardo, Department of Paediatric Haematology, Monza (Italy)

    2016-04-15

    To assess the diagnostic value of MRI examination in detecting and monitoring osteonecrotic lesions (ON) in childhood acute lymphoblastic leukaemia (ALL) after chemotherapy (CHT) and/or bone marrow transplantation (BMT). Seventy-three patients (37 males, mean age 12.4 years old) with ALL after treatment underwent a lower-limb MR examination between November 2006 and March 2012. In 47 there was clinical suspicion of ON, 26 were asymptomatic. Studies were performed with a 1 T and a 1.5 T scanner, acquiring short tau inversion recovery (STIR) and T1-weighted sequences in coronal plane from the hips to the ankles. The average acquisition time was 18 min. Considering baseline and follow-up examinations, the overall number of MRI studies was 195. Fifty-four of 73 patients showed ON at MRI study, with an overall number of 323 ON (89 involving articular surface, 24 with joint deformity, JD). Twenty-five of 47 symptomatic patients showed subchondral ON lesions, 11 developed JD. Three of 26 asymptomatic patients showed subchondral bone ON at baseline examination but no JD at follow-up. Twenty-two of 28 BMT, 32/45 CHT patients developed ON. Our MRI protocol proved to be feasible in evaluating ON in paediatric patients. Studies should be addressed only to symptomatic patients. (orig.)

  2. The impact of therapy for childhood acute lymphoblastic leukaemia on intelligence quotients; results of the risk-stratified randomized central nervous system treatment trial MRC UKALL XI

    Vargha-Khadem Faraneh

    2011-10-01

    Full Text Available Abstract Background The MRC UKALLXI trial tested the efficacy of different central nervous system (CNS directed therapies in childhood acute lymphoblastic leukaemia (ALL. To evaluate morbidity 555/1826 randomised children underwent prospective psychological evaluations. Full Scale, verbal and performance IQs were measured at 5 months, 3 years and 5 years. Scores were compared in; (1 all patients (n = 555 versus related controls (n = 311, (2 low-risk children (presenting white cell count (WCC 9/l randomised to intrathecal methotrexate (n = 197 versus intrathecal and high-dose intravenous methotrexate (HDM (n = 202, and (3 high-risk children (WCC ≥ 50 × 109/l, age ≥ 2 years randomised to HDM (n = 79 versus cranial irradiation (n = 77. Results There were no significant differences in IQ scores between the treatment arms in either low- or high-risk groups. Despite similar scores at baseline, results at 3 and 5 years showed a significant reduction of between 3.6 and 7.3 points in all three IQ scores in all patient groups compared to controls (P Conclusion Children with ALL are at risk of CNS morbidity, regardless of the mode of CNS-directed therapy. Further work needs to identify individuals at high-risk of adverse CNS outcomes. Trial registration ISRCTN: ISRCTN16757172

  3. The frequency and management of asparaginase-related thrombosis in paediatric and adult patients with acute lymphoblastic leukaemia treated on Dana-Farber Cancer Institute consortium protocols.

    Grace, Rachael F; Dahlberg, Suzanne E; Neuberg, Donna; Sallan, Stephen E; Connors, Jean M; Neufeld, Ellis J; Deangelo, Daniel J; Silverman, Lewis B

    2011-02-01

    The optimal management of asparaginase-associated thrombotic complications is not well-defined. We report the features, management and outcome of paediatric (ages 0-18years) and adult (18-50years) patients with acute lymphoblastic leukaemia (ALL) with asparaginase-related venous thromboembolic events (VTE) treated at Dana-Farber Cancer Institute on clinical trials for newly diagnosed ALL between 1991-2008. Of 548 patients, 43 (8%) had VTE, including 27/501 (5%) paediatric and 16/47 (34%) adult patients. Sinus venous thrombosis occurred in 1·6% of patients. Age was the only significant predictor of VTE, with those aged >30years at very high risk (VTE rate 42%). 74% of patients received low molecular weight heparin after VTE. Complications of anticoagulation included epistaxis (9%), bruising (2%) and, in two adult patients, major bleeding. Thirty patients (70%) ultimately received at least 85% of the intended doses of asparaginase. 33% of patients experienced recurrent VTE (paediatric 17% vs. adults 47%, P=0·07). The 48-month event-free survival for patients with VTE was 85±6% compared with 88±2% for those without VTE (P=0·36). This study confirms that, after VTE, asparaginase can be restarted with closely monitored anticoagulation after imaging demonstrates clot stabilization or improvement. With this management strategy, a history of VTE does not appear to adversely impact prognosis. PMID:21210774

  4. Direct X-ray radiogrammetry versus dual-energy X-ray absorptiometry: assessment of bone density in children treated for acute lymphoblastic leukaemia and growth hormone deficiency

    In recent years interest in bone densitometry in children has increased. To evaluate the clinical application of digital X-ray radiogrammetry (DXR) and compare the results with those of dual-energy X-ray absorptiometry (DXA). A total of 41 children with acute lymphoblastic leukaemia (ALL) and 26 children with growth hormone deficiency (GHD) were included in this longitudinal study. Radiographs of the left hand were obtained and used for DXR. DXA of the total body and of the lumbar spine was performed. In both study populations significant correlations between DXR and DXA were found, and, with the exception of the correlation between DXR bone mineral density (DXR-BMD) and bone mineral apparent density in the GHD population, all correlations had a P-value of <0.001. During treatment a change in DXR-BMD was found in children with GHD. Our study showed that DXR in a paediatric population shows a strong correlation with DXA of the lumbar spine and total body and that it is able to detect a change in BMD during treatment. (orig.)

  5. l-asparaginase loaded red blood cells in refractory or relapsing acute lymphoblastic leukaemia in children and adults: results of the GRASPALL 2005-01 randomized trial.

    Domenech, Carine; Thomas, Xavier; Chabaud, Sylvie; Baruchel, Andre; Gueyffier, François; Mazingue, Françoise; Auvrignon, Anne; Corm, Selim; Dombret, Herve; Chevallier, Patrice; Galambrun, Claire; Huguet, Françoise; Legrand, Faezeh; Mechinaud, Françoise; Vey, Norbert; Philip, Irène; Liens, David; Godfrin, Yann; Rigal, Dominique; Bertrand, Yves

    2011-04-01

    l-asparaginase encapsulated within erythrocytes (GRASPA(®) ) should allow serum asparagine depletion over a longer period than the native form of the enzyme, using lower doses and allowing better tolerance. The GRASPALL 2005-01 study, a multicentre randomized controlled trial, investigated three doses of GRASPA(®) for the duration of asparagine depletion in a phase I/II study in adults and children with acute lymphoblastic leukaemia (ALL) in first relapse. Between February 2006 and April 2008, 18 patients received GRASPA(®) (50 iu/kg: n = 6,100 iu/kg: n = 6, 150 iu/kg: n = 6) after randomization, and six patients were assigned to the Escherichia coli native l-asparaginase (E. colil-ASNase) control group. GRASPA(®) was effective at depleting l-asparagine. One single injection of 150 iu/kg of GRASPA(®) provided similar results to 8 × 10,000 iu/m(2) intravenous injections of E. colil-ASNase. The safety profile of GRASPA(®) showed a reduction in the number and severity of allergic reactions and a trend towards less coagulation disorders. Other expected adverse events were comparable to those observed with E. colil-ASNase and there was also no difference between the three doses of GRASPA(®) . PMID:21332712

  6. 9-O-acetylated sialic acids differentiating normal haematopoietic precursors from leukemic stem cells with high aldehyde dehydrogenase activity in children with acute lymphoblastic leukaemia.

    Chowdhury, Suchandra; Chandra, Sarmila; Mandal, Chitra

    2014-10-01

    Childhood acute lymphoblastic leukaemia (ALL) originates from mutations in haematopoietic progenitor cells (HPCs). For high-risk patients, treated with intensified post-remission chemotherapy, haematopoietic stem cell (HSC) transplantation is considered. Autologous HSC transplantation needs improvisation till date. Previous studies established enhanced disease-associated expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs) on lymphoblasts of these patients at diagnosis, followed by its decrease with clinical remission and reappearance with relapse. Based on this differential expression of Neu5,9Ac2-GPs, identification of a normal HPC population was targeted from patients at diagnosis. This study identifies two distinct haematopoietic progenitor populations from bone marrow of diagnostic ALL patients, exploring the differential expression of Neu5,9Ac2-GPs with stem cell (CD34, CD90, CD117, CD133), haematopoietic (CD45), lineage-commitment (CD38) antigens and cytosolic aldehyde dehydrogenase (ALDH). Normal haematopoietic progenitor cells (ALDH(+)SSC(lo)CD45(hi)Neu5,9Ac2 -GPs(lo)CD34(+)CD38(-)CD90(+)CD117(+)CD133(+)) differentiated into morphologically different, lineage-specific colonies, being crucial for autologous HSC transplantation while leukemic stem cells (ALDH(+)SSC(lo)CD45(lo)Neu5,9Ac2 -GPs(hi)CD34(+)CD38(+)CD90(-)CD117(-)CD133(-)) lacking this ability can be potential targets for minimal residual disease detection and drug-targeted immunotherapy. PMID:25283637

  7. Slower early response to treatment and distinct expression profile of childhood high hyperdiploid acute lymphoblastic leukaemia with DNA index < 1.16.

    Zaliova, Marketa; Hovorkova, Lenka; Vaskova, Martina; Hrusak, Ondrej; Stary, Jan; Zuna, Jan

    2016-09-01

    Acute lymphoblastic leukaemias (ALL) with 51-67 chromosomes are defined as high hyperdiploid (HHD) and are generally associated with good prognosis. However, several studies show heterogeneity in HHD ALL and suggest that the favourable prognosis is associated rather with higher ploidy defined by DNA index (DNAi) ≥ 1.16 or with a presence of specific single or combined trisomies. HHD ALL with DNAi < 1.16 are only rarely studied separately. Using single nucleotide polymorphism array, we analysed 89 childhood HHD ALL patients divided into groups with lower (<1.16; n = 34) and higher (≥1.16; n = 55) DNAi. We assessed treatment response, presence of secondary aberrations, mutations in RAS pathway genes and CREBBP and also gene expression profile (GEP) to reveal differences between the two subgroups. Cases with 51-54 chromosomes had DNAi 1.1-1.16 and cases with 55-67 chromosomes had DNAi ≥ 1.16. The groups with lower and higher DNAi had distinct response to early treatment and distinct GEP. The better response of the group with higher DNAi was associated with specific trisomies (trisomy of chromosome 10 or combined with trisomies 4 and/or 17). Our results suggest that cytogenetically defined HHD ALL can in fact be divided into two biologically distinguishable subgroups and that DNAi 1.16 is a relevant value to separate between the two. © 2016 Wiley Periodicals, Inc. PMID:27163296

  8. Lower-limb MRI in the staging and re-staging of osteonecrosis in paediatric patients affected by acute lymphoblastic leukaemia after therapy

    To assess the diagnostic value of MRI examination in detecting and monitoring osteonecrotic lesions (ON) in childhood acute lymphoblastic leukaemia (ALL) after chemotherapy (CHT) and/or bone marrow transplantation (BMT). Seventy-three patients (37 males, mean age 12.4 years old) with ALL after treatment underwent a lower-limb MR examination between November 2006 and March 2012. In 47 there was clinical suspicion of ON, 26 were asymptomatic. Studies were performed with a 1 T and a 1.5 T scanner, acquiring short tau inversion recovery (STIR) and T1-weighted sequences in coronal plane from the hips to the ankles. The average acquisition time was 18 min. Considering baseline and follow-up examinations, the overall number of MRI studies was 195. Fifty-four of 73 patients showed ON at MRI study, with an overall number of 323 ON (89 involving articular surface, 24 with joint deformity, JD). Twenty-five of 47 symptomatic patients showed subchondral ON lesions, 11 developed JD. Three of 26 asymptomatic patients showed subchondral bone ON at baseline examination but no JD at follow-up. Twenty-two of 28 BMT, 32/45 CHT patients developed ON. Our MRI protocol proved to be feasible in evaluating ON in paediatric patients. Studies should be addressed only to symptomatic patients. (orig.)

  9. After the chemotherapy: potential mechanisms for chemotherapy-induced delayed skeletal muscle dysfunction in survivors of acute lymphoblastic leukaemia in childhood

    Celena eScheede-Bergdahl

    2013-04-01

    Full Text Available There is evidence that survivors of childhood cancers, such as acute lymphoblastic leukaemia (ALL, have increased rates of longterm skeletal muscle dysfunction. This places them at higher risk of physical restriction and functional impairment as well as potentially contributing to observed increases in cardiovascular disease and insulin resistance in later life. The mechanisms underlying these changes in skeletal muscle are unknown but chemotherapy drugs used in treatment for ALL are strongly implicated. Normal skeletal muscle growth, development and function are dependent on correctly functioning muscle satellite cells, muscle motor neurons and muscle mitochondria. Each of these key components is potentially susceptible to damage by chemotherapy in childhood, particularly prolonged courses including repeated administration of combination chemotherapy. If this chemotherapy-induced damage is not fully reversible, impairment of satellite cells, muscle motor innervation and mitochondria could, either singly or together, lead to the emergence of delayed or persistent skeletal muscle dysfunction many years later. The known effects of individual drugs used in the treatment of ALL are outlined and the need for specific targeted studies to investigate the mechanisms underlying persistent muscle dysfunction in survivors of childhood cancers is highlighted.

  10. Activation of NF-ĸB in leukemic cells in response to initial prednisone therapy in children with acute lymphoblastic leukaemia: relation to other prognostic factors.

    Kamieńska, Elżbieta; Ociepa, Tomasz; Wysocki, Mariusz; Kurylak, Andrzej; Matysiak, Michał; Urasiński, Tomasz; Urasińska, Elżbieta; Domagała, Wenancjusz

    2011-01-01

    Nuclear factor ĸB (NF-ĸB) is a transcription regulator of proliferation and cell death. Increased activation of NF-ĸB may be responsible for treatment failure in children with acute lymphoblastic leukaemia (ALL). This study aimed to assess changes in NF-ĸB activation in peripheral blood mononuclear cells prior to and after 6 and 12 h of prednisone administration in relation to age, initial WBC count at diagnosis and early treatment response in childhood ALL. The study comprised 55 children with de novo ALL. Cells were stained with mouse anti-NF-ĸB (p65) antibody followed by goat anti-mouse antibody conjugated with FITC and measured by laser scanning cytometer. The nuclear/cytoplasmic (N/C) ratio of NF-ĸB reflecting activation of NF-ĸB was decreased 12 h after treatment in the standard risk group patients, whereas it remained statistically unchanged in the non-standard risk group patients. Changes in the N/C ratio of NF-ĸB were not associated with age and early treatment response; however, in children with an initial WBC count higher than 20 000/μl at diagnosis, this ratio was increased after 6 and 12 h from prednisone administration. The association of higher activation of NF-ĸB with an elevated initial WBC count suggests that activation of NF-ĸB may be responsible for treatment failure in children with ALL. PMID:21574100

  11. Childhood leukaemia in Ireland

    In response to professional and public concern about health consequences, in particular cancer risk, from previous and current levels of ionising radiation in the Irish Sea, a study of incidence and mortality from acute lymphoid leukaemia (ALL) and other lymphoid malignancies in children was undertaken. Overall rates were similar to those found in other western populations and distribution of high rates was quite random over the country as a whole. There was a small but significant excess in incidence of ALL for the years 1974-76 in a narrow three mile strip along the east coast. it is not possible in the context of this study to postulate aetiological factors which might explain this finding. (author)

  12. Procedural Predictors of Outcome in Patients Undergoing Endovascular Therapy for Acute Ischemic Stroke

    Rai, Ansaar T., E-mail: ansaar.rai@gmail.com; Jhadhav, Yahodeep; Domico, Jennifer [West Virginia University Health Sciences Center, Interventional Neuroradiology (United States); Hobbs, Gerald R. [West Virginia University Health Sciences Center, Department of Community Medicine (United States)

    2012-12-15

    Purpose: To identify factors impacting outcome in patients undergoing interventions for acute ischemic stroke (AIS). Materials and Methods: This was a retrospective analysis of patients undergoing endovascular therapy for AIS secondary during a 30 month period. Outcome was based on modified Rankin score at 3- to 6-month follow-up. Recanalization was defined as Thrombolysis in myocardial infarction score 2 to 3. Collaterals were graded based on pial circulation from the anterior cerebral artery either from an ipsilateral injection in cases of middle cerebral artery (MCA) occlusion or contralateral injection for internal carotid artery terminus (ICA) occlusion as follows: no collaterals (grade 0), some collaterals with retrograde opacification of the distal MCA territory (grade 1), and good collaterals with filling of the proximal MCA (M2) branches or retrograde opacification up to the occlusion site (grade 2). Occlusion site was divided into group 1 (ICA), group 2 (MCA with or without contiguous M2 involvement), and group 3 (isolated M2 or M3 branch occlusion). Results: A total of 89 patients were studied. Median age and National Institutes of health stroke scale (NIHSS) score was 71 and 15 years, respectively. Favorable outcome was seen in 49.4% of patients and mortality in 25.8% of patients. Younger age (P = 0.006), lower baseline NIHSS score (P = 0.001), successful recanalization (P < 0.0001), collateral support (P = 0.0008), distal occlusion (P = 0.001), and shorter procedure duration (P = 0.01) were associated with a favorable outcome. Factors affecting successful recanalization included younger age (P = 0.01), lower baseline NIHSS score (P = 0.05), collateral support (P = 0.01), and shorter procedure duration (P = 0.03). An ICA terminus occlusion (P < 0.0001), lack of collaterals (P = 0.0003), and unsuccessful recanalization (P = 0.005) were significantly associated with mortality. Conclusion: Angiographic findings and preprocedure variables can help

  13. Causes of childhood leukaemia and lymphoma

    Childhood cancer is rare comprising less than 1% of all malignancies diagnosed each year in developed countries. Leukaemia is the commonest form of cancer in children accounting for around a third of all childhood cancer, with acute lymphoblastic leukaemia (ALL) being the most prevalent. Biologically specific subtypes of ALL and acute myeloblastic leukaemia (AML), the other major morphological type of childhood leukaemia, are characterised by chromosomal changes. Whilst over 200 genes have been associated with chromosomal translocations, to date, only MLL, TEL, and AML1 have been linked with childhood leukaemia. Interestingly, there is increasing evidence to support the theory that gene rearrangements such as these may originate in utero. As with many other human diseases, both genetic and environmental factors have been implicated in the aetiology of the disease. Although much has been documented with regard to diet, smoking, alcohol consumption and recreational and prescription drug use during pregnancy, there is no consistent evidence to support a link with any of these factors and childhood leukaemia. However, findings from studies investigating prenatal and early life exposures are often based on small numbers of cases as both the type of cancer and exposure are rare. Furthermore, accurate information relating to past exposures can be difficult to obtain and is often reliant on self-reporting. To further our understanding of the aetiology of childhood leukaemia and lymphoma, there are areas which clearly warrant investigation. These include collection of parental dietary folate data combined with genetic analysis of the folate related genes, in utero exposure to DNA topoisomerase II inhibitors, and the possible effects of assisted reproduction technology on disease susceptibility

  14. Effects of Parasternal Block on Acute and Chronic Pain in Patients Undergoing Coronary Artery Surgery.

    Doğan Bakı, Elif; Kavrut Ozturk, Nilgün; Ayoğlu, Rauf Umut; Emmiler, Mustafa; Karslı, Bilge; Uzel, Hanife

    2016-09-01

    Background Sternotomy causes considerable postoperative pain and postoperative pain management encompasses different analgesic regimens. In this study, we aimed to investigate the effect of peroperative parasternal block with levobupivacaine on acute and chronic pain after coronary artery bypass graft surgery. Materials and Methods A total of 81 patients undergoing coronary artery bypass graft surgery were included in this study. Patients were randomly allocated by opening an envelope to receive either parasternal block with pharmacologic analgesia (group P; before sternal wire placement: sternotomy and mediastinal tube sites were infiltrated with local anesthetics) or pharmacologic analgesia alone (group C) for postoperative pain relief. All patients received intravenous tramadol with patient-controlled analgesia at the end of the surgery. Demographic characteristics, vital signs, tramadol consumption, analgesic intake, and intensity of pain with a visual analogue scale were recorded for each patient. Six months after surgery, the patients' type of chronic pain was evaluated using the Leeds Assessment Neuropathic Symptoms and Signs pain scale questionnaire. Results Patients who received parasternal block experienced less pain and needed less opioid analgesic (125.75 ± 28.9 mg in group P vs 213.17 ± 61.25 mg in group C) for 24 hours postoperatively (P block had a benefical effect on the management of postoperative acute pain and decreased opioid consumption after surgery but had no significant effect in chronic post surgical pain. PMID:25900900

  15. 骨髓纤维化转化为急性淋巴细胞白血病1例报道并文献复习%Report and Documentary Review on Myelofibrosis Transferring to Acute Lymphocyte Leukaemia

    郑兵荣; 范翠华; 杨阳; 胥昀; 傅丽娟

    2012-01-01

    [目的]通过骨髓纤维化(myelofibrosis,MF)转化为急性淋巴细胞白血病(简称急淋)1例报道,结合文献分析,探讨MF的转归及预后.[方法]对2011年7月就诊于浙江中医药大学第二附属医院血液科的1例MF转化为急淋的患者的诊治过程进行报道,并检索文献复习分析.[结果]MF患者转化为急淋极为罕见,且预后极差,本例患者通过中西医结合治疗,取得一定疗效.[结论]MF患者有5%~20%的机会转化成急性白血病,转化为急性淋巴细胞白血病极为罕见,且预后极差,中西医结合治疗具有一定疗效,但总体预后仍欠佳.%[Objective] To explore the lapse and prognosis of myelofibrosis by combing documentary analysis and report on myelofibrosis transferring to acute lymphocyte leukaemia. [Method] Make a report on the diagnosis and treatment to one case of myelofibrosis transferring to acute lymphocyte leukaemia, and retrieve documents for analysis. [Result] Such disease is very rare with bad prognosis; with treatment of combining TCM and WM, it got good cure effect. [Conclusion] Myelofibrosis has 5%~20% of opportunity for acute lymphocyte leukaemia. Combination of TCM and WM has definite advantages in such disease, but without very good prognosis.

  16. Near infrared spectroscopy (NIRS as a new non-invasive tool to detect oxidative skeletal muscle impairment in children survived to acute lymphoblastic leukaemia.

    Francesca Lanfranconi

    Full Text Available BACKGROUND: Separating out the effects of cancer and treatment between central and peripheral components of the O2 delivery chain should be of interest to clinicians for longitudinal evaluation of potential functional impairment in order to set appropriate individually tailored training/rehabilitation programmes. We propose a non-invasive method (NIRS, near infrared spectroscopy to be used in routine clinical practice to evaluate a potential impairment of skeletal muscle oxidative capacity during exercise in children previously diagnosed with acute lymphoblastic leukaemia (ALL. The purpose of this study was to evaluate the capacity of skeletal muscle to extract O2 in 10 children diagnosed with ALL, 1 year after the end of malignancy treatment, compared to a control group matched for gender and age (mean±SD = 7.8±1.5 and 7.3±1.4 years, respectively. METHODS AND FINDINGS: Participants underwent an incremental exercise test on a treadmill until exhaustion. Oxygen uptake ([Formula: see text], heart rate (HR, and tissue oxygenation status (Δ[HHb] of the vastus lateralis muscle evaluated by NIRS, were measured. The results showed that, in children with ALL, a significant linear regression was found by plotting [Formula: see text] vs Δ[HHb] both measured at peak of exercise. In children with ALL, the slope of the HR vs [Formula: see text] linear response (during sub-maximal and peak work rates was negatively correlated with the peak value of Δ[HHb]. CONCLUSIONS: The present study proves that the NIRS technique allows us to identify large inter-individual differences in levels of impairment in muscle O2 extraction in children with ALL. The outcome of these findings is variable and may reflect either muscle atrophy due to lack of use or, in the most severe cases, an undiagnosed myopathy.

  17. Analysis of the interaction of induction regimens with p-glycoprotein expression in patients with acute myeloid leukaemia: results from the MRC AML15 trial

    Retrospective analyses in non-randomised cohorts suggest that regimens containing fludarabine/Ara C and/or idarubicin/ara C may be more effective than daunorubicin/AraC (DA)-containing regimens in cases of acute myeloid leukaemia (AML) overexpressing p-glycoprotein (Pgp). We prospectively measured Pgp protein and function by flow cytometry in CD45-gated blasts from 434 AML15 trial patients randomised to remission induction therapy with two courses of FLAG-Ida or DA±etoposide (DA/ADE). In all, 34% were positive for Pgp protein and 38% for function. Pgp protein-positive cases had a higher incidence of resistant disease (14% vs 5%), adjusted odds ratio 2.67 (1.14–6.24). There was a trend towards a higher cumulative incidence of relapse at 5 years for Pgp-positive cases (46% vs 55%), adjusted hazard ratio 1.42 (0.98–2.07) (P=0.06). For patients treated with FLAG-Ida, the complete remission (CR) rate was 86% for both Pgp-positive and Pgp-negative patients. In patients treated with DA/ADE, 78% of Pgp-positive and 90% of Pgp-negative cases achieved CR (P=0.06). In analyses of overall survival, there was no interaction between treatment received and Pgp expression. Data for Pgp function followed similar trends. Our data suggest that FLAG-Ida may improve the remission rate for Pgp-positive AML, but the malignant clone is reduced rather than eradicated such that the relapse rate remains high in Pgp-positive patients

  18. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Highlights: ► Development of a quantitative high throughput in situ expression profiling method. ► Application to a tissue microarray of 242 AML bone marrow samples. ► Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  19. Quantitative multiplex quantum dot in-situ hybridisation based gene expression profiling in tissue microarrays identifies prognostic genes in acute myeloid leukaemia

    Tholouli, Eleni [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); MacDermott, Sarah [The Medical School, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Hoyland, Judith [School of Biomedicine, Faculty of Medical and Human Sciences, The University of Manchester, Oxford Road, M13 9PT Manchester (United Kingdom); Yin, John Liu [Department of Haematology, Manchester Royal Infirmary, Oxford Road, Manchester, M13 9WL (United Kingdom); Byers, Richard, E-mail: richard.byers@cmft.nhs.uk [School of Cancer and Enabling Sciences, Faculty of Medical and Human Sciences, The University of Manchester, Stopford Building, Oxford Road, M13 9PT Manchester (United Kingdom)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Development of a quantitative high throughput in situ expression profiling method. Black-Right-Pointing-Pointer Application to a tissue microarray of 242 AML bone marrow samples. Black-Right-Pointing-Pointer Identification of HOXA4, HOXA9, Meis1 and DNMT3A as prognostic markers in AML. -- Abstract: Measurement and validation of microarray gene signatures in routine clinical samples is problematic and a rate limiting step in translational research. In order to facilitate measurement of microarray identified gene signatures in routine clinical tissue a novel method combining quantum dot based oligonucleotide in situ hybridisation (QD-ISH) and post-hybridisation spectral image analysis was used for multiplex in-situ transcript detection in archival bone marrow trephine samples from patients with acute myeloid leukaemia (AML). Tissue-microarrays were prepared into which white cell pellets were spiked as a standard. Tissue microarrays were made using routinely processed bone marrow trephines from 242 patients with AML. QD-ISH was performed for six candidate prognostic genes using triplex QD-ISH for DNMT1, DNMT3A, DNMT3B, and for HOXA4, HOXA9, Meis1. Scrambled oligonucleotides were used to correct for background staining followed by normalisation of expression against the expression values for the white cell pellet standard. Survival analysis demonstrated that low expression of HOXA4 was associated with poorer overall survival (p = 0.009), whilst high expression of HOXA9 (p < 0.0001), Meis1 (p = 0.005) and DNMT3A (p = 0.04) were associated with early treatment failure. These results demonstrate application of a standardised, quantitative multiplex QD-ISH method for identification of prognostic markers in formalin-fixed paraffin-embedded clinical samples, facilitating measurement of gene expression signatures in routine clinical samples.

  20. Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

    Mohr Brigitte

    2003-01-01

    Full Text Available Abstract Background The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. Results We developed a simplified computer readable cytogenetic notation (SCCN by which chromosome findings are normalised at a resolution of 400 bands. Lost or gained chromosomes or chromosome segments are specified in detail, and ranges of chromosome breakpoint assignments are recorded. Software modules were written to summarise the recorded chromosome changes with regard to the respective chromosome involvement. To assess the degree of karyotype alterations the ploidy levels and numbers of numerical and structural changes were recorded separately, and summarised in a complex karyotype aberration score (CKAS. The SCCN and CKAS were used to analyse the extend and the spectrum of additional chromosome aberrations in 94 patients with Philadelphia chromosome positive (Ph-positive acute lymphoblastic leukemia (ALL and secondary chromosome anomalies. Dosage changes of chromosomal material represented 92.1% of all additional events. Recurring regions of chromosome losses were identified. Structural rearrangements affecting (pericentromeric chromosome regions were recorded in 24.6% of the cases. Conclusions SCCN and CKAS provide unifying elements between karyotypes and computer processable data formats. They proved to be useful in the investigation of additional chromosome aberrations in Ph-positive ALL, and may represent a step towards full automation of the analysis of large and complex karyotype databases.

  1. The role of total body irradiation in preparation for bone marrow transplantation in acute leukaemia. A review

    From extrapolation obtained from animal studies and radiation accidents, it is assumed that for man the LD 50 (30) will be between 300-500 rads total body irradiation (TBI) and the LD 100 at least 600 rads TBI. A dose of 1000 rads TBI is generally used in man for conditioning for bone marrow transplantation. In acute leukemia, total body irradiation is usually associated with cytoreductive chemotherapy. In Seattle 110 patients underwent bone marrow transplantation for acute leukemia in relapse. 15 patients became long term survivors. The main cause of failure were GVH, interstitial pneumonitis and leukemic relapse. New attempts are being made to improve the results: (1) better cytoreductive therapy preceding transplantation, (2) bone marrow transplantation during remission of the disease, (3) prevention of interstitial pneumonitis by modifications of the TBI technique

  2. Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

    Atra, A; Gerrard, M; Hobson, R.; Imeson, J. D.; Ashley, S.; Pinkerton, C. R.

    1998-01-01

    From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubici...

  3. A soluble form of CTLA-4 is present in serum of pediatric patients with acute lymphoblastic leukaemia

    R. Simone

    2011-01-01

    Full Text Available CTLA-4 can regulate and maintain self-telerance, providing a negative signal limiting immunoresponses. Acute lymphoblastic leukemia is a clonal disorder of lymphoid progenitors representing the most frequent malignancy of childhood. Here, we show the presence of significantly elevated levels of a soluble form of CTLA-4 in 70% of B-ALL patients. A possible role of this soluble molecule in the pathogenesis of this neoplastic disease can be envisaged.

  4. Factors affecting long-term outcome after allogeneic haematopoietic stem cell transplantation for acute myelogenous leukaemia: a retrospective study of 172 adult patients reported to the Austrian Stem Cell Transplantation Registry.

    Greinix, Hildegard T; Nachbaur, David; Krieger, Otto; Eibl, Margit; Knöbl, Paul; Kalhs, Peter; Lutz, Dieter; Linkesch, Werner; Niederwieser, Dietger; Hinterberger, Wolfgang; Lechner, Klaus; Rosenmayr, Agathe; Gritsch, Beate

    2002-06-01

    Between 1982 and 2000, 172 patients with acute myelogenous leukaemia (AML) received haematopoietic stem cell transplants (SCT) from related (n = 132) or unrelated (n = 40) donors at four Austrian transplant centres and their results were reported to the Austrian Stem Cell Transplantation Registry. Conditioning for SCT consisted of cyclophosphamide and total body irradiation in 156 (91%) patients. Graft-versus-host disease (GVHD) prophylaxis was with standard cyclosporine and methotrexate in 95 (55%) patients. Median post-transplant follow-up was 5.6 years (range, 0.2--16.7). Multivariate analysis of transplant-related mortality (TRM) identified four variables associated with a lower risk: disease status of first complete remission (CR) at SCT, patient age of 45 years and younger, transplant performed during or after 1995, and lack of acute GVHD. Variables associated with significantly improved leukaemia-free survival were: bone marrow as the stem cell source, disease status of first CR at SCT, and occurrence of chronic GVHD. In multivariate analysis, transplantation performed during or after 1995, first CR at SCT, occurrence of limited chronic GVHD and lack of acute GVHD grades III to IV were associated with increased overall survival. Based on these analyses, options for the improvement of results obtained with allogeneic SCT in patients with AML could be defined. PMID:12060131

  5. Acute T-cell lymphoblastic leukaemia presenting with cutaneous involvement in a child: a rare case report

    Lohit Kumar Kalita

    2015-05-01

    Full Text Available Primary cutaneous involvement in T-cell lymphoblastic leukemia is rare in childhood. We present a case of 6-year-old girl admitted to our hospital because of multiple skin lesions. She was looked pale and weak. Generalized lymphadenopathy was present. Complete blood count revealed 216,000/mm3 white blood cell count. Peripheral blood smear showed 80% lymphoblasts. Bone marrow aspiration revealed 96% blastic cells with immunophenotype and morphological characteristics of acute lymphoblastic leukemia (T-ALL which was confirmed by flowcytometry. ALL BFM -95 remission induction treatment protocol was started. Skin lesion remained same after two month of the cytotoxic therapy. The symptoms became more aggressive and she died after 4 months of treatment. [Int J Res Med Sci 2015; 3(5.000: 1285-1287

  6. Acute secondary effects in the esophagus in patients undergoing radiotherapy for carcinoma of the lung

    Mascarenhas, F.; Silvestre, M.E.; Sa da Costa, M.; Grima, N.; Campos, C.; Chaves, P.

    1989-02-01

    The incidence and nature of acute secondary irradiation esophagitis was studied in a series of 38 patients undergoing 60Co teletherapy for carcinoma of the lung. Thirty-four patients were male and four female, with ages ranging from 38 to 78 years. The mediastinum being irradiated in the process, all the patients underwent endoscopy for signs of esophagitis and/or gastritis after a dose of 30-40 Gy was delivered to the esophagus. Eighteen patients complained of dysphagia, but only in 12 of them did endoscopy show esophagitis. Of the remaining patients without complaints five had endoscopic signs of esophagitis. Gastritis was found in 18 cases and confirmed histologically in 14. In 17 cases, esophagitis and/or gastritis were confirmed histologically. It is believed that there is a fairly close correlation among clinical, endoscopic, and histological findings to support the claim that esophagitis in these patients is radiation induced. However, the cause of gastritis is not well understood. Data in the literature suggest that nonsteroid anti-inflammatory agents can act as prophylactic means of preventing radiation esophagitis.

  7. Acute secondary effects in the esophagus in patients undergoing radiotherapy for carcinoma of the lung

    The incidence and nature of acute secondary irradiation esophagitis was studied in a series of 38 patients undergoing 60Co teletherapy for carcinoma of the lung. Thirty-four patients were male and four female, with ages ranging from 38 to 78 years. The mediastinum being irradiated in the process, all the patients underwent endoscopy for signs of esophagitis and/or gastritis after a dose of 30-40 Gy was delivered to the esophagus. Eighteen patients complained of dysphagia, but only in 12 of them did endoscopy show esophagitis. Of the remaining patients without complaints five had endoscopic signs of esophagitis. Gastritis was found in 18 cases and confirmed histologically in 14. In 17 cases, esophagitis and/or gastritis were confirmed histologically. It is believed that there is a fairly close correlation among clinical, endoscopic, and histological findings to support the claim that esophagitis in these patients is radiation induced. However, the cause of gastritis is not well understood. Data in the literature suggest that nonsteroid anti-inflammatory agents can act as prophylactic means of preventing radiation esophagitis

  8. Cell proliferation and DNA dependent DNA polymerase estimation in acute lymphoblastic leukaemia during treatment with prednisone and vincristine

    The presence of DNA polymerase and primer-template DNA in lymphoblast nuclei by measuring the in vitro incorporation of 3H-thymidine-5'-triphosphate (3H-TTP) was studied in 10 patients with acute lymphoblastic leukemia. Protein synthesis and various other cytokinetic parameters were also studied. After prednisone (P) administration a marked decrease in 3H-TTP labelling index (3H-TTP LI) was apparent together with an inhibition of 3H-leucine incorporation (3H-LEU LI) into lymphoblasts. A moderate decrease in 3H-TDR labelling index (3H-TDR LI) and a later decrease in mitotic index (MI) were seen. Single cell DNA measurements showed a depletion of 3H-TDR labelled lymphoblasts in early part of S-phase apparent at 24 h lasting up to 54 h after P administration. Vincristine given as a flash injection later in the study period caused an immediate rise of the MI, at the same time the P induced decline in 3H-TTP LI, 3H-TDR LI and 3H-LEU LI were continued in most patients. P is thought to damage the cells both in and outside the cell cycle. In the cell cycle the effect of P is an arresting effect in G1. (author)

  9. High bolus tirofiban vs abciximab in acute STEMI patients undergoing primary PCI - The tamip study

    Mohammed A Balghith

    2012-01-01

    Full Text Available Background: Primary percutaneous coronary intervention (PCI has been shown to be an effective therapy for patients with acute myocardial infarction (MI. Glycoprotein (GP IIb/IIIa receptor blockers reduce thrombotic complications in patients undergoing PCI. Most available data relate to Reopro, which has been registered for this indication. GP IIb/IIIa reduce unfavorable outcome in U/A and non ST-elevation myocardial infarction (STEMI patients. Only few studies focused on high dose Aggrastat for STEMI patients in the emergency department (ED before PCI. The aim is to increase the patency during the time awaiting coronary angioplasty in patients with acute MI. Objectives: To study the effect of upfront high bolus dose (HDR of tirofiban on the extent of residual ST segment deviation 1 hour after primary PCI and the incidence of TIMI 3 flow of the infarct-related artery (IRA. Materials and Methods: A randomized, open label, single center study in the ED. A total of 90 patients with acute ST-elevation MI, diagnosed clinically by ECG criteria (ST segment elevation of >2 mm in two adjacent ECG leads, and with an expectation that a patient will undergo primary PCI. Patients were aged 21-85 years and all received heparin 5000 u, aspirin 160 mg, and Plavix 600 mg. Patients were divided in two groups (group I: triofiban high bolus vs group II: Reopro with 45 patients in each group. In group I, high bolus triofiban 25 mcg/kg over 3 min was started in the ED with maintenance infusion of 0.15 mcg/ kg/min continued for 12 hours and transferred to cath lab for PCI. Patients in group II were transferred to cath lab, where a standard dose of Reopro was given with a bolus of 0.25 mcg/kg and maintenance infusion of 0.125 mcg/kg/min over 12 hours. Results: ST segment resolution and TIMI flow were evaluated in both groups before and after PCI. Thirty-five patients (78% enrolled in group I and 29 patients (64% in group II had resolution of ST segment (P-value 0

  10. P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA

    Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of the ABC drug transporter proteins P-glycoprotein (Pgp) and Breast cancer resistance protein (BCRP) is a major obstacle for chemotherapy in many tumour types with Pgp conferring particularly poor prognosis in acute myeloid leukaemia (AML). Barasertib-hQPA is a highly selective inhibitor of aurora-B kinase that has shown tumouricidal activity against a range tumour cell lines including those of leukaemic AML origin. Effect of barasertib-hQPA on the pHH3 biomarker and cell viability was measured in a panel of leukaemic cell lines and 37 primary AML samples by flow cytometry. Pgp status was determined by flow cytometry and BCRP status by flow cytometry and real-time PCR. In this study we report the creation of the cell line OCI-AML3DNR, which over-expresses Pgp but not BCRP or multidrug resistance-associated protein (MRP), through prolonged treatment of OCI-AML3 cells with daunorubicin. We demonstrate that Pgp (OCI-AML3DNR and KG-1a) and BCRP (OCI-AML6.2) expressing AML cell lines are less sensitive to barasertib-hQPA induced pHH3 inhibition and subsequent loss of viability compared to transporter negative cell lines. We also show that barasertib-hQPA resistance in these cell lines can be reversed using known Pgp and BCRP inhibitors. We report that barasertib-hQPA is not an inhibitor of Pgp or BCRP, but by using 14[C]-barasertib-hQPA that it is effluxed by these transporters. Using phosphoHistone H3 (pHH3) as a biomarker of barasertib-hQPA responsiveness in primary AML blasts we determined that Pgp and BCRP positive primary samples were less sensitive to barasertib-hQPA induced pHH3 inhibition (p = <0.001) than samples without these transporters. However, we demonstrate that IC50 inhibition of pHH3 by barasertib-hQPA was achieved in

  11. P-glycoprotein and breast cancer resistance protein in acute myeloid leukaemia cells treated with the Aurora-B Kinase Inhibitor barasertib-hQPA

    Russell Nigel H

    2011-06-01

    Full Text Available Abstract Background Aurora kinases play an essential role in orchestrating chromosome alignment, segregation and cytokinesis during mitotic progression, with both aurora-A and B frequently over-expressed in a variety of human malignancies. Over-expression of the ABC drug transporter proteins P-glycoprotein (Pgp and Breast cancer resistance protein (BCRP is a major obstacle for chemotherapy in many tumour types with Pgp conferring particularly poor prognosis in acute myeloid leukaemia (AML. Barasertib-hQPA is a highly selective inhibitor of aurora-B kinase that has shown tumouricidal activity against a range tumour cell lines including those of leukaemic AML origin. Methods Effect of barasertib-hQPA on the pHH3 biomarker and cell viability was measured in a panel of leukaemic cell lines and 37 primary AML samples by flow cytometry. Pgp status was determined by flow cytometry and BCRP status by flow cytometry and real-time PCR. Results In this study we report the creation of the cell line OCI-AML3DNR, which over-expresses Pgp but not BCRP or multidrug resistance-associated protein (MRP, through prolonged treatment of OCI-AML3 cells with daunorubicin. We demonstrate that Pgp (OCI-AML3DNR and KG-1a and BCRP (OCI-AML6.2 expressing AML cell lines are less sensitive to barasertib-hQPA induced pHH3 inhibition and subsequent loss of viability compared to transporter negative cell lines. We also show that barasertib-hQPA resistance in these cell lines can be reversed using known Pgp and BCRP inhibitors. We report that barasertib-hQPA is not an inhibitor of Pgp or BCRP, but by using 14[C]-barasertib-hQPA that it is effluxed by these transporters. Using phosphoHistone H3 (pHH3 as a biomarker of barasertib-hQPA responsiveness in primary AML blasts we determined that Pgp and BCRP positive primary samples were less sensitive to barasertib-hQPA induced pHH3 inhibition (p = 50 inhibition of pHH3 by barasertib-hQPA was achieved in 94.6% of these samples after 1

  12. Wernicke's encephalopathy induced by total parenteral nutrition in patient with acute leukaemia: unusual involvement of caudate nuclei and cerebral cortex on MRI

    We report a 13-year-old girl with leukaemia and Wernicke's encephalopathy induced by total parenteral nutrition. MRI showed unusual bilateral lesions of the caudate nuclei and cerebral cortex, as well as typical lesions surrounding the third ventricle and aqueduct. After intravenous thiamine, the patient improved, and the abnormalities on MRI disappeared. (orig.)

  13. Antibiotic use from conception to diagnosis of child leukaemia as compared to the background population

    Gradel, Kim Oren; Kaerlev, Linda

    2015-01-01

    BACKGROUND: The role of infection in the aetiology of childhood leukaemia is unknown. We used prescriptions of antibiotics from Danish pharmacies as a proxy measure for the occurrence of infections. PROCEDURE: We investigated the association between exposure to antibiotics, from conception to...... leukaemia diagnosis, and the risk of leukaemia. Incident cases of leukaemia among children in Denmark, 1995-2008, with mothers having their earliest conception date in 1995, were individually matched to population controls by age, sex and municipality. Conditional logistic regression analyses assessed...... antibiotic redemptions in different time periods from conception up to 6 months before the diagnoses of all leukaemia types, acute lymphoblastic leukaemia [ALL] and ALL in 2- to 5-year-old children, adjusting for several potential confounders. RESULTS: A total of 120/360 (33.3%) leukaemia mothers and 1...

  14. Effects of Acute Normovolemic Hemodilution on Perioperative Coagulation and Fibrinolysis in Elderly Patients Undergoing Hepatic Carcinectomy

    Jian-rong Guo; Jun Yu; Xiao-ju Jin; Jin-man Du; Wei Guo; Xiao-hong Yuan

    2010-01-01

    Objective To observe the effects of acute normovolemie hemodilution (ANH) on coagulation func-tion and fibrinolysis in elderly patients undergoing hepatic carcinectomy.Methods Thirty elderly patients (aged 60-70 years) with liver cancer (American Society of Anesthe-siologists physical status Ⅰ-Ⅱ) scheduled for hepatic carcinectomy from February 2007 to February 2008 were randomly divided into ANH group (n= 15) and control group (n= 15). After tracheal intubation, patients in ANH group and control group were infused with 6% hydroxyethyl starch (HES) (130/0.4), and basic liquid containing 6% HES and routine Ringer's solution, respectively. In all the studied patients, blood samples were drawn at five different time points: before anesthesia induction (T1), 30 minutes after ANH (T2), I hour after start of operation (T3), immediately after operation (T4), and 24 hours after operation (T5). Then co-agulation function, soluble fibrin monomer complex (SFMC), prothrombin fragment (F1+2), and platelet membrane glycoprotein (activated GPIIb/GPIIIa and P-selectin) were measured.Results The perioperative blood loss was not significantly different between the two groups (P> 0.05). The volume of allogeneic blood transfusion in ANH group was significantly smaller than that in control group (350.5±70.7 mL vs. 457.8±181.3 mL, P0.05). SFMC and F1 +2 increased in both groups, but without statistical significance. P-selectin expression on the platelet surface of ANH group was significantly low-ered at T2 and T3 compared with the level at T1 (P< 0.05). Compared with control group, P-selectin was sig-nificandy lower in ANH group at T2-T5 (all P<0.05).Conclusions In elderly patients undergoing resection of liver cancer, ANH may not hamper fibri-nolysis and coagulation function. It could therefore be safe to largely reduce allogeneic blood transfusion.

  15. Another leukaemia theory

    Considerable publicity was given to an article 'Evidence for an infective cause of childhood leukaemia: comparison of a Scottish new town with nuclear reprocessing sites in Britain', at the end of 1988 which asserted that increases of leukaemia in young people near Dounreay and Sellafield may be caused by a virus. However, the choice of the new town taken as a comparison is criticised and hence the evidence is considered inconclusive. It is suggested that the risk of leukaemia did increase due to fallout from atmospheric nuclear tests in areas of high rainfall. (author)

  16. T-cell depleted haploidentical three loci mismatched bone-marrow and peripheral blood stem cell transplantation in acute leukaemia patients

    Objectives: Allogeneic bone-marrow transplantation (BMT) is an established treatment for many haematological malignancies. Unfortunately, most patients lack an HLA geno typically identical sibling and require an alternative donor, such as an HLA-haploidentical mismatched related donor, an HLA phenotypically matched or partially mismatched unrelated donor or an HLA-similar cord blood stem cell donor. However, these types of BMT increase the risk of graft-versus-host disease (GvHD), graft failure, delayed immuno reconstitution and fatal infection that observed after a sibling matched donor. Many centers are exploring the possibility of using donors other than matched sibling. Our approach has been to employ T-cell depleted mismatched haploidentical familial donor BMT to solve the problem of GvHD, a highly immuno- and myelo-suppressive conditioning regimen to reduce the incidence of graft failure and relapse, a graft inoculum plus G-CSF donor mobilized peripheral blood stem cells (PBSC) to overcome the host-versus-graft barrier. Patients and methods: Thirty-six patients (25 male, 11 female; median age 22 years, range 2-51) were treated with an allogeneic T-depleted haploidentical three loci mismatched bone-marrow and G-CSF mobilized PBSC transplantation from a familiar donor (18 siblings, 17 parents and 1 cousin) between March 1993 and June 1995. All had high-risk or advanced stage acute myeloid (12) or acute lymphoid (24) leukaemia; 18 were in haematological complete remission (CR) and 18 in chemo resistant relapse. Patients were conditioned with 8 Gy single dose TBI administered on day -5 at an instantaneous dose-rate of 13.4-31.7 cGy/min/midplane and average of 6.7-12.12 cGy/min/midplane. Shields were used to reduce the lung dose to 7 Gy in the first 23 cases and to 6 Gy in the last 13. 10 mg/Kg thiotepa were administered on day -4, 5 mg/Kg rabbit ATG from day -4 to day -1, 60 or 50 mg/Kg/cyclophosphamide on days -3 and -2. Bone-marrow and PBSC were infused on day

  17. Preoperative serum h-FABP concentration is associated with postoperative incidence of acute kidney injury in patients undergoing cardiac surgery

    Oezkur, Mehmet; Gorski, Armin; Peltz, Jennifer; Wagner, Martin; Lazariotou, Maria; Schimmer, Christoph; Heuschmann, Peter U.; Leyh, Rainer G

    2014-01-01

    Background Fatty acid binding protein (FABP) is an intracellular transport protein associated with myocardial damage size in patients undergoing cardiac surgery. Furthermore, elevated FABP serum concentrations are related to a number of common comorbidities, such as heart failure, chronic kidney disease, diabetes mellitus, and metabolic syndrome, which represent important risk factors for postoperative acute kidney injury (AKI). Data are lacking on the association between preoperative FABP se...

  18. Preoperative serum h-FABP concentration is associated with postoperative incidence of acute kidney injury in patients undergoing cardiac surgery

    Oezkur, Mehmet; Gorski, Armin; Peltz, Jennifer; Wagner, Martin; Lazariotou, Maria; Schimmer, Christoph; Heuschmann, Peter U.; Leyh, Rainer G

    2015-01-01

    Background Fatty acid binding protein (FABP) is an intracellular transport protein associated with myocardial damage size in patients undergoing cardiac surgery. Furthermore, elevated FABP serum concentrations are related to a number of common comorbidities, such as heart failure, chronic kidney disease, diabetes mellitus, and metabolic syndrome, which represent important risk factors for postoperative acute kidney injury (AKI). Data are lacking on the association between preoperative FAB...

  19. Low level leukaemia link

    The debate over whether cases of childhood leukaemia recorded in the vicinity of nuclear installations are radiation induced is discussed. The damage caused by alpha-beta and gamma radiation is explained. The United Kingdom National Radiological Protection Board claims that exposure to plutonium is not the cause of the larger-than-average number of cases of leukaemia round nuclear sites. Low doses of radium have been shown to cause bone cancer but not leukaemia possibly because the dose levels used kill off potential leukaemia forming cells. Experiments on mice seem to bear this out. Evidence from Sellafield suggests that the greatest risk from radiation is to in utero foetuses. Risk estimates need to be revised and the questions raised need to be answered. (UK)

  20. Expression profile of heat shock proteins in acute myeloid leukaemia patients reveals a distinct signature strongly associated with FLT3 mutation status--consequences and potentials for pharmacological intervention.

    Reikvam, Håkon; Hatfield, Kimberley J; Ersvaer, Elisabeth; Hovland, Randi; Skavland, Jørn; Gjertsen, Bjørn T; Petersen, Kjell; Bruserud, Oystein

    2012-02-01

    Heat shock proteins (HSPs) are molecular chaperones that assist proteins in their folding to native structures. HSPs are regarded as possible therapeutic targets in acute myeloid leukaemia (AML). We used bioinformatical approaches to characterize the HSP profile in AML cells from 75 consecutive patients, in addition to the effect of the HSP90 inhibitor 17-DMAG. Patients harbouring a FLT3-internal tandem duplication (FLT3-ITD) were extensively overrepresented in the cluster with high HSP levels, indicating a strong dependence of HSPs in stabilizing FLT3-ITD encoded oncoproteins. FLT3 ligation further increased the levels of HSP90 and its co-chaperone HSP70. HSP90 inhibition had a stronger pro-apoptotic effect for AML cells with FLT3-ITD than for cells with wild-type FLT3, whereas the anti-proliferative effect of HSP90 inhibition was similar for the two patient subsets. HSP90 inhibition altered the constitutive cytokine release profile in an anti-angiogenic direction independent of FLT3 mutational status: (i) pro-angiogenic CXCL8, MMP-2 and MMP-9 showed a stronger decrease than anti-angiogenic CXCL9-11, (ii) the Tie-2 agonist Ang-1 showed a stronger decrease than the potentially antagonistic Ang-2, and (iii) VEGF and HGF levels were decreased. Finally, HSP90 inhibition counteracted the leukaemia-stimulating effect of endothelial cells. Our studies demonstrate that HSP90 inhibition mediates anti-leukaemic effects through both direct and indirect activity. PMID:22150087

  1. Evaluation of the radiosensitivity of acute myeloblastic leukaemia progenitor cells by culture methods exploring self-renewal. Evaluation de la radiosensibilite des progeniteurs de leucemie aigue myeloblastique par des methodes de culture explorant ou non l'autorenouvellement

    Cowen, D.; Richaud, P.; Landriau, S.; Lagarde, P.; Gualde, N. (Fondation Bergonie, 33 - Bordeaux (France)); Boiron, J.M. (Hopital du Haut-Leveque, 33 - Pessac (France)); Mahon, F.X.; Belloc, F. (Hopital Regional, 33 - Bordeaux (France)); Reiffers, J. (Hopital du Haut-Leveque, 33 - Pessac (France) Hopital Regional, 33 - Bordeaux (France))

    1993-01-01

    The progenitor cells of acute myeloblastic leukaemia (AML) are usually cultured in methylcellulose which selects for terminal dividing cells. Suspension cultures have been developed because they reflect self-renewal: the exponential growth of the progenitors of AML cultured in suspension is due to self-renewal. We have compared the radiosensitivity of the progenitors of AML grown either in methylcellulose alone or first in suspension for 7 days before being plated in methylcellulose. Cells were harvested from leukaemic bone marrows at the moment of diagnosis. The myeloblastic lineage of the colonies was assessed by morphological, cytochemical and immunophenotypic analysis and by the use of growth factors which do not stimulate T-lymphocytes. The cell-cycle distribution of leukaemic blasts was comparable for all the samples. This method enabled aggressive leukaemias to be selected. The radiosensitivity showed wide variations from one patient to another (Do ranging from 0.35 to 2.6 Gy) whichever culture method used. The progenitor cells capable of self-renewal were more radiosensitive (Mean Do 0.9[+-]0.4 Gy) than terminal dividing cells (Mean Do = 1.35[+-]0.5 Gy). In two cases, a shoulder was found in the initial part of the cell-survival curves of cells capable of self-renewal. The shape of the curves was better fitted by the linear quadratic model with very low values of [alpha]/[beta], suggesting a reduced antileukaemic effect in case of fractionation.

  2. Overview of recent studies on childhood leukaemia, intra-uterine growth and diet

    Many studies have looked at the association between birth weight and risk of acute lymphoblastic leukaemia in children, but few have been able to examine the growth by incorporating estimates of gestational age. Recent results suggest that increased growth is associated with increased risk of childhood leukaemia. Evidence is also gathering that certain dietary intakes, possibly folate, in mothers, are also related to leukaemia occurrence. If these associations are real, they may be operating through growth factor pathways. (authors)

  3. Leukaemia in East Suffolk

    An investigation was conducted by the East Suffolk Health Authority to determine whether there were any geographical variations in the incidence of leukaemia over the last fifteen years in East Suffolk suggesting an environmental hazard, e.g. Sizewell Power Station. No areas were found to have a statistically significant increased incidence of leukaemia cases although there did appear to be a cluster of cases in the Leiston area. (U.K.)

  4. Prevention of central nervous system involvement with intrathecal 198Au colloid and methotrexate in non-Hodgkin lymphoma, acute non-lymphatic leukaemia and Ewing's sarcoma

    Intrathecal 198Au colloid and methotrexate were administered to 27 children (between 1972 and 1981) with non-lymphatic leukaemia, 21 with non-Hodgkin lymphoma and two with Ewing's sarcoma to prevent CNS involvement. In one boy with non-lymphatic leukaemia a stable remission after a three-year period of cytostatic treatment ended with isolated CNS involvement. No isolated CNS recurrence occurred in children with non-Hodgkin lymphoma receiving regular radiogold administration. Combined iris and CNS recurrence occurred in one child with non-Hodkin lymphoma. Eleven of 21 children with non-Hodgkin lymphoma have been in complete initial remission for 4-39 months without cytostatic treatment. Late cerebral complications have not been observed after 198Au colloid and methotrexate. (orig.)

  5. Leukaemia morbidity in Bavaria

    As a contribution to the discussion as to whether there might be any positive relation between low level radiation of natural origin or even of nuclear power plants (NPPs) and the increase in leukaemia morbidity, the Federal Health Office carried out a study on leukaemia mortality in Bavaria. The results of this study suggest that there is a need for morbidity studies for various reasons - e.g. because of te changes and improvements that have been achieved in therapy, especially for childhood leukaemia, as a result of which morbidity patterns might possibly differ from those of mortality. As with the mortality study, the morbidity study was not limited to radiation effects only but did also include other environmental factors relevant for leukaemia. The purpose of our study is to prepare a map of leukaemia in Bavaria and to find out whether there are regional differences in morbidity and, if so, whether the environmental factors influencing morbidity may be identified. For epidemiological studies on the potential effects of lowlevel radiation it is very helpful that there are considerable differences in the levels of natural radiation in different regions of Bavaria. In addition an NPP is located in the regions of Bavaria which has been in operation for more than 15 years. This is the longest time of operation of an NPP in the Federal Republic of Germany, and it is equal to the maximum latency period of leukaemia (according to surveys on the Japanese atom bomb survivors). (Author)

  6. Computer aided analysis of additional chromosome aberrations in Philadelphia chromosome positive acute lymphoblastic leukaemia using a simplified computer readable cytogenetic notation

    Mohr Brigitte; Jauch Anna; Heinze Barbara; Fonatsch Christa; Balz Harald; Bradtke Jutta; Schoch Claudia; Rieder Harald

    2003-01-01

    Abstract Background The analysis of complex cytogenetic databases of distinct leukaemia entities may help to detect rare recurring chromosome aberrations, minimal common regions of gains and losses, and also hot spots of genomic rearrangements. The patterns of the karyotype alterations may provide insights into the genetic pathways of disease progression. Results We developed a simplified computer readable cytogenetic notation (SCCN) by which chromosome findings are normalised at a resolution...

  7. Selected biochemical and oxidative stress parameters and ceruloplasmin as acute phase protein associated with bovine leukaemia virus infection in dairy cows

    Akalın Pınar Peker; Ataseven Veysel Soydal; Fırat Doğan; Ergün Yaşar; Başpınar Nuri; Özcan Oğuzhan

    2015-01-01

    The aim of this study was to determine the ceruloplasmin (Cp) and vitamin C concentrations, the total antioxidant status (TAS), and selected biochemical parameters in dairy cows spontaneously infected with bovine leukaemia virus (BLV). Of the 27 cows included in the study, 18 animals were seropositive for enzootic bovine leukosis (EBL), whereas nine cows were seronegative and were used as controls. The serum aspartate aminotransferase (AST) (P = 0.003) and Cp concentrations (P = 0.03) decreas...

  8. Acute normovolemic hemodilution is not beneficial in patients undergoing primary elective valve surgery

    Virmani Sanjula

    2010-01-01

    Full Text Available The objective of this study was to evaluate the effectiveness of acute normovolemic hemodilution (ANH as a sole method of reducing allogenic blood requirement in patients undergoing primary elective valve surgery. One hundred eighty eight patients undergoing primary elective valve surgery were prospectively randomized into two groups: Group I (n=100 acted as control and in Group II (n=88 autologous blood was removed (10% of estimated blood volume in patients with hemoglobin (Hb > 12g% and 7% when the Hb was < 12g% in the pre-cardiopulmonary bypass (CPB period for subsequent re-transfusion after protamine administration. The autologous blood withdrawn was replaced simultaneously with an equal volume of hydroxyl-ethyl starch solution. Banked blood was transfused in both the groups when Hb was ≤6g % on CPB and ≤8g% after CPB. Platelets were transfused when the count fell to < 100´10 9 /L and fresh frozen plasma (FFP was transfused whenever there was diffuse bleeding with laboratory evidence of coagulopathy. The two groups were comparable as regards demographic data, type of surgical procedures performed, duration of CPB and ischemia, duration of elective ventilation and re-exploration for excessive bleeding. The autologous blood withdrawn in patients with Hb≥12g% was 288.3±69.4 mL and 244.4±41.3 mL with Hb < 12g% (P=NS. The Hb concentration (g % was comparable pre-operatively (Group I= 12.1±1.6, Group II= 12.4±1.4, on postoperative day 1 (Group I =10.3±1.1, Group II= 10.6±1.2 and day 7 (Group I = 10.9±1.5, Group II=10.4±1.5. However, the lowest Hb recorded on CPB was significantly lower in Group II (Group I =7.7±1.2, Group II=6.7±0.9, P < 0.05. There was no difference in the chest tube drainage (Group I =747.2±276.5 mL, Group II=527.6±399.5 mL, blood transfusion (Group I=1.1±1.0 units vs. Group II=1.3±1.0 units intra-operatively and Group I=1.7±1.2 units vs. Group II=1.7±1.4 units post-operatively and FFP transfusion (Group I

  9. Functional changes of dendritic cells derived from allogeneic partial liver graft undergoing acute rejection in rats

    Ming-Qing Xu; Zhen-Xiang Yao

    2003-01-01

    AIM: To investigate functional change of dendritic cells (DCs)derived from allogeneic partial liver graft undergoing acuterejection in rats.METHODS: Allogeneic (SD rat to LEW rat) whole and 50 %partial liver transplantation were performed. DCs from livergrafts 0 hr and 4 days after transplantation were isolated andpropagated in the presence of GM-CSFin vitro. Morphologicalcharacteristics of DCs propagated for 4 days and 10 dayswere observed by electron rmicroscopy. Phenotypical featuresof DCs propagated for 10 days were analyzed by flowcytometry. Expression of IL-12 protein and IL-12 receptormRNA in DCs propagated for 10 days was also measured byWestern blotting and semiquantitative RT-PCR, respectively.Histological grading of rejection were determined.RESULTS: Allogeneic whole liver grafts showed no featuresof rejection at day 4 after transplantation. In contrast,allogeneic partial liver grafts demonstrated moderate tosevere rejection at day 4 after transplantation. DCs derivedfrom allogeneic partial liver graft 4 days after transplantationexhibited typical morphological characteristics of DC after 4days' culture in the presence of GM-CSF. DCs from allogeneicwhole liver graft 0 hr and 4 days after transplantation didnot exhibit typical morphological characteristics of DC untilafter 10 days' culture in the presence of GM-CSF. After 10days' propagationin vitro, DCs derived from allogeneic wholeliver graft exhibited features of immature DC, with absenceof CD40, CD80 and CD86 surface expression, and low levelsof IL-12 proteins (IL-12 p35 and IL-12 p40) and IL-12receptor (IL-12Rβ1 and IL-12Rβ2) mRNA, whereas DCs fromallogeneic partial liver graft 4 days after transplantationdisplayed features of mature DC, with high levels of CD40,CD80 and CD86 surface expression, and as a consequence,higher expression of IL-12 proteins (IL-12 p35 and IL-12 p40)and IL-12 receptors (IL-12Rβ1 and IL-12Rβ2) mRNA thanthose of DCs both from partial liver graft 0 hr and whole livergraft

  10. Birth weight in offspring and leukaemia risk in parents-A nation-wide register-based cohort study from Denmark

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa;

    2013-01-01

    Spurred by previous observations we assessed the relationship between offspring birth weight and parental leukaemia risk in a register-based investigation including 2.4 million parents of 2 million Danish children. Regardless of analytical approach, offspring birth weight was not associated with...... parental risk of leukaemia overall or of leukaemia subtypes except for a twofold increased acute lymphatic leukaemia risk in fathers of high birth weight offspring and an increasing paternal risk of chronic myeloid leukaemia with increasing offspring birth weight. These may both be chance findings. Our...... investigation indicates that offspring birth weight is not strongly associated with parental leukaemia risk....

  11. High-dose vincristine, fractionated total-body irradiation and cyclophosphamide as conditioning regimen in allogeneic and autologous bone marrow transplantation for childhood acute lymphoblastic leukaemia in second remission: a 7-year Italian multicentre study

    We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m2 over 4 d) combined with fractionated total body irradiation (F-TBI) (200 cGy x 2 over 3 d) and cyclophosphamide (60 mg/kg for 2 d) as a preparative regimen in allogeneic (AlloBMT) and autologous (ABMT) bone marrow transplantation for 75 consecutive children (median age at transplant 8.5 years) with acute lymphoblastic leukaemia in second complete remission (CR). Median duration of first CR was 26 and 25 months in the AlloBMT and ABMT group, respectively. We conclude that the conditioning regimen with high-dose vincrostine combined with cyclophosphamide and F-TBI is feasible and promising although its therapeutic advantage should be tested in larger series of patients enrolled in randomized studies. (author)

  12. Fusion of NUP98 and the SET binding protein 1 (SETBP1) gene in a paediatric acute T cell lymphoblastic leukaemia with t(11;18)(p15;q12)

    Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels;

    2007-01-01

    Three NUP98 chimaeras have previously been reported in T cell acute lymphoblastic leukaemia (T-ALL): NUP98/ADD3, NUP98/CCDC28A, and NUP98/RAP1GDS1. We report a T-ALL with t(11;18)(p15;q12) resulting in a novel NUP98 fusion. Fluorescent in situ hybridisation showed NUP98 and SET binding protein 1......(SETBP1) fusion signals; other analyses showed that exon 12 of NUP98 was fused in-frame with exon 5 of SETBP1. Nested polymerase chain reaction did not amplify the reciprocal SETBP1/NUP98, suggesting that NUP98/SETBP1 transcript is pathogenetically important. SETBP1 has previously not been implicated...

  13. Improved clinical outcomes with intracoronary compared to intravenous abciximab in patients with acute coronary syndromes undergoing percutaneous coronary intervention: a systematic review and meta-analysis

    Hansen, Peter Riis; Iversen, Allan; Abdulla, Jawdat

    2010-01-01

    Intracoronary (IC) administration of abciximab may increase local drug levels by several orders of magnitude compared to intravenous (IV) treatment and may improve clinical outcomes in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI). In the absence...

  14. Gene profiling of the erythro- and megakaryoblastic leukaemias induced by the Graffi murine retrovirus

    Ben-David Yaacov

    2010-01-01

    Full Text Available Abstract Background Acute erythro- and megakaryoblastic leukaemias are associated with very poor prognoses and the mechanism of blastic transformation is insufficiently elucidated. The murine Graffi leukaemia retrovirus induces erythro- and megakaryoblastic leukaemias when inoculated into NFS mice and represents a good model to study these leukaemias. Methods To expand our understanding of genes specific to these leukaemias, we compared gene expression profiles, measured by microarray and RT-PCR, of all leukaemia types induced by this virus. Results The transcriptome level changes, present between the different leukaemias, led to the identification of specific cancerous signatures. We reported numerous genes that may be potential oncogenes, may have a function related to erythropoiesis or megakaryopoiesis or have a poorly elucidated physiological role. The expression pattern of these genes has been further tested by RT-PCR in different samples, in a Friend erythroleukaemic model and in human leukaemic cell lines. We also screened the megakaryoblastic leukaemias for viral integrations and identified genes targeted by these integrations and potentially implicated in the onset of the disease. Conclusions Taken as a whole, the data obtained from this global gene profiling experiment have provided a detailed characterization of Graffi virus induced erythro- and megakaryoblastic leukaemias with many genes reported specific to the transcriptome of these leukaemias for the first time.

  15. Frequency of various types of leukaemias diagnosed at PAF hospital mianwali

    Objective: To determine the frequencies of various types of leukaemias in a secondary care hospital. Study Design: Descriptive Place and Duration of Study: PAF Hospital Mianwali, from Jan 2009 to Dec 2012. Material and Methods: Record of all the cases of acute lymphoblastic leukaemia (ALL), acute myeloid leukaemia (AML), chronic lymphocytic leukaemia (CLL) and chronic myeloid leukaemia (CML) diagnosed during the period of study was retrieved from the laboratory and total number of leukaemia cases were counted. The ages and the genders of the patients were noted. Median age at diagnosis for each type of leukaemia was worked out. Frequency of each leukaemia type was noted and relative frequency was calculated as percentage. Results: Out of a total of 67 patients, AML was diagnosed in 22 (32.8%), CML in 16 (23.8%), ALL in 15 (22.4%) and CLL in 14 (20.9%) cases. Median age at diagnosis for ALL, AML, CLL and CML was 5, 41, 70 and 40 years respectively while male to female ratio was 2.7, 1.4, 1.3 and 1.5 respectively. Conclusion: AML was the commonest leukaemia type, followed by CML, ALL and CLL. In children, ALL was found to be four times more common than AML. (author)

  16. The emerging role of exercise and health counseling in patients with acute leukemia undergoing chemotherapy during outpatient management

    Jarden, Mary; Adamsen, Lis; Kjeldsen, Lars;

    2013-01-01

    This study investigates the feasibility, safety and benefits of a 6-week exercise and health counseling intervention in patients with acute leukemia undergoing consolidation chemotherapy during outpatient management. Seventeen of twenty patients completed study requirements (85%), adherence to...... exercise was 73% and for health counseling 92%. There were improvements in the 6-min-walk-distance (p=0.0013), sit-to-stand test (p=0.0062), the right and left biceps arm-curl tests p=0.0002 and p=0.0002, respectively; health-related quality of life (p=0.0209) (FACT-An), vitality (p=0.0015), mental health...

  17. Leukaemia and radiation

    In February 1990 Martin Gardner and colleagues published the results of their study of the apparent excess cases of childhood leukaemia near the nuclear waste reprocessing plant at Sellafield, West Cumbria. Their suggestion is that the excess is due to the increased risk to children of fathers working at the plant. That conclusion, however, is questioned. Comparisons between the relative risks of leukaemia and non-Hodgkin's lymphoma for occupations at Sellafield and for those with other industries have often been ignored. But there are some findings that suggest an excess of childhood cancers among offspring of workers exposed to certain organic chemicals such as benzene, a known leukaemogen. For radiation workers, external radiation exposure is measured by a film badge, and it is this that allows a more detailed analysis of the Sellafield workers as opposed to those in the other industries. It is argued that there is no evidence that childhood leukaemia is associated with an inherited single gene and overall the evidence that an inherited mutational change produced by low doses of radiation is a cause of the excess leukaemia among the offspring of radiation workers is still inconclusive. Possible explanations for the excess could be chance or chemical agents. (author)

  18. Leukaemia incidence in Somerset

    Analysis I confirms two previous studies. There is a high rate of leukaemia incidence (all ages) in the MPH catchment area, compared with rates found by the Leukaemia Research Fund (LRF) for a large part of the country. LRF rates are only available for 1984-1986. For 1971-1987, local rates are 24% higher than LRF rates for 1984-1986. Limiting analysis to the three-year period for which LRF rates are available reveals a local rate for 1984-1986 that is 61% higher than the LRF rate. Analysis II thus identifies an unusual pattern of leukaemia and non-Hodgkins Lymphoma incidence in the vicinity of Hinkley Point. A relatively high rate exists for the period 1964-1986 but excess cases are concentrated in the period 1964-1973; after 1973, the rate is unremarkable. There is no ready explanation for this pattern. If radioactive emissions from Hinkley Point are responsible, large unreported releases would need to have occurred in the 1960's. This possibility needs to be explored. There are other possible explanations but current knowledge about causes of leukaemia is insufficient to offer definite answers. (Author)

  19. Impact of chronic obstructive pulmonary disease on patient with acute myocardial infarction undergoing primary percutaneous coronary intervention

    Pei-Hsun Sung

    2013-12-01

    Full Text Available Background: This study reported the incidence and prognostic outcome of chronic obstructive lung disease (COPD patients with acute ST-segment elevation myocardial infarction (STEMI undergoing primary percutaneous coronary intervention (PCI. Methods: Between January 2002 and May 2011, totally 1554 consecutive patients who experienced STEMI undergoing primary PCI were enrolled into the study. Results: Of the 1554 patients, 124 (9.7% with diagnosis of COPD and 1430 (90.3% without COPD were categorized into group 1 and group 2. Although no difference in in-hospital mortality was noted between the two groups (p = 0.726. However, the hospitalization duration was notably longer (p = 0.003, the incidences of recurrent MI and re-hospitalization for congestive heart failure were significantly higher in group 1 than in group 2 (all p < 0.02. Although Kaplan-Meier analysis demonstrated that the incidence of freedom from one-year major adverse clinical outcome (MACO (defined as recurrent MI, re-admission for congestive heart failure was significantly lower in group 1 than group 2 (p = 0.012, multivariate Cox regression analysis showed COPD was not an independent predictor of MACO-free time after adjusting traditional risk factors. Conclusion: COPD was not an independent predictor of short-term and medium-term MACO in patients with STEMI undergoing primary PCI.

  20. Direct thrombin inhibitors in acute coronary syndromes: effect in patients undergoing early percutaneous coronary intervention

    Sinnaeve, Peter; Simes, John; Yusuf, Salim; Garg, Jyotsna; Mehta, Shamir; Eikelboom, John; Bittl, John A; Serruys, Patrick; Topol, Eric J.; Granger, Christopher B

    2005-01-01

    AIMS: We evaluated the effect of direct thrombin inhibitors (DTIs) in patients undergoing early percutaneous coronary intervention (PCI), using the DTI Trialists' Collaboration database of 35,970 patients from 11 randomized trials of DTIs vs. heparin. METHODS AND RESULTS: We performed a Cox proportional hazards regression analysis with PCI as a time-dependent covariate to assess the independent impact of DTIs according to the performance of early PCI. PCI was performed in 7049 patients in the...

  1. Signs or Symptoms of Acute HIV Infection in a Cohort Undergoing Community-Based Screening

    Hoenigl, Martin; Green, Nella; Camacho, Martha; Gianella, Sara; Mehta, Sanjay R; Smith, Davey M.; Little, Susan J.

    2016-01-01

    We analyzed signs and symptoms in 90 patients diagnosed with acute HIV infection in a community-based program that offered universal HIV-1 nucleic acid amplification testing. Forty-seven (52%) patients reported ongoing signs or symptoms at the time of testing. Another 25 (28%) reported signs or symptoms that had occurred during the 14 days before testing.

  2. Hemophagocytic syndrome in patients with acute myeloid leukemia undergoing intensive chemotherapy

    Delavigne, Karen; Bérard, Emilie; Bertoli, Sarah; Corre, Jill; Duchayne, Eliane; Demur, Cécile; Mas, Véronique Mansat-De; Borel, Cécile; Picard, Muriel; Alvarez, Muriel; Sarry, Audrey; Huguet, Françoise; Récher, Christian

    2014-01-01

    Hemophagocytic lymphohistiocytosis is a condition of immune dysregulation characterized by severe organ damage induced by a hyperinflammatory response and uncontrolled T-cell and macrophage activation. Secondary hemophagocytic lymphohistiocytosis typically occurs in association with severe infections or malignancies. Patients with acute myeloid leukemia may be prone to develop hemophagocytic lymphohistiocytosis because of an impaired immune response and a high susceptibility to severe infecti...

  3. Acute Appendicitis in a Man Undergoing Therapy for Mantle Cell Lymphoma

    Michael Linden

    2012-01-01

    Full Text Available A 71-year-old man was diagnosed with an aggressive mantle cell lymphoma and was started on six cycles of R-CHOP chemotherapy. Approximately two weeks after starting his first cycle of chemotherapy, he complained of severe right lower quadrant abdominal pain, and an abdominal CT scan demonstrated an enlarged appendix with evidence of contained perforation. The man underwent open appendectomy for acute appendicitis and recovered. The appendectomy specimen was submitted for routine pathological analysis. There was histologic evidence of perforation in association with an inflammatory infiltrate with fibrin adhered to the serosal surface; scattered small lymphoid aggregates were present on the mucosal surface. Although the lymphoid aggregates in the submucosa and lamina propria were rather unremarkable by routine histologic examination, immunohistochemistry revealed the lymphocytes to be predominantly Cyclin D1-overexpressing B cells. To our knowledge, this is the first reported case of acute appendicitis in association with appendiceal involvement by mantle cell lymphoma.

  4. Post-operative acute exacerbation of pulmonary fibrosis in lung cancer patients undergoing lung resection

    YANO, MOTOKI; Sasaki, Hidefumi; MORIYAMA, SATORU; HIKOSAKA, YU; YOKOTA, KEISUKE; Kobayashi, Susumu; HARA, MASAKI; Fujii, Yoshitaka

    2011-01-01

    Acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF) in lung cancer patients is a critical factor in post-operative mortality. The cause of AE development is unknown and AE may occur in patients without the diagnosis of IPF. We have conducted a retrospective study of consecutive patients who underwent lung cancer surgery since January 2004. Sixty-two patients with fibrous findings in preoperative high-resolution computed tomography were enrolled in the present study and clinicopatho...

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

    2016-04-08

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

  6. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    2011-01-01

    Background Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiatio...

  7. Ulinastatin Protects against Acute Kidney Injury in Infant Piglets Model Undergoing Surgery on Hypothermic Low-Flow Cardiopulmonary Bypass.

    Xiaocou Wang

    Full Text Available Infants are more vulnerable to kidney injuries induced by inflammatory response syndrome and ischemia-reperfusion injury following cardiopulmonary bypass especially with prolonged hypothermic low-flow (HLF. This study aims to evaluate the protective role of ulinastatin, an anti-inflammatory agent, against acute kidney injuries in infant piglets model undergoing surgery on HLF cardiopulmonary bypass.Eighteen general-type infant piglets were randomly separated into the ulinastatin group (Group U, n = 6, the control group (Group C, n = 6, and the sham operation group (Group S, n = 6, and anaesthetized. The groups U and C received following experimental procedure: median thoracotomy, routine CPB and HLF, and finally weaned from CPB. The group S only underwent sham median thoracotomy. Ulinastatin at a dose of 5,000 units/kg body weight and a certain volume of saline were administrated to animals of the groups U and C at the beginning of CPB and at aortic declamping, respectively. Venous blood samples were collected at 3 different time points: after anesthesia induction in all experimental groups, 5 minutes, and 120 minutes after CPB in the Groups U and C. Markers for inflammation and acute kidney injury were tested in the collected plasma. N-acetyl-β-D-glucosaminidase (NAG from urine, markers of oxidative stress injury and TUNEL-positive cells in kidney tissues were also detected.The expressions of plasma inflammatory markers and acute kidney injury markers increased both in Group U and Group C at 5 min and 120 min after CPB. Also, numbers of TUNEL-positive cells and oxidative stress markers in kidney rose in both groups. At the time point of 120-min after CPB, compared with the Group C, some plasma inflammatory and acute kidney injury markers as well as TUNEL-positive cells and oxidative stress markers in kidney were significantly reduced in the Group U. Histologic analyses showed that HLF promoted acute tubular necrosis and dilatation

  8. Leukaemia and lymphoma

    A report is presented of the Leukaemia Research Fund Data Collection Study of haematological malignancies undertaken from 1984 to 1988. It is the largest single survey carried out in Britain into the incidence of leukaemia, lymphoma and related diseases. In Chapter 1, the background to the study is given, followed by a summary of the geographical areas covered and the methods used for registration and for cross-checking with other data sources. Fuller details of the areal breakdown and of the broad statistical approaches used in calculating and comparing disease incidence are given in Chapter 2. In Chapter 3, the results of the study are presented in tables, graphs and colour maps, showing the incidence of all the main groups of myeloid and lymphoid neoplasms at County and Administrative District levels. Chapter 4 discusses the results with some consideration of possible causative factors for areal differences. (UK)

  9. Postoperative acute kidney injury defined by RIFLE criteria predicts early health outcome and long-term survival in patients undergoing redo coronary artery bypass graft surgery

    Zakkar, Mustafa; Bruno, Vito D; Guida, Guida A; Angelini, Gianni D; Chivasso, Pierpaolo; Suleiman, M Sadeeh; Bryan, Alan J.; Ascione, Raimondo

    2016-01-01

    OBJECTIVE: To investigate the impact of postoperative acute kidney injury (AKI) on early health outcome and on long-term survival in patients undergoing redo coronary artery bypass grafting (CABG).METHODS: We performed a Cox analysis with 398 consecutive patients undergoing redo CABG over a median follow-up of 7 years (interquartile range, 4-12.2 years). Renal function was assessed using baseline and peak postoperative levels of serum creatinine. AKI was defined according to the risk, injury,...

  10. Association of elevated radiation dose with mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention

    Objectives: This study sought to identify clinical and procedural predictors of elevated radiation dose received by patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) and to determine if elevated radiation dose was predictive of mortality in this population. Background: Little data exist regarding the impact of excessive radiation burden on clinical outcomes in patients undergoing PCI. Methods: The study population included 1,039 patients who underwent PCI for an AMI between January 1, 2007 and December 31, 2008 at an academic tertiary care teaching hospital. Cumulative skin dose (measured in milligray [mGy]) was selected as a measurement of patient radiation burden. Clinical and procedural variables were analyzed in multiple logistic and linear regression models to determine predictors of higher skin dose, and its impact was evaluated on all-cause intermediate-term mortality at two years. Results: Median skin dose was 2120 mGy (IQR 1379–3190 mGy) in the overall population, of which 153 (20.8%) patients received an elevated skin dose (defined as a skin dose > 4,000 mGy). Independent predictors of elevated skin dose included male gender, obesity, multivessel intervention, and presentation with a non-ST-elevation MI (NSTEMI) versus an ST-elevation MI (STEMI). Increased skin dose was not predictive of intermediate-term mortality by multivariate analysis in the overall population or in either subgroup of STEMI and NSTEMI. Conclusions: In this contemporary observational study examining patients with AMI undergoing PCI, male gender, obesity, multivessel intervention, and presentation with a NSTEMI were associated with increased radiation exposure

  11. Association of elevated radiation dose with mortality in patients with acute myocardial infarction undergoing percutaneous coronary intervention

    Parikh, Puja B.; Prakash, Sheena; Tahir, Usman; Kort, Smadar; Gruberg, Luis; Jeremias, Allen, E-mail: allen.jeremias@stonybrook.edu

    2014-09-15

    Objectives: This study sought to identify clinical and procedural predictors of elevated radiation dose received by patients with acute myocardial infarction (AMI) undergoing percutaneous coronary intervention (PCI) and to determine if elevated radiation dose was predictive of mortality in this population. Background: Little data exist regarding the impact of excessive radiation burden on clinical outcomes in patients undergoing PCI. Methods: The study population included 1,039 patients who underwent PCI for an AMI between January 1, 2007 and December 31, 2008 at an academic tertiary care teaching hospital. Cumulative skin dose (measured in milligray [mGy]) was selected as a measurement of patient radiation burden. Clinical and procedural variables were analyzed in multiple logistic and linear regression models to determine predictors of higher skin dose, and its impact was evaluated on all-cause intermediate-term mortality at two years. Results: Median skin dose was 2120 mGy (IQR 1379–3190 mGy) in the overall population, of which 153 (20.8%) patients received an elevated skin dose (defined as a skin dose > 4,000 mGy). Independent predictors of elevated skin dose included male gender, obesity, multivessel intervention, and presentation with a non-ST-elevation MI (NSTEMI) versus an ST-elevation MI (STEMI). Increased skin dose was not predictive of intermediate-term mortality by multivariate analysis in the overall population or in either subgroup of STEMI and NSTEMI. Conclusions: In this contemporary observational study examining patients with AMI undergoing PCI, male gender, obesity, multivessel intervention, and presentation with a NSTEMI were associated with increased radiation exposure.

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

    2016-02-22

    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

  13. Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.

    Chessells, J M; Durrant, J; Hardy, R M; Richards, S

    1986-12-01

    The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival

  14. Acute Kidney Injury and the Risk of Mortality in Children Undergoing Hematopoietic Stem Cell Transplantation.

    Kizilbash, Sarah J; Kashtan, Clifford E; Chavers, Blanche M; Cao, Qing; Smith, Angela R

    2016-07-01

    Acute kidney injury (AKI) is a well-documented complication of pediatric hematopoietic stem cell transplantation (HSCT). Dialysis after HSCT is associated with a lower overall survival (OS); however, the association between less severe AKI and OS is unclear. We retrospectively studied 205 consecutive pediatric HSCT patients to determine the incidence and impact of all stages of AKI on OS in pediatric HSCT recipients. We used the peak pRIFLE grade during the first 100 days to classify AKI (ie, R = risk, I = injury, F = failure, L = loss of function, E = end-stage renal disease) and used the modified Schwartz formula to estimate glomerular filtration rate. AKI was observed in 173 of 205 patients (84%). The 1-year OS rate decreased significantly with an increasing severity of pRIFLE grades (P OS between patients without AKI and the R/I group. Regardless of the dialysis status, stages F/L/E had significantly lower rates of OS compared with patients without AKI or R/I (P OS among patients with dialysis and F/L/E without dialysis (P = .65). Stages F/L/E predicted mortality independent of acute graft-versus-host disease, gender, and malignancy. The OS of children after HSCT decreases significantly with an increasing severity of AKI within the first 100 days post-transplant. Although our data did not show an increased risk of mortality with stages R/I, stages F/L/E predicted mortality regardless of dialysis. Prevention and minimization of AKI may improve survival after pediatric HSCT. PMID:27034153

  15. Evaluation of the door-to-needle time in patients undergoing fibrinolytic therapy after acute myocardial infarction

    Early thrombolysis with fibrinolytic therapy has reduced mortality following acute myocardial infarction (AMI) with the major effect coming from early achievement of infarct-related artery potency. This study was carried out to determine the door-to-needle time in patients undergoing fibrinolytic therapy after acute myocardial infarction and to identify factors associated with a prolonged door-to-needle time. This was a cross sectional study in which patients who were thrombolysed for AMI with streptokinase at Punjab Institute of Cardiology, Lahore, from December 12, 2008 to February 18, 2009 were included. All patients admitted with AMI, who were candidates for fibrinolysis, were included. The time of infarction and time of arrival in hospital was determined with ECG changes and asking from patient and/or relatives. The reasons for delay of arrival were asked from patient and accompanying attendants where possible. A door-to-needle time of <30 min could be achieved in 110 of our 201 patients (54.72%). Mean door-to-needle time was 55.13 (+-71.04) minutes. A door-to-needle time of less than 30 minutes in 54.72% is comparable to most contemporary studies however there is a need to look into factors associated with delay. (author)

  16. Selected biochemical and oxidative stress parameters and ceruloplasmin as acute phase protein associated with bovine leukaemia virus infection in dairy cows

    Akalın Pınar Peker

    2015-09-01

    Full Text Available The aim of this study was to determine the ceruloplasmin (Cp and vitamin C concentrations, the total antioxidant status (TAS, and selected biochemical parameters in dairy cows spontaneously infected with bovine leukaemia virus (BLV. Of the 27 cows included in the study, 18 animals were seropositive for enzootic bovine leukosis (EBL, whereas nine cows were seronegative and were used as controls. The serum aspartate aminotransferase (AST (P = 0.003 and Cp concentrations (P = 0.03 decreased (65.17 ± 5.03 and 7.70 ± 0.72 respectively in BLV-infected cows, as compared to healthy animals (100.67 ± 11.50 and 10.40 ± 0.70 respectively. A slight insignificant increase in alkaline phosphatase activity and unchanged levels of alanine aminotransferase, lactate dehydrogenase, calcium, magnesium, and TAS were demonstrated in EBL cows. As the TAS and vitamin C levels remained unchanged in EBL cows, it may be suggested that ruminants may compensate for the impaired oxidative/antioxidative balance. The results obtained also indicate that BLV may suppress AST and Cp synthesis or secretion in the liver through an unknown mechanism. The mechanism of action of BLV in hepatocytes, especially on AST and Cp, requires further investigation to elucidate the immune suppression caused by oncogenic retroviruses.

  17. A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

    Naiel, Abdulbasit [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom); Vetter, Michael [MetaSystems, Altlussheim 68804 (Germany); Plekhanova, Olga [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Fleischman, Elena; Sokova, Olga [N.N. Blokhin Russian Cancer Research Center Russian Academy of Medical Science, Moscow 115478 (Russian Federation); Tsaur, Grigory [Regional Children’s Hospital N 1, Ekaterinburg 620149 (Russian Federation); Research Institute of Medical Cell Technologies, Ekaterinburg 620149 (Russian Federation); Harbott, Jochen [Oncogenetic Laboratory, Department of Paediatric Haematology and Oncology, Justus Liebig University, Giessen 35392 (Germany); Tosi, Sabrina, E-mail: sabrina.tosi@brunel.ac.uk [Leukaemia and Chromosome Research Laboratory, Division of Biosciences, Brunel University, London, Middlesex UB8 3PH (United Kingdom)

    2013-03-11

    The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting.

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

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

    2015-08-01

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

  19. A Novel Three-Colour Fluorescence in Situ Hybridization Approach for the Detection of t(7;12)(q36;p13) in Acute Myeloid Leukaemia Reveals New Cryptic Three Way Translocation t(7;12;16)

    The t(7;12)(q36;p13) translocation is a recurrent chromosome abnormality that involves the ETV6 gene on chromosome 12 and has been identified in 20–30% of infant patients with acute myeloid leukaemia (AML). The detection of t(7;12) rearrangements relies on the use of fluorescence in situ hybridization (FISH) because this translocation is hardly visible by chromosome banding methods. Furthermore, a fusion transcript HLXB9-ETV6 is found in approximately 50% of t(7;12) cases, making the reverse transcription PCR approach not an ideal screening method. Considering the report of few cases of variant translocations harbouring a cryptic t(7;12) rearrangement, we believe that the actual incidence of this abnormality is higher than reported to date. The clinical outcome of t(7;12) patients is believed to be poor, therefore an early and accurate diagnosis is important in the clinical management and treatment. In this study, we have designed and tested a novel three-colour FISH approach that enabled us not only to confirm the presence of the t(7;12) in a number of patients studied previously, but also to identify a cryptic t(7;12) as part of a complex rearrangement. This new approach has proven to be an efficient and reliable method to be used in the diagnostic setting

  20. Ciprofloxacin prophylaxis delays initiation of broad-spectrum antibiotic therapy and reduces the overall use of antimicrobial agents during induction therapy for acute leukaemia: A single-centre study.

    Hallböök, Helene; Lidström, Anna-Karin; Pauksens, Karlis

    2016-06-01

    Background Due to an outbreak of extended-spectrum β-lactamase (ESBL)-producing Escherichia coli and Klebsiella pneumoniae, the routine use of fluoroquinolone prophylaxis was questioned. As a result, this study was conducted with the aim to evaluate the impact of ciprofloxacin-prophylaxis on the use of broad-spectrum antibioctics and anti-mycotics. Methods A cohort of 139 consecutive patients with acute leukaemia treated with remission-inducing induction chemotherapy between 2004-2012 at the Department of Haematology in Uppsala University Hospital was analysed. Results Fifty-three patients (38%) received broad-spectrum antibiotics at the initiation of chemotherapy and were not eligible for prophylaxis. Of the remaining patients, the initiation of broad-spectrum antibiotics was delayed by 3 days in those receiving ciprofloxacin prophylaxis (n = 47) compared with those receiving no prophylaxis (n = 39). The median duration of systemic antibiotic treatment was 6 days shorter in patients receiving ciprofloxacin prophylaxis (12 vs 18 days; p = 0.0005) and the cumulative (total) median days on systemic antibiotic treatment was shortened by 8 days (15 vs 23 days, p = 0.0008). Piperacillin/tazobactam (p = 0.02), carbapenems (p = 0.05) and empiric broad-spectrum antifungals (p antibiotic use in this study. These benefits must be evaluated vs the risks of development of resistant bacterial strains, making fluoroquinolone prophylaxis an open question for debate. PMID:27030917

  1. 急性白血病下呼吸道感染特点及危险因素分析%Analysis of characteristics and risk factors of lower respiratory infections in patients with acute leukaemia

    王文松; 钱美华; 王曼玲; 杨天新; 王晓刚

    2013-01-01

    目的 探讨急性白血病下呼吸道感染病原菌分布及耐药性,并分析造成下呼吸道感染的危险因素,为临床治疗提供参考.方法 选择87例急性白血病住院患者作为研究对象,收集其痰液标本,进行病原菌培养与药敏试验;采用logistic回归分析急性白血病患者下呼吸道感染的危险因素.结果 发生下呼吸道感染共40例,检出革兰阴性菌占67.21%,革兰阳性菌占24.59%,真菌占8.20%,菌种主要为肺炎克雷伯菌、大肠埃希菌、金黄色葡萄球菌、铜绿假单胞菌及鲍氏不动杆菌;检出病原菌对多种抗菌药物耐药,肺炎克雷伯菌对亚胺培南及美罗培南敏感,耐药率分别为18.75%以及12.50%;金黄色葡萄球菌对万古霉素及替考拉宁敏感,耐药率均为0;而白色假丝酵母菌对两性霉素B敏感,耐药率为0;研究最终确定急性白血病下呼吸道感染的危险因素为血红蛋白≤50 g/L、血小板计数≤30×109/L、预防性使用抗菌药物以及使用糖皮质激素.结论 对急性白血病发生下呼吸道感染治疗时可对其危险因素进行干预,感染发生后,应选用敏感抗菌药物进行治疗.%OBJECTIVE To explore characteristics of composition and drug resistance of pathogens and analyze the risk factors of lower respiratory tract infections in the acute leukaemia patients so as to guide the clinical treatment. METHODS A total of 40 patients with lower respiratory tract infections were selected from 87 patients with acute leukaemia. The sputum specimens were collected and processed by bacterial culture and drug susceptibility testing. The risk factors were analyzed by logistic regression analysis. RESULTS Of the pathogens causing lower respiratory tract infections in 40 patients, the gram-negative bacteria accounted for 67.21%, the gram-positive bacteria 24. 59%, fungi 8. 20% ; the predominant species were Klebsiella pneumoniae, Escherichia coli, Staphylococcus aureics

  2. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Mitochondrial DNA (mtDNA) alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD), are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI) treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL) patients as well as to take them as predictors for radiation toxicity. Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively). Extracted DNA was analyzed by real-time PCR method. Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048). Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. mtDNA and CD content may be considered as predictive factors to radiation toxicity

  3. Clofarabine-associated acute kidney injury in patients undergoing hematopoietic stem cell transplant.

    Petri, Camille R; O'Donnell, Peter H; Cao, Hongyuan; Artz, Andrew S; Stock, Wendy; Wickrema, Amittha; Hard, Marjie; van Besien, Koen

    2014-12-01

    Abstract We examined clofarabine pharmacokinetics and association with renal toxicity in 62 patients participating in a phase I-II study of clofarabine-melphalan-alemtuzumab conditioning for hematopoietic stem cell transplant (HSCT). Pharmacokinetic parameters, including clofarabine area under the concentration-time curve (AUC), maximum concentration and clearance, were measured, and patients were monitored for renal injury. All patients had normal pretreatment creatinine values, but over half (55%) experienced acute kidney injury (AKI) after clofarabine administration. Age was the strongest predictor of AKI, with older patients at greater risk (p = 0.002). Clofarabine AUC was higher in patients who developed AKI, and patients with the highest dose-normalized AUCs experienced the most severe grades of AKI (p = 0.01). Lower baseline renal function, even when normal, was associated with lower clofarabine clearance (p = 0.008). These data suggest that renal-adjustment of clofarabine dosing should be considered for older and at-risk patients even when renal function is ostensibly normal. PMID:24564572

  4. Mitochondrial DNA alterations of peripheral lymphocytes in acute lymphoblastic leukemia patients undergoing total body irradiation therapy

    Ji Fuyun

    2011-10-01

    Full Text Available Abstract Background Mitochondrial DNA (mtDNA alterations, including mtDNA copy number and mtDNA 4977 bp common deletion (CD, are key indicators of irradiation-induced damage. The relationship between total body irradiation (TBI treatment and mtDNA alterations in vivo, however, has not been postulated yet. The aim of this study is to analyze mtDNA alterations in irradiated human peripheral lymphocytes from acute lymphoblastic leukemia (ALL patients as well as to take them as predictors for radiation toxicity. Methods Peripheral blood lymphocytes were isolated from 26 ALL patients 24 hours after TBI preconditioning (4.5 and 9 Gy, respectively. Extracted DNA was analyzed by real-time PCR method. Results Average 2.31 times mtDNA and 0.53 fold CD levels were observed after 4.5 Gy exposure compared to their basal levels. 9 Gy TBI produced a greater response of both mtDNA and CD levels than 4.5 Gy. Significant inverse correlation was found between mtDNA content and CD level at 4.5 and 9 Gy (P = 0.037 and 0.048. Moreover, mtDNA content of lymphocytes without irradiation was found to be correlated to age. Conclusions mtDNA and CD content may be considered as predictive factors to radiation toxicity.

  5. Drawing the line with leukaemia

    The cluster of cases of childhood leukaemia near nuclear installations in the United Kingdom are considered. The paper examines whether these clusters have occurred by chance, or are an artefact of the statistical methodology, or the result of variability in the reporting of these leukaemias, or the result of some local agent, such as radiation. Statistical methodology including tests of significance involve choices available to researchers when boundaries of the test cells are selected. Choice of the wrong boundaries can lead to misleading results, such as in the town of Lydney, Gloucestershire where an apparent cluster of leukaemias was reported in 1987. The quality of data is also a problem, and there is evidence that some registration of childhood leukaemia is 'missed'. The authors conclude that it is easy to manipulate data and produce scare stories, and research workers on clusters of leukaemia near nuclear installations must be vigilant about the methods they employ. (U.K.)

  6. Leukaemia induction in man by radionuclides and some relevant experimental and human observations

    Specific differences in induction of specific kinds of leukaemia are found in Thorotrast-containing subjects, in males occupationally exposed to Ra isotopes, in bomb survivors and in patients with ankylosing spondylitis after a single course of X-ray treatment. Analyses of leukaemia induction by ionizing radiation simply in terms of total numbers of leukaemia must be inadequate. Deaths from marrow failure have been nearly as frequent as from leukaemias in 3 groups only, Thorotrast-containing subjects, patients given cancericidal radiotherapy with Sulphur-35, and U.S. radiologists beginning their occupational exposure in the 1920's. In them severe radiation damage to the marrow may be an important contributor to leukaemia induction. Dosimetry of focal α-particle irradiation of the bone marrow, polycytic microdisometry, seems essential for an understanding of leukaemia induction by high LET irradiation. The regional distribution of Thorotrast deposits in relation to the active marrow content of different bones seems to be an unexplored but relevant issue. Induction of acute myeloid leukaemia in the laboratory mouse provides a model allowing experimental analysis of interaction biological and radiological factors in radiation induction of this specific type of leukaemia. (orig.)

  7. Short- or long-outcome of early tirofiban in ST-segment elevated acute myocardial infarction undergoing elective percutaneous coronary intervention

    张优

    2014-01-01

    Objective To explore the optimal timing of tirofiban early treatment in ST-segment elevated acute myocardial infarction(STEMI)undergoing elective percutaneous coronary intervention(PCI).Methods A total of 118 consecutive STEMI patients were enrolled in the study.They were randomly assigned to the tirofiban early treatment

  8. Age of onset and type of leukaemia

    The factors that influence leukaemia type are complex and differ for various leukaemogenic agents. Some leukaemogens increase the age-related risk of specific leukaemia, whereas other induce several or a single leukaemia type without age correlation. In most situations, age has no influence on leukaemia type. Consequently, other factors may explain the pronounced age-related differences seen for ''spontaneously'' occurring leukaemias in human beings. (author)

  9. Symptom-Adapted Physical Activity Intervention in Minimizing Physical Function Decline in Older Patients With Acute Myeloid Leukemia Undergoing Chemotherapy

    2015-02-24

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

  10. Traffic-related air pollution and risk for leukaemia of an adult population.

    Raaschou-Nielsen, Ole; Ketzel, Matthias; Harbo Poulsen, Aslak; Sørensen, Mette

    2016-03-01

    Air pollution causes lung cancer, but associations with other cancers have not been established. We investigated whether long-term exposure to traffic-related air pollution is associated with the risk of the general population for leukaemia. We identified 1,967 people in whom leukaemia was diagnosed in 1992-2010 from a nation-wide cancer registry and selected 3,381 control people at random, matched on sex and year of birth, from the entire Danish population. Residential addresses since 1971 were traced in a population registry, and outdoor concentrations of NOx and NO2 , as indicators of traffic-related air pollution, were calculated at each address in a dispersion model. We used conditional logistic regression to estimate the risk for leukaemia after adjustment for income, educational level, cohabitation status and co-morbidity. In linear analyses, we found odds ratios for acute myeloid leukaemia of 1.20 (95% confidence interval: 1.04-1.38) per 20 µg/m(3) increase in NOx and 1.31 (1.02-1.68) per 10 µg/m(3) increase in NO2 , calculated as time-weighted average exposure at all addresses since 1971. We found no association with chronic myeloid or lymphocytic leukaemia. This study indicates an association between long-term exposure to traffic-related air pollution and acute myeloid leukaemia in the general population, but not for other subtypes of leukaemia. PMID:26415047

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

    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

  12. Leukaemia near british nuclear installations

    An excess of childhood leukaemia has been seen near some British nuclear installations, especially near the Sellafield reprocessing plant. The same result was found in a more general study including a large number of nuclear sites. Similar studies made in USA, Canada and France have been negative. Moreover, epidemiological studies made in England have discovered other childhood leukaemia clusters in areas far from nuclear facilities, and especially near potential sites of nuclear installations. Several explanations are suggested but no definite conclusion is yet possible. Doses from radioactive releases seem to be too low to account for the additional deaths from leukaemia by environmental contamination. A virus activation, which might be associated with population influx into rural isolated areas, has been considered. The hypothesis of genetic mutation induced by ionising radiation in the fathers of children with leukaemia has been made because a higher risk of leukaemia was observed for children of fathers employed at Sellafield. No firm conclusion is possible considering the small number of observed cases and the lack of excess leukaemias in the offspring of Hiroshima and Nagasaki survivors. The possibility of internal contamination, chemicals or even radon is discussed as other causes. Studies in progress might allow to find an answer to the problem of leukaemia in the vicinity of British nuclear installations

  13. Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study.

    Stiller, C A; Chessells, J M; Fitchett, M

    1994-01-01

    There is a well-known raised risk of leukaemia in children with neurofibromatosis type 1 (NF-1). We carried out the first detailed population-based study of leukaemia and non-Hodgkin lymphoma (NHL) associated with NF-1 in order to estimate the risk and elucidate the relationship between these conditions. Over the 17 year study period there were five cases of chronic myelomonocytic leukaemia (CMML) in patients with NF-1 (relative risk 221; 95% CI 71-514), 12 cases of acute lymphoblastic leukae...

  14. Combined Value of Red Blood Cell Distribution Width and Global Registry of Acute Coronary Events Risk Score for Predicting Cardiovascular Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

    Zhao, Na; Mi, Lan; Liu, Xiaojun; Pan, Shuo; Xu, Jiaojiao; Xia, Dongyu; Liu, Zhongwei; Zhang, Yong; Xiang, Yu; Yuan, Zuyi; Guan, Gongchang; Wang, Junkui

    2015-01-01

    Global Registry of Acute Coronary Events (GRACE) risk score and red blood cell distribution width (RDW) content can both independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). We investigated the combined predictive value of RDW and GRACE risk score for cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI) for the first time. We enrolled 480 ACS patients. During a median follow-up time of 37.2 months,...

  15. Dicentric chromosome in the bone marrow of a child with megakaryoblastic leukaemia and Down's syndrome.

    Wilkie, A O; Kitchen, C.; Oakhill, A; Howell, R T; Berry, P J

    1988-01-01

    A two year old girl with Down's syndrome (constitutional karyotype: 47 + 21), presenting with pancytopenia, developed acute megakaryoblastic leukaemia (AMKL). Her bone marrow contained an abnormal clone with a novel dicentric chromosome derived from chromosomes 5 and 7 (karyotype 46, XX, -5, -7, +dic (5;7) (p 13; p 11.2), +21. This case provides further evidence for a connection between chromosome 21 and this unusual form of childhood leukaemia, and raises questions about the loss of short ar...

  16. Improved cure rate in children with B-cell acute lymphoblastic leukaemia (B-ALL) and stage IV B-cell non-Hodgkin's lymphoma (B-NHL)--results of the UKCCSG 9003 protocol.

    Atra, A; Gerrard, M; Hobson, R; Imeson, J D; Ashley, S; Pinkerton, C R

    1998-06-01

    From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern. PMID:9649146

  17. Paediatric B-cell precursor acute lymphoblastic leukaemia with t(1;19)(q23;p13): clinical and cytogenetic characteristics of 47 cases from the Nordic countries treated according to NOPHO protocols.

    Andersen, Mette K; Autio, Kirsi; Barbany, Gisela; Borgström, Georg; Cavelier, Lucia; Golovleva, Irina; Heim, Sverre; Heinonen, Kristina; Hovland, Randi; Johannsson, Johann H; Johansson, Bertil; Kjeldsen, Eigil; Nordgren, Ann; Palmqvist, Lars; Forestier, Erik

    2011-10-01

    The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19)t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1·8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 × 10(9)/l, and the female/male ratio was 1·2. The predicted event-free survival (EFS) at 5 and 10 years was 0·79, whereas the predicted overall survival (OS) at 5 and 10 years was 0·85 and 0·82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19)t(1;19) (P = 0·004). PMID:21902680

  18. Acute leukaemoid reaction following cardiac surgery

    Webb Stephen T

    2007-01-01

    Full Text Available Abstract Chronic myelomonocytic leukaemia is an atypical myeloproliferative disorder with a natural history of progression to acute myeloid leukaemia, a complex and poorly understood response by the bone marrow to stress. Cardiac surgery activates many inflammatory cascades and may precipitate a systemic inflammatory response syndrome. We present a case of undiagnosed chronic myelomonocytic leukaemia who developed rapidly fatal multi-organ dysfunction following cardiac surgery due to an acute leukaemoid reaction.

  19. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Wong, Jeffrey Y.C., E-mail: jwong@coh.org [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Forman, Stephen; Somlo, George [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Rosenthal, Joseph [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States); Department of Pediatrics, City of Hope National Medical Center, Duarte, California (United States); Liu An; Schultheiss, Timothy; Radany, Eric [Department of Radiation Oncology, City of Hope National Medical Center, Duarte, California (United States); Palmer, Joycelynne [Department of Biostatistics, City of Hope National Medical Center, Duarte, California (United States); Stein, Anthony [Department of Hematology/Hematopoietic Cell Transplantation, City of Hope National Medical Center, Duarte, California (United States)

    2013-01-01

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days -10 to -6, etoposide (VP16) on Day -5 (60 mg/kg), and cyclophosphamide (CY) on Day -3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days -12 to -8 (800 {mu}M min), TMI on Days -8 to -4, and VP16 on Day -3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible with BU/VP16 due to

  20. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Purpose: We have demonstrated that toxicities are acceptable with total marrow irradiation (TMI) at 16 Gy without chemotherapy or TMI at 12 Gy and the reduced intensity regimen of fludarabine/melphalan in patients undergoing hematopoietic cell transplantation (HCT). This article reports results of a study of TMI combined with higher intensity chemotherapy regimens in 2 phase I trials in patients with advanced acute myelogenous leukemia or acute lymphoblastic leukemia (AML/ALL) who would do poorly on standard intent-to-cure HCT regimens. Methods and Materials: Trial 1 consisted of TMI on Days −10 to −6, etoposide (VP16) on Day −5 (60 mg/kg), and cyclophosphamide (CY) on Day −3 (100 mg/kg). TMI dose was 12 (n=3 patients), 13.5 (n=3 patients), and 15 (n=6 patients) Gy at 1.5 Gy twice daily. Trial 2 consisted of busulfan (BU) on Days −12 to −8 (800 μM min), TMI on Days −8 to −4, and VP16 on Day −3 (30 mg/kg). TMI dose was 12 (n=18) and 13.5 (n=2) Gy at 1.5 Gy twice daily. Results: Trial 1 had 12 patients with a median age of 33 years. Six patients had induction failures (IF), and 6 had first relapses (1RL), 9 with leukemia blast involvement of bone marrow ranging from 10%-98%, 5 with circulating blasts (24%-85%), and 2 with chloromas. No dose-limiting toxicities were observed. Eleven patients achieved complete remission at Day 30. With a median follow-up of 14.75 months, 5 patients remained in complete remission from 13.5-37.7 months. Trial 2 had 20 patients with a median age of 41 years. Thirteen patients had IF, and 5 had 1RL, 2 in second relapse, 19 with marrow blasts (3%-100%) and 13 with peripheral blasts (6%-63%). Grade 4 dose-limiting toxicities were seen at 13.5 Gy (stomatitis and hepatotoxicity). Stomatitis was the most frequent toxicity in both trials. Conclusions: TMI dose escalation to 15 Gy is possible when combined with CY/VP16 and is associated with acceptable toxicities and encouraging outcomes. TMI dose escalation is not possible

  1. Cytogenetics Does Not Impact Outcomes in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation.

    Aldoss, Ibrahim; Tsai, Ni-Chun; Slovak, Marilyn L; Palmer, Joycelynne; Alvarnas, Joseph; Marcucci, Guido; Forman, Stephen J; Pullarkat, Vinod

    2016-07-01

    The prognostic relevance of cytogenetics at diagnosis on the outcome of allogeneic hematopoietic stem cell transplantation (alloHCT) for adult acute lymphoblastic leukemia (ALL) remains unclear. We retrospectively analyzed outcomes of 333 adult ALL patients who underwent alloHCT at our institution over a 10-year period. Patients were classified according to disease status at transplantation (complete response [CR] 1 [n = 202] or > CR1) and according to cytogenetic risk, defined as good (2%), intermediate (42%), poor (46%), or unknown (10%) based on available outcome data for each of the cytogenetic abnormalities. Three-year overall survival (OS), leukemia-free survival (LFS), and relapse incidence (RI) were 55.7%, 47.9% and 27.5%, respectively; 1-year nonrelapse mortality (NRM) was 17.3%. For patients undergoing alloHCT in CR1, 3-year OS, LFS, and RI were 69.8%, 62.3%, and 17.1%, respectively. In multivariable analysis, cytogenetic risk did not impact OS or LFS for the whole cohort or for patients who underwent transplantation in CR1. Disease status at alloHCT was an independent predictor for LFS (CR1 versus others: hazard ratio [HR], 3.17; P OS (CR1 versus others: HR, 2.90; P < .01). Graft-versus-host disease prophylaxis with tacrolimus/sirolimus was associated with a low NRM of 11.5% in the alloHCT recipients in CR1. Our data indicate that cytogenetic risk is not an independent predictor of outcomes in alloHCT performed to treat adult ALL. PMID:27044907

  2. Antithrombotic therapy in anticoagulated patients with atrial fibrillation presenting with acute coronary syndromes and/or undergoing percutaneous coronary intervention/stenting

    Benjamin J. Wrigley

    2010-07-01

    Full Text Available The management of antithrombotic therapy in atrial fibrillation patients presenting with acute coronary syndrome and/or undergoing percutaneous coronary inter vention/stenting cannot be done according to a regimented common protocol, and stroke and bleeding risk stratification schema should be employed to individualize treatment options. A delicate balance is needed between the prevention of thromboembolism, against recurrent cardiac ischemia or stent thrombosis, and bleeding risk. New guidance from a consensus document of the European Society of Cardiology Working Group on Thrombosis, endorsed by the European Heart Rhythm Association and the European Association ofPercutaneous Cardiovascular Interventions on the management of Antithrombotic Therapy in Atrial Fibrillation Patients Presenting with Acute Coronary Syndrome and/or Undergoing Percutaneous Coronary Intervention/Stenting has sought to clarify some of the major issues and problems surrounding this practice, and will allow clinicians to make much more informed decisions when faced with treating such patients.

  3. Adult leukaemia: what is the role of currently known risk factors?

    Leukaemias are a heterogeneous group of tumours including acute and chronic forms. Considerable efforts have been made to identify risk factors for these diseases, but only a minority of leukaemia cases can currently be attributed to identified or hypothesized factors. This review highlights recent epidemiological literature concerning adult leukaemia, discussing in detail the hereditary, environmental and medical risks. Chromosomal syndromes and genetically based diseases carry a high risk of leukaemia, but rarely occur in the population. Environmental and occupational exposures to chemicals including pesticides have been widely studied, although the results are not consistent, with the exception of benzene. Smoking seems to be a weak causal risk factor. The risk of ionizing radiation has further been quantified in recent studies, although the effects of low doses have not yet been clarified. The results for non-ionizing radiation continue to be inconsistent, but a large effect of electromagnetic fields on the risk of leukaemia appears to be unlikely. Medically applied radio- and chemotherapy are clearly associated with subsequent leukaemia development, and there are links between leukaemia and viral infections. Future research should emphasize the shortcomings in exposure assessment that pervade many studies, and interactions between different risk factors need to be taken into consideration. (orig.)

  4. Adult leukaemia: what is the role of currently known risk factors?

    Zeeb, H. [Deutsches Krebsforschungszentrum, Abt. Epidemiologie, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany); Blettner, M. [International Agency for Research on Cancer (IARC), Unit of Carcinogen Identification and Evaluation, 150 Cours Albert Thomas, F-69372 Lyon (France)

    1998-02-01

    Leukaemias are a heterogeneous group of tumours including acute and chronic forms. Considerable efforts have been made to identify risk factors for these diseases, but only a minority of leukaemia cases can currently be attributed to identified or hypothesized factors. This review highlights recent epidemiological literature concerning adult leukaemia, discussing in detail the hereditary, environmental and medical risks. Chromosomal syndromes and genetically based diseases carry a high risk of leukaemia, but rarely occur in the population. Environmental and occupational exposures to chemicals including pesticides have been widely studied, although the results are not consistent, with the exception of benzene. Smoking seems to be a weak causal risk factor. The risk of ionizing radiation has further been quantified in recent studies, although the effects of low doses have not yet been clarified. The results for non-ionizing radiation continue to be inconsistent, but a large effect of electromagnetic fields on the risk of leukaemia appears to be unlikely. Medically applied radio- and chemotherapy are clearly associated with subsequent leukaemia development, and there are links between leukaemia and viral infections. Future research should emphasize the shortcomings in exposure assessment that pervade many studies, and interactions between different risk factors need to be taken into consideration. (orig.) With 1 fig., 5 tabs., 114 refs.

  5. Clofarabine Combined with Busulfan Provides Excellent Disease Control in Adult Patients with Acute Lymphoblastic Leukemia Undergoing Allogeneic Hematopoietic Stem Cell Transplantation

    Kebriaei, P.; Basset, Roland; Ledesma, C.; Ciurea, S; Parmar, S.; Shpall, EJ; Hosing, C.; Khouri, Issa; Qazilbash, M; Popat, U; Alousi, A.; Nieto, Y; Jones, RB; Lima, M.; Champlin, RE

    2012-01-01

    We investigated the safety and early disease-control data obtained with intravenous busulfan (Bu) combined with clofarabine (Clo) in patients with acute lymphoblastic leukemia (ALL) undergoing allogeneic hematopoietic stem cell transplantation (SCT). Fifty-one patients with median age 36 years (range 20–64) received a matched sibling (n=24), syngeneic (n=2) or matched unrelated donor transplant (n=25) for ALL in first complete remission (n=30), second complete remission (n=13), or with active...

  6. Use of platelet glycoprotein IIb/IIIa inhibitors in diabetics undergoing PCI for non-ST-segment elevation acute coronary syndromes: impact of clinical status and procedural characteristics

    Bauer, Timm; Möllmann, Helge; Weidinger, Franz; Zeymer, Uwe; Seabra-Gomes, Ricardo; Eberli, Franz Robert; Serruys, Patrick; Vahanian, Alec; Silber, Sigmund; Wijns, William; Hochadel, Matthias; Nef, Holger; Hamm, Christian; Marco, Jean; Gitt, Anselm

    2010-01-01

    textabstractBackground: The most recent ESC guidelines for percutaneous coronary intervention (PCI) recommend the use of glycoprotein IIb/IIIa inhibitors (GPI) in high risk patients with non-ST-segment elevation acute coronary syndromes (NSTE-ACS), particularly in diabetics. Little is known about the adherence to these guidelines within Europe. Methods and results: Between May 2005 and April 2008 a total of 47,407 consecutive patients undergoing PCI were prospectively enrolled into the PCI-Re...

  7. Are maternal fertility problems related to childhood leukaemia

    A study was conducted in the Netherlands, from a nationwide register of childhood leukaemia (1973-1980). Controls were matched with cases for year of birth, sex and place of residence. Information about exposures of the mother to potential risk factors in the year before and during pregnancy was collected via mailed questionnaires. Analyses concerned data on 519 patients with acute lymphocytic leukaemia and 507 controls. An association between maternal subfertility and childhood leukaemia might be suggested by several findings. A history of two or more miscarriages (OR 1.6; 95% Cl 1.0-2.7) and fertility problems (OR 6.0; 95% Cl 0.9-38.2) were more frequently reported among mothers of cases. Use of oral contraceptives (OC) was significantly higher (OR 1.3; 95% Cl 1.0-1.8) and the duration between discontinuation of OC and the relevant pregnancy was significantly longer. The OR for threatened abortion during the relevant pregnancy was 1.6 (95% Cl 1.0-2.6) and the related use of 'drugs to maintain pregnancy' was 1.9; 95% Cl 1.0-3.5. Among known risk factors, an increased OR for diagnostic irradiation was confirmed (OR 2.2; 95% Cl 1.2-3.8). No association between childhood leukaemia and prenatal viral infections, smoking and alcohol was found. (author)

  8. Use of Multifrequency Bioimpedance Analysis in Male Patients with Acute Kidney Injury Who Are Undergoing Continuous Veno-Venous Hemodiafiltration.

    Harin Rhee

    Full Text Available Fluid overload is a well-known predictor of mortality in patients with acute kidney injury (AKI. Multifrequency bioimpedance analysis (MF-BIA is a promising tool for quantifying volume status. However, few studies have analyzed the effect of MF-BIA-defined volume status on the mortality of critically ill patients with AKI. This retrospective medical research study aimed to investigate this issue.We retrospectively reviewed the medical records of patients with AKI who underwent continuous veno-venous hemodiafiltration (CVVHDF from Jan. 2013 to Feb. 2014. Female patients were excluded to control for sex-based differences. Volume status was measured using MF-BIA (Inbody S20, Seoul, Korea at the time of CVVHDF initiation, and volume parameters were adjusted with height squared (H2. Binary logistic regression analyses were performed to test independent factors for prediction of in-hospital mortality.A total of 208 male patients were included in this study. The mean age was 65.19±12.90 years. During the mean ICU stay of 18.29±27.48 days, 40.4% of the patients died. The in-hospital mortality rate increased with increasing total body water (TBW/H2 quartile. In the multivariable analyses, increased TBW/H2 (OR 1.312(1.009-1.705, p=0.043 and having lower serum albumin (OR 0.564(0.346-0.919, p=0.022 were independently associated with higher in-hospital mortality. When the intracellular water (ICW/H2 or extracellular water (ECW/H2 was adjusted instead of the TBW/H2, only excess ICW/H2 was independently associated with increased mortality (OR 1.561(1.012-2.408, p=0.044.MF-BIA-defined excess TBW/H2 and ICW/H2 are independently associated with higher in-hospital mortality in male patients with AKI undergoing CVVHDF.

  9. A Ten Year Descriptive Study of Adult Leukaemia at Al-Jomhori Teaching Hospital in Sana'a, Yemen

    Jameel Al-Ghazaly

    2014-12-01

    Full Text Available Background: There is scarcity of data of the epidemiology of leukaemia in Arab countries including Yemen. Understanding patterns of leukaemia underpins epidemiology and can provide insight into disease etiology. The aim of this research is to determine the epidemiologic pattern of adult leukaemia in Yemen. Methods: The research is a descriptive cross-sectional study. We analyzed the data of 702 adult patients with leukaemia, who were newly diagnosed over a ten-year period between October 1999 and October 2009 at the referral haematology centre in Sana’a at Al-Jomhori Teaching Hospital, according to type of leukaemia, age, sex, geographic distribution and time of diagnosis. Results: Acute Myeloid Leukaemia (AML was found to be the most common (45.1% followed by Chronic Myeloid Leukaemia (CML (26.5%, Acute Lymphoid Leukaemia (ALL (17.7% and Chronic Lymphoid Leukaemia (CLL (10.7%, respectively. There was an almost equal prevalence of AML and CML for males and females but males had significantly more cases of ALL and CLL (p =0.008. A significant variation in geographic pattern showed that the highest number of cases is seen the Central mountainous region and the least number of cases in the South-eastern region which is coastal and lowland (p<0.001. The seasonal variation showed that higher number of ALL cases was seen in the summer months (33% compared with other seasons (21% in the spring, 24.2% in autumn and 21.8% in winter. Conclusions: The pattern of adult leukaemia in Yemen is different from that seen in western countries which could be attributed to different environmental exposure. The geographic pattern indicates a possible role of certain environmental factors which warrant further investigations. The pattern of seasonal variation needs further studies for evaluating the seasonality.

  10. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  11. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Mikell, John L., E-mail: jmikell@emory.edu [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Waller, Edmund K. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Switchenko, Jeffrey M. [Department of Biostatistics and Bioinformatics, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Rangaraju, Sravanti; Ali, Zahir; Graiser, Michael [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Hall, William A. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Langston, Amelia A. [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Esiashvili, Natia [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khoury, H. Jean [Department of Hematology and Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States); Khan, Mohammad K. [Department of Radiation Oncology, Winship Cancer Institute, Emory University, Atlanta, Georgia (United States)

    2014-06-01

    Purpose: Hematopoietic stem cell transplantation (HSCT) is the mainstay of treatment for adults with acute leukemia. Total body irradiation (TBI) remains an important part of the conditioning regimen for HCST. For those patients unable to tolerate myeloablative TBI (mTBI), reduced intensity TBI (riTBI) is commonly used. In this study we compared outcomes of patients undergoing mTBI with those of patients undergoing riTBI in our institution. Methods and Materials: We performed a retrospective review of all patients with acute leukemia who underwent TBI-based conditioning, using a prospectively acquired database of HSCT patients treated at our institution. Patient data including details of the transplantation procedure, disease status, Karnofsky performance status (KPS), response rates, toxicity, survival time, and time to progression were extracted. Patient outcomes for various radiation therapy regimens were examined. Descriptive statistical analysis was performed. Results: Between June 1985 and July 2012, 226 patients with acute leukemia underwent TBI as conditioning for HSCT. Of those patients, 180 had full radiation therapy data available; 83 had acute lymphoblastic leukemia and 94 had acute myelogenous leukemia; 45 patients received riTBI, and 135 received mTBI. Median overall survival (OS) was 13.7 months. Median relapse-free survival (RFS) for all patients was 10.2 months. Controlling for age, sex, KPS, disease status, and diagnosis, there were no significant differences in OS or RFS between patients who underwent riTBI and those who underwent mTBI (P=.402, P=.499, respectively). Median length of hospital stay was shorter for patients who received riTBI than for those who received mTBI (16 days vs 23 days, respectively; P<.001), and intensive care unit admissions were less frequent following riTBI than mTBI (2.22% vs 12.69%, respectively, P=.043). Nonrelapse survival rates were also similar (P=.186). Conclusions: No differences in OS or RFS were seen between

  12. The effect of music on pain and acute confusion in older adults undergoing hip and knee surgery.

    McCaffrey, Ruth; Locsin, Rozzano

    2006-01-01

    The purpose of this study was to examine the effects of music listening in older adults following hip or knee surgery. Acute confusion and pain after surgery can increase length of stay and reduce function. Study results demonstrate a reduction in acute confusion and pain and improved ambulation and higher satisfaction scores in older adults who listened to music. PMID:16974175

  13. Genetic variegation of clonal architecture and propagating cells in leukaemia.

    Anderson, Kristina; Lutz, Christoph; van Delft, Frederik W; Bateman, Caroline M; Guo, Yanping; Colman, Susan M; Kempski, Helena; Moorman, Anthony V; Titley, Ian; Swansbury, John; Kearney, Lyndal; Enver, Tariq; Greaves, Mel

    2011-01-20

    Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγ(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer. PMID:21160474

  14. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    Purpose: To test the hypothesis that increased bowel radiation dose is associated with acute gastrointestinal (GI) toxicity in cervical cancer patients undergoing concurrent chemotherapy and intensity-modulated radiation therapy (IMRT), using a previously derived normal tissue complication probability (NTCP) model. Methods: Fifty patients with Stage I–III cervical cancer undergoing IMRT and concurrent weekly cisplatin were analyzed. Acute GI toxicity was graded using the Radiation Therapy Oncology Group scale, excluding upper GI events. A logistic model was used to test correlations between acute GI toxicity and bowel dosimetric parameters. The primary objective was to test the association between Grade ≥2 GI toxicity and the volume of bowel receiving ≥45 Gy (V45) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V45 was 143 mL (99). The mean V45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V45 >150 mL was 65% vs. 33% (p = 0.03). Logistic model parameter estimates V50 and γ were 161 mL (95% confidence interval [CI] 60–399) and 0.31 (95% CI 0.04–0.63), respectively. On multivariable logistic regression, increased V45 was associated with an increased odds of Grade ≥2 GI toxicity (odds ratio 2.19 per 100 mL, 95% CI 1.04–4.63, p = 0.04). Conclusions: Our results support the hypothesis that increasing bowel V45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  15. Effect of acute kidney injury requiring extended dialysis on 28 day and 1 year survival of patients undergoing interventional lung assist membrane ventilator treatment

    Hadem Johannes

    2011-04-01

    Full Text Available Abstract Background Extracorporeal lung assist devices are increasingly used in the intensive care unit setting to improve extracorporeal gas exchange mainly in patients with acute respiratory distress syndrome. ARDS is frequently accompanied by acute kidney injury; however it is so far unknown how the combination of these two conditions affects long term survival of critically ill patients. Methods In a retrospective analysis of a tertiary care hospital we evaluated all patients undergoing interventional lung assist (iLA treatment between January 1st 2005 and December 31st 2009. Data from all 61 patients (31 F/30 M, median age 40 (28 to 52 years were obtained by chart review. Follow up data up to one year were obtained. Results Of the 61 patients undergoing iLA membrane ventilator treatment 21 patients had acute kidney injury network (AKIN stage 3 and were treated by extended dialysis (ED. Twenty-eight day survival of all patients was 33%. While patients without ED showed a 28 day survival of 40%, the survival of patients with ED was only 19%. Patients on ED were not different in respect to age, weight, Horowitz index and underlying disease. Conclusions AKI requiring ED therapy in patients undergoing iLA treatment increases mortality in ICU patients. Patients in whom iLA was placed as a bridge to lung transplantation and that were successfully transplanted showed the best outcome. Future studies have to clarify whether it is possible to identify patients that truly benefit from the combination of these two extracorporeal treatment methods.

  16. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Thappa Devinder Mohan

    2002-01-01

    Full Text Available We herewith report a case of extramedullary myeloid cell tumour presenting as leukaemia cutis for its rarity. It occurred in a 50 year old male patient who presented to us with a 40 days history of painless raised solid skin swellings over the trunk. Histopathological examination of the skin biopsy and bone marrow biopsy showed features suggestive of non-Hodgkin’s lymphoma. Immunophenotyping on skin biopsy specimens and bone marrow biopsy found tumour cells expressing CD43 and Tdt but were negative for CD3 and CD20. These features were consistent with extramedullary myeloid cell tumour involving skin and subcutis (cutaneous manifestation of acute myeloid leukaemia.

  17. Control of feline leukaemia virus.

    K. Weijer (Kees); F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Ab)

    1989-01-01

    textabstractFeline leukaemia virus (FeLV) usually occurs in its natural species, the domestic cat. FeLV is also important to human individuals as a comparative model, as it may cause a variety of diseases, some malignant and some benign, such as immunosuppression, which bears a resemblance to AIDS (

  18. Utility of an Australasian registry for children undergoing radiation treatment

    The aim of this study was to evaluate the utility of an Australasian registry ('the Registry') for children undergoing radiation treatment (RT). Children under the age of 16years who received a course of radiation between January 1997 and December 2010 and were enrolled on the Registry form the subjects of this study. A total of 2232 courses of RT were delivered, predominantly with radical intent (87%). Registrations fluctuated over time, but around one-half of children diagnosed with cancer undergo a course of RT. The most prevalent age range at time of RT was 10–15years, and the most common diagnoses were central nervous system tumours (34%) and acute lymphoblastic leukaemia (20%). The Registry provides a reflection of the patterns of care of children undergoing RT in Australia and a mechanism for determining the resources necessary to manage children by RT (human, facilities and emerging technologies, such as proton therapy). It lacks the detail to provide information on radiotherapy quality and disease outcomes which should be the subject of separate audit studies. The utility of the Registry has been hampered by its voluntary nature and varying needs for consent. Completion of registry forms is a logical requirement for inclusion in the definition of a subspecialist in paediatric radiation oncology.

  19. THE OCCURRENCE OF HIGH-LEVELS OF ACUTE BEHAVIORAL DISTRESS IN CHILDREN AND ADOLESCENTS UNDERGOING ROUTINE VENIPUNCTURES

    HUMPHREY, GB; BOON, CMJ; VANDENHEUVELL, GFECV; VANDEWIEL, HBM

    1992-01-01

    While there is no question that children dislike needles, there are very little data available on the occurrence of high levels of distress experienced by children undergoing routine venipunctures. To provide some insight into this problem, trained observers evaluated distress in 223 different child

  20. The incidence of and mortality from leukaemias in the UK: a general population-based study

    McKeever Tricia

    2009-07-01

    Full Text Available Abstract Background The acute and chronic leukaemias constitute about 2.5% of all newly diagnosed malignancies and kill over 4000 people/year in the UK, yet there is little accurate up-to-date data on how the incidence of and mortality from leukaemias vary with socio-economic status in the UK. We aimed to quantify the incidence of and mortality from leukaemias in the UK and their variation with gender, age, year of diagnosis as well as socio-economic status. Methods All incident cases of leukaemia were identified in 'The Health Improvement Network' (THIN General Practice dataset. Crude incidence rates and incidence rate ratios (using Poisson Regression stratified by age, gender, year of diagnosis and socio-economic status were calculated. Median survival and hazard ratios for risk of death (using Cox regression were then calculated, and stratified in a similar manner. Results A total of 4162 cases of leukaemia were identified, 2314 (56% of whom were male. The overall incidence of leukaemia was 11.25 per 100 000 person-years. The age and gender distributions of ALL, AML, CLL and CML were similar to UK cancer registry data. The incidence of leukaemias was independent of socio-economic class. Median survival from leukaemia was 6.58 years and mortality increased with increasing age at diagnosis. The prognosis in AML was dismal and worsened with increasing socio-economic deprivation. For other leukaemias mortality was independent of socio-economic status. Conclusion This is the first general population study to describe the incidence of and mortality from leukaemias in the UK by socio-economic status. Similar mortality across socio-economic gradients in the leukaemias studied suggests equal access to and uptake of services. The exception to this was in AML, where poorer survival in AML patients from lower socio-economic classes may represent a class bias in treatment offered and/or greater co-morbidity in these patients, and warrants further

  1. The role of hematopoietic stem cell transplantation in the elderly patient with acute myeloid leukaemia O papel do transplante de célula-tronco hematopoiética em pacientes idosos com leucemia mielóide aguda

    Attilio Olivieri

    2008-06-01

    Full Text Available Older adults with Acute Myeloid Leukaemia (AML, when compared to younger patients with the same disease, have a poor prognosis and represent a discrete population in terms of disease biology, treatment-related complications, and overall outcome. As a result, older patients require distinctive management approaches. For 85%-95% of older AML patients, any therapy ultimately will be purely palliative. No randomized trial has ever demonstrated that any amount of post-remission therapy in older AML patients provides better outcomes than no post-remission therapy. The only studies demonstrating that long-term Disease Free Survival (DFS is possible in older AML patients have included remission induction and post-remission therapy. For these reasons alternative post-remission strategies, including autologous or allogeneic transplantation have been explored also in people over sixty considered fit for aggressive therapy. Up to now the data available from clinical trials suggest that the stem cell transplant procedure is promising, and can lead to long-term survival, but it is feasible only in a minority of fit elderly patients. The main limits of Autologous Stem Cell Transplantation (ASCT are represented by the low percentage of patients able to mobilize a sufficient amount of stem cells and by the still high relapse incidence after ASCT, especially in those with poor prognostic factors; for these patients the allogeneic transplant procedure, by using non myeloablative conditioning regimens, could offer a better chance of cure, thanks to the Graft versus Leukemia (GVL effect, but there are no prospective trials showing the superiority of any transplant approach over conventional treatment in this subset of patients.Pacientes idosos com leucemia mielóide aguda (LMA, quando comparados com pacientes jovens com a mesma doença, apresentam prognóstico pobre e representam uma população particular em termos biológicos, complicações relacionadas ao

  2. Risk Behavior and Sexually Transmitted Infections Among Transgender Women and Men Undergoing Community-Based Screening for Acute and Early HIV Infection in San Diego.

    Green, Nella; Hoenigl, Martin; Morris, Sheldon; Little, Susan J

    2015-10-01

    The transgender community represents an understudied population in the literature. The objective of this study was to compare risk behavior, and HIV and sexually transmitted infection (STI) rates between transgender women and transgender men undergoing community-based HIV testing.With this retrospective analysis of a cohort study, we characterize HIV infection rates as well as reported risk behaviors and reported STI in 151 individual transgender women and 30 individual transgender men undergoing community based, voluntary screening for acute and early HIV infection (AEH) in San Diego, California between April 2008 and July 2014.HIV positivity rate was low for both, transgender women and transgender men undergoing AEH screening (2% and 3%, respectively), and the self-reported STI rate for the prior 12 months was 13% for both. Although transgender women appeared to engage in higher rates of risk behavior overall, with 69% engaged in condomless receptive anal intercourse (CRAI) and 11% engaged in sex work, it is important to note that 91% of transgender women reported recent sexual intercourse, 73% had more than 1 sexual partner, 63% reported intercourse with males, 37% intercourse with males and females, and 30% had CRAI.Our results indicate that in some settings rates of HIV infection, as well as rates of reported STIs and sexual risk behavior in transgender men may resemble those found in transgender women. Our findings support the need for comprehensive HIV prevention in both, transgender women and men. PMID:26469928

  3. Leukaemia and nuclear power in Britain

    Ever since the YTV programme, 'Windscale, the Nuclear Laundry' (November 1983) showed a tenfold excess of childhood leukaemia near the Sellafield nuclear reprocessing plant, there has been debate about the possible connection between nuclear power and leukaemia. In this chapter the authors look at the evidence published so far and give the results of an investigation into young leukaemia death rates around fourteen nuclear installations in England and Wales in the period 1963 to 1980. (author)

  4. Cluster of childhood leukaemia in Elbmarsch, Germany

    The cluster of leukaemia cases in the four villages making up the community of Elbmarsch occurred within less than 24 months. Five children and one young adult were taken ill with leukaemia and one child with aplastic anemia, which can develop into leukaemia. During the search for possible causes, all of the known exogenic risk factors, especially of a chemical and pharmacological nature, were investigated. 1 ref., 3 figs, 1 tab

  5. Acute serum sodium concentration changes in pediatric patients undergoing cardiopulmonary bypass and the association with postoperative outcomes

    Lee, Jeong Jin; Kim, Young-Soon; Jung, Hae Hyuk

    2015-01-01

    The objective of this study is to investigate the degree of serum sodium changes and its association with patient outcomes in pediatrics undergoing heart surgery with cardiopulmonary bypass (CPB). We reviewed the medical records of 275 pediatric patients who underwent heart surgery with CPB. Prior to CPB, hyponatremia (≤135 mmol/L) was observed in 21 of 275 patients. After initiation of CPB, serum sodium decreased significantly and severe hyponatermia (≤130 mmol/L) subsequently developed in 3...

  6. Vincristine in childhood leukaemia : no pharmacokinetic rationale for dose reduction in adolescents

    Frost, BM; Lonnerholm, G; Koopmans, P; Abrahamsson, J; Behrendtz, M; Castor, A; Forestier, E; Uges, DRA

    2003-01-01

    Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on

  7. Childhood leukaemia: Radiological changes caused by the disease and by treatment

    The radiological changes caused by acute lymphatic leukaemia in childhood, and by the treatment of this condition, are described for the individual organ systems. Of particular importance are changes in the skeleton, thoracic organs, kidneys, gastro-intestinal tract and central nervous system. Changes in the skeleton and mediastinal tumours are important for the initial diagnosis. (orig.)

  8. Childhood leukaemia around nuclear facilities

    In December 2007 the German Federal Office for Radiation Protection (BfS) published a report on the incidence of childhood cancers among children living in the vicinity of 16 German nuclear power plants. The results show a significantly enhanced risk of leukaemia in children aged below 5 years, who live within 5 km from a nuclear power plant. The study is known as KiKK (Epidemiologische Studie zu Kinderkrebs in der Umgebung von Kernkraftwerken) and stirred considerable concern about the safety of nuclear installations. In this review we summarise the present state-of-the art regarding childhood leukaemia in the vicinity of nuclear installations and present the main results of the KiKK study with a critical evaluation

  9. Childhood leukaemia around nuclear facilities

    Wojcik, Andrzej (Centre for Radiation Protection Research, GMT Dept., Stockholm Univ., Stockholm (Sweden)); Feychting, Maria (Inst. of Environmental Medicine, Karolinska Inst., Stockholm (Sweden))

    2010-06-15

    In December 2007 the German Federal Office for Radiation Protection (BfS) published a report on the incidence of childhood cancers among children living in the vicinity of 16 German nuclear power plants. The results show a significantly enhanced risk of leukaemia in children aged below 5 years, who live within 5 km from a nuclear power plant. The study is known as KiKK (Epidemiologische Studie zu Kinderkrebs in der Umgebung von Kernkraftwerken) and stirred considerable concern about the safety of nuclear installations. In this review we summarise the present state-of-the art regarding childhood leukaemia in the vicinity of nuclear installations and present the main results of the KiKK study with a critical evaluation

  10. Identification of novel Notch target genes in T cell leukaemia

    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

  11. Nuclear power and childhood leukaemia

    Grimston, M. (AEA Technology, London (UK))

    1991-06-19

    The possibility of illness caused by exposure to emissions from nuclear power plants continues to raise enormous public concern. Nowhere is this more evident than in the debate over the aetiology of childhood leukaemias. This review explores the evidence in relation to this and other diseases which are linked in the public's mind to nuclear power. The scientific evidence presented suggests that these links are more tenuous than is commonly believed. (author).

  12. Leukaemia incidents after Chernobyl accident

    Romania and especially its Eastern territory were among the most heavily affected area after Chernobyl accident. The objective of our study was to investigate whether or not the nuclear accident determined an increased number of leukaemia cases. The specific rates of leukaemia incidents by age group were calculated in 588167 children aged 0-6 years in April 1986 and 99917 children which have been exposed 'in utero'. The rates of 1989-1994 period were compared with the rates of 1980-1985 period. The incidence rates were lower in the exposed group than that in controls for children under 1 year (20.52/105 inh vs 23.11/105 inh), 1-3 years (13.26/105 inh vs 16.11/105 inh) and 4-6 years (9.58/105 inh vs 10.58/105 inh). The cohort of 'in utero' exposed children presented a leukaemia incidences insignificantly higher than that before the accident (23.10/105 inh vs 15.93/105 inh)

  13. Acute contractile recovery extent during biventricular pacing is not associated with follow-up in patients undergoing resynchronization

    Federica DeVecchi; Emanuela Facchini; Anna Degiovanni; Chiara Sartori; Chiara Cavallino; Matteo Santagostino; Virginia Di Ruocco; Andrea Magnani; Eraldo Occhetta; Paolo Nicola Marino

    2016-01-01

    Background: It has been reported that contractility, as assessed using dobutamine infusion, is independently associated with reverse remodeling after CRT. Controversy, however, exists about the capacity of this approach to predict a long-term clinical response. This study's purpose was to assess whether long-term CRT clinical effects can be predicted according to acute inotropic response induced by biventricular stimulation (CRT on), as compared with AAI–VVI right stimulation pacing mode (CRT...

  14. Clofarabine Does Not Negatively Impact the Outcomes of Patients With Acute Myeloid Leukemia Undergoing Allogeneic Stem Cell Transplantation

    Mathisen, Michael S.; Kantarjian, Hagop; Jabbour, Elias; Garcia-Manero, Guillermo; Ravandi, Farhad; Faderl, Stefan; Borthakur, Gautam; Cortes, Jorge E.; Quintás-Cardama, Alfonso

    2012-01-01

    We evaluated whether clofarabine-containing chemotherapy predisposed patients to hepatic toxicity (particularly venoocclusive disease [VOD]) after allogeneic stem cell transplantation (allo-SCT). In the group who received clofarabine and subsequent transplantation, there were no cases of VOD, and liver toxicity was comparable to a control group who received standard acute myeloid leukemia (AML) chemotherapy. Other transplant-specific outcomes, including overall survival (OS), were also simila...

  15. Summary curves for patients transplanted for chronic myeloid leukaemia salvaged by a donor lymphocyte infusion: the current leukaemia-free survival curve

    Klein, John P.; Keiding, Niels; Shu, Youyi;

    2000-01-01

    CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods......CML, donor lymphocyte infusion, leukaemia-free survival, current leukaemia-free survival, statistical methods...

  16. Childhood leukaemia incidence around French nuclear installations using geographic zoning based on gaseous discharge dose estimates.

    Evrard, Anne-Sophie; Hémon, Denis; Morin, Aline; Laurier, Dominique; Tirmarche, Margot; Backe, Jean-Claude; Chartier, Michel; Clavel, Jacqueline

    2006-01-01

    The present study investigated for the first time the incidence of childhood leukaemia (1990–2001) around French nuclear installations using a geographic zoning based on estimated doses to the red bone marrow due to gaseous radioactive discharges. The observed number of cases of acute leukaemia (O=750) in 40 km2 centred on 23 French nuclear installations between 1990 and 2001 was lower than expected (E=795.01), although not significantly so (standardised incidence ratio SIR=0.94, 95% confiden...

  17. The molecular biology of radiation-induced carcinogenesis: thymic lymphoma, myeloid leukaemia and osteosarcoma

    Janowski, M. (Centre d' Etude de l' Energie Nucleaire, Mol (Belgium)); Cox, R. (Medical Research Council, Harwell (UK). Radiobiological Research Unit); Strauss, P.G. (GSF, Neuherberg (Germany, F.R.). Abt. fuer Molekulare Zellpathologie)

    1990-04-01

    In mice, external X- or {gamma}-irradiation may induce thymic lymphomas or myeloid leukaemias, while bone-seeking {alpha}-emitters may induce osteosarcomas, and to a lesser extent acute myeloid leukaemia. The paper reviews briefly some experimental data in respect to molecular mechanisms underlying these radio-carcinogenic processes. Thymic lymphomagenesis proceeds by an indirect mechanism in which recombinant proviruses could be involved. Myeloid leukaemogenesis is characterized by a very early putative initiating event, consisting of non-random rearrangements and/or deletions of chromosome 2. Osteosarcomagenesis in mice is often associated with the expression of proviruses, and the tumors often contain somatically acquired proviruses. (UK).

  18. The role of neutrophil gelatinase-associated lipocalin in predicting acute kidney injury in patients undergoing off-pump coronary artery bypass graft: A pilot study

    Vishal Jain

    2016-01-01

    Full Text Available Objective: Acute kidney injury (AKI is a commonly encountered postoperative complication after cardiac surgery especially in high risk patients. AKI though seen more commonly after conventional on pump coronary artery bypass surgery (CCABG, is not uncommon after off pump coronary bypass surgery (OPCAB. Various biomarkers have shown promise over last one decade as an early marker for predicting AKI postoperatively. NGAL is one such biomarker whose concentration is increased in urine after any nephrotoxic and ischemic insult. The objective of this study was to assess the role of urine NGAL in predicting AKI after OPCAB in patients with increased risk of developing AKI. Design: A prospective cohort study. Setting: A clinical study in a multi specialty hospital. Participants: Eighty patients. Materials and Methods: study was approved by the hospital research ethics committee. 80 patients posted for OPCAB with an increased risk of developing AKI defined as having a Cleveland Clinic Foundation Acute renal failure scoring System score of ≥6 were included in the study. Patients with coronary angiography (CAG within 48 hrs prior to surgery, pre-existing AKI, preoperative renal replacement therapy (RRT and CKD stage 5 were excluded. Urine NGAL level before the start of surgery baseline and at 4 hrs post surgery were done. Renal function tests were assessed on the day of surgery (4 hrs post surgery and on the next three days. Result: Seven patients developed AKI as defined by acute kidney infection network (AKIN and risk injury failure loss end stage (RIFLE criteria for AKI. NGAL value at 4 hrs in patients who developed AKI was significantly higher than in those patients who did not develop AKI (P < 0.05. Conclusion: urine NGAL is an early biomarker of acute kidney injury in patients undergoing OPCAB surgeries. However, large multicentre studies may be needed to confirm it.

  19. The role of neutrophil gelatinase-associated lipocalin in predicting acute kidney injury in patients undergoing off-pump coronary artery bypass graft: A pilot study

    Jain, Vishal; Mehta, Yatin; Gupta, Abhinav; Sharma, Reetesh; Raizada, Arun; Trehan, Naresh

    2016-01-01

    Objective: Acute kidney injury (AKI) is a commonly encountered postoperative complication after cardiac surgery especially in high risk patients. AKI though seen more commonly after conventional on pump coronary artery bypass surgery (CCABG), is not uncommon after off pump coronary bypass surgery (OPCAB). Various biomarkers have shown promise over last one decade as an early marker for predicting AKI postoperatively. NGAL is one such biomarker whose concentration is increased in urine after any nephrotoxic and ischemic insult. The objective of this study was to assess the role of urine NGAL in predicting AKI after OPCAB in patients with increased risk of developing AKI. Design: A prospective cohort study. Setting: A clinical study in a multi specialty hospital. Participants: Eighty patients. Materials and Methods: study was approved by the hospital research ethics committee. 80 patients posted for OPCAB with an increased risk of developing AKI defined as having a Cleveland Clinic Foundation Acute renal failure scoring System score of ≥6 were included in the study. Patients with coronary angiography (CAG) within 48 hrs prior to surgery, pre-existing AKI, preoperative renal replacement therapy (RRT) and CKD stage 5 were excluded. Urine NGAL level before the start of surgery baseline and at 4 hrs post surgery were done. Renal function tests were assessed on the day of surgery (4 hrs post surgery) and on the next three days. Result: Seven patients developed AKI as defined by acute kidney infection network (AKIN) and risk injury failure loss end stage (RIFLE) criteria for AKI. NGAL value at 4 hrs in patients who developed AKI was significantly higher than in those patients who did not develop AKI (P < 0.05). Conclusion: urine NGAL is an early biomarker of acute kidney injury in patients undergoing OPCAB surgeries. However, large multicentre studies may be needed to confirm it. PMID:27052061

  20. Image-Guided Total-Marrow Irradiation Using Helical Tomotherapy in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation

    Purpose: Total-body irradiation (TBI) has an important role in patients undergoing hematopoietic cell transplantation (HCT), but is associated with significant toxicities. Targeted TBI using helical tomotherapy results in reduced doses to normal organs, which predicts for reduced toxicities compared with standard TBI. Methods and Materials: Thirteen patients with multiple myeloma were treated in an autologous tandem transplantation Phase I trial with high-dose melphalan, followed 6 weeks later by total-marrow irradiation (TMI) to skeletal bone. Dose levels were 10, 12, 14, and 16 Gy at 2 Gy daily/twice daily. In a separate allogeneic HCT trial, 8 patients (5 with acute myelogenous leukemia, 1 with acute lymphoblastic leukemia, 1 with non-Hodgkin's lymphoma, and 1 with multiple myeloma) were treated with TMI plus total lymphoid irradiation plus splenic radiotherapy to 12 Gy (1.5 Gy twice daily) combined with fludarabine/melphalan. Results: For the 13 patients in the tandem autologous HCT trial, median age was 54 years (range, 42-66 years). Median organ doses were 15-65% that of the gross target volume dose. Primarily Grades 1-2 acute toxicities were observed. Six patients reported no vomiting; 9 patients, no mucositis; 6 patients, no fatigue; and 8 patients, no diarrhea. For the 8 patients in the allogeneic HCT trial, median age was 52 years (range, 24-61 years). Grades 2-3 nausea, vomiting, mucositis, and diarrhea were observed. In both trials, no Grade 4 nonhematologic toxicity was observed, and all patients underwent successful engraftment. Conclusions: This study shows that TMI using helical tomotherapy is clinically feasible. The reduced acute toxicities observed compare favorably with those seen with standard TBI. Initial results are encouraging and warrant further evaluation as a method to dose escalate with acceptable toxicity or to offer TBI-containing regimens to patients unable to tolerate standard approaches

  1. Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam

    Surfactants are synthetic organic compounds widely used in cosmetic, food, textile, dyers and paper production industries and in particular detergents and others cleaning products industries. The world consumption is nearly 8 million tons per year. One of the main environmental issues coming from the use of these compounds is their toxicity that compromises the biological treatment of effluents and the quality of receiving waters. The objective of this work was the application of ionizing radiation by electron beam in the degradation and reduction of acute and chronic toxicities of surfactants sodium dodecylsulfate (SDS), dodecyl p-benzenesulfonate acid (LAS) and sodium dodecyl p-benzenesulfonate (LAS). This treatment technology has been studied as a pre-treatment for effluents containing toxic and non-biodegradable compounds, before the biological treatment. Two acute toxicity assays were employed, one with the micro-crustacean Daphnia similis and the other with the luminescent bacterium Vibrio fischeri along with a chronic toxicity assay with the micro-crustacean Ceriodaphnia dubia (just for SDS and acid LAS) for the non-irradiated and irradiated samples and radiation doses 3.0 kGy, 6.0 kGy, 9.0 kGy and 12.0 kGy. Physical-chemical parameters were evaluated for the following up the degradation of the surfactant molecules. The reductions of acute toxicity varied between 72.49% and 90.98% for SDS, 18.22% and 78.98% for acid LAS and 82.66% and 94.26% for sodium LAS. For the chronic toxicity, the reduction percentages varied between 64.03% and 83.01% for SDS and 47.48% and 64.91% for acid LAS. When one considers the application of the electron beam as a pre-treatment of effluents containing high concentrations of surfactants, the toxicity is an essential parameter allowing the further biological treatment of these effluents. (author)

  2. Inhibition of histone deacetylases in cancer therapy: lessons from leukaemia

    Ceccacci, Elena; Minucci, Saverio

    2016-01-01

    Histone deacetylases (HDACs) are a key component of the epigenetic machinery regulating gene expression, and behave as oncogenes in several cancer types, spurring the development of HDAC inhibitors (HDACi) as anticancer drugs. This review discusses new results regarding the role of HDACs in cancer and the effect of HDACi on tumour cells, focusing on haematological malignancies, particularly acute myeloid leukaemia. Histone deacetylases may have opposite roles at different stages of tumour progression and in different tumour cell sub-populations (cancer stem cells), highlighting the importance of investigating these aspects for further improving the clinical use of HDACi in treating cancer. PMID:26908329

  3. Safety and efficacy of early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention: a meta-analysis

    Liu Yangchun; Su Qiang; Li Lang

    2014-01-01

    Background Tirofiban has been widely used as an adjunctive pharmacologic agent for revascularization in patients undergoing percutaneous coronary intervention,and the outcomes appear attractive.However,the potential benefits from early administration of tirofiban in patients with acute ST-segment elevation myocardial infarction (STEMI) undergoing primary percutaneous coronary intervention (PPCI) remain unclear.Methods We conducted a search in MEDLINE,EMBASE,and the Cochrane Central Register of Controlled Trials up to September 2012 without language restriction.A total of eight randomized trials (n=1 577 patients) comparing early (emergency department or ambulance) versus late (catheterization laboratory) administration of tiroflban in STEMI patients undergoing PPCI were included in this meta-analysis.Risk ratio (RR) was computed from individual studies and pooled with random-or fixed-effect models.Results There were no differences in post-procedural Thrombolysis In Myocardial Infarction (TIMI) flow grade 3 and Corrected TIMI Frame Count (RR=1.02,95% confidence interval (C/):0.99-1.05,P=0.18; weighted mean difference (WMD)=-0.93,95% CI:-5.37-3.52,P=0.68,respectively) between the two groups.Similarly,there were no significant differences in the incidence of 30-day mortality (RR=1.69,95% CI:0.69-4.13,P=0.25) and re-myocardial infarction (RR=0.71,95% CI:0.21-2.35,P=0.57) between early and late administration of tirofiban.As to the safety end points,no significant difference was observed in hospital minor bleeding (RR=1.08,95% CI:0.54-2.14,P=0.83) and hospital and 30-day major bleeding between the two groups (RR=0.98,95% CI:0.46-2.10,P=0.96; RR=1.32,95% CI:0.59-2.97,P=0.49,respectively).Conclusions Early administration of tiroflban in patients undergoing PPCI for STEMI was safe,but no beneficial effects on post-procedural angiographic or clinical outcomes could be identified as compared with late administration.Besides the negative finding,more high

  4. Efficacy of short-term cordyceps sinensis for prevention of contrast-induced nephropathy in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention.

    Zhao, Kai; Lin, Yu; Li, Yong-Jian; Gao, Sheng

    2014-01-01

    Contrast-induced nephropathy (CIN) is one of the major causes of hospital-acquired acute renal failure. The pathophysiological mechanism of CIN remains unknown. There has been little evidence regarding the effects of Traditional Chinese Medicine (TCM) on CIN. Cordyceps sinensis (CS), a traditional Chinese herb, has been widely used clinically for the prevention of the progression of renal failure. We performed a prospective, randomized controlled trial to investigate the role of CS in the prevention of CIN in patients with acute coronary syndrome (ACS) undergoing elective percutaneous coronary intervention (PCI). The 150 ACS patients were randomly assigned to three groups, basic treatment group (n=51), standard CS therapy group (n=49, corbrin capsule 2 g, 3 times/d were used 3 days before and after angiography), and intensive CS therapy group (n=50, corbrin capsule 3 g, 3 times/d were used 3 days before and after angiography). Renal function was assessed at the time of hospital admission and on days 1, 2, and 3 after PCI. CIN occurred in 13 of 150 patients (8.67%). The incidence of CIN was lower in the CS treatment groups than in the basic treatment group (P<0.05), and a significant decrease in the incidence of CIN in the intensive CS therapy group was shown (P<0.01). In conclusion, prophylactic treatment with CS during the peri-procedural stage in ACS patients undergoing elective PCI has a preventive role against CIN, and intensive CS therapy could be more effective. PMID:25664103

  5. Leukaemia and lymphoma mortality in the vicinity of nuclear power stations in Japan, 1973-1987

    In many countries, studies have been carried out on cancer mortality near nuclear facilities. In the present paper, we examine the standardised mortality ratios (SMR) and the relative risks (RR) of five malignant neoplasms (leukaemia, malignant lymphoma, non-Hodgkin's lymphoma, multiple myeloma and acute non-lymphatic leukaemia) for two age groups (0-14 years and all ages) during different periods (1973-1977), 1978-1982, 1983-1987 and 1973-1987) in the 18 site municipalities and in the four control municipalities selected near each nuclear power station site in Japan. For some sites, as well as for control groups, SMRs of certain malignant neoplasms were sometimes high, even before the startup of a nuclear power station. It is concluded that leukaemia and lymphoma mortality in the Japanese municipalities containing nuclear power stations is not significantly different from the control areas. (author)

  6. A New Model for Predicting Acute Mucosal Toxicity in Head-and-Neck Cancer Patients Undergoing Radiotherapy With Altered Schedules

    Strigari, Lidia, E-mail: strigari@ifo.it [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Pedicini, Piernicola [Department of Medical Physics, Regional Cancer Hospital C.R.O.B, Rionero in Vulture (Italy); D' Andrea, Marco [Laboratory of Medical Physics and Expert Systems, Regina Elena National Cancer Institute, Rome (Italy); Pinnaro, Paola; Marucci, Laura; Giordano, Carolina [Department of Radiotherapy, Regina Elena National Cancer Institute, Rome (Italy); Benassi, Marcello [Department of Medical Physics, Istituto Scientifico Romagnolo per lo Studio e la Cura dei tumori, Meldola (Italy)

    2012-08-01

    Purpose: One of the worst radiation-induced acute effects in treating head-and-neck (HN) cancer is grade 3 or higher acute (oral and pharyngeal) mucosal toxicity (AMT), caused by the killing/depletion of mucosa cells. Here we aim to testing a predictive model of the AMT in HN cancer patients receiving different radiotherapy schedules. Methods and Materials: Various radiotherapeutic schedules have been reviewed and classified as tolerable or intolerable based on AMT severity. A modified normal tissue complication probability (NTCP) model has been investigated to describe AMT data in radiotherapy regimens, both conventional and altered in dose and overall treatment time (OTT). We tested the hypothesis that such a model could also be applied to identify intolerable treatment and to predict AMT. This AMT NTCP model has been compared with other published predictive models to identify schedules that are either tolerable or intolerable. The area under the curve (AUC) was calculated for all models, assuming treatment tolerance as the gold standard. The correlation between AMT and the predicted toxicity rate was assessed by a Pearson correlation test. Results: The AMT NTCP model was able to distinguish between acceptable and intolerable schedules among the data available for the study (AUC = 0.84, 95% confidence interval = 0.75-0.92). In the equivalent dose at 2 Gy/fraction (EQD2) vs OTT space, the proposed model shows a trend similar to that of models proposed by other authors, but was superior in detecting some intolerable schedules. Moreover, it was able to predict the incidence of {>=}G3 AMT. Conclusion: The proposed model is able to predict {>=}G3 AMT after HN cancer radiotherapy, and could be useful for designing altered/hypofractionated schedules to reduce the incidence of AMT.

  7. Rituximab in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    2014-05-28

    Accelerated Phase Chronic Myelogenous Leukemia; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Nasal Type Extranodal NK/T-cell Lymphoma; Blastic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Noncontiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Noncontiguous Stage II Adult Lymphoblastic Lymphoma; Noncontiguous Stage II Grade 1 Follicular Lymphoma; Noncontiguous Stage II Grade 2 Follicular Lymphoma; Noncontiguous Stage II Grade 3 Follicular Lymphoma; Noncontiguous Stage II Mantle Cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Previously Treated Myelodysplastic Syndromes; Recurrent Adult Acute Lymphoblastic Leukemia; 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

  8. Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI: A Meta-Analysis of Randomized Controlled Trials

    Grossman P Michael

    2010-02-01

    Full Text Available Abstract Background Clinical trials comparing thrombectomy devices with conventional percutaneous coronary interventions (PCI in patients with acute ST elevation myocardial infarction (STEMI have produced conflicting results. The objective of our study was to systematically evaluate currently available data comparing thrombectomy followed by PCI with conventional PCI alone in patients with acute STEMI. Methods Seventeen randomized trials (n = 3,909 patients of thrombectomy versus PCI were included in this meta-analysis. We calculated the summary odds ratios for mortality, stroke, post procedural myocardial blush grade (MBG, thrombolysis in myocardial infarction (TIMI grade flow, and post procedural ST segment resolution (STR using random-effects and fixed-effects models. Results There was no difference in risk of 30-day mortality (44/1914 vs. 50/1907, OR 0.84, 95% CI 0.54-1.29, P = 0.42 among patients randomized to thrombectomy, compared with conventional PCI. Thrombectomy was associated with a significantly greater likelihood of TIMI 3 flow (1616/1826 vs. 1533/1806, OR 1.41, P = 0.007, MBG 3 (730/1526 vs. 486/1513, OR 2.42, P Conclusions Thrombectomy devices appear to improve markers of myocardial perfusion in patients undergoing primary PCI, with no difference in overall 30-day mortality but an increased likelihood of stroke. The clinical benefits of thrombectomy appear to be influenced by the device type with a trend towards survival benefit with MAT and worsening outcome with mechanical devices.

  9. Extracorporeal Photopheresis for the Prevention of Acute GVHD in Patients Undergoing Standard Myeloablative Conditioning and Allogeneic Hematopoietic Stem Cell Transplantation

    Shaughnessy, Paul J; Bolwell, Brian J; van Besien, Koen; Mistrik, Martin; Grigg, Andrew; Dodds, Anthony; Prince, H Miles; Durrant, Simon; Ilhan, Osman; Parenti, Dennis; Rogers, Jon; Gallo, Jose; Foss, Francine; Apperley, Jane; Zhang, Mei-Jie; Horowitz, Mary M; Abhyankar, Sunil

    2012-01-01

    Summary Graft-versus-host disease (GVHD) is partly mediated by host antigen presenting cells (APCs) that activate donor T-cells. Extracorporeal photopheresis (ECP) can modulate APC function and benefit some patients with GVHD. We report the results of a study using ECP administered prior to a standard myeloablative preparative regimen intended to prevent GVHD. Grade II-IV aGVHD developed in 9 (30%) of 30 recipients of HLA-matched related transplants and 13 (42%) of 31 recipients of HLA-matched unrelated or HLA-mismatched related donor transplants. Actuarial estimates of overall survival (OS) at day 100 and 1 year post transplant were 89% (95% CI, 78%-94%) and 77% (95% CI, 64%-86%), respectively. There were no unexpected adverse effects of ECP. Historical controls receiving similar conditioning and GVHD prophylaxis regimens but no ECP were identified from the database of the Center for International Blood and Marrow Transplant Research and multivariate analysis indicated a lower risk of grade II-IV aGVHD in patients receiving ECP (p=0.04). Adjusted OS at one year was 83% in the ECP study group and 67% in the historical control group (relative risk 0.44, 95% CI, 0.24-0.80) (p= 0.007). These preliminary data may indicate a potential survival advantage with ECP for transplant recipients undergoing standard myeloablative hematopoietic cell transplantation. PMID:19915634

  10. Helical tomotherapy targeting total bone marrow after total body irradiation for patients with relapsed acute leukemia undergoing an allogeneic stem cell transplant

    Background and purpose: To report our clinical experience in planning and delivering total marrow irradiation (TMI) after total body irradiation (TBI) in patients with relapsed acute leukemia undergoing an allogeneic stem-cell transplant (SCT). Materials and Methods: Patients received conventional TBI as 2 Gy BID/day for 3 days boosted the next day by TMI (2 Gy in a single fraction) and followed by cyclophosphamide (Cy) 60 mg/kg for 2 days. While TBI was delivered with linear accelerator, TMI was performed with helical tomotherapy (HT). Results: Fifteen patients were treated from July 2009 till May 2010, ten with acute myeloid leukemia, and five with acute lymphoid leukemia. At the time of radiotherapy eight patients were in relapse and seven in second or third complete remission (CR) after relapse. The donor was a matched sibling in 7 cases and an unrelated donor in 8 cases. Median organ-at-risk dose reduction with TMI ranged from 30% to 65% with the largest reduction (-50%-65%) achieved for brain, larynx, liver, lungs and kidneys. Target areas (bone marrow sites and spleen in selected cases) were irradiated with an optimal conformity and an excellent homogeneity. Follow-up is short ranging from 180 to 510 days (median 310 days). However, tolerance was not different from a conventional TBI-Cy. All patients treated with TBI/TMI reached CR after SCT. Three patients have died (2 for severe GvHD, 1 for infection) and 2 patients showed relapsed leukemia. Twelve patients are alive with ten survivors in clinical remission of disease. Conclusions: This study confirms the clinical feasibility of using HT to deliver TMI as selective dose boost modality after TBI. For patients with advanced leukemia targeted TMI after TBI may be a novel approach to increase radiation dose with low risk of severe toxicity.

  11. NF-κB activation and zinc finger protein A20 expression in mature dendritic cells derived from liver allografts undergoing acute rejection

    Ming-Qing Xu; Wei Wang; Lan Xue; Lv-Nan Yan

    2003-01-01

    AIM: To investigate the role of NF-κB activation and zinc finger protein A20 expression in the regulation of maturation of dendritic cells (DCs) derived from liver allografts undergoing acute rejection. METHODS: Sixty donor male SD rats and sixty recipient male LEW rats weighing 220-300 g were randomly divided into whole liver transplantation group and partial liver transplantation group. Allogeneic (SD rat to LEW rat) whole and 50 % partial liver transplantation were performed. DCs from liver grafts 0 hour and 4 days after transplantation were isolated and propagated in the presence of GM-CSF in vitro. Morphological characteristics and phenotypical features of DCs propagated for 10 days were analyzed by electron microscopy and flow cytometry, respectively. NF-κB binding activity, IL-12p70 protein and zinc finger protein A20expression in these DCs were measured by EMSA and Western blotting, respectively. Histological grading of rejection was determined. RESULTS: Allogeneic whole liver grafts showed no signs of rejection on day 4 after the transplantation. In contrast,allogeneic partial liver grafts demonstrated moderate to severe rejection on day 4 after the transplantation. After propagation for 10 days in the presence of GM-CSF in vitro,DCs from allogeneic whole liver grafts exhibited features of immature DC with absence of CD40 surface expression,these DCs were found to exhibit detectable but very low level of NF-κB activity, IL-12 p70 protein and zinc finger protein A20 expression. Whereas, DCs from allogeneic partial liver graft 4 days after transplantation displayed features of mature DC, with high level of CD40 surface expression, and as a consequence, higher expression of IL-12p70 protein, higher activities of NF-κB and higher expression of zinc finger protein A20 compared with those of DCs from whole liver grafts (P<0.001). CONCLUSION: These results suggest that A20expression is up-regulated in response to NF-κB activation in mature DCs derived from

  12. Eradication of Pulmonary Aspergillosis in an Adolescent Patient Undergoing Three Allogeneic Stem Cell Transplantations for Acute Lymphoblastic Leukemia

    Michaela Döring

    2012-01-01

    Full Text Available Systemic fungal infections are a major cause of infection-related mortality in patients with hematologic malignancies. This report addresses the case of an adolescent patient with acute lymphoblastic leukemia who underwent three allogeneic hematopoietic stem cell transplantations and developed pulmonary aspergillosis. Combination therapy with liposomal amphotericin B (L-AmB, 3 mg/kg bw/day and caspofungin (CAS, 50 mg/day during the first allogeneic hematopoietic stem cell transplantation (HSCT improved the pulmonary situation. After shifting the antifungal combination therapy to oral voriconazole (2 × 200 mg/day and CAS, a new pulmonal lesion occurred alongside the improvements in the existing pulmonary aspergillosis. An antifungal combination during a second HSCT with L-AmB (3 mg/kg bw/day and CAS showed an improvement in the pulmonary aspergillosis. A combination therapy with CAS and L-AmB (1 mg/kg bw/day during the third HSCT led once again to progress the pulmonary aspergillosis, after increasing the L-AMB to 3 mg/kg bw/day for recovery. The presented case provides an example of how, despite severe immunosuppression, a combination of antifungal drugs administered intravenously at therapeutic dosages may be more efficient than either intravenous monotherapy or combinations of intravenous and oral antifungals in selecting pediatric and adolescent patients with proven fungal infections.

  13. Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation

    Sander Dirk

    2012-09-01

    Full Text Available Abstract Background Patients in neurologic in-patient rehabilitation are at risk of cardio- and cerebrovascular events. Microalbuminuria (MAU is frequent and an important risk predictor but has not been validated in in-patient rehabilitation. We therefore aimed to examine MAU as an indicator of risk and predictor of vascular events in a prospective study. Methods The INSIGHT (INvestigation of patients with ischemic Stroke In neuroloGic reHabiliTation registry is the first to provide large scale data on 1,167 patients with acute stroke (χ2 or Mann–Whitney-U Test. Relative risks (RR with 95% confidence intervals (CI were estimated using log-binominal models. To evaluate the association between MAU and new vascular events as well as mortality, we calculated hazard ratios (HR using Cox proportional hazard regression. Results A substantial proportion of patients was MAU positive at baseline (33.1%. Upon univariate analysis these patients were about 4 years older (69 vs. 65 years; p 2; p = 0.03 and increased waist circumference (79.5 vs. 50.4% for women [p  Conclusions INSIGHT demonstrated a significant association between MAU and polyvascular disease and further supports previous findings that MAU predicts cardio-/cerebrovascular events in patients recovering from ischemic stroke. This biomarker may also be used in patients during neurologic in-patient rehabilitation, opening a window of opportunity for early intervention in this patient group at increased risk for recurrent events.

  14. Leukaemia incidence after iodine-131 exposure

    Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46 988 Swedish patients exposed to iodine-131 (131I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy. 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09. Similar increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from 131I. One reason for the absence of a radiation effect includes the possible lowering of risk when exposure is protracted over time as occurs with 131I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to 131I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident. (Author)

  15. Leukaemia incidence after iodine-131 exposure

    Hall, Per (Karolinska Hospital, Stockholm (Sweden). Dept. of General Oncology); Boice, J.D. Jr. (National Cancer Inst., Bethesda, MD (United States). Div. of Cancer Etiology); Berg, Gertrud (Sahlgren' s Hospital, Gothenburg (Sweden). Dept. of General Oncology) (and others)

    1992-07-04

    Leukaemia is one of the most prominent late effects of exposure to ionising radiation. We have studied the incidence of leukaemia among 46 988 Swedish patients exposed to iodine-131 ([sup 131]I) for diagnostic reasons or to treat hyperthyroidism or thyroid cancer. The observed number of leukaemias was compared with that expected based on incidence data from the general population. The mean absorbed dose to the bone marrow was estimated as 14 mGy. 195 leukaemias occurred more than 2 years after exposure, and the standardised incidence ratio (SIR) was 1.09. Similar increased risks were seen for chronic lymphocytic leukaemia (CLL) (SIR = 1.08), a malignant condition not found to be increased after irradiation, and for non-CLL (SIR = 1.09). The risk of leukaemia did not vary by sex, age, time, or radiation dose from [sup 131]I. One reason for the absence of a radiation effect includes the possible lowering of risk when exposure is protracted over time as occurs with [sup 131]I. Excess leukaemia risks of more than 25% could thus be excluded with high assurance in this population of mainly adults. These results should be reassuring to patients exposed to [sup 131]I in medical practice and to most individuals exposed to the fall-out from the Chernobyl accident. (Author).

  16. Genetic variant in CD44 confer susceptibility to acute skin reaction in breast cancer patients undergoing radiotherapy

    Heterogeneity in toxicity to normal tissue is observed in 10% of cancer patients after radiotherapy (RT) which limits the therapeutic outcome. Response to RT is manifested from alterations in gene of vivid pathways involving DNA damage-repair, inflammatory cytokine, cell cycle regulation, antioxidant response etc. Therefore, the common sequence variants in these radioresponsive genes may modify the severity of normal tissue toxicity and identification of the same may have clinical relevance as a predictive biomarker. The present study was aimed to evaluate the potential modifying role of genetic variants in NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, LIG3, SH3GL1, BAXS, XRCC1, MAD2L2 and TGFBR3 on the individual susceptibility to RT induced acute skin reactions. All the 132 breast cancer patients were treated with a total dose of 50 Gy in case of mastectomy and 60 Gy in breast conservation surgery. The severity of skin damage was scored according to the Radiation Therapy Oncology Group (RTOG) criteria and the toxicity scores were dichotomized as non-over-responders (NOR; RTOG<2) and over-responders (NOR;RTOG>2) for analysis. Out of the 132 subjects, 44 were ORs. Among the 20 studied SNPs of indicated genes, the rs8193 (CD44) polymorphism lying in the miRNA binding site was significantly (p<0.05) associated with the RT induced adverse skin reactions. The non-coding CD44 3'-UTR serves as a competitor for miRNA binding and subsequently inactivates miRNA functions, by freeing the target mRNAs from being repressed. Therefore, though the role of CD44 in radiosensitivity is unknown, the change in the miRNA binding to CD44mRNA transcripts may regulate expression of several genes involved in pathophysiology of normal tissue radiosensitivity leading to the observed outcome. (author)

  17. Genetics Home Reference: acute promyelocytic leukemia

    ... Z. Acute promyelocytic leukaemia: novel insights into the mechanisms of cure. Nat Rev Cancer. 2010 Nov;10( ... with a qualified healthcare professional . About Genetics Home Reference Site Map Contact Us Selection Criteria for Links ...

  18. Childhood leukaemia and nuclear power

    There has been considerable scientific and media interest in the question of whether the risk of childhood leukemia is raised near nuclear facilities, and, if so, the reasons why. Serious consideration of this issue was initiated by a media report of an unusually large number of cases around the Sellafield installation in England, and reports of excess cases in the vicinity of other facilities in Britain have followed. Detailed radiological assessments have demonstrated that radioactive discharges are most unlikely to have been the cause of these reported excess cases, seemingly contradicting the epidemiological evidence. However, epidemiology is an observational (non-experimental) science, and the results of such studies must be interpreted with considerable care. The influence of prior knowledge of data upon the structure of a study has been a particular inferential problem. Furthermore, there are indications that non-radiological factors may be important in communities near nuclear facilities. Recently, a study has shown an association between childhood leukaemia cases near Sellafield and the recorded occupational radiation doses received by fathers before the conception of these children; but this novel finding has received little independent scientific support. At present, the British childhood leukaemia findings have not been replicated in studies based in other countries, and the reasons for the reported case excesses around British nuclear facilities remain unclear

  19. Effects of upstream tirofiban versus downstream tirofiban on myocardial damage and 180-day clinical outcomes in high-risk acute coronary syndromes patients undergoing percutaneous coronary interventions

    LIU Tao; XIE Ying; ZHOU Yu-jie; LI Yue-ping; MA Han-ying; GUO Yong-he; LIU Yu-yang; ZHAO Ying-xin; SHI Dong-mei

    2009-01-01

    Background For patients with moderate to high-risk acute coronary syndromes(ACS)who undergo early,invasive treatment strategies,current guidelines recommend the usage of glycoprotein(GP)lib/Illa inhibitors as an upstream treatment for a coronary care unit or as an downstream provisional treatment for selected patients who are undergoing percutaneous coronary intervention(PCI).The relative advantage of either strategy is unknown.The purpose of this study was to evaluate the effects of upstream tirofiban versus the effects of downstream tirofiban on myocardial damage and 180-day major adverse cardiovascular events(MACE)after PCI in high-risk non-ST-segment elevation ACS (NSTE-ACS)undergoing PCI.Methods From July 2006 to July 2007,160 high-risk NSTE-ACS undergoing PCI were randomized to receive upstream (within 4-6 hours before coronary angiography)tirofiban or downstream(the guidewire crossing the lesion)tirofiban,to evaluate the extent of myocardial damage after PCI by quantitatively and qualitatively analyzing the value of cardiac troponin I(cTnl)as well as MB isoenzyme of creatine kinase(CK-MB)before and after PCI.The incidences of 24-hour,3-day,7-day,30-day and 180-day MACE after PCI were followed up and the rates of bleeding complications and thrombocytopenia during tirofiban administration were recorded.Results The peak release and cumulative release of cTnl levels within 48 hours after PCI were significantly lower with upstream tirefiban than downstream tirofiban(0.45 vs 0.63 and 0.32 vs 0.43,respectively;P<0.05).Post-procedural cTnl elevation within 48 hours was significantly less frequent among patients who received the upstream tirofiban than those who received the downstream tirefiban(66.3%vs 87.5%,P<0.05).The peak and cumulative release of CK-MB levels as well as post-procedural CK-MB elevation within 48 hours after PCI were not significantly different between the two groups (16 vs 14,5 vs 3 and 26.3%vs 36.3%,respectively;P>0.05).The incidences of

  20. The Effect of Gabapentin on Acute Postoperative Pain in Patients Undergoing Total Knee Arthroplasty: A Meta-Analysis.

    Zhai, Lifeng; Song, Zhoufeng; Liu, Kang

    2016-05-01

    consumption via PCA at 24 hours (MD = -8.28; 95% CI -12.57 to -3.99; P = 0.000) and 48 hours (MD = -4.50; 95% CI -10.98 to -3.61; P = 0.221). Furthermore, gabapentin decreased the rate of postoperative dizziness (relative risk [RR], 0.68; 95% CI 0.47-0.99, P = 0.044) and the occurrence of pruritus (RR, 0.50; 95% CI 0.37-0.67, P = 0.000).Based on the current meta-analysis, gabapentin exerts an analgesic and opioid-sparing effect in acute postoperative pain management without increasing the rate of dizziness and pruritus. PMID:27196473

  1. Space-time clustering of childhood leukaemia in Greece: evidence supporting a viral aetiology.

    Petridou, E.; Revinthi, K.; Alexander, F. E.; Haidas, S.; Koliouskas, D.; Kosmidis, H.; Piperopoulou, F.; Tzortzatou, F.; Trichopoulos, D.

    1996-01-01

    The method introduced by Knox for evaluation of space-time clustering has been applied to 872 cases of childhood (0-14 year old) leukaemia diagnosed in Greece over the 10 year period 1980-89. Greek towns are characterised by substantial population mixing due to internal migration, whereas there is relative isolation in mountainous rural areas. Predetermined space (5 km) and time (1 year) limits were used on the basis of previous reports in order to define the clustering cell. There is highly significant evidence for clustering of childhood leukaemia in Greece as a whole, the observed number of pairs that are close in both spaces and time exceeding the expected number by 5.2% (P = 0.004). The excess is particularly evident for leukaemia cases in 0 to 4-year-old children, among whom the observed number of pairs that are close in both space and time exceeded the expected number by 9.4% (P = 0.004). There is no evidence of space-time clustering for leukaemia cases older than 5 years. The overall pattern is descriptively similar in urban and semiurban areas and is especially marked for acute lymphoblastic leukaemia at the childhood peak ages (2-4 years) with an excess of 19% (P = 0.0006). In the rural population there is evidence for clustering of cases belonging to older and broader age groups, a phenomenon compatible with a delay in the development of herd immunity against putative infectious aetiological agents. The findings of the present study provide support for the hypothesis that a substantial proportion of cases of childhood leukaemia may arise as a rare sequel to exposure to an agent or agents, most probably viral in nature. PMID:8630293

  2. Impact of Dual Antiplatelet Therapy with Proton Pump Inhibitors on the Outcome of Patients with Acute Coronary Syndrome Undergoing Drug-Eluting Stent Implantation

    Macaione, Francesca; Montaina, Carla; Evola, Salvatore; Novo, Giuseppina; Novo, Salvatore

    2012-01-01

    This study aimed to assess if proton pump inhibitors (PPIs) may reduce the effectiveness of clopidogrel, than H2 antagonist (anti-H2) in order to determine rehospitalization for acute coronary syndrome (re-ACS), target vessel revascularization (TVR) and cardiac death. This case-control study included 176 patients with ACS undergoing angioplasty (PCI) with drug-eluting stent implantation. The population was divided into two groups: PPI group (n = 121) consisting of patients receiving at discharge dual antiplatelet therapy (DAT) plus PPI and anti-H2 group (n = 55), consisting of patients receiving at discharge DAT + H2 receptor antagonist (H2RA). In a followup of 36 months the prevalence of ACS event (P = 0.014), TVR (P = 0.031) was higher in the PPI group than in the anti-H2 group; instead there was no statistically significant difference between groups for death. The variables independently associated with ACS were the diabetes, omeprazole, and esomeprazole; instead the variables independently associated with TVR were only omeprazole. Our data shows that the use of omeprazole and esomeprazole, with clopidogrel, is associated with increased risk of adverse outcomes after PCI with drug-eluting stent implantation. PMID:22792485

  3. Urinary KIM-1, NGAL and L-FABP for the diagnosis of AKI in patients with acute coronary syndrome or heart failure undergoing coronary angiography.

    Torregrosa, Isidro; Montoliu, Carmina; Urios, Amparo; Andrés-Costa, María Jesús; Giménez-Garzó, Carla; Juan, Isabel; Puchades, María Jesús; Blasco, María Luisa; Carratalá, Arturo; Sanjuán, Rafael; Miguel, Alfonso

    2015-11-01

    Acute kidney injury (AKI) is a common complication after coronary angiography. Early biomarkers of this disease are needed since increase in serum creatinine levels is a late marker. To assess the usefulness of urinary kidney injury molecule-1 (uKIM-1), neutrophil gelatinase-associated lipocalin (uNGAL) and liver-type fatty acid-binding protein (uL-FABP) for early detection of AKI in these patients, comparing their performance with another group of cardiac surgery patients. Biomarkers were measured in 193 patients, 12 h after intervention. In the ROC analysis, AUC for KIM-1, NGAL and L-FABP was 0.713, 0.958 and 0.642, respectively, in the coronary angiography group, and 0.716, 0.916 and 0.743 in the cardiac surgery group. Urinary KIM-1 12 h after intervention is predictive of AKI in adult patients undergoing coronary angiography, but NGAL shows higher sensitivity and specificity. L-FABP provides inferior discrimination for AKI than KIM-1 or NGAL in contrast to its performance after cardiac surgery. This is the first study showing the predictive capacity of KIM-1 for AKI after coronary angiography. Further studies are still needed to answer relevant questions about the clinical utility of biomarkers for AKI in different clinical settings. PMID:24989970

  4. The Time Profile of Pentraxin 3 in Patients with Acute ST-Elevation Myocardial Infarction and Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention

    Ragnhild Helseth

    2014-01-01

    Full Text Available Background. High levels of Pentraxin 3 (PTX3 are reported in acute myocardial infarction (AMI. Aim. To investigate circulating levels and gene expression of PTX3 in patients with AMI and stable angina pectoris (AP undergoing PCI. Methods. Ten patients with AP and 20 patients with AMI were included. Blood samples were drawn before PCI in the AP group and after 3 and 12 hours and days 1, 3, 5, 7, and 14 in both groups. Results. Circulating PTX3 levels were higher in AMI compared to AP at 3 and 12 hours (P<0.001 and P=0.003. Within the AMI group, reduction from 3 hours to all later time points was observed (all P≤0.001. Within the AP group, increase from baseline to 3 hours (P=0.022, followed by reductions thereafter (all P<0.05, was observed. PTX3 mRNA increased in the AMI group from 3 hours to days 7 and 14 in a relative manner of 62% and 73%, while a relative reduction from baseline to 3 and 12 hours of 29% and 37% was seen in the AP group. Conclusion. High circulating PTX3 levels shortly after PCI in AMI indicate that AMI itself influences PTX3 levels. PTX3 mRNA might be in response to fluctuations in circulating levels.

  5. Statistical frequency of childhood leukaemia-clusters

    Based upon the Poisson statistics we have estimated the probability for statistically significant accumulations (clusters) of leukaemia diseases in children. Considering the distribution of the time intervals between succeeding events we have found that in larger countries with some 107 inhabitants there is to be expected an average of one or more leukaemia clusters with an exceptionally high frequency of diseases of e.g. 5 or more cases of leukaemia in communities with som 100 children within a relatively short period of one or a few years. This frequency of diseases is much greater than the expectation value. The probability for at least one such cluster to occur within a follow-up period of approximately 10 years is >0.5. As examples we have analyzed the leukaemia clusters observed in children in Elbmarsch, in Seascale near Sellafield and in Scotland. The occurence of clusters of leukaemia can be statistically explained in principle but the possible existence of specific causes for the emergence of leukaemia clusters cannot be excluded by statistical considerations. (orig.)

  6. Childhood leukaemia clusters around Sellafield and Dounreay

    In 1983, a television programme identified a striking cluster of childhood leukaemia in the coastal village of Seascale, adjacent to the Sellafield nuclear complex in England. Excesses of childhood leukaemia near certain other nuclear installations in Britain were later reported during the 1980s, notably a cluster in west Thurso near Dounreay in Scotland. Detailed radiological investigations demonstrated that radiation exposures from discharged radioactive material were most unlikely to be the cause of these excesses and no serious deficiencies in these assessments have been discovered despite exhaustive searches. In 1990, a report was published suggesting that occupational radiation exposure of men before the conception of their children could be responsible for the Seascale cluster. Extensive research has not supported a causal link between paternal preconceptional radiation dose and childhood leukaemia, and the idea that radiation exposure of fathers materially increases the risk of leukaemia in offspring and could account for the clusters has now effectively been abandoned. In contrast, evidence has mounted that childhood leukaemia has an infectious basis and that unusual population mixing increases the risk of the disease. It now seems that population mixing is the explanation for the excesses of childhood leukaemia near nuclear sites and at other locations with no enhanced exposure to radiation. (author)

  7. Radiation-associated chronic myelogenous leukaemia in younger people

    Chronic myelogenous leukaemia (CML) is known to be induced by exposure to ionizing radiation, as is acute leukaemia. However, CML has been recorded only rarely as a complication of radiation exposure early in life. During the period from 1973 to 1976, 75 patients with CML were admitted to Roswell Park Memorial Institute (RPMI). In addition, 64 patients admitted to RPMI previously were also available for study in 1973. Among 79 patients who were born after 1925, information regarding radiation exposure was obtained in 89%; 49 were interviewed and 21 responded to a mailed questionnaire. Consultation with parents was achieved in 52 of the 70 responding cases (74%). Replies were obtained from 15 of the 18 patients below the age of 25, and were confirmed by parents or siblings in all instances. Replies to the mailed questionnaire were obtained from 45 age- and sex-matched controls. In addition to two patients already known to have radiation exposure for treatment of malignant neoplasms, these inquiries yielded a total of nine patients with histories of radiation exposure for benign conditions. Three had therapeutic irradiation, two for thymic enlargement and one for eczema. Three had exposure in utero by pelvimetry. Two had diagnostic exposure during the perinatal period and one had occupational exposure as a nurse. Four of these patients were below the age of 25. All nine patients had the Ph' chromosome. The course of CML in these patients was not different from that of other patients with Ph' chromosome-positive CML without a history of radiation exposure. A history of radiation exposure was elicited in one-fourth of the younger patients (<25) in this study, compared with one of 45 age- and sex-matched controls without leukaemia (p<0.02)

  8. The presence of C/EBPα and its degradation are both required for TRIB2-mediated leukaemia

    O'Connor, C; Lohan, F; Campos, J;

    2016-01-01

    C/EBPα (p42 and p30 isoforms) is commonly dysregulated in cancer via the action of oncogenes, and specifically in acute myeloid leukaemia (AML) by mutation. Elevated TRIB2 leads to the degradation of C/EBPα p42, leaving p30 intact in AML. Whether this relationship is a cooperative event in AML...

  9. Leukaemia complicating treatment for Hodgkin's disease: the experience of the British National Lymphoma Investigation.

    Devereux, S; Selassie, T G; Vaughan Hudson, G.; Vaughan Hudson, B; Linch, D. C.

    1990-01-01

    OBJECTIVE--To determine the incidence of and risk factors for the development of secondary acute leukaemia and myelodysplasia in patients treated in British National Lymphoma Investigation's studies of Hodgkin's disease since 1970. PATIENTS--2676 Patients entered into Hodgkin's disease studies between February 1970 and November 1986. Data accrued up to November 1988 were analysed, ensuring a minimum follow up period of two years. DESIGN--Retrospective analysis of multicentre trial data by cas...

  10. An investigation into childhood leukaemia in Northamptonshire

    This report has been written specifically for the families of children who have had leukaemia in Northamptonshire. It gives the Health Authority's answers to the questions and worries that they raised at a meeting we had on 22nd September 1995. The report will also be circulated to other people who have been concerned by this problem and will, therefore, include some background information as well. The report thus has several different purposes: to give a brief summary of what is known about leukaemia and its causes; to explain the implications of having five cases of childhood leukaemia in a small area over a number of years; to let people know what Northamptonshire Health Authority has done in response to their concerns; to explain why a local epidemiological study of these cases could not tell us what caused leukaemia in the affected children; to reassure residents in the Pembroke Road area that we have found no reason to be concerned that their children are at an increased risk of developing leukaemia; to give information to the families about the current scientific evidence on the relationship between several potential environmental hazards they have identified and childhood leukaemia; to let people know that the important questions about what causes leukaemia in children are being addressed in several important and well-designed scientific studies. We hope that this report can be understood by people who are not familiar with medical jargon. Sometimes it has been necessary to use medical and technical terms, so at the back of this report there is a glossary which gives the meaning of any medical terms used

  11. Effect of Beta Blockers and Renin-Angiotensin System Inhibitors on Survival in Patients With Acute Myocardial Infarction Undergoing Percutaneous Coronary Intervention.

    Lee, Pil Hyung; Park, Gyung-Min; Kim, Young-Hak; Yun, Sung-Cheol; Chang, Mineok; Roh, Jae-Hyung; Yoon, Sung-Han; Ahn, Jung-Min; Park, Duk-Woo; Kang, Soo-Jin; Lee, Seung-Whan; Lee, Cheol Whan; Park, Seong-Wook; Park, Seung-Jung

    2016-03-01

    Because it remains uncertain whether β-blockers (BBs) and/or renin-angiotensin system inhibitors benefit a broad population of acute myocardial infarction (AMI) patients, we sought to evaluate the effectiveness of these drugs in improving survival for post-AMI patients who underwent a percutaneous coronary intervention (PCI).From the nationwide data of the South Korea National Health Insurance, 33,390 patients with a diagnosis of AMI who underwent a PCI between 2009 and 2013 and survived at least 30 days were included in this study. We evaluated the risk of all-cause death for patients treated with both BB and angiotensin-converting enzyme inhibitor (ACEI)/angiotensin II receptor antagonist (ARB) (n = 16,280), only BB (n = 3683), and only ACEI/ARB (n = 9849), with the drug-untreated patients (n = 3578) as the reference.Over a median follow-up of 2.4 years, although treated patients displayed a trend toward improved survival, there were no significant differences in the adjusted risk of all-cause death when patients were treated with both drugs (hazard ratio [HR] 0.86, 95% confidence interval [CI] 0.70-1.06, P = 0.154), BB (HR 0.88, 95% CI 0.68-1.14, P = 0.325), or ACEI/ARB (HR 0.84, 95% CI 0.68-1.04, P = 0.111). No additional benefit was found for the combination therapy compared with either isolated BB (HR 0.98, 95% CI 0.80-1.21, P = 0.856) or ACEI/ARB (HR 1.03, 95% CI 0.89-1.19, P = 0.727) therapy.Treatment with BB and/or ACEI/ARB has limited effect on survival in unselected nonfatal AMI patients who undergo PCI. PMID:26962802

  12. Wilms Tumor 1 Expression and Pre-emptive Immunotherapy in Patients with Acute Myeloid Leukemia Undergoing an Allogeneic Hemopoietic Stem Cell Transplantation.

    Di Grazia, Carmen; Pozzi, Sarah; Geroldi, Simona; Grasso, Raffaella; Miglino, Maurizio; Colombo, Nicoletta; Tedone, Elisabetta; Luchetti, Silvia; Lamparelli, Teresa; Gualandi, Francesca; Ibatici, Adalberto; Bregante, Stefania; Van Lint, Maria Teresa; Raiola, Anna Maria; Dominietto, Alida; Varaldo, Riccardo; Galaverna, Federica; Ghiso, Anna; Sica, Simona; Bacigalupo, Andrea

    2016-07-01

    Minimal residual disease (MRD) was monitored by Wilms tumor 1 (WT1) expression in 207 patients with acute myeloid leukemia (AML) after an allogeneic hemopoietic stem cell transplantation (HSCT) as a trigger to initiate pre-emptive immunotherapy (IT) with cyclosporin discontinuation and/or donor lymphocyte infusion. The trigger for IT was WT1 ≥ 180 copies/10(4) Abelson cells in marrow cells in the first group of 122 patients (WT1-180) and ≥ 100 copies in a subsequent group of 85 patients (WT1-100). Forty patients received IT. The cumulative incidence (CI) of relapse was 76% in WT1-180 (n = 17) versus 29% in WT1-100 patients (n = 23) receiving IT (P = .006); the leukemia-free survival from MRD positivity was 23% versus 74%, respectively (P = .003). We then looked at the entire AML patient population (n = 207). WT1-180 and WT1-100 patients were comparable for disease phase and age. The overall 4-year CI of transplantation-related mortality was 13% in both groups; the CI of leukemia relapse was 38% in the WT1-180 and 28% in the WT1-100 patients (P = .05) and leukemia-free survival was 56% versus 48%, respectively (P = .07). In conclusion, we suggests that WT1-based pre-emptive immunotherapy is feasible in patients with undergoing an allogeneic HSCT. The protective effect on relapse is greater when IT is triggered at lower levels of WT1. PMID:26970379

  13. Combined Value of Red Blood Cell Distribution Width and Global Registry of Acute Coronary Events Risk Score for Predicting Cardiovascular Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention

    Zhao, Na; Mi, Lan; Liu, Xiaojun; Pan, Shuo; Xu, Jiaojiao; Xia, Dongyu; Liu, Zhongwei; Zhang, Yong; Xiang, Yu; Yuan, Zuyi; Guan, Gongchang; Wang, Junkui

    2015-01-01

    Global Registry of Acute Coronary Events (GRACE) risk score and red blood cell distribution width (RDW) content can both independently predict major adverse cardiac events (MACEs) in patients with acute coronary syndrome (ACS). We investigated the combined predictive value of RDW and GRACE risk score for cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI) for the first time. We enrolled 480 ACS patients. During a median follow-up time of 37.2 months, 70 (14.58%) patients experienced MACEs. Patients were divided into tertiles according to the baseline RDW content (11.30–12.90, 13.00–13.50, 13.60–16.40). GRACE score was positively correlated with RDW content. Multivariate Cox analysis showed that both GRACE score and RDW content were independent predictors of MACEs (hazard ratio 1.039; 95% confidence interval [CI] 1.024–1.055; p < 0.001; 1.699; 1.294–2.232; p < 0.001; respectively). Furthermore, Kaplan–Meier analysis demonstrated that the risk of MACEs increased with increasing RDW content (p < 0.001). For GRACE score alone, the area under the receiver operating characteristic (ROC) curve for MACEs was 0.749 (95% CI: 0.707–0.787). The area under the ROC curve for MACEs increased to 0.805 (0.766–0.839, p = 0.034) after adding RDW content. The incremental predictive value of combining RDW content and GRACE risk score was significantly improved, also shown by the net reclassification improvement (NRI = 0.352, p < 0.001) and integrated discrimination improvement (IDI = 0.023, p = 0.002). Combining the predictive value of RDW and GRACE risk score yielded a more accurate predictive value for long-term cardiovascular events in ACS patients who underwent PCI as compared to each measure alone. PMID:26468876

  14. Combined Value of Red Blood Cell Distribution Width and Global Registry of Acute Coronary Events Risk Score for Predicting Cardiovascular Events in Patients with Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

    Na Zhao

    Full Text Available Global Registry of Acute Coronary Events (GRACE risk score and red blood cell distribution width (RDW content can both independently predict major adverse cardiac events (MACEs in patients with acute coronary syndrome (ACS. We investigated the combined predictive value of RDW and GRACE risk score for cardiovascular events in patients with ACS undergoing percutaneous coronary intervention (PCI for the first time. We enrolled 480 ACS patients. During a median follow-up time of 37.2 months, 70 (14.58% patients experienced MACEs. Patients were divided into tertiles according to the baseline RDW content (11.30-12.90, 13.00-13.50, 13.60-16.40. GRACE score was positively correlated with RDW content. Multivariate Cox analysis showed that both GRACE score and RDW content were independent predictors of MACEs (hazard ratio 1.039; 95% confidence interval [CI] 1.024-1.055; p < 0.001; 1.699; 1.294-2.232; p < 0.001; respectively. Furthermore, Kaplan-Meier analysis demonstrated that the risk of MACEs increased with increasing RDW content (p < 0.001. For GRACE score alone, the area under the receiver operating characteristic (ROC curve for MACEs was 0.749 (95% CI: 0.707-0.787. The area under the ROC curve for MACEs increased to 0.805 (0.766-0.839, p = 0.034 after adding RDW content. The incremental predictive value of combining RDW content and GRACE risk score was significantly improved, also shown by the net reclassification improvement (NRI = 0.352, p < 0.001 and integrated discrimination improvement (IDI = 0.023, p = 0.002. Combining the predictive value of RDW and GRACE risk score yielded a more accurate predictive value for long-term cardiovascular events in ACS patients who underwent PCI as compared to each measure alone.

  15. Effect of rosuvastatin dose-loading on serum sLox-1, hs-CRP, and postoperative prognosis in diabetic patients with acute coronary syndromes undergoing selected percutaneous coronary intervention (PCI)

    Jiao, Yungen; Hu, Feng; Zhang, Zhengang; Gong, Kaizheng; Sun, Xiaoning; Li, Aihua; Liu, Naifeng

    2015-01-01

    Objective: To investigate the effect of rosuvastatin dose-loading on serum levels of lectin-like oxidized low-density lipoprotein receptor-1 (Lox-1) and high-sensitivity c-reactive protein (hs-CRP) and postoperative prognosis in patients with diabetes and non-ST segment elevation acute coronary syndromes (NSTEACS) undergoing selected percutaneous coronary intervention (PCI). Methods: A total of 72 patients with diabetes and NSTEACS were randomized to either the group treated with 20 mg rosuva...

  16. Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study

    Franco, Pierfrancesco; Potenza, Ilenia; Moretto, Francesco; Segantin, Mattia; Grosso, Mario; Lombardo, Antonello; Taricco, Daniela; Vallario, Patrizia; Filippi, Andrea Riccardo; Rampino, Monica; Ricardi, Umberto

    2014-01-01

    Background Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. Me...

  17. 急性淋巴细胞白血病患儿诱导缓解期合并可逆性后部白质脑病临床特征%Reversible posterior leukoencephalopathy syndrome in children with acute lymphocytic leukaemia after remission induction chemotherapy

    林巍; 谢静; 郑胡镛; 程华; 张元元; 张瑞东

    2014-01-01

    Objective To investigate the etiology,clinical manifestations,imaging characteristics and treatment of reversible posterior leukoencephalopathy syndrome in children with acute lymphocytic leukaemia after remission induction chemotherapy.Methods Analysize the clinico-radiological features、central nervous system symptoms and associated symptoms、treatment and prognosis of reversible posterior leukoencephalopathy syndrome in children with acute lymphocytic leukaemia receiving induction chemotherapy in hematology center of Beijing children′s hospita from June 201 1 to March 2012.Results Eight children (3 males and 5 females)with a mean age of 5 years were identified.Presenting symptoms included seizures (8/8 ),disturbance of consciousness (3/8 ),and visual disturbance (2/8 ).High blood pressure,agranulocytosis,and coagulation disorders,electrolyte disturbance were existed,and they all used granulocyte colony-stimulating factor.All children had typical radiological features of reversible posterior leukoencephalopathy syndrome.Six cases of children with head magnetic resonance imaging results suggest that vasogenic edema,the prognosis is good.Two cases of cytotoxic edema,in one case of recurrence,the prognosis is bad.Conclusion reversible posterior leukoencephalopathy syndrome is an underappreciated complication in cancer children receiving remission induction chemotherapy.Head magnetic resonance imaging is an important means of diagnosis and assessment of reversible posterior leukoencephalopathy syndrome prognosis. During chemotherapy require close monitoring of blood pressure,electrolyte,blood coagulation,actively is needed.%目的:探讨急性淋巴细胞白血病(acute lymphoblastic leukemiu,ALL)患儿,在诱导缓解化疗期间发生可逆性后部白质性脑病综合征(reversible posterior leukoencephalopathy sysdrome,RPLS)的病因、临床表现、影像学特征及治疗。方法2011年6月至2012年3月,北京儿童医院血液病中

  18. Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renal insufficiency undergoing percutaneous coronary intervention

    LI Xi-ming; CONG Hong-liang; LI Ting-ting; HE Li-jun; ZHOU Yu-jie

    2011-01-01

    Background The role of angiotensin-converting enzyme inhibitors (ACEI) in contrast-induced acute kidney injury (CI-AKI) is controversial. Some studies pointed out that it was effective in the prevention of CI-AKI, while some concluded that it was one risk for CI-AKI, especially for patients with pre-existing renal impairment. The purpose of this study was to assess the influence of benazepril administration on the development of CI-AKI in patients with mild to moderate renal insufficiency undergoing coronary intervention.Methods One hundred and fourteen patients with mild to moderate impairment of renal function were enrolled before coronary angioplasty, who were randomly assigned to benazepril group (n=52) and control group (n=62). In the benazepril group, the patients received benazepril tablets 10 mg per day at least for 3 days before procedure. CI-AKI was defined as an increase of≥25% in creatinine over the baseline value or increase of 0.5 mg/L within 72 hours of angioplasty.Results Patients were well matched with no significant differences at baseline in all measured parameters between two groups. The incidence of CI-AKI was lower by 64% in the benazepril group compared with control group but without statistical significance (3.45% vs. 9.68%, P=0.506). Compared with benazepril group, estimated glomerular filtration rate (eGFR) level significantly decreased from (70.64+16.38) ml·min-1·1.73 m-2 to (67.30+11.99) ml·min-1·1.73 m-2 in control group (P=0.038). There was no significant difference for the post-procedure decreased eGFR from baseline (△eGFR)between two groups (benazepril group (0.67+12.67) ml·min-1·1.73 m-2 vs. control group (-3.33±12.39) ml·min-1·1.73 m-2,P=0.092). In diabetic subgroup analysis, △eGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant.Conclusions Benazepril has a protective effect on mild to moderate impairment of renal function during

  19. Experiencia y resultados en el tratamiento de la leucemia linfoblástica aguda en la edad pediátrica en el periodo comprendido entre 1989 y 2005 en la Comunidad de Navarra Experience and results of acute lymphoblastic leukaemia treatment in children between 1989-2005 in Navarre

    J. Molina

    2007-12-01

    Full Text Available Fundamento. El conocimiento de factores que se comportan como pronósticos en la leucemia linfoblástica aguda (LLA es cada vez más importante para establecer una estrategia de tratamiento correcta. Se analiza la supervivencia global (SG, supervivencia libre de eventos (SLE y los factores pronósticos en 16 años de experiencia en nuestra comunidad. Material y métodos. Estudio descriptivo retrospectivo en el que se incluyen los pacientes diagnosticados de leucemia aguda (LA en ese periodo de tiempo. Análisis uni y multivariante de aquellos factores que hemos considerado relevantes en nuestra serie aplicando el paquete estadístico SPSS para Windows versión 12. Resultados. En el periodo comprendido entre enero de 1989 y diciembre de 2005 se diagnosticaron 58 pacientes de LA, 50 de ellos tipo linfoblástica aguda (LLA. Se analiza un subgrupo de 41 pacientes de forma más exhaustiva por ser el tipo de leucemia más frecuente y por haber estado incluidos en protocolos bien establecidos. En este grupo la SLE fue del 78% y la SG del 87,8%. Las variables multivariante predictoras en nuestra serie fueron: el inmunofenotipo (B-Común/Otras con un HR de 13,82 (IC95%: 1.019-166.008 pBackground. The determination of prognostic factors in acute lymphoblastic leukaemia (ALL is increasingly important in establishing a correct treatment. We analyse the overall survival (OS, event free survival (EFS and prognostic factors in our 16 years experience of treating acute lymphoblastic leukaemia. Methods. We performed univariate and multivariate analyses of the prognostic factors we considered most significant in our serie of patients Results. From January 1989 to December 2005, 50 cases of ALL were reported in 58 patients with LA. We analysed a subgroup of 41 patients with LLA as they were included in standard protocols. In this group the EFS was 78% and OS 87.8%. Inmunophenotype is a predictor of prognosis when we compare Common with Others, with a HR of 13

  20. Anti-leukaemic effects induced by APR-246 are dependent on induction of oxidative stress and the NFE2L2/HMOX1 axis that can be targeted by PI3K and mTOR inhibitors in acute myeloid leukaemia cells.

    Ali, Dina; Mohammad, Dara K; Mujahed, Huthayfa; Jonson-Videsäter, Kerstin; Nore, Beston; Paul, Christer; Lehmann, Sören

    2016-07-01

    The small molecule APR-246 (PRIMA-1(MET) ) is a novel drug that restores the activity of mutated and unfolded TP53 protein. However, the mechanisms of action and potential off-target effects are not fully understood. Gene expression profiling in TP53 mutant KMB3 acute myeloid leukaemia (AML) cells showed that genes which protected cells from oxidative stress to be the most up-regulated. APR-246 exposure also induced reactive oxygen species (ROS) formation and depleted glutathione in AML cells. The genes most up-regulated by APR-246, confirmed by quantitative real time polymerase chain reaction, were heme oxygenase-1 (HMOX1, also termed HO-1), SLC7A11 and RIT1. Up-regulation of HMOX1, a key regulator of cellular response to ROS, was independent of TP53 mutational status. NFE2L2 (also termed Nrf2), a master regulator of HMOX1 expression, showed transcriptional up-regulation and nuclear translocation by APR-246. Down-regulation of NFE2L2 by siRNA in AML cells significantly increased the antitumoural effects of APR-246. The PI3K inhibitor wortmannin and the mTOR inhibitor rapamycin inhibited APR-246-induced nuclear translocation of NFE2L2 and counteracted the protective cellular responses to APR-246, resulting in synergistic cell killing together with APR-246. In conclusion, ROS induction is important for antileukaemic activities of APR-246 and inhibiting the protective response of the Nrf-2/HMOX1 axis using PI3K inhibitors, enhances the antileukaemic effects. PMID:26991755

  1. Leukaemia and lymphoma among Czech uranium miners

    Tomasek, L.; Malatova, I. [National Radiation Protection Institute, Prague (Czech Republic)

    2006-07-01

    Leukaemia is one of the most sensitive cancers in relation to ionizing radiation. It is surprising that in studies of uranium miners, no risk of leukaemia in relation to cumulated radon exposure was observed (Darby et al, 1995). However, when the risk among Czech uranium miners was analyzed in dependence on duration of exposure, the trend was significant. These results were based on 10 cases (Tomasek, 1993). Since then the original cohort of 4320 miners has been extended by another cohort, now including nearly 10 000 uranium miners and the follow-up is longer by 10 years. The present report aims to analyze the risk of haemopoietic cancers in the Czech cohort accounting for both external and internal doses, similarly as reported by Jacobi and Roth (1995), and using available data on metal content and airborne particulates for dose estimates.The present results of follow-up show that increased risk of leukaemia among uranium miners is significantly associated with cumulated equivalent red bone marrow doses which is dominated by exposures to long lived alpha radionuclides in airborne particulates. The increased mortality is mainly observed decades after exposure and is consistent with estimated internal dose to red bone marrow. The estimated risk coefficient for leukaemia is consistent with results from other studies, however, further studies are needed to reduce uncertainty in the risk estimates. (N.C.)

  2. An algorithm for leukaemia immunophenotype pattern recognition.

    Petrovecki, M; Marusić, M; Dezelić, G

    1993-01-01

    Since leukaemia-specific leucocyte antigen has not been identified to date, the immunological diagnosis of leukaemia is achieved through the application of a wide set of monoclonal antibodies specific for surface markers on leukaemic cells. Thus, the interpretation of leukaemia immunophenotype seems to be a mathematically determined comparison of 'what we found' and 'what we know' about it. The objective of this study was to establish an algorithm for transformation of empirical rules into mathematical values to achieve proper decisions. Recognition of leukaemia phenotype was performed by comparison of phenotyping data with reference data, followed by scoring of such comparisons. Systematic scoring resulted in the formation of new numerical variables allocated to each state, whereas a most significant variable was described as a complex measure of compatibility. A system of recognized states was described by mathematical variables measuring the confidence of information systems, i.e. maximal, total and relative entropy. The entire algorithm was derived by matrix algebra and coded in a high-level program language. The list of the states recognized appeared to be especially helpful in differential diagnosis, occasionally pointing to states that had not been in the scientist's mind at the start of the analysis. PMID:8366688

  3. Cytogenetics of Post-Irradiation Mouse Leukaemia

    The interrelationship between radiation, cytogenetic abnormalities, and viruses in leukaemogenesis has been studied in the RF/Un mouse which develops a high incidence of granulocytic leukaemia on radiation exposure. A virus-like agent has been demonstrated in such leukaemic animals and the disease has been transmitted by passage of apparently acellular materials from irradiated primary animals to normal recipients. Pilot cytogenetic studies revealed consistent abnormal chromosome markers and modal shifts in both irradiated leukaemic animals and in non-irradiated animals developing leukaemia after passage injection. To define better the relationship between consistent bone-marrow chromosome aberrations and postirradiation primary and passaged leukaemia, 100 RF/Un mice were studied which were irradiated with 300 R of 250-kVp X-rays at 100 weeks of age and subsequently developed leukaemia. Eighty-seven had granulocytic leukaemia and in 72 of these, bone-marrow cytogenetic abnormalities were found. The distribution of-numerical and structural chromosome aberrations in 3225 cells studied are reviewed in derail. The correlation of specific aberrations to clinical and histopathologic findings has been attempted: Sequential passages of apparently cell-free material from the post-irradiation leukaemic mice into unirradiated RE/Un recipients and subsequent passages from leukaemic recipients were performed to observe the evolution of any initial chromosome markers and shifts in modal chromosome number in the passage generations. Two-hundred-thirty-six mice were inoculated with the material obtained either from primary post-irradiation leukaemic mice or from serially-passaged leukaemia cases. In the most extensive passaged line, 22 transfer generations containing 129 leukaemic mice were examined by clinical, histopathologic, -haematologic and cytogenetic procedures. Evolution of abnormal chromosome modes from 41 in the early passages to 39 chromosomes consistently after the 4

  4. Leukaemia among Czech uranium miners

    The study presents recent findings in an extended cohort of miners, now including nearly 10 000 uranium and 2 000 tin miners and followed up to 1999. A total of 30 cases of leukaemia were observed among Czech uranium miners, corresponding to standardized mortality ratio of 1.5, 90% CI: 1.0-2.1. The risk is analyzed in relation to cumulated dose from radon, external gamma radiation and alpha radiation from long lived radionuclides contained in mining aerosol. Doses to red bone marrow were estimated using measurements of external gamma activities since the early 1960s and measurements of long lived radionuclides in the aerosol since the 1970s. The red bone marrow dose from inhaled long lived radionuclides is estimated by applying respiratory tract model and relevant biokinetic models. The substantial point is that the dose is cumulated even after the underground work has stopped. Another important point is the difference of the exposure by job category. By extrapolating available exposure data and applying models based on ICRP-66 and ICRP-68, individual doses were estimated using working histories, job matrix, and time since exposure. The cumulated red bone marrow dose includes external gamma radiation, dose from radon and its progeny, and committed equivalent dose from long lived alpha-emitters in dependence on the individual length of follow-up. The mean cumulated dose is 158 mSv. Among uranium miners, about 52% of the total dose is due to inhalation of uranium and its decay products with aerosol in mines, about 33% is due to gamma radiation, and some 15% of the dose is from radon and its progeny. The risk coefficient (excess relative risk per sievert) corresponding to these estimates in the present study is 3.1 (90% CI: 1.3 - 5.4). The estimated risk is subject to a considerable uncertainty, due to small numbers and the uncertainty in the estimated dose. However, the magnitude of the risk is consistent with estimates from other studies. (orig.)

  5. The acute phase response of haptoglobin and serum amyloid A (SAA) in cattle undergoing experimental infection with bovine respiratory syncytial virus

    Heegaard, Peter M. H.; Godson, D.L.; Toussaint, M.J.M.; Tjørnehøj, Kirsten; Larsen, Lars Erik; Viuff, B.; Rønsholt, Leif

    The ability of a pure virus infection to induce an acute phase protein response is of interest as viral infections are normally considered to be less efficient in inducing an acute phase protein response than bacterial infections. This was studied in a bovine model for infection with bovine respi...

  6. Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention: a nationwide study

    Bonde, Lisbeth; Sorensen, Rikke; Fosbøl, Emil Loldrup;

    2010-01-01

    We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI).......We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI)....

  7. Transient Appearance of Blasts in Peripheral Smear in Paediatric Patient with Acute Aleukemic Leukemia

    Vaghasiya Viren L; Parikh Hina S; Patel Divyesh V; Taviad Dilip S

    2012-01-01

    Acute leukemia can present as leukemic blast in peripheral blood & bone marrow or in some cases in only in bone marrow. Here we present unique case of paediatric acute leukaemia which shows blast cells in peripheral blood transiently and without any definitive treatment blast cell disappear from peripheral blood. So diagnosis made previously was questioned, but later on when bone marrow examination was performed it turn out to be acute leukaemia. We haven’t found any reference o...

  8. The novel RASSF6 and RASSF10 candidate tumour suppressor genes are frequently epigenetically inactivated in childhood leukaemias

    Maher Eamonn R

    2009-07-01

    Full Text Available Abstract Background The Ras-assocation family (RASSF of tumour suppressor genes (TSGs contains 10 members that encode proteins containing Ras-assocation (RA domains. Several members of the RASSF family are frequently epigenetically inactivated in cancer, however, their role in leukaemia has remained largely uninvestigated. Also, RASSF10 is a predicted gene yet to be experimentally verified. Here we cloned, characterised and demonstrated expression of RASSF10 in normal human bone marrow. We also determined the methylation status of CpG islands associated with RASSF1–10 in a series of childhood acute lymphocytic leukaemias (ALL and normal blood and bone marrow samples. Results COBRA and bisulphite sequencing revealed RASSF6 and RASSF10 were the only RASSF members with a high frequency of leukaemia-specific methylation. RASSF6 was methylated in 94% (48/51 B-ALL and 41% (12/29 T-ALL, whilst RASSF10 was methylated in 16% (8/51 B-ALL and 88% (23/26 T-ALL. RASSF6 and RASSF10 expression inversely correlated with methylation which was restored by treatment with 5-aza-2'deoxycytidine (5azaDC. Conclusion This study shows the hypermethylation profile of RASSF genes in leukaemias is distinct from that of solid tumours and represents the first report of inactivation of RASSF6 or RASSF10 in cancer. These data show epigenetic inactivation of the candidate TSGs RASSF6 and RASSF10 is an extremely frequent event in the pathogenesis of childhood leukaemia. This study also warrants further investigation of the newly identified RASSF member RASSF10 and its potential role in leukaemia.

  9. Platelet PIA1/PIA2 polymorphism and the risk of periprocedural myocardial infarction in patients with acute coronary syndromes undergoing coronary angioplasty

    Verdoia, M.; Secco, G.G.; Cassetti, E.; Schaffer, A.; Barbieri, L.; Perrone-Filardi, P.; Marino, P.; Suryapranata, H.; Sinigaglia, F.; Luca, G. De

    2014-01-01

    Acute coronary syndromes (ACSs) represent a high-risk condition, as enhanced platelet reactivity importantly influences myocardial perfusion and procedural results after percutaneous coronary intervention (PCI). In fact, higher rate of periprocedural myocardial infarction (PMI) and reduced event-fre

  10. Meta-analysis of time-related benefits of statin therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention

    Navarese, E.P.; Kowalewski, M.; Andreotti, F.; Wely, M. van; Camaro, C.; Kolodziejczak, M.; Gorny, B.; Wirianta, J.; Kubica, J.; Kelm, M.; Boer, M.J. de; Suryapranata, H.

    2014-01-01

    Patients with acute coronary syndromes (ACSs) still experience high rates of recurrent coronary events, particularly, early in their presentation. Statins yield substantial cardiovascular benefits, but the optimal timing of their administration, before or after percutaneous coronary intervention (PC

  11. Hypericum perforatum and neem oil for the management of acute skin toxicity in head and neck cancer patients undergoing radiation or chemo-radiation: a single-arm prospective observational study

    Radiation dermatitis is common in patients treated with combined radiotherapy and chemotherapy for head and neck malignancies. Its timely and adequate management is of uttermost importance for both oncological outcomes and global quality of life. We prospectively evaluated the role of hypericum perforatum and neem oil (Holoil®; RIMOS srl, Mirandola, Italy) in the treatment of acute skin toxicity for patients undergoing radiotherapy or chemo-radiotherapy for head and neck cancer. A consecutive series of 28 head and neck cancer patients submitted to radiotherapy (RT) was enrolled onto this mono-institutional single-arm prospective observational study. Patients undergoing both definitive or post-operative radiotherapy were allowed, either as exclusive modality or combined with (concomitant or induction) chemotherapy. We started Holoil treatment whenever bright erythema, moderate oedema or patchy moist desquamation were observed. Holoil® was used during all RT course and during follow up time, until acute skin toxicity recovery. The maximum detected acute skin toxicity was Grade 1 in 7% of patients, Grade 2 in 68%, Grade 3 in 25%, while at the end of RT was Grade 0 in 3.5%, Grade 1 in 32%, Grade 2 in 61%, Grade 3 in 3.5%. For patients having G2 acute skin toxicity, it mainly started at weeks 4-5; for those having G3, it began during weeks 5-6. Median times spent with G2 or G3 toxicity were 17.5 and 11 days. Patients having G2 acute skin toxicity had a dermatitis worsening in 27% of case (median occurrence time: 7 days). G3 events were reconverted to a G2 profile in all patients (median time: 7 days). Those experiencing a G2 skin event were converted to a G1 score in 23% of cases (median time: 14 days). Time between maximum acute skin toxicity and complete skin recovery after RT was 27 days. Holoil® proved to be a safe and active option in the management of acute skin toxicity in head and neck cancer patients submitted to RT or chemo-radiotherapy. A prophylactic

  12. Leukaemia and non-Hodgkin lymphoma risk among Chernobyl liquidators

    Full text: Chernobyl liquidators were workers involved in the clean-up of contaminated areas around the Chernobyl power plant following the accident on 26 April 1986. These workers form a potentially important population for evaluation of the effects of protracted low doses of ionizing radiation. A collaborative case-control study of leukaemia and non-Hodgkin lymphoma (NHL) was set-up, nested within cohorts of Belarus, Russian and Baltic countries liquidators. The objective was to evaluate the radiation-induced risk of these diseases in this population and to study the effect of exposure protraction and radiation type on the risk of radiogenic cancer in the low to medium (0-500 mSv) radiation dose range. The study population consisted of approximately 66,000 Belarus, 65,000 Russian and 15,000 Baltic countries liquidators who took part in the clean-up activities between 26 April 1986 and 31 December 1987. In Belarus and Russia, liquidators are followed through the Chernobyl Registries and must undergo regular health check-ups, while in the Baltic countries their migration, vital and cancer status are assessed through population, death and cancer registries. The case ascertainment period ranged from 1990 to 2000 with minor differences among the countries. Information on study subjects was obtained through a face-to-face interview with the study subject and/or a proxy (a relative or a colleague), using a standardized questionnaire on demographic factors, time, place and conditions of work as a liquidator and on potential risk and confounding factors for leukaemia. A method of analytical dose reconstruction, entitled RADRUE (Realistic Analytical Dose Reconstruction with Uncertainty Estimation), was developed within the study, validated and applied to estimate individual dose to the bone marrow and related uncertainties for each subject. 117 cases (69 leukaemia, 34 NHL and 14 other malignancies of lymphoid and haematopoietic tissue) and 481 matched controls were

  13. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG)

    Groninger, E; Meeuwsen-de Boer, T; Koopmans, P; Uges, D; Sluiter, W; Veerman, A; Kamps, W

    2005-01-01

    The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Ther

  14. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG).

    Groninger, E.; Boer, T. de; Koopmans, P.P.; Uges, D.R.A.; Sluiter, W.J.; Veerman, A.; Kamps, W.; Graaf, S.S.N. de

    2005-01-01

    The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Ther

  15. Leukaemia cluster in the Dueren district

    Whenever a sudden increase in the local leukaemia rate occurs, the underlying causes are frequently searched for in vain. In the absence of scientific research, speculation abounds. How clusters come about is a question difficult to answer, in the marshes of the river Elbe, where an allegedly unreported accident at the Kruemmel Nuclear Power Station was said to have been the cause, as in Sellafield, where a connection was said to exist with BNFL and has meanwhile been disproved, or in the Dueren District, where the geographical distribution of the cases encountered makes the nuclear installations of the Juelich Research Center an unlikely culprit. The reasons for the diseases summarized under the generic term of leukaemia can vary just as much as the symptoms. No valid statistical survey is possible because of the very small number of cases generally encountered. (orig.)

  16. The UK Childhood Cancer Study: Maternal occupational exposures and childhood leukaemia and lymphoma

    Risks of childhood leukaemia and lymphoma were investigated for specific work-related exposures of mothers in the UK Childhood Cancer Study. Interviews with parents of 1881 leukaemia and lymphoma cases (0-14 years) and 3742 controls collected job histories recording exposure to eight specific agents. Exposure was (1) self-reported and (2) reviewed, based mainly on exposure probability and exposure level. Completeness, consistency and sufficiency evaluated data quality. Of all job exposures which were self-reported as exposed, 33% cases and 34% controls remained classified as exposed after review, with the remainder designated as partially exposed or unexposed. No review of underreporting of exposure was made. Data quality was 'good' for 26% of cases and 24% of controls. For self-reported exposure, significant risks of acute lymphoblastic leukaemia (ALL) were observed for solvents and petrol in all time windows. For reviewed exposure, solvents remained significant for ALL during pregnancy and post-natality. Restricting analyses to good-quality information removed all significant results. Refinement of exposure assessment revealed misclassification of self-reported exposures and data quality influenced risk assessment. Maternal exposure to solvents should further be investigated. These findings must invoke caution in the interpretation of risks reliant on self-reported occupational data. (authors)

  17. Residential exposures to pesticides and childhood leukaemia

    Metayer, Catherine; Buffler, Patricia A.

    2008-01-01

    Like many chemicals, carcinogenicity of pesticides is poorly characterised in humans, especially in children, so that the present knowledge about childhood leukaemia risk derives primarily from epidemiological studies. Overall, case–control studies published in the last decade have reported positive associations with home use of insecticides, mostly before the child's birth, while findings for herbicides are mixed. Previous studies relied solely on self-reports, therefore lacking information ...

  18. Residential exposures to pesticides and childhood leukaemia

    Like many chemicals, carcinogenicity of pesticides is poorly characterised in humans, especially in children, so that the present knowledge about childhood leukaemia risk derives primarily from epidemiological studies. Overall, case-control studies published in the last decade have reported positive associations with home use of insecticides, mostly before the child's birth, while findings for herbicides are mixed. Previous studies relied solely on self-reports, therefore lacking information on active ingredients and effects of potential recall bias. Few series to date have examined the influence of children's genetic susceptibility related to transport and metabolism of pesticides. To overcome these limitations, investigators of the Northern California Childhood Leukaemia Study (NCCLS) have undertaken, in collaboration with a multidisciplinary team, a comprehensive assessment of residential pesticide exposure, including: (1) quality control of self-reports; (2) home pesticide inventory and linkage to the Environmental Protection Agency to obtain data on active ingredients; (3) collection and laboratory analyses of ∼600 home dust samples for over 60 pesticides and (4) geographic information studies using California environmental databases to assess exposure to agricultural pesticides. The NCCLS is also conducting large-scale geno-typing to evaluate the role of genes in xenobiotic pathways relevant to the transport and metabolism of pesticides. A better quantification of children's exposures to pesticides at home is critical to the evaluation of childhood leukaemia risk, especially for future gene-environment interaction studies. (authors)

  19. Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression

    Wiebe Thomas

    2008-08-01

    Full Text Available Abstract Background Childhood pre-B acute lymphoblastic leukemia (ALL is a bone marrow (BM derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB. Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. Results Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. Conclusion The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.

  20. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

    Niedobitek Gerald

    2010-03-01

    Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

  1. Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens.

    Ingram, L; Mott, M G; Mann, J R; Raafat, F; Darbyshire, P J; Morris Jones, P. H.

    1987-01-01

    Eight children treated between 1977 and 1983 with the UK Children's Cancer Study Group's non-Hodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma. These eight children were included among 261 children studied in...

  2. Tacrolimus and Mycophenolate Mofetil With or Without Sirolimus in Preventing Acute Graft-Versus-Host Disease in Patients Who Are Undergoing Donor Stem Cell Transplant for Hematologic Cancer

    2015-10-14

    Myelodysplastic/Myeloproliferative Neoplasm, Unclassifiable; Previously Treated Myelodysplastic Syndrome; Refractory Chronic Lymphocytic Leukemia; Refractory Plasma Cell Myeloma; Waldenstrom Macroglobulinemia; Accelerated Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Adult Acute Lymphoblastic Leukemia in Remission; Adult Acute Myeloid Leukemia in Remission; Adult Acute Myeloid Leukemia With t(9;11)(p22;q23); MLLT3-; Adult Acute Myeloid Leukemia With Inv(16)(p13.1q22); CBFB-MYH11; Adult Acute Promyelocytic Leukemia With t(15;17)(q22;q12); PML-RARA; Adult Acute Myeloid Leukemia With t(8;21)(q22;q22); RUNX1-RUNX1T1; Atypical Chronic Myeloid Leukemia, BCR-ABL1 Negative; Blast Phase Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Acute Lymphoblastic Leukemia in Remission; Childhood Acute Myeloid Leukemia in Remission; Childhood Burkitt Lymphoma; Childhood Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Childhood Diffuse Large Cell Lymphoma; Childhood Immunoblastic Lymphoma; Childhood Myelodysplastic Syndrome; Stage II Contiguous Adult Burkitt Lymphoma; Stage II Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Contiguous Immunoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Contiguous Follicular Lymphoma; Stage II Grade 2 Contiguous Follicular Lymphoma; Stage II Grade 3 Contiguous Follicular Lymphoma; Stage II Contiguous Mantle Cell Lymphoma; Stage II Non-Contiguous Adult Burkitt Lymphoma; Stage II Non-Contiguous Adult Diffuse Large Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Mixed Cell Lymphoma; Stage II Non-Contiguous Adult Diffuse Small Cleaved Cell Lymphoma; Stage II Adult Non-Contiguous Immunoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage II Grade 1 Non-Contiguous Follicular Lymphoma; Stage II Grade 2 Non-Contiguous Follicular Lymphoma; Stage

  3. Exposure to infections through day-care attendance and risk of childhood leukaemia

    There is growing evidence supporting a role for infections in the aetiology of childhood leukaemia. Hypotheses proposed by both Greaves and Kinlen describe childhood leukaemia to be a rare response to one or more common infections acquired through personal contacts. Previous epidemiological studies have used day-care attendance as an indicator of the increased likelihood of early and frequent exposure to infections. It is well-documented that in developed countries, exposures to common infections occur more frequently in this type of setting. Within the Northern California Childhood Leukaemia Study, the role of social contact has been assessed and a unique 'child-hours' summary measure incorporating information on the number of months attending a day-care, mean hours per week at this day-care and the number of children in the day-care setting was constructed. In this review, the previously reported day-care results have been described, showing that in non-Hispanic White children, children in the highest category of total child-hours of exposure had a reduced risk of acute lymphoblastic leukaemia (ALL), particularly common B-cell precursor ALL (c-ALL), compared with children without such exposures, with evidence of a dose-response effect. In addition, a literature review of relevant studies has been conducted, examining the relationship between day-care attendance and risk of childhood ALL. Overall, the 14 studies identified provided consistent support for this hypothesis, with the majority of studies reporting some evidence of a reduced risk. A meta-analysis is currently underway, which will provide a quantitative evaluation of the overall consistency and strength of the association between day-care attendance or social contact and risk of childhood ALL. (authors)

  4. Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study

    Chandra Sarmila

    2008-02-01

    Full Text Available Abstract Background Over expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs, abbreviated as OAcSGP has been demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL. Achatinin-H, a lectin, has selective affinity towards terminal 9-O-acetylated sialic acids-α2-6-Nacetylated galactosamine. Exploring this affinity, enhanced expression of OAcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD responsible for relapse. Our aim was to select a suitable template by using the differential expression of OAcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB and bone marrow (BM of Indian patients with B- or T-ALL during treatment and correlate it with the disease status. Methods A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667 and BM (n = 999 were monitored by flow cytometry. Three templates selected for this investigation were OAcSGP+CD10+CD19+ or OAcSGP+CD34+CD19+ for B-ALL and OAcSGP+CD7+CD3+ for T-ALL. Results Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR. 81.65% of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well. Conclusion A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 ± 0.01% (PB and 0.05 ± 0.015% (BM. These

  5. Risk Behavior and Sexually Transmitted Infections Among Transgender Women and Men Undergoing Community-Based Screening for Acute and Early HIV Infection in San Diego

    Green, Nella; Hoenigl, Martin; Morris, Sheldon; Little, Susan J.

    2015-01-01

    Abstract The transgender community represents an understudied population in the literature. The objective of this study was to compare risk behavior, and HIV and sexually transmitted infection (STI) rates between transgender women and transgender men undergoing community-based HIV testing. With this retrospective analysis of a cohort study, we characterize HIV infection rates as well as reported risk behaviors and reported STI in 151 individual transgender women and 30 individual transgender ...

  6. Site- and allele-specific polycomb dysregulation in T-cell leukaemia

    Navarro, Jean-Marc; Touzart, Aurore; Pradel, Lydie C.; Loosveld, Marie; Koubi, Myriam; Fenouil, Romain; Le Noir, Sandrine; Maqbool, Muhammad Ahmad; Morgado, Ester; Gregoire, Claude; Jaeger, Sebastien; Mamessier, Emilie; Pignon, Charles; Hacein-Bey-Abina, Salima; Malissen, Bernard

    2015-01-01

    T-cell acute lymphoblastic leukaemias (T-ALL) are aggressive malignant proliferations characterized by high relapse rates and great genetic heterogeneity. TAL1 is amongst the most frequently deregulated oncogenes. Yet, over half of the TAL1+ cases lack TAL1 lesions, suggesting unrecognized (epi)genetic deregulation mechanisms. Here we show that TAL1 is normally silenced in the T-cell lineage, and that the polycomb H3K27me3-repressive mark is focally diminished in TAL1+ T-ALLs. Sequencing reve...

  7. Infant leukaemia after in utero exposure to radiation from Chernobyl

    There has been no documented increase in childhood leukaemia following the Chernobyl accident. However, different forms of childhood leukaemia may not be equally susceptible to radiation carcinogenesis. Infant leukaemia is a distinct form associated with a specific genetic abnormality. Outside the former Soviet Union, contamination resulting from the Chernobyl accident has been highest in Greece and Austria and high also in the Scandinavian countries. All childhood leukaemia cases diagnosed throughout Greece since 1 January 1980 have been recorded. Here we report that infants exposed in utero to ionizing radiation from the Chernobyl accident had 2.6 times the incidence of leukaemia compared to unexposed children (95% confidence interval, 1.4 to 5.1; P ∼ 0.003), and those born to mothers residing in regions with high radioactive fallout were at higher risk of developing infant leukaemia. No significant difference in leukaemia incidence was found among children aged 12 to 47 months. Preconceptional irradiation had no demonstrable effect on leukaemia risk at any of the studied age groups. (author)

  8. Defective monocyte function in Legionnaires' disease complicating hairy cell leukaemia

    Nielsen, H; Bangsborg, Jette Marie; Rechnitzer, C;

    1986-01-01

    We describe a case of Legionnaires' disease in a 64-year-old man, in which hairy cell leukaemia was diagnosed after the onset of the infection. Immunological studies revealed a complete suppression of blood monocyte chemotactic and oxidative burst activities. We suggest that in hairy cell leukaemia...

  9. Co-infusion of ex vivo-expanded, parental MSCs prevents life-threatening acute GVHD, but does not reduce the risk of graft failure in pediatric patients undergoing allogeneic umbilical cord blood transplantation.

    Bernardo, M E; Ball, L M; Cometa, A M; Roelofs, H; Zecca, M; Avanzini, M A; Bertaina, A; Vinti, L; Lankester, A; Maccario, R; Ringden, O; Le Blanc, K; Egeler, R M; Fibbe, W E; Locatelli, F

    2011-02-01

    When compared with BMT, umbilical cord blood transplantation (UCBT) is associated with a lower rate of engraftment and delayed hematological/immunological recovery. This leads to increased risk of TRM in the early post transplantation period due to infection. Acute GVHD, although occurring less frequently in UCBT compared with BMT, is also significantly associated with increased rate of early TRM. BM MSCs are known to support normal in vivo hematopoiesis, and co-transplantation of MSCs has been shown to enhance engraftment of human cord blood hematopoietic cells in nonobese diabetic/SCID mice. In 13 children with hematological disorders (median age 2 years) undergoing UCBT, we co-transplanted paternal, HLA-disparate MSCs with the aim of improving hematological recovery and reducing rejection. We observed no differences in hematological recovery or rejection rates compared with 39 matched historical controls, most of whom received G-CSF after UCBT. However, the rate of grade III and IV acute GVHD was significantly decreased in the study cohort when compared with controls (P=0.05), thus resulting in reduced early TRM. Although these data do not support the use of MSCs in UCBT to support hematopoietic engraftment, they suggest that MSCs, possibly because of their immunosuppressive effect, may abrogate life-threatening acute GVHD and reduce early TRM. PMID:20400983

  10. Efficacy of short-term cordyceps sinensis for prevention of contrast-induced nephropathy in patients with acute coronary syndrome undergoing elective percutaneous coronary intervention

    Zhao, Kai; Lin, Yu; Li, Yong-Jian; Gao, Sheng

    2014-01-01

    Contrast-induced nephropathy (CIN) is one of the major causes of hospital-acquired acute renal failure. The pathophysiological mechanism of CIN remains unknown. There has been little evidence regarding the effects of Traditional Chinese Medicine (TCM) on CIN. Cordyceps sinensis (CS), a traditional Chinese herb, has been widely used clinically for the prevention of the progression of renal failure. We performed a prospective, randomized controlled trial to investigate the role of CS in the pre...

  11. Beclomethasone Dipropionate in Preventing Acute Graft-Versus-Host Disease in Patients Undergoing a Donor Stem Cell Transplant for Hematologic Cancer

    2015-03-05

    Hematopoietic/Lymphoid Cancer; 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 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); Atypical Chronic Myeloid Leukemia; 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 Eosinophilic Leukemia; Chronic Myelomonocytic Leukemia; Chronic Neutrophilic Leukemia; Chronic Phase Chronic Myelogenous Leukemia; Contiguous Stage II Adult Burkitt Lymphoma; Contiguous Stage II Adult Diffuse Large Cell Lymphoma; Contiguous Stage II Adult Diffuse Mixed Cell Lymphoma; Contiguous Stage II Adult Diffuse Small Cleaved Cell Lymphoma; Contiguous Stage II Adult Immunoblastic Large Cell Lymphoma; Contiguous Stage II Adult Lymphoblastic Lymphoma; Contiguous Stage II Grade 1 Follicular Lymphoma; Contiguous Stage II Grade 2 Follicular Lymphoma; Contiguous Stage II Grade 3 Follicular Lymphoma; Contiguous Stage II Mantle Cell Lymphoma; Contiguous Stage II Marginal Zone Lymphoma; Contiguous Stage II Small Lymphocytic Lymphoma; de Novo Myelodysplastic Syndromes; Essential Thrombocythemia; Extramedullary Plasmacytoma; Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Graft Versus Host Disease; Isolated Plasmacytoma of Bone; Juvenile Myelomonocytic Leukemia; Meningeal Chronic Myelogenous Leukemia; Myelodysplastic/Myeloproliferative Disease, Unclassifiable; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Adult Burkitt Lymphoma; Noncontiguous Stage II Adult Diffuse Large Cell Lymphoma; Noncontiguous Stage II Adult Diffuse Small

  12. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy

    Trněný Marek

    2011-10-01

    Full Text Available Abstract Background The current situation in the treatment of chronic myeloid leukaemia (CML presents a new challenge for attempts to measure the therapeutic results, as the CML patients can experience multiple leukaemia-free periods during the course of their treatment. Traditional measures of treatment efficacy such as leukaemia-free survival and cumulative incidence are unable to cope with multiple events in time, e.g. disease remissions or progressions, and as such are inappropriate for the efficacy assessment of the recent CML treatment. Methods Standard nonparametric statistical methods are used for estimating two principal characteristics of the current CML treatment: the probability of being alive and leukaemia-free in time after CML therapy initiation, denoted as the current cumulative incidence of leukaemia-free patients; and the probability that a patient is alive and in any leukaemia-free period in time after achieving the first leukaemia-free period on the CML treatment, denoted as the current leukaemia-free survival. The validity of the proposed methods is further documented in the data of the Czech CML patients consecutively recorded between July 2003 and July 2009 as well as in simulated data. Results The results have shown a difference between the estimates of the current cumulative incidence function and the common cumulative incidence of leukaemia-free patients, as well as between the estimates of the current leukaemia-free survival and the common leukaemia-free survival. Regarding the currently available follow-up period, both differences have reached the maximum (12.8% and 20.8%, respectively at 3 years after the start of follow-up, i.e. after the CML therapy initiation in the former case and after the first achievement of the disease remission in the latter. Conclusions Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in

  13. Differentiating intraparenchymal hemorrhage from contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients undergoing endovascular treatment

    Payabvash, Seyedmehdi [Zeenat Qureshi Stroke Institute, Minneapolis, MN (United States); University of Minnesota, Department of Radiology, Minneapolis, MN (United States); Qureshi, Mushtaq H.; Khan, Shayaan M.; Khan, Mahnoor; Majidi, Shahram; Pawar, Swaroop; Qureshi, Adnan I. [Zeenat Qureshi Stroke Institute, Minneapolis, MN (United States)

    2014-09-15

    This study aimed to identify the imaging characteristics that can help differentiate intraparenchymal hemorrhage from benign contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients after endovascular treatment. We reviewed the clinical and imaging records of all acute ischemic stroke patients who underwent endovascular treatment in two hospitals over a 3.5-year period. The immediate post-procedural CT scan was evaluated for the presence of hyperdense lesion(s). The average attenuation of the lesion(s) was measured. Intraparenchymal hemorrhage was defined as a persistent hyperdensity visualized on follow-up CT scan, 24 h or greater after the procedure. Of the 135 patients studied, 74 (55 %) patients had hyperdense lesion(s) on immediate post-procedural CT scan. Follow-up scans confirmed the diagnosis of intraparenchymal hemorrhage in 20 of these 74 patients. A receiver operating characteristic analysis showed that the average attenuation of the most hyperdense lesion can differentiate intraparenchymal hemorrhage from contrast extravasation with an area under the curve of 0.78 (p = 0.001). An average attenuation of <50 Hounsfield units (HU) in the most visually hyperattenuating hyperdense lesion had 100 % specificity and 56 % sensitivity for identification of contrast extravasations. Petechial hyperdensity was seen in 46/54 (85 %) patients with contrast extravasation versus 9/20 (45 %) patients with intraparenchymal hemorrhage on the immediate post-procedural CT scan (p < 0.001). An average attenuation <50 HU of the most hyperattenuating hyperdense parenchymal lesion on immediate post-procedural CT scan was very specific for differentiating contrast extravasation from intraparenchymal hemorrhage in acute ischemic stroke patients after endovascular treatment. (orig.)

  14. Differentiating intraparenchymal hemorrhage from contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients undergoing endovascular treatment

    This study aimed to identify the imaging characteristics that can help differentiate intraparenchymal hemorrhage from benign contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients after endovascular treatment. We reviewed the clinical and imaging records of all acute ischemic stroke patients who underwent endovascular treatment in two hospitals over a 3.5-year period. The immediate post-procedural CT scan was evaluated for the presence of hyperdense lesion(s). The average attenuation of the lesion(s) was measured. Intraparenchymal hemorrhage was defined as a persistent hyperdensity visualized on follow-up CT scan, 24 h or greater after the procedure. Of the 135 patients studied, 74 (55 %) patients had hyperdense lesion(s) on immediate post-procedural CT scan. Follow-up scans confirmed the diagnosis of intraparenchymal hemorrhage in 20 of these 74 patients. A receiver operating characteristic analysis showed that the average attenuation of the most hyperdense lesion can differentiate intraparenchymal hemorrhage from contrast extravasation with an area under the curve of 0.78 (p = 0.001). An average attenuation of <50 Hounsfield units (HU) in the most visually hyperattenuating hyperdense lesion had 100 % specificity and 56 % sensitivity for identification of contrast extravasations. Petechial hyperdensity was seen in 46/54 (85 %) patients with contrast extravasation versus 9/20 (45 %) patients with intraparenchymal hemorrhage on the immediate post-procedural CT scan (p < 0.001). An average attenuation <50 HU of the most hyperattenuating hyperdense parenchymal lesion on immediate post-procedural CT scan was very specific for differentiating contrast extravasation from intraparenchymal hemorrhage in acute ischemic stroke patients after endovascular treatment. (orig.)

  15. Validated Contemporary Risk Model of Acute Kidney Injury in Patients Undergoing Percutaneous Coronary Interventions: Insights From the National Cardiovascular Data Registry Cath‐PCI Registry

    Tsai, Thomas T.; Uptal D Patel; Chang, Tara I.; Kennedy, Kevin F.; Masoudi, Frederick A; Michael E Matheny; Kosiborod, Mikhail; Amin, Amit P.; Weintraub, William S.; Curtis, Jeptha P.; Messenger, John C.; Rumsfeld, John S; Spertus, John A.

    2014-01-01

    Background We developed risk models for predicting acute kidney injury (AKI) and AKI requiring dialysis (AKI‐D) after percutaneous coronary intervention (PCI) to support quality assessment and the use of preventative strategies. Methods and Results AKI was defined as an absolute increase of ≥0.3 mg/dL or a relative increase of 50% in serum creatinine (AKIN Stage 1 or greater) and AKI‐D was a new requirement for dialysis following PCI. Data from 947 012 consecutive PCI patients and 1253 sites ...

  16. Impact of abciximab in elderly patients with high-risk acute coronary syndrome undergoing percutaneous coronary intervention: an observational registry study

    Iversen, Allan Z; Galatius, Soeren; Haahr-Pedersen, Sune Ammentorp; Madsen, Jan K; Jensen, Jan S

    2011-01-01

    higher all-cause mortality than younger patients. The age/abciximab stratified analysis revealed no effect of abciximab on any of the endpoints in elderly patients (combined endpoint: no abciximab 22.6% vs abciximab 23.4%, p=0.85; all-cause mortality: no abciximab 15.4% vs abciximab 15.9%, p=0.91; TVR......: no abciximab 3.4% vs abciximab 5.5%, p=0.21; MI: no abciximab 7.0% vs abciximab 8.5%, p=0.54), whereas all-cause mortality and the risk of reaching the combined endpoint were significantly reduced in younger patients (combined endpoint: no abciximab 14.0% vs abciximab 9.4%, p=0.03; all...... elderly high-risk ACS patients who underwent PCI. These findings should be taken into consideration when deciding on the treatment strategy for elderly ACS patients undergoing PCI....

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

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

    2016-07-01

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

  18. Leukaemia and lymphoma near the Sellafield reprocessing plant

    Studies have shown an excess of childhood leukaemia near nuclear establishments but have been unable to establish whether known causes or factors associated with the nuclear plants themselves are responsible for the observed excess. Such an association has, however, been discovered in a study where the recorded external dose of whole-body ionizing radiation to fathers working at Sellafield is associated with the development of leukaemia among their children. A circle, centered on the Sellafield nuclear plant, of radius 5 kilometers contained a cluster of 5 cases of leukaemia and 3 cases of non-Hodgkin's lymphoma in children. All the leukaemias and 2 of the 3 lymphomas occurred in children born to parents living in Seascale, a village some 3 kilometers from the nuclear plant. Taking the national incidence of childhood leukaemia, less than one case of leukaemia would be expected in Seascale. The finding that 'exposure of fathers to ionising radiation before conception is related to the development of leukaemia in their offspring' is the first such finding with human data

  19. Safety, Pharmacokinetics, and Efficacy of Palifermin in Children and Adolescents with Acute Leukemias Undergoing Myeloablative Therapy and Allogeneic Hematopoietic Stem Cell Transplantation: A Pediatric Blood and Marrow Transplant Consortium Trial.

    Morris, Joan; Rudebeck, Mattias; Neudorf, Steven; Moore, Theodore; Duerst, Reggie; Shah, Ami J; Graham, Michael; Aquino, Victor; Morris, Christopher; Olsson, Birgitta

    2016-07-01

    Currently, effective pharmacologic treatment to reduce severe oral mucositis (OM) resulting from high-dose myeloablative cytotoxic therapy in the pediatric population is not available. Palifermin has been proven to decrease the incidence and duration of severe OM in adults with hematologic malignancies undergoing hematopoietic stem cell transplantation (HSCT). In the pediatric population, however, data on palifermin treatment are limited. A phase I dose-escalation study of palifermin in pediatric patients with acute leukemias undergoing myeloablative HSCT with total body irradiation, etoposide, and cyclophosphamide was performed to determine a safe and tolerable dose and to characterize the pharmacokinetic (PK) profile and efficacy of palifermin. Twenty-seven patients in 3 age groups (1 to 2, 3 to 11, and 12 to 16 years) and 3 dose levels (40, 60, and 80 μg/kg/day) were studied. There were no deaths, dose-limiting toxicities, or treatment-related serious adverse events. Long-term safety outcomes did not differ from what would be expected in this population. PK data showed no differences between the 3 age groups. Exposure did not increase with increase in dose. The maximum severity of OM (WHO grade 4) occurred in 6 patients (22%), none of whom was in the 80-μg/kg/day dosing group. This study showed that all doses were well tolerated and a good safety profile in all 3 pediatric age groups was seen. PMID:26968792

  20. Trace elements in scalp hair of leukaemia patients

    Khuder Ali; Bakir Mohammad Adel; Hasan Reem; Mohammad Ali; Habil Khozama

    2014-01-01

    The aim of this study was to determine the concentration of Fe, Ni, Cu, Zn and Pb in scalp hair of leukaemia patients and healthy volunteers, using the optimised XRF method. Leukaemia hair samples were classifi ed corresponding to type, growth and age of the participants. The results showed that the studied trace elements (TEs) in both of leukaemia and control groups were positively skewed. In comparison with the control group, lower Fe, Cu, Zn and Pb and higher of Ni medians were found in al...

  1. Leukaemia [near Dounreay and COMARE statement of advice

    The report of the case study of leukaemia in the Dounreay area of Scotland, near to the Dounreay reactor site is discussed. The report concludes that the observed excess incidence of childhood leukaemia and non-Hodgkin's lymphoma in the area within 25 km of Dounreay cannot be explained by paternal exposure to ionising radiations prior to conception. The study has been referred to the Committee on Medical Aspects of Radiation in the Environment (COMARE) which concluded that the study does not identify an explanation for the excess childhood leukaemia around Dounreay. However it is considered that there is enough evidence to recommend an intensified programme of investigation. (UK)

  2. Risk assessment of relapse by lineage-specific monitoring of chimerism in children undergoing allogeneic stem cell transplantation for acute lymphoblastic leukemia

    Preuner, Sandra; Peters, Christina; Pötschger, Ulrike; Daxberger, Helga; Fritsch, Gerhard; Geyeregger, Rene; Schrauder, André; von Stackelberg, Arend; Schrappe, Martin; Bader, Peter; Ebell, Wolfram; Eckert, Cornelia; Lang, Peter; Sykora, Karl-Walter; Schrum, Johanna; Kremens, Bernhard; Ehlert, Karoline; Albert, Michael H.; Meisel, Roland; Lawitschka, Anita; Mann, Georg; Panzer-Grümayer, Renate; Güngör, Tayfun; Holter, Wolfgang; Strahm, Brigitte; Gruhn, Bernd; Schulz, Ansgar; Woessmann, Wilhelm; Lion, Thomas

    2016-01-01

    Allogeneic hematopoietic stem cell transplantation is required as rescue therapy in about 20% of pediatric patients with acute lymphoblastic leukemia. However, the relapse rates are considerable, and relapse confers a poor outcome. Early assessment of the risk of relapse is therefore of paramount importance for the development of appropriate measures. We used the EuroChimerism approach to investigate the potential impact of lineage-specific chimerism testing for relapse-risk analysis in 162 pediatric patients with acute lymphoblastic leukemia after allogeneic stem cell transplantation in a multicenter study based on standardized transplantation protocols. Within a median observation time of 4.5 years, relapses have occurred in 41/162 patients at a median of 0.6 years after transplantation (range, 0.13–5.7 years). Prospective screening at defined consecutive time points revealed that reappearance of recipient-derived cells within the CD34+ and CD8+ cell subsets display the most significant association with the occurrence of relapses with hazard ratios of 5.2 (P=0.003) and 2.8 (P=0.008), respectively. The appearance of recipient cells after a period of pure donor chimerism in the CD34+ and CD8+ leukocyte subsets revealed dynamics indicative of a significantly elevated risk of relapse or imminent disease recurrence. Assessment of chimerism within these lineages can therefore provide complementary information for further diagnostic and, potentially, therapeutic purposes aiming at the prevention of overt relapse. This study was registered at clinical.trials.gov with the number NC01423747. PMID:26869631

  3. Acute renal toxicity of 2 conditioning regimens in patients undergoing autologous peripheral blood stem-cell transplantation. Total body irradiation-cyclophosphamide versus ifosfamide, carboplatin, etoposide

    Objective was to compare renal toxicity of 2 conditioning regimens of total body irradiation/cyclophosphamide TBI-Cy and Ifosfamide, Carboplatin, Etoposide ICE. Between August 1996 and February 2004, patients treated with autologous peripheral stem cell transplantation in the Department of Medical and radiation Oncology, Gulhane Military Medical School, Ankara, Turkey with 2 different conditioning regimens was comparatively analyzed for acute renal toxicity in the early post-transplant period. Forty-even patients received ICE regimen with 12 g/m2; 1.2 g/m2 and 1.2 g/m2 divided to 6 consecutive days, whereas 21 patients received 12 Gy TBI 6 fractions twice daily in 3 consecutive days and 60 mg/m2/day cyclophosphamide for 2 days. Sixty-eight patients were evaluated in this study. There was no significant difference in baseline renal function between patients in the ICE and TBI-Cy groups. Eleven patients developed nephrotoxicity 23.4% in the ICE group while one patient 4.8% in the TBI-Cy group developed nephrotoxicity in ICEgroup required hemodialysis and subsequently 48.5% of them died. In contrast, one patient 4.8% died due to nephrotoxicity despite hemodialysis in the TBI-Cy arm. This study reveals that the TBI-Cy conditioning regimen seems no more nephrotoxic than an ICE regimen particularly in patients who had used cisplatin prior to transplantation. (author)

  4. An analysis of childhood leukaemia and natural radiation in Britain

    Following claims that indoor radon may be responsible for a significant proportion of leukaemia cases, a correlation study has been performed of childhood leukaemia and levels of natural radiation in small areas throughout Britain. Analysis at the district level showed no statistically significant results. Based on larger geographical areas (counties) there were indications of a statistically significant positive trend in the leukaemia risk with indoor radon level and of a significant negative trend with indoor gamma level, under an analysis that included radon and gamma terms simultaneously. However, these trends were reversed (but were not significant) for an analysis at the district level adjusted for county. This discrepancy could not be explained by random errors in the measurement of natural radiation levels, and seems likely to have been caused by confounding factors affecting the analysis based on larger areas (counties). Consequently this study does not support the claims of a measurable link between radon exposure and leukaemia. (author)

  5. Childhood leukaemia, fallout and radiation doses near Dounreay

    The possible explanations of the recently reported increase in the incidence of childhood leukaemia around Dounreay are examined in the light of the changes in national leukaemia incidence that occurred during the period of exposure to fallout from international atmospheric testing of nuclear weapons. It is concluded that the increase cannot be due to underestimation of the risk of leukaemia per unit dose of radiation, nor to an underestimate of the relative biological efficiency of high as compared with low LET radiation. Possible explanations of the increase include an underestimate of the red bone marrow doses due to the Dounreay discharges relative to those from fallout, a misconception of the site of origin of childhood leukaemia, epidemics of infectious disease and exposure to some other unidentified environmental agent. (author)

  6. Childhood leukaemia around Canadian nuclear facilities. Phase 1

    A ninefold excess risk of leukaemia, as observed in vicinity of the Sellafield facility, was not observed amongst children born to mothers residing in the areas around nuclear research facilities and uranium mining, milling and refining facilities in Ontario. In the vicinity of nuclear research facilities, the rate of leukaemia was, in fact, less than expected. In the areas around the uranium mining, milling and refining facilities; leukaemia occurred slightly more frequently than expected; however, due to small frequencies these results may have risen by chance. A slightly greater than expected occurrence of leukaemia was also detected, which may well have been due to chance, in an exploratory study of the areas around nuclear power generating stations in Ontario

  7. Trace elements in scalp hair of leukaemia patients

    Khuder Ali

    2014-08-01

    Full Text Available The aim of this study was to determine the concentration of Fe, Ni, Cu, Zn and Pb in scalp hair of leukaemia patients and healthy volunteers, using the optimised XRF method. Leukaemia hair samples were classifi ed corresponding to type, growth and age of the participants. The results showed that the studied trace elements (TEs in both of leukaemia and control groups were positively skewed. In comparison with the control group, lower Fe, Cu, Zn and Pb and higher of Ni medians were found in all studied leukaemia patients. The median rank obtained by Mann-Whitney U-test revealed insignifi cant differences between the leukaemia patients subgroups and the controls. An exact probability (α 0.70 in the scalp hair of control group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn, Pb/Fe-Pb, Cu/Ni-Zn/Ni, Cu/Ni-Pb/Ni, Zn/Ni-Pb/Ni, Zn/Fe-Zn/Cu, Pb/Ni-Ni and Ni/Fe-Pb/Ni, whereas only very strong positive ratios in the scalp hair of leukaemia patients group were observed between Ni/Fe-Ni, Cu/Fe-Cu, Zn/Fe-Zn and Pb/Fe-Pb, all correlations were signifi cant at p < 0.05. Other strong and signifi cant correlations were also observed in scalp hair of both groups. Signifi cant differences between grouping of studied TEs in all classifi ed leukaemia groups and controls were found using principal component analysis (PCA. The results of PCA confi rmed that the type and the growth of leukaemia factors were more important in element loading than the age factor.

  8. Oxidative Stress Responses and NRF2 in Human Leukaemia

    Amina Abdul-Aziz; MacEwan, David J; Bowles, Kristian M.; Rushworth, Stuart A

    2015-01-01

    Oxidative stress as a result of elevated levels of reactive oxygen species (ROS) has been observed in almost all cancers, including leukaemia, where they contribute to disease development and progression. However, cancer cells also express increased levels of antioxidant proteins which detoxify ROS. This includes glutathione, the major antioxidant in human cells, which has recently been identified to have dysregulated metabolism in human leukaemia. This suggests that critical balance of intra...

  9. Adult T-cell leukaemia lymphoma in an aborigine.

    Kirkland, M A; Frasca, J; Bastian, I

    1991-10-01

    A 44-year-old Aborigine with Adult T-cell Leukaemia/Lymphoma (ATLL) due to HTLV-I is reported. He presented with transverse myelitis of subacute onset, and subsequently developed frank T-cell leukaemia complicated by splenomegaly and hypercalcaemia. Cell surface marker studies showed a phenotype of CD3+ CD4+ CD8- CD25+, and serological and molecular studies confirmed HTLV-I infection. This is the first report of ATLL in an Australian Aborigine. PMID:1759923

  10. Clinicopathological features of transient myeloproliferative syndrome and congenital leukaemia

    The objectives of the study were to determine the spectrum of the clinical and pathological findings, the management and prognosis of patients of transient myeloproliferative syndrome (TMS) and congenital leukaemia. Study Design: Case series. Place and Duration of Study: The study was conducted over a period of 8 years, from January 2000 to December 2007, at the Children's Hospital and the Institute of Child Health, Lahore. Methodology: Suspected patients presenting with fever, pallor, bruises and hepatosplenomegaly and diagnosed as either transient myeloproliferative disorder or congenital leukaemia were studied. The complete blood count, reticulocyte count, leukocyte alkaline phosphatase score, liver function tests, karyotyping studies and bone marrow aspiration biopsy were performed in all of those patients. Management and out come was noted. Results were described as frequency percentages. Results: Out of 10,000 patients presenting during this period, 24 patients were diagnosed as either of transient myeloproliferative syndrome or congenital leukaemia. Fifteen of these were diagnosed as patients of TMS and 9 as patients of congenital leukaemia. Down syndrome (DS) was diagnosed in 75% of these patients. TMS patients were put on supportive treatment and recovered spontaneously. One DS patient with congenital leukaemia went into spontaneous remission and 2 of DS patients with congenital leukaemia responded to chemotherapy while rest of them either died or lost to follow-up. Conclusion: TMS and congenital leukaemia were not very uncommon in the studied population. Majority had Down syndrome. It is important to differentiate their clinical and pathological presentations for proper management. TMS may resolve with supportive treatment while congenital leukaemia is a fatal condition requiring chemotherapy. (author)

  11. Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

    Glabglay Prapakorn

    2010-10-01

    Etoricoxib is more effective than celecoxib and placebo for using as preemptive analgesia for acute postoperative pain control in patients underwent arthroscopic anterior cruciate ligament reconstruction. Trial registration number NCT01017380

  12. Effect of Catechol-O-methyltransferase-gene (COMT) Variants on Experimental and Acute Postoperative Pain in 1,000 Women undergoing Surgery for Breast Cancer

    Kambur, Oleg; Kaunisto, Mari A.; Tikkanen, Emmi; Leal, Suzanne M.; Ripatti, Samuli; Kalso, Eija A.

    2016-01-01

    Background Catechol-O-methyltransferase (COMT) metabolizes catecholamines in different tissues. Polymorphisms in COMT gene can attenuate COMT activity and increase sensitivity to pain. Human studies exploring the effect of COMT polymorphisms on pain sensitivity have mostly included small, heterogeneous samples and have ignored several important single nucleotide polymorphisms (SNPs). This study examines the effect of COMT polymorphisms on experimental and postoperative pain phenotypes in a large ethnically homogeneous female patient cohort. Methods Intensity of cold (+2–4°C) and heat (+48°C) pain and tolerance to cold pain were assessed in 1,000 patients scheduled for breast cancer surgery. Acute postoperative pain and oxycodone requirements were recorded. Twenty-two COMT SNPs were genotyped and their association with six pain phenotypes analyzed with linear regression. Results There was no association between any of the tested pain phenotypes and SNP rs4680. The strongest association signals were seen between rs165774 and heat pain intensity as well as rs887200 and cold pain intensity. In both cases, minor allele carriers reported less pain. Neither of these results remained significant after strict multiple testing corrections. When analyzed further, the effect of rs887200 was, however, shown to be significant and consistent throughout the cold pressure test. No evidence of association between the SNPs and postoperative oxycodone consumption was found. Conclusions SNPs rs887200 and rs165774 located in the untranslated regions of the gene had the strongest effects on pain sensitivity. Their effect on pain is described here for the first time. These results should be confirmed in further studies and the potential functional mechanisms of the variants studied. PMID:24343288

  13. Leukaemia clusters around Sellafield and Dounreay. Dosimetry and epidemiology

    In 1983, a television programme identified a striking cluster of childhood leukaemia in the coastal village of Seascale, adjacent to the Sellafield nuclear complex in England. Excesses of childhood leukaemia near certain other nuclear installation in Britain were later reported during the 1980s. Detailed radiological investigations demonstrated that radiation exposures from discharged radioactive material were most unlikely to be the cause of these excesses and no serious deficiencies in these assessments have been discovered despite exhaustive searches. In 1990, a report was published suggesting that occupational radiation exposure of men before the conception of their children could be responsible for the Seascale cluster. Extensive research has not supported a causal link between paternal preconceptional radiation dose and childhood leukaemia, and the idea that radiation exposure of fathers materially increases the risk of leukaemia in offspring and could account for the clusters has now effectively been abandoned. In contrast, evidence has mounted that childhood leukaemia has an infectious basis and that unusual population mixing increases the risk of the disease. It now seems that population mixing is the explanation for the excesses of childhood leukaemia near nuclear sites and at other locations with no enhanced exposure to radiation. (orig.)

  14. Childhood leukaemia and socioeconomic status: What is the evidence?

    The objectives of this systematic review are to summarise the current literature on socioeconomic status (SES) and the risk of childhood leukaemia, to highlight methodological problems and formulate recommendations for future research. Starting from the systematic review of Poole et al. (Socioeconomic status and childhood leukaemia: a review. Int. J. Epidemiol. 2006;35(2):370-384.), an electronic literature search was performed covering August 2002-April 2008. It showed that (1) the results are heterogeneous, with no clear evidence to support a relation between SES and childhood leukaemia; (2) a number of factors, most importantly selection bias, might explain inconsistencies between studies; (3) there is some support for an association between SES at birth (rather than later in childhood) and childhood leukaemia and (4) if there are any associations, these are weak, limited to the most extreme SES groups (the 10-20% most or least deprived). This makes it unlikely that they would act as strong confounders in research addressing associations between other exposures and childhood leukaemia. Future research should minimise case and control selection bias, distinguish between different SES measures and leukaemia subtypes and consider timing of exposures and cancer outcomes. (authors)

  15. Fallout, radiation doses near Dounreay, and childhood leukaemia

    Possible explanations for the recently reported increased incidence of childhood leukaemia around Dounreay were examined in the light of changes in the national incidence of leukaemia that occurred during the period of exposure to fallout from international testing of nuclear weapons in the atmosphere. It was concluded that the increase could not be accounted for by underestimate of the risk of leukaemia per unit dose of radiation at low doses and low dose rates, nor by underestimate of the relative biological efficiency of high compared with low linear energy transfer radiation. One possible explanation was underestimation of doses to the red bone marrow due to the discharges at Dounreay relative to dose from fallout, though investigation of ways in which this might have occurred did not suggest anything definite. Other explanations included a misconception of the site of origin of childhood leukaemia, outbreaks of an infectious disease and exposure to other, unidentified environmental agents. These findings weigh against the hypothesis that the recent increase in childhood leukaemia near Dounreay might be accounted for by radioactive discharges from nuclear plants, unless the doses to the stem cells from which childhood leukaemia originates have been grossly underestimated. (author)

  16. Evolution of resistance to Aurora kinase B inhibitors in leukaemia cells.

    Timothy W Failes

    Full Text Available Aurora kinase inhibitors are new mitosis-targeting drugs currently in clinical trials for the treatment of haematological and solid malignancies. However, knowledge of the molecular factors that influence sensitivity and resistance remains limited. Herein, we developed and characterised an in vitro leukaemia model of resistance to the Aurora B inhibitor ZM447439. Human T-cell acute lymphoblastic leukaemia cells, CCRF-CEM, were selected for resistance in 4 µM ZM447439. CEM/AKB4 cells showed no cross-resistance to tubulin-targeted and DNA-damaging agents, but were hypersensitive to an Aurora kinase A inhibitor. Sequencing revealed a mutation in the Aurora B kinase domain corresponding to a G160E amino acid substitution. Molecular modelling of drug binding in Aurora B containing this mutation suggested that resistance is mediated by the glutamate substitution preventing formation of an active drug-binding motif. Progression of resistance in the more highly selected CEM/AKB8 and CEM/AKB16 cells, derived sequentially from CEM/AKB4 in 8 and 16 µM ZM447439 respectively, was mediated by additional defects. These defects were independent of Aurora B and multi-drug resistance pathways and are associated with reduced apoptosis mostly likely due to reduced inhibition of the catalytic activity of aurora kinase B in the presence of drug. Our findings are important in the context of the use of these new targeted agents in treatment regimes against leukaemia and suggest resistance to therapy may arise through multiple independent mechanisms.

  17. Distribution of HLA antigens in families of patients with leukaemias

    Vojvodić Svetlana

    2008-01-01

    Full Text Available Introduction. Since the discovery of major histocompatihility complex influence on manse leukaemia in 1964, an HLA association with leukaemia in humans has been considered as a possible genetic risk factor that contributes to development of leukaemia. In addition to associations of several IILA antigens with leukaemias, it has been observed that patients with leukaemia have an increase in the frequency of HLA identical siblings, higher degree of HLA compatibility with their parents as well as higher parental HLA sharing rate in comparison to the families without patients suffering from leukaemia. Material and methods. To test hypothesis that susceptibility to leukaemia can be caused bv influence of a recessive genes associated with the major histocompatibilily complex in man, we analyzed the distribution of I class HLA antigens in 77 families of patients suffering from different types of leukaemia. In the affected families and in 72 families of healthy controls, we investigated HLA identical sibling frequency, parental sharing of one, two or three HLA antigens and degree of compatibility of parents and off springs: existence of haploidentity, compatibility in l' and 4/4 HLA antigens of A and B loci. Results We have found that in families with affected persons there is a statistically significant difference in number of HLA identical siblings in comparison to the group of healthy controls (t=2,63. Also the results have shown that among the parents of affected persons there is a statistically significant difference in mutual compatibility in one (t=3,012 and two ft= 2,4 HLA antigens. In addition, we observed an increase in the frequency of higher rate of compatibility between patients and their parents (t=3,88 in l' HLA antigens, to their mothers (t=2,83 and to their fathers (t=2,55, respectively, in comparison to the healthy control group. Conclusion The results of this study show that in families with persons suffering from leukaemia there are

  18. Translating microarray data for diagnostic testing in childhood leukaemia

    Recent findings from microarray studies have raised the prospect of a standardized diagnostic gene expression platform to enhance accurate diagnosis and risk stratification in paediatric acute lymphoblastic leukaemia (ALL). However, the robustness as well as the format for such a diagnostic test remains to be determined. As a step towards clinical application of these findings, we have systematically analyzed a published ALL microarray data set using Robust Multi-array Analysis (RMA) and Random Forest (RF). We examined published microarray data from 104 ALL patients specimens, that represent six different subgroups defined by cytogenetic features and immunophenotypes. Using the decision-tree based supervised learning algorithm Random Forest (RF), we determined a small set of genes for optimal subgroup distinction and subsequently validated their predictive power in an independent patient cohort. We achieved very high overall ALL subgroup prediction accuracies of about 98%, and were able to verify the robustness of these genes in an independent panel of 68 specimens obtained from a different institution and processed in a different laboratory. Our study established that the selection of discriminating genes is strongly dependent on the analysis method. This may have profound implications for clinical use, particularly when the classifier is reduced to a small set of genes. We have demonstrated that as few as 26 genes yield accurate class prediction and importantly, almost 70% of these genes have not been previously identified as essential for class distinction of the six ALL subgroups. Our finding supports the feasibility of qRT-PCR technology for standardized diagnostic testing in paediatric ALL and should, in conjunction with conventional cytogenetics lead to a more accurate classification of the disease. In addition, we have demonstrated that microarray findings from one study can be confirmed in an independent study, using an entirely independent patient cohort

  19. Gastrointestinal bleeding due to large bowel infiltration by chronic lymphocytic leukaemia.

    Tucker, J.; Cachia, P. G.

    1986-01-01

    A 66 year old woman with a 9 year history of chronic lymphocytic leukaemia developed intermittent rectal bleeding for 9 months; sigmoidoscopic biopsy proved that this was due to large bowel infiltration by leukaemia. This is a very rare occurrence.

  20. Tracer‐Based Metabolic NMR‐Based Flux Analysis in a Leukaemia Cell Line

    Carrigan, John B.; Reed, Michelle A. C.; Ludwig, Christian; Khanim, Farhat L.; Bunce, Christopher M.

    2016-01-01

    Abstract High levels of reactive oxygen species (ROS) have a profound impact on acute myeloid leukaemia cells and can be used to specifically target these cells with novel therapies. We have previously shown how the combination of two redeployed drugs, the contraceptive steroid medroxyprogesterone and the lipid‐regulating drug bezafibrate exert anti‐leukaemic effects by producing ROS. Here we report a 13C‐tracer‐based NMR metabolic study to understand how these drugs work in K562 leukaemia cells. Our study shows that [1,2‐13C]glucose is incorporated into ribose sugars, indicating activity in oxidative and non‐oxidative pentose phosphate pathways alongside lactate production. There is little label incorporation into the tricarboxylic acid cycle from glucose, but much greater incorporation arises from the use of [3‐13C]glutamine. The combined medroxyprogesterone and bezafibrate treatment decreases label incorporation from both glucose and glutamine into α‐ketoglutarate and increased that for succinate, which is consistent with ROS‐mediated conversion of α‐ketoglutarate to succinate. Most interestingly, this combined treatment drastically reduced the production of several pyrimidine synthesis intermediates. PMID:27347458