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  1. Oral manifestations of acute leukaemia

    Directory of Open Access Journals (Sweden)

    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.

  2. Pneumocystis carinii Pneumonia in Acute Lymphatic Leukaemia ...

    African Journals Online (AJOL)

    A case report of a patient who developed fatal pneumocystis pneumonia while in remission from acute lymphatic leukaemia is presented. Clinical and aetiological aspects of this rare infection are discussed. Attention is drawn to diagnostic pitfalls encountered in leukaemia.

  3. Acute myeloid leukaemia presenting as faecal incontinence

    Science.gov (United States)

    Lim, Hoon; Cho, Young Soon; Jang, Pyung Moon; Kim, Ho Jung; Jang, Hye Young

    2007-01-01

    Epidural sacral nerve compression as an initial feature of leukaemia is a rare complication. The findings in a 16‐year‐old boy who presented to an emergency department with symptoms of faecal incontinence are reported herein. Radiological imaging demonstrated soft‐tissue masses in the sacral epidural space. The diagnosis of acute myeloid leukaemia was confirmed on bone marrow aspirate. The characteristics and management of extramedullary leukaemia are discussed. PMID:17452690

  4. immunophenotyping of acute leukaemias by flow cytometry

    African Journals Online (AJOL)

    2009-12-01

    Dec 1, 2009 ... ... of acute leukaemias within our resource constrained setting. ACKNOWLEDGEMENTS. To the University of Nairobi, and the American. Society of Hematology (ASH), which enabled me to undertake training in flow cytometry of leukaemias and lymphomas at the M.D. Anderson Cancer Center,. Houston ...

  5. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

    de Jonge, H. J. M.; Huls, G.; de Bont, E. S. J. M.

    Acute myeloid leukaemia (AML) is a heterogeneous disease characterised by clonal malignant haematopoiesis with a differentiation arrest and excessive proliferation of leukaemic blasts. Over the past decades, the heterogeneity of AML has been illustrated by evolving classifications based on

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

    LENUS (Irish Health Repository)

    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.

  7. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic

    African Journals Online (AJOL)

    PROF. EZECHUKWU

    2013-04-28

    Apr 28, 2013 ... malignancies that occur in children <15year of age and. Acute lymphoblastic leukaemia (ALL) accounts for about 77% of cases of childhood leukemias.1 Bone pain, particularly of the lower extremities is a common manifestation of childhood ALL. Although the initial presentation of childhood ALL is usually ...

  8. Unusual presentations of childhood acute lymphoblastic leukaemia ...

    African Journals Online (AJOL)

    Childhood acute lymphoblastic leukaemia, (ALL) is increasingly reported to present in an atypical fashion which may have significant implications for treatment outcomes and survival. This case report presents a Nigerian child who's clinical and radiological features together with effusion cytological findings were suggestive ...

  9. Acute Lymphoblastic Leukaemia presenting as Juvenile Idiopathic ...

    African Journals Online (AJOL)

    Background: Acute Lymphoblastic Leukaemia in children commonly presents with osteo articular manifestations that may mimic Juvenile Idiopathic Arthritis. This may create considerable diagnostic difficulty and lead to delay in commencing appropriate treatment. Case: An eight year old boy who presented with multiple ...

  10. Analysis of images of acute human and animal leukaemia

    International Nuclear Information System (INIS)

    Feinermann, Emmanuel

    1981-01-01

    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

  11. Proteomic profile of acute myeloid leukaemia: A review update

    African Journals Online (AJOL)

    pathophysiology of acute myeloid leukaemia (AML) through proteome expressions, thus confirming the viability of ..... affected by acute lymphoid leukaemia) were .... these cells resistant to FTY-720 increase the expression of miR-191-5p and a suppression of. miR-142-3pcan be attributable to reduction of the. B subunit.

  12. Exploring the acute myeloid leukaemias

    Directory of Open Access Journals (Sweden)

    TB Thapa

    2013-10-01

    Full Text Available The acute myeloid leukemias are genetically a diverse group of neoplasm with varied clinical behavior and response to treatment. Advances in immunophenotyping, cytogenetics and molecular genetics have resulted in better understanding of their genesis. Risk stratification of different variants is now emerging. Therapy strategies are now increasingly being developed considering the inherent biological behavior of the different subtypes. It is anticipated that in the future, deeper secrets of these once fatal diseases will be unraveled by advances in newer genomic techniques. It is hoped that future use of gene specific tailored therapy and strategies will result in longer survival in cases showing poorer prognosis at present. DOI: http://dx.doi.org/10.3126/jpn.v3i6.9001 Journal of Pathology of Nepal (2013 Vol. 3, 497-501

  13. [An immunological approach to acute myeloid leukaemia].

    Science.gov (United States)

    González, B; Bueno, D; Rubio, P M; San Román, S; Plaza, D; Sastre, A; García-Miguel, P; Fernández, L; Valentín, J; Martínez, I; Pérez-Martínez, A

    2016-04-01

    Acute myeloid leukaemia (AML) is the second haematological malignancy in the paediatric population, and one of the leading causes of childhood cancer mortality. Survival is currently around 60%, with no improvement in last decades, suggesting that new therapeutic approaches are needed. The anti-leukaemia effect mediated by the lymphocytes and natural killer (NK) cells of the immune system has been established in haematopoietic stem cell transplantation, and also as adoptive immunotherapy after consolidation chemotherapy schemes. A retrospective study was conducted on the clinical characteristics of patients diagnosed and treated for AML in our centre during 1996-2014. The mean fluorescence intensities of HLA-I, MICA/B and ULBP1-4, ligands for NK cell receptors, were also analysed in ten new diagnosed leukaemia cases, five myeloid and five lymphoid. A total of 67 patients were used in this analysis. With a median follow up of 25 months, the event-free survival was 62% (95% CI: 55-67). Secondary AML, non-M3 phenotype, and the absence of favourable cytogenetic markers had a lower survival. The probability of relapse was 38% (95% CI: 31-45). The expression of HLA-I and ULBP-4 was significantly lower in myeloid than in lymphoid blast cells. Our clinical results are similar to those described in the literature. Survival did not significantly change in recent decades, and the likelihood of relapse remains high. Myeloid blasts might be more susceptible to the cytotoxicity of NK cells through their lower expression of HLA-I. NK therapy strategies in minimal disease situation could be effective, as reported by other groups. Copyright © 2015 Asociación Española de Pediatría. Published by Elsevier España, S.L.U. All rights reserved.

  14. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    genes and genetic signatures and for reducing dimensionally of gene expression data. Next, we have used machine-learning methods to predict survival and to assess important predictors based on these results. General application of a number of these methods has been implemented into two public query......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....... Here GEPs from purified healthy haematopoietic populations, with different levels of differentiation, form the basis for comparison with diseased samples. We present a mathematical transformation of mRNA microarray data to make it possible to compare AML samples, carrying expanded aberrant...

  15. Serum & cerebrospinal fluid ferritin levels in children with acute leukaemia.

    Science.gov (United States)

    Srinivasan, A; Rusia, U; Anand, N K; Sood, S K

    1989-06-01

    Serum and CSF ferritin were estimated in 35 consecutive patients of acute leukaemia at the time of admission and on induction of remission. Serum ferritin levels were significantly raised in 94 per cent patients of acute leukaemia. The mean (+/- SD) serum ferritin (314.36 +/- 158.4 micrograms/1) was significantly higher when compared with control values (P less than 0.001). Remission induction resulted in significant fall in serum ferritin values to a mean of 149 (+/- 98.7) micrograms/l (P less than 0.05). Serum ferritin is thus of value in assessing the state of remission and is a sensitive indicator of the leukaemic cell mass and the state of activity of the disease. CSF ferritin levels in acute leukaemia were comparable to normal control values. CSF ferritin did not reflect CNS involvement in acute leukaemia and therefore its value as a tumour marker of CNS infiltration is doubtful.

  16. Acute lymphocytic leukaemia in children in the Netherlands

    International Nuclear Information System (INIS)

    Does-van den Berg, A. van der.

    1980-01-01

    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.)

  17. Imaging findings of upper abdominal involvement by acute megakaryoblastic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Amemiya, Shiori; Akahane, Masaaki; Ohtomo, Kuni [University of Tokyo, Department of Radiology, Graduate School of Medicine, Tokyo (Japan); Takita, Junko; Igarashi, Takashi [University of Tokyo, Department of Paediatrics, Graduate School of Medicine, Tokyo (Japan)

    2008-04-15

    Acute megakaryoblastic leukaemia (AMKL), a relatively rare type of acute myeloid leukaemia, is characterized by frequent involvement of the liver, spleen and lymph nodes in addition to myelofibrosis in children. Diagnosis is difficult both clinically and pathologically, and the hepatic or lymph node involvement is not uncommonly misinterpreted as solid tumour. We report the imaging findings of upper abdominal involvement by AMKL in an infant. The hepatic lesion, initially suspected to be hepatoblastoma, showed a distinctive appearance on MRI suggesting its infiltrative nature. With the association of splenic lesion and lymphadenopathy, the imaging findings were considered indicative of a haematological disorder. (orig.)

  18. ETV6-RUNX1+Acute Lymphoblastic Leukaemia in Identical Twins.

    Science.gov (United States)

    Ford, Anthony M; Greaves, Mel

    2017-01-01

    Acute leukaemia is the major subtype of paediatric cancer with a cumulative risk of 1 in 2000 for children up to the age of 15 years. Childhood acute lymphoblastic leukaemia (ALL) is a biologically and clinically diverse disease with distinctive subtypes; multiple chromosomal translocations exist within the subtypes and each carries its own prognostic relevance. The most common chromosome translocation observed is the t(12;21) that results in an in-frame fusion between the first five exons of ETV6 (TEL) and almost the entire coding region of RUNX1 (AML1).The natural history of childhood ALL is almost entirely clinically silent and is well advanced at the point of diagnosis. It has, however, been possible to backtrack this process through molecular analysis of appropriate clinical samples: (i) leukaemic clones in monozygotic twins that are either concordant or discordant for ALL; (ii) archived neonatal blood spots or Guthrie cards from individuals who later developed leukaemia; and (iii) stored, viable cord blood cells.Here, we outline our studies on the aetiology and pathology of childhood ALL that provide molecular evidence for a monoclonal, prenatal origin of ETV6-RUNX1+ leukaemia in monozygotic identical twins. We provide mechanistic support for the concept that altered patterns of infection during early childhood can deliver the necessary promotional drive for the progression of ETV6-RUNX1+ pre-leukaemic cells into a postnatal overt leukaemia.

  19. Cryptic Chromosome Abormalities in Acute Leukaemia: Identification and Detection

    NARCIS (Netherlands)

    L.J.C.M. van Zutven

    2005-01-01

    textabstractSpecific chromosome aberrations are observed in 50% of all new acute leukaemia patients. As a result of chromosome aberrations, genes located at the breakpoints can be disrupted and fusion genes can be formed. In addition, genes can be lost or amplified. An increasing number of these

  20. Therapy related Acute Myeloid Leukaemia 8 Years after Treatment ...

    African Journals Online (AJOL)

    Hodgkin's Disease (HD) is a curable malignancy even in Nigeria, our limitations in health care delivery notwithstanding. However, secondary malignancies especially Acute Myeloid Leukaemia (AML) may occur as late complications following alkylating cytotoxic drugs therapy, with or without radiotherapy. This is a case ...

  1. Incidence of acute lymphoblastic leukaemia in white and coloured ...

    African Journals Online (AJOL)

    Objectives. To record the age-specific incidence rate (ASIR) for diagnosed acute lymphoblastic leukaemia (ALL) in coloured and white children aged 0 - 12 years in the Western Cape (WC). Design. A retrospective population-based study using the 1991 population census to calculate the mean annual childhood population ...

  2. Academic career after treatment for acute lymphoblastic leukaemia

    NARCIS (Netherlands)

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

    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

  3. Effective control of acute myeloid leukaemia and acute lymphoblastic leukaemia progression by telomerase specific adoptive T-cell therapy.

    Science.gov (United States)

    Sandri, Sara; De Sanctis, Francesco; Lamolinara, Alessia; Boschi, Federico; Poffe, Ornella; Trovato, Rosalinda; Fiore, Alessandra; Sartori, Sara; Sbarbati, Andrea; Bondanza, Attilio; Cesaro, Simone; Krampera, Mauro; Scupoli, Maria T; Nishimura, Michael I; Iezzi, Manuela; Sartoris, Silvia; Bronte, Vincenzo; Ugel, Stefano

    2017-10-20

    Telomerase (TERT) is a ribonucleoprotein enzyme that preserves the molecular organization at the ends of eukaryotic chromosomes. Since TERT deregulation is a common step in leukaemia, treatments targeting telomerase might be useful for the therapy of hematologic malignancies. Despite a large spectrum of potential drugs, their bench-to-bedside translation is quite limited, with only a therapeutic vaccine in the clinic and a telomerase inhibitor at late stage of preclinical validation. We recently demonstrated that the adoptive transfer of T cell transduced with an HLA-A2-restricted T-cell receptor (TCR), which recognize human TERT with high avidity, controls human B-cell chronic lymphocytic leukaemia (B-CLL) progression without severe side-effects in humanized mice. In the present report, we show the ability of our approach to limit the progression of more aggressive leukemic pathologies, such as acute myeloid leukaemia (AML) and B-cell acute lymphoblastic leukaemia (B-ALL). Together, our findings demonstrate that TERT-based adoptive cell therapy is a concrete platform of T cell-mediated immunotherapy for leukaemia treatment.

  4. L-asparaginase induced hyperlipidaemia in acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Nesheli, H. M.; Tamaddoni, A.; Hosseinzadeh, F.; Moghaddam, T. G.

    2013-01-01

    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)

  5. Presence of clone-specific markers at birth in children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Hjalgrim, L L; Madsen, H O; Melbye, M; Jørgensen, P; Christiansen, M; Andersen, M T; Pallisgaard, N; Hokland, P; Clausen, N; Ryder, L P; Schmiegelow, K; Hjalgrim, H

    2002-10-21

    Recent studies have suggested that development of childhood acute lymphoblastic leukaemia may often be initiated in utero. To provide further evidence of an prenatal origin of childhood leukaemia, we conducted a molecular biological investigation of nine children with B-precursor acute lymphoblastic leukaemia carrying the chromosomal translocation t(12;21), the most common subtype of all childhood acute lymphoblastic leukaemia. Specifically, for each child we identified the non-constitutive chromosomal sequences made up by the t(12;21) fusion gene. From these, leukaemia clone-specific DNA primers were constructed and applied in nested polymerase chain reaction analyses of DNA extracted from the patients' Guthrie cards obtained at birth. Leukaemia clone-specific fusion gene regions were demonstrated in Guthrie card DNA of three patients, age 2 years 11 months, 3 years 4 months, and 5 years 8 months at leukaemia diagnosis. Our findings are consistent with previous observations, and thus provide further evidence that the development of t(12;21) B-precursor acute lymphoblastic leukaemia may be initiated in utero. Review of the current literature moreover indicates that age at leukaemia may be inversely correlated with the burden of cells with leukaemia clonal markers, i.e. leukaemia predisposed cells at birth, and that certain types of childhood acute lymphoblastic leukaemia develop as a multiple step process involving both pre- and postnatal genetic events.

  6. High-flow priapism in acute lymphatic leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    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. Granular acute lymphoblastic leukaemia of childhood: a morphological phenomenon.

    Science.gov (United States)

    Darbyshire, P J; Lilleyman, J S

    1987-01-01

    Three hundred and twenty consecutive children with lymphoblastic leukaemia (ALL), treated on the Medical Research Council UKALL VIII schedule, had their Romanowsky stained diagnostic marrows reviewed for the presence of azurophil granules in blast cell cytoplasm. Twenty patients (7%) had greater than 5% blasts showing this feature; 19 had the cell phenotype of "common ALL." Male children and those with French-American-British (FAB) L2 morphology predominantly showed this feature. There was also a strong correlation between granularity and non-diffuse acid phosphate positivity, but no obvious difference between the 20 patients in their response to treatment emerged during a minimum follow up of 15 months. The "granular" variant occurs in around 7% of children with ALL, but has no clear prognostic importance. Morphologists should be aware of its existence and incidence to avoid confusion with acute myeloid leukaemia. Images p252-a PMID:3470317

  8. Molecular processes involved in B cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Malouf, Camille; Ottersbach, Katrin

    2018-02-01

    B cell leukaemia is one of the most frequent malignancies in the paediatric population, but also affects a significant proportion of adults in developed countries. The majority of infant and paediatric cases initiate the process of leukaemogenesis during foetal development (in utero) through the formation of a chromosomal translocation or the acquisition/deletion of genetic material (hyperdiploidy or hypodiploidy, respectively). This first genetic insult is the major determinant for the prognosis and therapeutic outcome of patients. B cell leukaemia in adults displays similar molecular features as its paediatric counterpart. However, since this disease is highly represented in the infant and paediatric population, this review will focus on this demographic group and summarise the biological, clinical and epidemiological knowledge on B cell acute lymphoblastic leukaemia of four well characterised subtypes: t(4;11) MLL-AF4, t(12;21) ETV6-RUNX1, t(1;19) E2A-PBX1 and t(9;22) BCR-ABL1.

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

    DEFF Research Database (Denmark)

    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...

  10. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Directory of Open Access Journals (Sweden)

    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.

  11. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Wolthers, Benjamin O.; Frandsen, Thomas L.; Baruchel, André

    2017-01-01

    BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing pa......BACKGROUND: Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re...... of a second asparaginase-associated pancreatitis was not associated with severity of the first asparaginase-associated pancreatitis and a second asparaginase-associated pancreatitis did not involve an increased risk of complications, asparaginase re-exposure should be determined mainly by the anticipated need...... for asparaginase for antileukaemic efficacy. A study of the genetic risk factors identifying patients in whom asparaginase exposure should be restricted is needed. FUNDING: The Danish Childhood Cancer Foundation and The Danish Cancer Society (R150-A10181)....

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

    DEFF Research Database (Denmark)

    Henriksen, Louise Tram; 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...

  13. Cytogenetic abnormalities in acute leukaemia of ambiguous lineage: an overview.

    Science.gov (United States)

    Manola, Kalliopi N

    2013-10-01

    Acute leukaemia of ambiguous lineage (ALAL) is a rare complex entity with heterogeneous clinical, immunophenotypic, cytogenetic and molecular genetic features and adverse outcome. According to World Health Organization 2008 classification, ALAL encompasses those leukaemias that show no clear evidence of differentiation along a single lineage. The rarity of ALAL and the lack of uniform diagnostic criteria have made it difficult to establish its cytogenetic features, although cytogenetic analysis reveals clonal chromosomal abnormalities in 59-91% of patients. This article focuses on the significance of cytogenetic analysis in ALAL supporting the importance of cytogenetic analysis in the pathogenesis, diagnosis, prognosis, follow up and treatment selection of ALAL. It reviews in detail the types of chromosomal aberrations, their molecular background, their correlation with immunophenotype and age distribution and their prognostic relevance. It also summarizes some novel chromosome aberrations that have been observed only once. Furthermore, it highlights the ongoing and future research on ALAL in the field of cytogenetics. © 2013 John Wiley & Sons Ltd.

  14. Congenital Acute Myeloid Leukaemia with Pseudo-Chediak-Higashi Like Granules: A Case Report.

    Science.gov (United States)

    Puri, Vandana; Barman, Sandip; Sharma, Pooja; Sikka, Meera

    2016-11-01

    Congenital leukaemia is a very rare entity comprising 0.8% of all childhood leukaemias. Pseudo-Chediak-Higashi Anomaly (PCHA) in acute leukaemia is a rarely described entity. However, co-existence of congenital myeloid leukaemia with PCHA is a very rare entity and to the best of our knowledge has not been described in literature till date. A full term new-born presented on the 27 th day of life with severe gastroenteritis. Complete blood counts and peripheral smear examination revealed leucocytosis with presence of 76% blast cells. Approximately 15% of these blast cells showed presence of pseudo-Chediak-Higashi like granules. The diagnosis of acute myeloid leukaemia was confirmed by flow cytometry. The case report is presented due to its rarity and to highlight the differential diagnosis and clinical implications of this entity.

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

    DEFF Research Database (Denmark)

    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...

  16. Chicken pox and acute monocytic leukaemia skin lesions in an HIV-seropositive man.

    Science.gov (United States)

    De la Salmonière, P; Janier, M; Gilquin, J; Carlotti, A; Sutton, L; Leblond, V; Daniel, F

    1994-11-01

    Lymphoid neoplasia is now well known to occur in patients with human immunodeficiency virus (HIV) infection but the first case of acute monocytic leukaemia in an HIV-seropositive man has been only recently described. We report the case of an HIV-infected patient who simultaneously developed skin lesions of acute monocytic leukaemia and chicken pox. We suggest that HIV may produce a malignant transformation of monocytic cells.

  17. The experience of acute leukaemia in adult patients: a qualitative thematic synthesis.

    Science.gov (United States)

    Papadopoulou, Constantina; Johnston, Bridget; Themessl-Huber, Markus

    2013-10-01

    The aim of this review was to systematically identify and synthesise all qualitative evidence on how adult patients diagnosed with acute leukaemia experience living with their illness. A systematic search strategy was developed comprising of two search strings: i) acute leukaemia and ii) qualitative methodology. The search strategy was run in seven electronic databases (Medline, CINAHL, PsychINFO, EMBASE, BNI & Archive, SSCI and ASSIA). Nine qualitative studies in adult patients with acute leukaemia, published in peer reviewed journals between 01/1990 and 01/2013 were included in the final sample. The qualitative thematic synthesis resulted in the development of a conceptual model describing a person's path to build a renewed self. Following the initial blow of diagnosis with the range of initial reactions, patients with acute leukaemia are living in a contracting world; they have to deal with the life in hospital, the several losses and the impact of their illness on their emotions and interpersonal relationships. Several factors take up a buffering role at that stage: coping, support, information and hope. Finally, patients accommodate acute leukaemia in their lives through re-evaluating personal values and assigning new meaning to their experience. Results from this thematic synthesis are indicative of the impact of acute leukaemia on patients' lives and the processes they use to make sense and accommodate the illness in their life. Increasing our understanding of these processes is warranted to improve patient care. Copyright © 2013. Published by Elsevier Ltd.

  18. Co-trimoxazole alone for prevention of bacterial infection in patients with acute leukaemia.

    Science.gov (United States)

    Starke, I D; Donnelly, P; Catovsky, D; Darrell, J; Johnson, S A; Goldman, J M; Galton, D A

    1982-01-02

    43 patients undergoing treatment for acute leukaemia were randomised to receive either co-trimoxazole alone or co-trimoxazole with framycetin and colistin as antibacterial prophylaxis during periods of neutropenia. There were no significant differences between the two treatment groups in the time before the onset of the first fever, the number of episodes of fever or of septicaemia per patient, the number of neutropenic days during which patients remained afebrile or did not require systemic antibiotics, or the number of resistant organisms acquired. Co-trimoxazole alone is cheaper and easier to take than co-trimoxazole with framycetin and colistin, and it is therefore preferable to the three-drug combination for the prophylaxis of bacterial infection.

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

    DEFF Research Database (Denmark)

    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...

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

    International Nuclear Information System (INIS)

    Roux, P.

    1987-01-01

    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

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

    Science.gov (United States)

    Abu-Ouf, Noran M; Jan, Mohammed M

    2015-01-01

    Metabolic syndrome is a common complication encountered in children surviving acute lymphoblastic leukaemia (ALL). Affected patients develop obesity, insulin resistance, hypertension, and hyperlipidemia. Metabolic syndrome is a consequence of multiple factors, particularly hormonal imbalance induced by various ALL treatments. This review aims to evaluate the risk factors and mechanisms leading to the development of metabolic syndrome. Further research is needed to improve our understanding of the mechanisms leading to insulin resistance and the associated endothelial and adipose tissue dysfunction. Future studies should also examine other possible contributing factors, such as environmental and genetic factors. Understanding these factors will help in guiding modifications of the current ALL treatment protocols in order to prevent the development of this syndrome and hence improve the quality of life of ALL survivors. Until this is achieved, clinicians should continue to identify patients at risk early and use a therapeutic approach that combines dietary restrictions and enhanced physical activity. Copyright © 2014 Asian Oceanian Association for the Study of Obesity. Published by Elsevier Ltd. All rights reserved.

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

    LENUS (Irish Health Repository)

    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.

  3. Gemtuzumab ozogamicin: an anti-CD33 immunoconjugate for the treatment of acute myeloid leukaemia.

    Science.gov (United States)

    Stasi, Roberto

    2008-04-01

    Gemtuzumab ozogamicin consists of a semisynthetic derivative of calicheamicin, a potent cytotoxic antibiotic, linked to a humanized anti-CD33 monoclonal antibody. To describe the pharmacology of gemtuzumab ozogamicin and to provide an overview of clinical trials in acute myeloid leukaemia. Review and summary of publications on gemtuzumab ozogamicin indexed in the PubMed electronic database. Gemtuzumab ozogamicin has shown moderate activity as a single agent in patients with CD33-positive refractory or relapsed acute myeloid leukaemia, with more promising results in acute promyelocytic leukaemia. The side effect profile may be an improvement on conventional chemotherapy, except for a higher frequency of veno-occlusive disease or sinusoidal obstructive syndrome, especially after a subsequent haematopoietic stem cell transplantation. Because of the different mechanisms of action and non-overlapping toxicities, the integration of this immunoconjugate with standard chemotherapy is a rational approach, and Phase III trials are ongoing both in the induction and in the post-remission settings.

  4. Benefit of oral nutritional supplements for children with acute lymphoblastic leukaemia during remission-induction chemotherapy: a quasi-experimental study.

    Science.gov (United States)

    Liang, Rui; Chen, Gai-Yun; Fu, San-Xian; Zhong, Jie; Ma, Yan

    2018-01-01

    To determine the effect of oral nutritional supplements (ONS) on children with acute lymphoblastic leukaemia undergoing remission-induction chemotherapy. We included 127 paediatric patients who were diagnosed with acute lymphoblastic leukaemia and undergoing remission- induction chemotherapy in the First Affiliated Hospital of Zhengzhou University. Children from two paediatric wards who met the inclusion criteria were enrolled. One ward was randomly chosen as the intervention group and the other ward as the control group. Children in the two groups were matched for age and sex. The ONS group was administered Peptamen® (n=60) and the control group was administered a low-fat diet (n=67). The baseline information before treatment was not significantly different between groups (p>0.05). In the control group, weight loss at the end of chemotherapy was significantly higher than that of ONS group (poral nutritional supplements can improve the nutritional status of children, reduce the incidence of complications, and decrease the costs of hospitalization.

  5. Radiation-induced acute myeloid leukaemia in mice

    Energy Technology Data Exchange (ETDEWEB)

    Bouffler, S.D.; Silver, A.R.J.; Cox, R. [National Radiological Protection Board, Chilton (United Kingdom)

    2000-07-01

    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)

  6. Childhood vaccinations and risk of acute lymphoblastic leukaemia in children.

    Science.gov (United States)

    Søegaard, Signe Holst; Rostgaard, Klaus; Schmiegelow, Kjeld; Kamper-Jørgensen, Mads; Hargreave, Marie; Hjalgrim, Henrik; Hviid, Anders

    2017-06-01

    It has been proposed that childhood vaccinations protect against acute lymphoblastic leukaemia (ALL) in children by modulation of future responses to common infections in childhood. However, the available studies provide inconsistent findings, and population-based cohort studies with longitudinal information on vaccinations are lacking. In a register-based cohort of all children born in Denmark from 1 January 1990 to 31 December 2008, followed up until age 15 years or 31 December 2009 ( n  = 1 225 404), we evaluated exposure to childhood vaccination and risk of childhood ALL, including information on ALL subtypes. Using Cox regression, we estimated hazard ratios (HRs) comparing vaccinated with unvaccinated children. Childhood ALL was diagnosed in 490 children during 10 829 194 person-years of follow-up. Neither the total number of vaccine doses received nor exposure to each vaccination given in childhood was associated with altered risk of ALL, including the following: (i) Haemophilus influenzae type b [HR, 1.04; 95% confidence interval (CI), 0.68-1.61]; ii) measles, mumps and rubella (HR, 1.01; 95% CI, 0.76-1.34); iii) whole-cell pertussis (HR, 1.10; 95% CI, 0.51-2.39); and iv) diphtheria, tetanus and inactivated polio (HR, 1.14; 95% CI, 0.42-3.13). Analyses conducted according to ALL subtypes defined by immunopheno- and karyotypes showed no association with childhood vaccination. This nationwide cohort study provides no support of the proposed protective effect of childhood vaccination against childhood ALL. © The Author 2017; all rights reserved. Published by Oxford University Press on behalf of the International Epidemiological Association

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

    LENUS (Irish Health Repository)

    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.

  8. The relationship between bcl-2 expression and response to chemotherapy in acute leukaemia.

    Science.gov (United States)

    Maung, Z T; MacLean, F R; Reid, M M; Pearson, A D; Proctor, S J; Hamilton, P J; Hall, A G

    1994-09-01

    Immunocytochemistry was used to assess bcl-2 expression in blasts obtained from the bone marrow of 28 patients with acute lymphoblastic leukaemia (ALL) (16 children and six adults at presentation and three children and three adults on relapse) and 20 with acute myeloid leukaemia (AML) (19 adults and one child, 13 with de novo AML, 11 at presentation and two on relapse, and seven secondary to myelodysplasia or chronic myeloid leukaemia). Slides were examined both for the percentage of positive cells and for the intensity of staining using a five-point scale. There was a statistically significant increase in both the percentage of positive cells seen (P presentation in ALL. There was a significantly greater intensity of staining in cells from patients with ALL (P important prognostic feature in both de novo AML and in ALL, but not in secondary AML.

  9. Detection and analysis of tumour biomarkers to strengthen the diagnosis of acute and chronic leukaemias

    Directory of Open Access Journals (Sweden)

    R. Cerón-Maldonado

    2015-04-01

    A panel of molecular markers that included 11 genes derived from chromosomal translocations BCR-ABL major and minor breakpoints, E2A-PBX1, MLL-AF4, TEL-AML1, PML-RARα, AML1-ETO was standardised; cancer testis antigens (CTA derived from NY-ESO1 and MAGE-A3 epigenetic alterations and multi-drug-resistant genes ABCB1 and ABCG2. 30 patients diagnosed with leukaemia from Mexico's General Hospital (Hospital General de Mexico were included. They suffered from acute lymphoblastic leukaemia (ALL and acute myeloblastic leukaemia (AML; bone marrow mononuclear cells were used, from which RNA was extracted for the synthesis of cDNA and RT-PCR for each of the markers. In acute lymphoblastic leukaemia (ALL, BCR-ABL biomarkers expressed under 30% (3/10, E2A-PBX1 10% (1/10, ABC-B1 80% (8/10, and ABC-G2 60% (6/10. Patients with acute myeloblastic leukaemia (AML expressed 30% PML-RARα (3/10, 40% ABC-B1 (4/10, and 10% ABC-G2 (1/10. Lastly, in patients with chronic myeloid leukaemia (CML, BCR-ABL was over 100% (10/10, ABC-B1 20% (2/10, and ABC-G2 50% (5/10. The presence of transcripts from chimeric genes minor BCR-ABL and E2A-PBX1 in ALL; PML-RARα in AML; and major BCR-ABL in CML, confirms the importance that the panel of molecular markers has in strengthening the diagnosis and prognosis of these conditions.

  10. Methylenetetrahydrofolate reductase A1298C genotypes are associated with the risks of acute lymphoblastic leukaemia and chronic myelogenous leukaemia in the Korean population.

    Science.gov (United States)

    Hur, M; Park, J Y; Cho, H C; Lee, K M; Shin, H Y; Cho, H I

    2006-06-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism, DNA methylation and synthesis. We investigated the association between MTHFR polymorphisms and the risks of acute and chronic leukaemias. MTHFR C677T and A1298C were genotyped in 396 Korean individuals using multiplex polymerase chain reaction/restriction fragment-length polymorphism. They were acute lymphoblastic leukaemia (ALL, n = 89), acute myeloid leukaemia (AML, n = 55), biphenotypic acute leukaemia (n = 12), chronic myelogenous leukaemia (CML, n = 40), and normal controls (n = 200). C677T genotypes were not associated with the risk of each disease. A1298C variants, however, significantly decreased the risks of ALL and CML compared with 1298AA. Odds ratios and 95% confidence intervals of 1298AC and 1298AC + CC were 0.53 (0.31-0.93) and 0.54 (0.31-0.93) in ALL, and 0.34 (0.14-0.80) and 0.40 (0.18-0.89) in CML, respectively, compared with 1298AA. These findings demonstrate that the development of ALL and CML is more dependent on folate status, and more susceptible to DNA instability than that of AML. In addition, A1298C rather than C677T may be a more important genetic risk modifier in leukaemogenesis at least in the Korean population.

  11. Mutational analysis of Bax and Bcl-2 in childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Salomons, G. S.; Buitenhuis, C. K.; Martínez Muñoz, C.; Verwijs-Jassen, M.; Behrendt, H.; Zsiros, J.; Smets, L. A.

    1998-01-01

    In childhood acute lymphoblastic leukaemia there are large interpatient variations in levels of the apoptosis-regulating proteins Bax and Bcl-2, but the molecular basis for this variation is unknown. Point-mutations in bax have been reported in cell lines derived from haematological malignancies.

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

    DEFF Research Database (Denmark)

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

    1998-01-01

    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....

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

    DEFF Research Database (Denmark)

    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...... towards patients at risk. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc....

  14. Prognostic value of minimal residual disease in acute lymphoblastic leukaemia in childhood

    NARCIS (Netherlands)

    van Dongen, JJM; Seriu, T; Panzer-Grumayer, ER; Biondi, A; Pongers-Willemse, MJ; Corral, L; Stolz, F; Schrappe, M; Masera, G; Kamps, WA; Gadner, H; van Wering, ER; Ludwig, WD; Basso, G; de Bruijn, MAC; Cazzaniga, G; Hettinger, A; van der Does-van den Berg, A; Hop, WCJ; Riehm, H; Bartram, CR

    1998-01-01

    Background Sensitive techniques for detection of minimal residual disease (MRD) at degrees of one leukaemic cell per 10(3)-10(6) cells (10(-3)-10(-6)) during follow-up of children with acute lymphoblastic leukaemia (ALL) can provide insight into the effectiveness of cytotoxic treatment. However, it

  15. Triple immunofluorescence staining for prediction of relapse in childhood precursor B acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Vervoordeldonk, S. F.; Merle, P. A.; Behrendt, H.; Steenbergen, E. J.; van Leeuwen, E. F.; van den Berg, H.; von dem Borne, A. E.; van der Schoot, C. E.; Slaper-Cortenbach, I. C.

    1996-01-01

    In this study we describe a fast and sensitive method using three-colour immunofluorescence for the detection of cells with phenotypes that are rare in normal bone marrow (BM) but occur frequently in children with precursor B acute lymphoblastic leukaemia. We show that, in the first year after

  16. Autoimmune diseases, infections, use of antibiotics and the risk of acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Østgård, Lene S G; Nørgaard, Mette; Pedersen, Lars

    2018-01-01

    Previous studies reported increased risk of acute myeloid leukaemia (AML) in individuals with inflammatory conditions. However, it is unclear whether this association is explained by preceding cytotoxic therapy or haematological diseases. We conducted a nationwide case-control study that included...

  17. An analysis of prognostic variables in acute lymphocytic leukaemia in a heterogenous South African population

    NARCIS (Netherlands)

    Hesseling, PB; Buurman, M; Oud, C; Nel, ED

    The records of all 96 children below the age of 15 years diagnosed with acute lymphoblastic leukaemia at Tygerberg Hospital in the Republic of South African between 1983 and 1995 were reviewed to determine risk factors which may predict poor outcome. Age <2 and > 8 years, and white cell count >20 x

  18. Survival of Mexican Children with Acute Myeloid Leukaemia Who Received Early Intensification Chemotherapy and an Autologous Transplant

    Directory of Open Access Journals (Sweden)

    Elva Jiménez-Hernández

    2015-01-01

    Full Text Available Background. In Mexico and other developing countries, few reports of the survival of children with acute leukaemia exist. Objective. We aimed at comparing the disease-free survival of children with acute myeloid leukaemia who, in addition to being treated with the Latin American protocol of chemotherapy and an autologous transplant, either underwent early intensified chemotherapy or did not undergo such treatment. Procedure. This was a cohort study with a historical control group, forty patients, less than 16 years old. Group A (20 patients, diagnosed in the period 2005–2007, was treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy: high doses of cytarabine and mitoxantrone. Group B (20 patients, diagnosed in the period 1999–2004, was treated as Group A, but without the early intensified chemotherapy. Results. Relapse-free survival for Group A was 90% whereas that for Group B it was 60% (P=0.041. Overall survival for Group A (18, 90% was higher than that for Group B (60%. Complete remission continued for two years of follow-up. Conclusions. Relapse-free survival for paediatric patients treated with the Latin American protocol of chemotherapy with an autologous transplant plus early intensified chemotherapy was higher than that for those who did not receive early intensified chemotherapy.

  19. [Acute pancreatitis during chemotherapy of acute lymphoblastic leukaemia complicated with pseudocyst].

    Science.gov (United States)

    Sikorska-Fic, Barbara; Stańczak, Elzbieta; Matysiak, Michał; Kamiński, Andrzej

    2008-01-01

    The incidence of pancreatitis in patients with haematopoetic neoplasms who are treated with L-asparaginase is fom 2 to 24%. In majority of cases the pancreatitis is oedematous and self-limiting. Acute haemorrhagic or necrotizing pancreatitis caused by L-asparaginase is rare but potentially life-threatening complication. We present 2 cases of acute pancreatitis in children aged 2 and 4 years. They were diagnosed to have acute lymphoblastic leukaemia and were treated according to the ALLLIC BFM 2002 protocol. Acute pancreatitis developed in these children after induction therapy and was followed by formation of a pseudocyst. In both cases the diagnosis of this complication was made directly after phase I of the protocol I (after eighth dose of L-Asparaginase). In the first case the course of acute pancreatitis was mild. Normalization of the amylase levels occurred after 7 days and the diagnosis of post inflammatory cyst was made 15 days after the first signs of the disease. But thereafter, during the additional complication (pneumonia with Pseudomonas aeruginosa bacteriemia) the pancreatic cyst became infected. In the second case acute pancreatitis had a severe course and the child required treatment in the Intensive Care Unit for 21 days. The cyst was diagnosed after 20 days from the beginning of symptoms. The surgical procedure, applied in both cases was internal drainage by anastomosis of the cyst with the back wall of the stomach. Antileukaemic treatment was recommenced after 6-8 weeks when complications resolved. Currently both children are well and remain in haematological remission and continue maintenance chemotherapy.

  20. Molecular evidence for a common leukaemic progenitor in acute mixed lymphoid and myeloid leukaemia.

    Science.gov (United States)

    Lim, S H; Culligan, D; Couzens, S; Fisher, J; John, S; Pollard, P; Burnett, A; Whittaker, J

    1996-01-01

    De novo acute leukaemia presenting with a mixed lymphoid and myeloid leukaemic population has rarely been described. We have used the consensus Ig heavy chain primers and DNA isolated from these two distinct populations of cells in polymerase chain reactions. We demonstrated that both populations of cells exhibited Ig heavy chain gene rearrangements. Cloning and subsequent DNA sequencing of the amplified products showed a common V-D-J junctional nucleotide sequence. This work therefore provides the first evidence that the leukaemic cells in de novo acute leukaemia with a mixed lymphoid and myeloid population are derived from a common progenitor clone and may offer an explanation for the poor prognosis in these patients.

  1. Successful treatment of acute promyelocytic leukaemia without chemotherapy and blood transfusion

    DEFF Research Database (Denmark)

    Tøstesen, Michael; Østgård, Lene S G; Kjeldsen, Eigil

    2018-01-01

    Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year-old fe......-old female patient, who due to religious conviction refused supportive therapy with blood products. A treatment regimen consisting of all-trans retinoic acid and arsenic trioxide was successful without the use of blood transfusions.......Untreated acute promyelocytic leukaemia (APL) is a rapidly lethal blood cancer. Conventional treatment consists of all-trans retinoic acid and chemotherapy. Standard chemo-therapy-containing treatments necessitate the use of blood products. This is a case report of typical APL in a 32-year...

  2. Isochromosome 9q as a sole anomaly in an Omani boy with acute lymphoblastic leukaemia

    Science.gov (United States)

    Achandira, Udayakumar Muthappa; Pathare, Anil V; Kindi, Salam Al; Dennison, David; Yahyaee, Said Al

    2009-01-01

    This report describes a case of acute lymphoblastic leukaemia in which isochromosome 9q (i(9q)) was the sole acquired cytogenetic abnormality. The Immunophenotype showed positivity for CD3, CD4, CD5, CD7, CD8, CD10, CD71, CD117 and TdT, consistent with T cell acute lymphoblastic leukaemia (ALL). The chromosomal analysis of bone marrow showed 46,XY,i(9)(q10) in all the metaphases analysed. The bone marrow morphology was ALL-L2 as per the French–American–British criteria. Isochromosomes are rare chromosomal abnormalities in childhood ALL and the effect of i(9q) is not well established. The patient’s good response to therapy with normal cytogenetics within a month of induction, and disease-free survival after bone marrow transplant are indicative of a good prognosis in such cases. PMID:21686579

  3. Detailed molecular characterisation of acute myeloid leukaemia with a normal karyotype using targeted DNA capture.

    Science.gov (United States)

    Conte, N; Varela, I; Grove, C; Manes, N; Yusa, K; Moreno, T; Segonds-Pichon, A; Bench, A; Gudgin, E; Herman, B; Bolli, N; Ellis, P; Haddad, D; Costeas, P; Rad, R; Scott, M; Huntly, B; Bradley, A; Vassiliou, G S

    2013-09-01

    Advances in sequencing technologies are giving unprecedented insights into the spectrum of somatic mutations underlying acute myeloid leukaemia with a normal karyotype (AML-NK). It is clear that the prognosis of individual patients is strongly influenced by the combination of mutations in their leukaemia and that many leukaemias are composed of multiple subclones, with differential susceptibilities to treatment. Here, we describe a method, employing targeted capture coupled with next-generation sequencing and tailored bioinformatic analysis, for the simultaneous study of 24 genes recurrently mutated in AML-NK. Mutational analysis was performed using open source software and an in-house script (Mutation Identification and Analysis Software), which identified dominant clone mutations with 100% specificity. In each of seven cases of AML-NK studied, we identified and verified mutations in 2-4 genes in the main leukaemic clone. Additionally, high sequencing depth enabled us to identify putative subclonal mutations and detect leukaemia-specific mutations in DNA from remission marrow. Finally, we used normalised read depths to detect copy number changes and identified and subsequently verified a tandem duplication of exons 2-9 of MLL and at least one deletion involving PTEN. This methodology reliably detects sequence and copy number mutations, and can thus greatly facilitate the classification, clinical research, diagnosis and management of AML-NK.

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

    Science.gov (United States)

    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. Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  5. Effect of Anacardium occidentale leaf extract on human acute lymphoblastic leukaemia cell lines.

    Science.gov (United States)

    Santos, Janaína M; Cury, Nathalia M; Yunes, José A; López, Jorge A; Hernández-Macedo, Maria L

    2018-01-16

    Anacardium occidentale leaves are used in folk medicine due its therapeutic properties attributed to phenolic compounds. Therefore, this study was undertaken on its hydroethanolic leaf extract (AoHE) to evaluate cytotoxicity and apoptosis induction on acute lymphoblastic leukaemia cells. Results indicated that AoHE interfered in the cell cycle progression, inducing apoptosis by activation of casp3 at lower concentrations, thence, a promising candidate for the development of new cancer drugs.

  6. Outcome after intensive reinduction therapy and allogeneic stem cell transplant in paediatric relapsed acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Karlsson, Lene; Forestier, Erik; Hasle, Henrik

    2017-01-01

    Given that 30-40% of children with acute myeloid leukaemia (AML) relapse after primary therapy it is important to define prognostic factors and identify optimal therapy. From 1993 to 2012, 543 children from the Nordic countries were treated according to two consecutive protocols: 208 children rel...... receiving SCT as part of relapse therapy. Our data show that intensive re-induction followed by SCT can give cure rates of 40% in children with relapsed AML....

  7. Platelet doubling after the first azacitidine cycle is a promising predictor for response in myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) patients in the Dutch azacitidine compassionate named patient programme

    NARCIS (Netherlands)

    van der Helm, Lieke H.; Alhan, Canan; Wijermans, Pierre W.; van Marwijk Kooy, Marinus; Schaafsma, Ron; Biemond, Bart J.; Beeker, Aart; Hoogendoorn, Mels; van Rees, Bastiaan P.; de Weerdt, Okke; Wegman, Jurgen; Libourel, Ward J.; Luykx-de Bakker, Sylvia A.; Minnema, Monique C.; Brouwer, Rolf E.; Croon-de Boer, Fransien; Eefting, Matthijs; Jie, Kon-Siong G.; van de Loosdrecht, Arjan A.; Koedam, Jan; Veeger, Nic J. G. M.; Vellenga, Edo; Huls, Gerwin

    2011-01-01

    The efficacy of azacitidine in the treatment of high-risk myelodysplastic syndromes (MDS), chronic myelomonocytic leukaemia (CMML) and acute myeloid leukaemia (AML) (20-30% blasts) has been demonstrated. To investigate the efficacy of azacitidine in daily clinical practice and to identify predictors

  8. Nutritional status and quality of life in patients with acute leukaemia prior to and after induction chemotherapy in three hospitals in Tehran, Iran: a prospective study.

    Science.gov (United States)

    Malihi, Z; Kandiah, M; Chan, Y M; Hosseinzadeh, M; Sohanaki Azad, M; Zarif Yeganeh, M

    2013-07-01

    The primary objective of the present study was to assess changes in the nutritional status and quality of life in acute leukaemia patients, aged ≥15 years, who had undergone induction chemotherapy. A preliminary and post-induction chemotherapy assessment of patients' nutritional status, quality of life, sociodemographic status and medical characteristics was conducted using the Patient Generated Subjective Global Assessment (PG-SGA) and the European Organization for Research and Treatment of Cancer quality of life (QOL-C30, version 3) questionnaires. The PG-SGA is a clinical nutrition assessment tool used to evaluate oncology patients. Patients with newly-diagnosed acute leukaemia, aged ≥15 years, at three hospitals in Tehran (from May 2009 to March 2010), were recruited for the present study. Sixty-three acute leukaemia patients [65% men and 35% women with a mean (SD) age of 33 (15.4) years] participated in the present study. A total of 19.4% were found to be malnourished prior to chemotherapy. After chemotherapy, 76.1% of patients were considered moderately malnourished, whereas 6.3% were severely malnourished. After induction chemotherapy, both the nutritional status and quality of life deteriorated in the majority of patients, as demonstrated by a paired t-test. A deteriorated nutritional status and quality of life was the result of the side effects posed by induction chemotherapy in the patients investigated in the present study. These findings highlight the need for an appropriate nutritional support programme to improve the nutritional status and quality of life in patients with leukaemia undergoing chemotherapy. © 2013 The Authors Journal of Human Nutrition and Dietetics © 2013 The British Dietetic Association Ltd.

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

    Directory of Open Access Journals (Sweden)

    Amanda Dixon-McIver

    2008-05-01

    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.

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

    DEFF Research Database (Denmark)

    Schmiegelow, K.

    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...... childhood ALL cases are due to such germline mutations, but the figure may be higher. Most of these syndromes are primarily characterized by their non-malignant phenotype, whereas ALL may be the dominating or even only striking manifestation of the syndrome in some families. Identification of such ALL...... 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...

  11. Allergy and acute leukaemia in children with Down syndrome: a population study. Report from the Mexican inter-institutional group for the identification of the causes of childhood leukaemia

    OpenAIRE

    Núñez-Enríquez, J C; Fajardo-Gutiérrez, A; Buchán-Durán, E P; Bernáldez-Ríos, R; Medina-Sansón, A; Jiménez-Hernández, E; Amador-Sanchez, R; Peñaloza-Gonzalez, J G; Paredes-Aguilera, R; Alvarez-Rodriguez, F J; Bolea-Murga, V; de Diego Flores-Chapa, J; Flores-Lujano, J; Bekker-Mendez, V C; Rivera-Luna, R

    2013-01-01

    Background: Allergies have been described as protective factors against the development of childhood acute leukaemia (AL). Our objective was to investigate the associations between allergy history and the development of AL and acute lymphoblastic leukaemia (ALL) in children with Down syndrome (DS). Methods: A case–control study was performed in Mexico City. The cases (n=97) were diagnosed at nine public hospitals, and the controls (n=222) were recruited at institutions for children with DS. O...

  12. Acute myeloid leukaemia presenting as bilateral proptosis in a young child

    Directory of Open Access Journals (Sweden)

    Charudutt Kalamkar

    2016-06-01

    Full Text Available Myeloid sarcoma is an extramedullary manifestation of acute myeloid leukaemia (AML. Aims We are reporting a paediatric case presenting with bilateral proptosis, which we were able to diagnose with peripheral blood smear (PBS examination. Methods Case Report Results This case highlights the utility of simple routinely available PBS test in diagnosing this rare disease. Conclusion Our case highlights the importance of haemogram and peripheral blood smear in the initial evaluation of proptosis. Correct diagnosis of this rare entity is vital especially in cases where (myeloid sarcoma MS is the presenting feature of AML.

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

    DEFF Research Database (Denmark)

    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...... under identical conditions. After restriction enzyme cleavage, the PCR products originating from the competitor and the malignant clone can be distinguished by size in a gel electrophoresis step and the amount of residual disease can be determined. The method is very sensitive with a detection limit...

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

    DEFF Research Database (Denmark)

    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.......2%), and the overall subsequent risk of induction death and death in first complete remission (CR1) was 1.2% and 1.8%, respectively. Infections were the major cause of death comprising 72% of all cases including 9 deaths from Pseudomonas aeruginosa and 11 deaths from fungal infections. Other causes of death included...

  15. Case Report: A child with acute lymphocytic leukaemia

    African Journals Online (AJOL)

    The patient was a child aged 5 years who had been diagnosed to have acute lymphocytic leukemia (ALL). Chemotherapy was given with wysolone, vincristine, daunomycin, l-asparaginase, and intrathecal methotrexate. In addition he was given fluconazole and co-trimoxazole to cover infections during the induction period ...

  16. Rapidly progressing, fatal and acute promyelocytic leukaemia that initially manifested as a painful third molar: a case report

    Directory of Open Access Journals (Sweden)

    Suárez-Cuenca Juan A

    2009-11-01

    Full Text Available Abstract Introduction Acute promyelocytic leukaemia, an uncommon and devastating subtype of leukaemia, is highly prevalent in Latin American populations. The disease may be detected by a dentist since oral signs are often the initial manifestation. However, despite several cases describing oral manifestations of acute promyelocytic leukaemia and genetic analysis, reports of acute promyelocytic leukaemia in Hispanic populations are scarce. The identification of third molar pain as an initial clinical manifestation is also uncommon. This is the first known case involving these particular features. Case presentation A 24-year-old Latin American man without relevant antecedents consulted a dentist for pain in his third molar. After two dental extractions, the patient experienced increased pain, poor healing, jaw enlargement and bleeding. A physical examination later revealed that the patient had pallor, jaw enlargement, ecchymoses and gingival haemorrhage. Laboratory findings showed pancytopaenia, delayed coagulation times, hypoalbuminaemia and elevated lactate dehydrogenase. Splenomegaly was detected on ultrasonography. Peripheral blood and bone marrow analyses revealed a hypercellular infiltrate of atypical promyelocytic cells. Cytogenetic analysis showing genetic translocation t(15;17 further confirmed acute promyelocytic leukaemia. Despite early chemotherapy, the patient died within one week due to intracranial bleeding secondary to disseminated intravascular coagulation. Conclusion The description of this unusual presentation of acute promyelocytic leukaemia, the diagnostic difficulties and the fatal outcome are particularly directed toward dental surgery practitioners to emphasise the importance of clinical assessment and preoperative evaluation as a minimal clinically-oriented routine. This case may also be of particular interest to haematologists, since the patient's cytogenetic analysis, clinical course and therapeutic response are well

  17. Cytochemical studies in leukaemias

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    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 an...... towards patients at risk. Pediatr Blood Cancer. © 2010 Wiley-Liss, Inc.......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 ALL-2000 protocols. Fifty-five TRDs were identified among the 1,645 ALL-92 patients and 33 among the 1,090 ALL-2000 patients. RESULTS: There was no significant difference in the incidence of TRDs between the two protocols (3.4% vs. 3.2%). Five patients died before initiation of therapy (0...

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

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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...

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

    Science.gov (United States)

    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.

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    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

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

    NARCIS (Netherlands)

    Groninger, E; Meeuwsen-De Boer, GJ; Kamps, WA; De Bont, ESJM

    2002-01-01

    Vincristine (VCR), a microtubule interfering anticancer 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

  6. Resilience factors play an important role in the mental health of parents when children survive acute lymphoblastic leukaemia.

    Science.gov (United States)

    Eilertsen, Mary-Elizabeth; Hjemdal, Odin; Le, Thien Thanh; Diseth, Trond H; Reinfjell, Trude

    2016-01-01

    Childhood cancer is a tremendous stressor that requires parents to adapt to new challenges, and research has mainly focused on psychopathology and rarely on a resource-oriented perspective, such as resilience. This study assessed resilience factors among parents of children surviving acute lymphoblastic leukaemia and parents of healthy children. We also explored the association between parental resilience and mental health. The study compared 57 parents of 40 children from eight to 15 years of age in remission from acute lymphoblastic leukaemia and 63 parents of 42 healthy children. The Resilience Scale for Adults and the General Health Questionnaire were used to assess parental resilience and mental health. Parents of children surviving acute lymphoblastic leukaemia showed significantly lower levels of resilience than parents of healthy children, but no significant difference was found for mental health. Certain resilience factors were positively associated with mental health, especially for mothers, such as family cohesion, good perception of self and being able to plan their future. Resilience factors may help to protect parents' mental health, especially mothers, when their child has survived acute lymphoblastic leukaemia and should be considered in a clinical setting. Further research on resilience factors for fathers is needed. ©2015 Foundation Acta Paediatrica. Published by John Wiley & Sons Ltd.

  7. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2012-01-01

    Background Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses may cause suppression of the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress

  8. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Gordijn, Maartje S.; Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2015-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  9. Hypothalamic-pituitary-adrenal (HPA) axis suppression after treatment with glucocorticoid therapy for childhood acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    Rensen, Niki; Gemke, Reinoud J. B. J.; van Dalen, Elvira C.; Rotteveel, Joost; Kaspers, Gertjan J. L.

    2017-01-01

    Glucocorticoids play a major role in the treatment of acute lymphoblastic leukaemia (ALL). However, supraphysiological doses can suppress the hypothalamic-pituitary-adrenal (HPA) axis. HPA axis suppression resulting in reduced cortisol response may cause an impaired stress response and an inadequate

  10. Genome‐wide analysis of cytogenetic aberrations in ETV6/RUNX1‐positive childhood acute lymphoblastic leukaemia

    DEFF Research Database (Denmark)

    Borst, Louise; Wesolowska, Agata; Joshi, Tejal

    2012-01-01

    The chromosomal translocation t(12;21) resulting in the ETV6/RUNX1 fusion gene is the most frequent structural cytogenetic abnormality among patients with childhood acute lymphoblastic leukaemia (ALL). We investigated 62 ETV6/RUNX1‐positive childhood ALL patients by single nucleotide polymorphism...

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

    DEFF Research Database (Denmark)

    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...

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

    DEFF Research Database (Denmark)

    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...... 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...

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

    DEFF Research Database (Denmark)

    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....

  14. Leukaemic infiltration and cytomegalovirus retinitis in a patient with acute T-cell lymphoblastic leukaemia in complete remission.

    Science.gov (United States)

    Saldaña Garrido, J D; Martínez Rubio, M; Carrión Campo, R; Moya Moya, M A; Rico Sergado, L

    2017-03-01

    A 43-year-old woman in remission from T- cell acute lymphoblastic leukaemia was referred to our hospital with suspected leukaemic retinitis. The funduscopic examination of her left eye revealed multifocal yellow-white peripheral retinitis and retinal haemorrhage. The patient was treated for cytomegalovirus retinitis after an extended haematological investigation showed no abnormalities. Initial improvement was followed by papillitis in the left eye and motility restriction in the right eye. Magnetic resonance and lumbar puncture confirmed leukaemia relapse. Specific treatment was initiated with complete resolution. Ocular involvement may precede haematological leukaemia relapse. Physicians should be alerted when ocular symptoms appear in these cases. Copyright © 2016 Sociedad Española de Oftalmología. Publicado por Elsevier España, S.L.U. All rights reserved.

  15. Disturbed pubertal growth in girls after acute leukaemia: a relative growth hormone insufficiency with late presentation.

    Science.gov (United States)

    Moëll, C

    1988-01-01

    Long-term follow-up of growth and development after acute lymphoblastic leukaemia (ALL) in childhood has previously been limited to the prepubertal period. This study describes pubertal growth, final height and the spontaneous secretion of GH in girls treated for ALL, including CNS irradiation with 24 Gy. Ten girls, treated earlier for ALL, experienced the menarche at a mean age of 12.2 years. This is significantly earlier than the mean for Swedish girls. Prepubertal growth was near normal after the end of therapy for leukaemia. Mean final height was -1.7 SD, which is 1.5 SD less than at onset and 1.0 SD less than 1 year after the end of treatment. Thirteen other girls had a blunted spontaneous secretion of GH, several years after treatment for ALL; there was no increase in GH secretion during puberty. These results suggest that girls who have been treated for ALL, including CNS irradiation, have a relative GH insufficiency. This insufficiency becomes obvious only when the girls cannot respond to the increased need for GH during the pubertal spurt.

  16. Persistent MRD before and after allogeneic BMT predicts relapse in children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Sutton, Rosemary; Shaw, Peter J; Venn, Nicola C; Law, Tamara; Dissanayake, Anuruddhika; Kilo, Tatjana; Haber, Michelle; Norris, Murray D; Fraser, Chris; Alvaro, Frank; Revesz, Tamas; Trahair, Toby N; Dalla-Pozza, Luciano; Marshall, Glenn M; O'Brien, Tracey A

    2015-02-01

    Minimal residual disease (MRD) during early chemotherapy is a powerful predictor of relapse in acute lymphoblastic leukaemia (ALL) and is used in children to determine eligibility for allogeneic haematopoietic stem cell transplantation (HSCT) in first (CR1) or later complete remission (CR2/CR3). Variables affecting HSCT outcome were analysed in 81 children from the ANZCHOG ALL8 trial. The major cause of treatment failure was relapse, with a cumulative incidence of relapse at 5 years (CIR) of 32% and treatment-related mortality of 8%. Leukaemia-free survival (LFS) and overall survival (OS) were similar for HSCT in CR1 (LFS 62%, OS 83%, n = 41) or CR2/CR3 (LFS 60%, OS 72%, n = 40). Patients achieving bone marrow MRD negativity pre-HSCT had better outcomes (LFS 83%, OS 92%) than those with persistent MRD pre-HSCT (LFS 41%, OS 64%, P 50. A Cox multivariate regression model for LFS retained both B-other ALL subtype (hazard ratio 4·1, P = 0·0062) and MRD persistence post-HSCT (hazard ratio 3·9, P = 0·0070) as independent adverse prognostic variables. Persistent MRD could be used to direct post-HSCT therapy. © 2014 John Wiley & Sons Ltd.

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

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Attarbaschi, Andishe; Barzilai, Shlomit

    2016-01-01

    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......, 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...

  18. Maternal diabetes and risk of childhood acute lymphoblastic leukaemia in the offspring

    DEFF Research Database (Denmark)

    Søegaard, Signe Holst; Rostgaard, Klaus; Kamper-Jørgensen, Mads

    2018-01-01

    BACKGROUND: Maternal diabetes may be linked to childhood acute lymphoblastic leukaemia (ALL) in the offspring. METHODS: We assessed the association between maternal pregestational or gestational diabetes and offspring risk of childhood ALL in a register-based study, including all singletons born...... in Denmark during 1996-2015 (n=1 187 482). RESULTS: Adjusted hazard ratios of childhood ALL were 2.91 (95% confidence interval (CI): 1.30-6.51) for maternal pregestational diabetes and 1.75 (95% CI: 1.02-2.98) for maternal gestational diabetes. Paternal diabetes did not alter offspring ALL risk, and we found...... no association between offspring ALL and later maternal risk of diabetes. CONCLUSIONS: Regardless that absolute ALL risk among offspring of women with diabetes remains low, our findings suggest that characteristics of the diabetic intrauterine environment promote ALL development. This offers a setting for future...

  19. E2A-PBX1 fusion in adult acute lymphoblastic leukaemia: biological and clinical features.

    Science.gov (United States)

    Foa, Robin; Vitale, Antonella; Mancini, Marco; Cuneo, Antonio; Mecucci, Cristina; Elia, Loredana; Lombardo, Romina; Saglio, Giuseppe; Torelli, Giuseppe; Annino, Luciana; Specchia, Giorgina; Damasio, Eugenio; Recchia, Anna; Di Raimondo, Francesco; Morra, Enrica; Volpe, Ettore; Tafuri, Agostino; Fazi, Paola; Hunger, Stephen P; Mandelli, Franco

    2003-02-01

    Molecular and cytogenetic studies performed in 305 adult acute lymphoblastic leukaemia (ALL) patients enrolled in the gimema (Gruppo Italiano Malattie EMatologiche dell'Adulto) multicentric protocols identified an E2A-PBX1 fusion and/or t(1;19) in 10 patients (3.3%). All had common ALL, were mostly CyIg+ and were CD34/CD13/CD33-. Nine patients achieved a complete remission (CR); five patients showed a haematological relapse after 7 months (median). Four patients are alive in first CR with a median follow-up of 29 months; three patients are molecularly negative. This abnormality is frequently associated with early treatment failure. E2A-PBX1+ adult ALL should be considered for intensified treatment strategies and monitoring of minimal residual disease.

  20. Growth hormone secretion in children after therapy for acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Pawlaczyk, B.; Krause, W.

    1990-01-01

    In eight children, after the termination of therapy for acute lymphoblastic leukaemia (ALL) the secretion of growth hormone (GH) was determined by the stimulation test with clonidine. The children were treated in the period from 1983 till 1988 and they were administered chemotherapy, intrathecal methotrexate therapy and cranial 60 Co irradiation in a dose of 1800 rads. In one case a complete GH deficiency was found, in three cases there was a partial deficiency and in the remaining cases the secretion was regular. No correlation was found between the biochemical values of GH and the clinical stature. There was also no interrelation between the duration of chemotherapy and the degree of pituitary gland failure. We have compared the results of GH output in children treated for ALL with those of 44 children in whom short stature was diagnosed. The age in both groups was similar. (author)

  1. RNAi screen identifies Brd4 as a therapeutic target in acute myeloid leukaemia.

    Science.gov (United States)

    Zuber, Johannes; Shi, Junwei; Wang, Eric; Rappaport, Amy R; Herrmann, Harald; Sison, Edward A; Magoon, Daniel; Qi, Jun; Blatt, Katharina; Wunderlich, Mark; Taylor, Meredith J; Johns, Christopher; Chicas, Agustin; Mulloy, James C; Kogan, Scott C; Brown, Patrick; Valent, Peter; Bradner, James E; Lowe, Scott W; Vakoc, Christopher R

    2011-08-03

    Epigenetic pathways can regulate gene expression by controlling and interpreting chromatin modifications. Cancer cells are characterized by altered epigenetic landscapes, and commonly exploit the chromatin regulatory machinery to enforce oncogenic gene expression programs. Although chromatin alterations are, in principle, reversible and often amenable to drug intervention, the promise of targeting such pathways therapeutically has been limited by an incomplete understanding of cancer-specific dependencies on epigenetic regulators. Here we describe a non-biased approach to probe epigenetic vulnerabilities in acute myeloid leukaemia (AML), an aggressive haematopoietic malignancy that is often associated with aberrant chromatin states. By screening a custom library of small hairpin RNAs (shRNAs) targeting known chromatin regulators in a genetically defined AML mouse model, we identify the protein bromodomain-containing 4 (Brd4) as being critically required for disease maintenance. Suppression of Brd4 using shRNAs or the small-molecule inhibitor JQ1 led to robust antileukaemic effects in vitro and in vivo, accompanied by terminal myeloid differentiation and elimination of leukaemia stem cells. Similar sensitivities were observed in a variety of human AML cell lines and primary patient samples, revealing that JQ1 has broad activity in diverse AML subtypes. The effects of Brd4 suppression are, at least in part, due to its role in sustaining Myc expression to promote aberrant self-renewal, which implicates JQ1 as a pharmacological means to suppress MYC in cancer. Our results establish small-molecule inhibition of Brd4 as a promising therapeutic strategy in AML and, potentially, other cancers, and highlight the utility of RNA interference (RNAi) screening for revealing epigenetic vulnerabilities that can be exploited for direct pharmacological intervention.

  2. Clinico-pathological profile of acute promyelocytic leukaemia at Al-Amal Oncology-Haematology Centre, Qatar.

    Science.gov (United States)

    Ibrahim, F A; Yassin, M A; El-Ayoubi, H R; Alhiji, I A; Albinali, A S; Almansour, S M; Qafoud, F M

    2010-09-01

    This cases series describes the profile of adult patients with acute promyelocytic leukaemia (APt) at a referral hospital in Qatar. Of 34 acute myeloid leukaemia (AML) cases diagnosed, 11(32%) were classified as APt. Disseminated intravascular coagulation was common at presentation (91%). Severe thrombocytopenia was seen in 73%, leukocytosis in 55% and severe anaemia in 45%. Only 2 patients were of the classic hypergranular type. In the remaining 9 patients, 3 morphological subtypes were recognized: microgranular variant (6 patients), hyperbasophilic (2 patients) and regular nuclear outline M3r (1 patient). Translocation t(15;17) was detected in 63% of cases. APL constitutes a high proportion of AML cases in Qatar, with considerable morphological heterogeneity and a oredominance of APL variants with unfavourable oresenting features.

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

    Directory of Open Access Journals (Sweden)

    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

  4. Andrographolide inhibits growth of acute promyelocytic leukaemia cells by inducing retinoic acid receptor-independent cell differentiation and apoptosis.

    Science.gov (United States)

    Manikam, Shiamala D; Manikam, Shiamala T; Stanslas, Johnson

    2009-01-01

    The growth inhibiting potential of andrographolide was evaluated in three acute promyelocytic leukaemia cell line models (HL-60, NB4 and all-trans retinoic acid (ATRA)-resistant NB4-R2). In elucidating the mechanisms of growth inhibition, a special emphasis was placed on assessing the induction of differentiation and apoptosis by andrographolide in the primary acute promyelocytic leukaemia NB4 cells. The compound was 2- and 3-fold more active in inhibiting the growth of HL-60 and NB4-R2 cells compared with NB4 cells, respectively. At IC50 (concentration at which growth of 50% of the cells (compared with medium only treated control cells) is inhibited; 4.5 microM) the compound exhibited strong cell-differentiating activity in NB4 cells, similar to ATRA (IC50 1.5 microM). In the presence of a pure retinoic acid receptor antagonist AGN193109, the growth inhibition of NB4 cells by ATRA was reversed, whereas the activity of andrographolide was not affected. This clearly suggested that andrographolide's cell differentiating activity to induce growth inhibition of NB4 cells most likely occurred via a retinoic acid receptor-independent pathway. At higher concentration (2xIC50), andrographolide was an efficient inducer of apoptosis in NB4 cells. Taken together, these results suggest andrographolide and its derivatives, apparently with a novel cell differentiating mechanism and with ability to induce apoptosis, might be beneficial in the treatment of primary and ATRA-resistant acute promyelocytic leukaemia.

  5. Procoagulant activity of extracellular vesicles as a potential biomarker for risk of thrombosis and DIC in patients with acute leukaemia.

    Science.gov (United States)

    Gheldof, Damien; Haguet, Hélène; Dogné, Jean-Michel; Bouvy, Céline; Graux, Carlos; George, Fabienne; Sonet, Anne; Chatelain, Christian; Chatelain, Bernard; Mullier, François

    2017-02-01

    Haemostatic complication is common for patients with hematologic malignancies. Recent studies suggest that the procoagulant activity (PCA) of extracellular vesicles (EV) may play a major role in venous thromboembolism and disseminated intravascular coagulation (DIC) in acute leukaemia. To study the impact of EVs from leukaemic patients on thrombin generation and to assess EV-PCA as a potential biomarker for thrombotic complications in patients with acute leukaemia. Blood samples from a cohort of patients with newly diagnosed acute leukaemia were obtained before treatment (D-0), 3 and 7 days after treatment (D-3 and D-7). Extracellular vesicles were isolated and concentrated by ultracentrifugation. EV-PCA was assessed by thrombin generation assay, and EV-associated tissue factor activity was measured using a commercial bio-immunoassay (Zymuphen MP-TF®). Of the 53 patients, 6 had increased EV-PCA at D-0 and 4 had a thrombotic event. Patients without thrombotic events (n = 47) had no elevated EV-PCA. One patient had increased EVs with procoagulant activity at D-3 and developed a DIC at D-5. This patient had no increased EVs-related tissue factor activity from D-0 to D-7 (2 pg/ml), of these, four had a thrombosis and two had haemorrhages. Procoagulant activity of extracellular vesicles could have a predictive value in excluding the risk of thrombotic events. Our findings also suggest a possible association between thrombotic events and EV-PCA.

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

    International Nuclear Information System (INIS)

    Buchmann, I.; Helisch, A.; Bartenstein, P.; Meyer, R.G.; Herr, W.

    2005-01-01

    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.)

  7. Acute sinusitis and blindness as the first presentation of chronic lymphocytic leukaemia

    NARCIS (Netherlands)

    Lim, K. H.; Thomas, G.; van Beers, E. J.; Hosman, A. E.; Mourits, M. P.; van Noesel, C. J. M.; Kater, A. P.; Reinartz, S. M.

    2014-01-01

    Chronic lymphocytic leukaemia (CLL) is the most frequent form of leukaemia among adults in the Western world, presenting at a median age of 65 years. The diagnosis is usually made incidentally during routine blood examination while the disease is still in its early phase. We report a case of

  8. PERCENTAGE OF CIPROFLOXACIN-RESISTANT STRAINS OF CITROBACTER FREUNDII IN ACUTE LEUKAEMIA PATIENTS WITH CIPROFLOXACIN PROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    Rika Strauch

    2004-12-01

    Full Text Available Background. Authors tried to determine an efficiency of ciprofloxacin as infection prophylaxis in patients with acute leukaemia treated at the Department of Haematology in Clinical Center of Ljubljana. Due to cytotoxic chemotherapy, aplasia of bone marrow is inevitable. Therefore, these patients are at high risk for bacterial and fungal infection. The authors have noticed a rise in the number of ciprofloxacin-resistant strains of Citrobacter freundii and decided to find out if ciprofloxacin is still usable in this setting.Patients and methods. 45 patients with acute leukaemia were admitted to the Department of Haematology in the Clinical Center of Ljubljana during the year 2001 and 2002. All the patients received ciprofloxacin 2 × 500 mg on a daily basis. Citrobacter freundii was isolated in 11 patients, to whom we determined the proportion of ciprofloxacin-resistant strains of Citrobacter freundii and other Enterobacteriaceae. Susceptibility testing was done by the NCCCLS standards by the disc diffusion method and minimal inhibitory concentration.Results. C. freundii was isolated in 11 patients with AL. Extended-spectrum beta-lactamases (ESBL C. freundii was isolated in 6 patients (54.5%. Ciprofloxacin-resistant C. freundii was isolated in 6 patients (54.5%. Six patients (54.5% had ciprofloxacin-resistant C. freundii which was ESBL positive at the same time. In AL patients with C. freundii (n = 11 almost half of isolated bacteria were Gram negative bacilli (45.2%, n = 292, mostly from the family of Enterobacteriaceae. More than half of enterobacteria were ciprofloxacin-resistant, one third of them were also ESBL positive. Out of 131 enterobacteria, C. freundii was isolated 37 times. (28.2%.Conclusions. C. freundii was isolated in one fourth of AL patients. Half of the isolates were ciprofloxacin-resistant. The same was true for isolated enterobacteria. Almost all of ciprofloxacin-resistant bacteria were ESBL positive. There is a question

  9. Effect of central nervous system radiotherapy in children with acute lymphoblastic leukaemia on lymphocyte subpopulations and indicators of leucocyte migration inhibition in the peripheral blood

    International Nuclear Information System (INIS)

    Cesarz-Kruz, E.; Lukas, A; Sroczynska, M.; Lukas, W; Sonta-Jakimczyk, D.

    1981-01-01

    The reported investigations of changes in lymphocyte subpopulations and indicators of leycocyte migration inhibition in the peripheral blood were carried out in 17 children with acute lymphoblastic leukaemia subjected to prophylactic irradiation of the central nervous system. It was found that the depressive effect of radioprophylaxis affected mostly lymphocytes B. The usefulness of immunomodulation application in children with this leukaemia immediately after completion of radiotherapy is considered. (author)

  10. Dose-adjusted arsenic trioxide for acute promyelocytic leukaemia in chronic renal failure.

    Science.gov (United States)

    Firkin, Frank; Roncolato, Fernando; Ho, Wai Khoon

    2015-10-01

    To determine the potential for arsenic trioxide (ATO) to be safely and effectively incorporated into induction therapy of newly diagnosed acute promyelocytic leukaemia (APL) in patients with severe chronic renal failure (CRF) by reduction of the ATO dosage to compensate for reduced renal elimination of arsenic in CRF. Two of the four CRF patients with APL in the study were dialysis-dependent, and two had eGFRs of 18 and 19 mL/min/1.73 m(2) . ATO dosage schedules were adjusted to obtain comparable whole-blood arsenic levels to those in APL patients with normal renal function who achieved molecular remission (MR) while receiving 10 mg ATO daily for 28 d. Average ATO administered per day in CRF patients ranged from 36 to 50% of the ATO administered to APL patients with normal renal function. No clinically significant cardiac, hepatic or other toxicities were detected. RT-PCR-negative MR was achieved after one treatment course in two patients and after two courses in the others. Relapse-free survival is 155, 60, 43 and 5 months. The observations in this pilot study have demonstrated whole-blood arsenic levels can provide a guide to adjustments of ATO dosage schedules that permit safe and effective therapeutic outcomes in APL patients with severely compromised renal function. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

    Édgar Cortés Reyes

    2013-10-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  14. Family circumstances and survival from childhood acute lymphoblastic leukaemia in West Germany.

    Science.gov (United States)

    Erdmann, Friederike; Kaatsch, Peter; Schüz, Joachim

    2015-04-01

    Little is known about the relationship between family characteristics and survival from childhood acute lymphoblastic leukaemia (ALL), which we studied for the first time in German children. ALL cases were diagnosed between 1992 and 1994 and information on family characteristics was collected during a previously conducted nationwide case-control study. Children were followed for 10 years after diagnosis, as few disease-related events occur afterwards. Cox proportional hazards models estimating hazard ratios (HR) were calculated using overall as well as event-free survival methods. Second born children showed statistically significant better survival compared to first or later born children, with HRs ranging between 0.54 and 0.64 compared to firstborns. Somewhat poorer survival was observed for children having 3 or more siblings. A relationship was found for parental age at child's diagnosis, with poorer survival for children with younger parents (≤25 years of age at child's diagnosis), or with older fathers. The HR was statistically significant for fathers being ≥41years of age (HR of 2.1). No relationship between degree of urbanization of the place of residence at diagnosis and ALL survival was observed. Family circumstances may have an impact on survival from childhood ALL in Germany. Further research is warranted to elaborate the relationship of specific family characteristics and ALL survival and to investigate possible differential adherence to therapy and interactions with physicians. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Osteonecrosis following treatment for childhood acute lymphoblastic leukaemia: The Southampton Children's Hospital experience.

    Science.gov (United States)

    Rhodes, A; Gray, J; Harvey, N; Davies, J H; Oreffo, R O C; Reading, I; Clarke, N M P; Aarvold, A

    2017-12-01

    To determine the prevalence of osteonecrosis (ON) in children following treatment of acute lymphoblastic leukaemia (ALL), characterise these cases and review treatment methods. All children diagnosed and treated for ALL between 01 January 2003 and 31 December 2013 at our centre were retrospectively reviewed. Logistic regression was used to investigate risk factors for ON occurrence. Of 235 children treated for ALL, 48/235 (20.4%) children suffered musculoskeletal symptoms necessitating radiological investigation. A total of 13 (5.5%) had MRI-diagnosed ON, with a median diagnosis time of 12 months (interquartile range 10 to 14) following initiation of chemotherapy.ON affected 40 joints in 13 children. The most commonly involved joints were hips (14 joints in eight patients) and knees (12 joints in seven patients).Older age at ALL diagnosis was associated with significantly increased risk of development of ON per year (odds ratio 1.35, 95% confidence interval 1.17 to 1.57, p < 0.001).Eight children underwent at least one surgical intervention. Joint arthroplasty was undertaken in nine joints of four children at a mean age of 18.3 years. All patients who underwent hip arthroplasty had previously received core decompression, with a mean time of 27.8 months (18 to 33) between treatments. ON is a significant complication of ALL treatment. Our results suggest risk stratification for development of ON by age, and targeted monitoring of high-risk joints is possible. ON treatment is varied with little evidence base.

  16. Targeting oncogenic interleukin-7 receptor signalling with N-acetylcysteine in T cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Mansour, Marc R; Reed, Casie; Eisenberg, Amy R; Tseng, Jen-Chieh; Twizere, Jean-Claude; Daakour, Sarah; Yoda, Akinori; Rodig, Scott J; Tal, Noa; Shochat, Chen; Berezovskaya, Alla; DeAngelo, Daniel J; Sallan, Stephen E; Weinstock, David M; Izraeli, Shai; Kung, Andrew L; Kentsis, Alex; Look, A Thomas

    2015-01-01

    Activating mutations of the interleukin-7 receptor (IL7R) occur in approximately 10% of patients with T cell acute lymphoblastic leukaemia (T-ALL). Most mutations generate a cysteine at the transmembrane domain leading to receptor homodimerization through disulfide bond formation and ligand-independent activation of STAT5. We hypothesized that the reducing agent N-acetylcysteine (NAC), a well-tolerated drug used widely in clinical practice to treat acetaminophen overdose, would reduce disulfide bond formation, and inhibit mutant IL7R-mediated oncogenic signalling. We found that treatment with NAC disrupted IL7R homodimerization in IL7R-mutant DND-41 cells as assessed by non-reducing Western blot, as well as in a luciferase complementation assay. NAC led to STAT5 dephosphorylation and cell apoptosis at clinically achievable concentrations in DND-41 cells, and Ba/F3 cells transformed by an IL7R-mutant construct containing a cysteine insertion. The apoptotic effects of NAC could be rescued in part by a constitutively active allele of STAT5. Despite using doses lower than those tolerated in humans, NAC treatment significantly inhibited the progression of human DND-41 cells engrafted in immunodeficient mice. Thus, targeting leukaemogenic IL7R homodimerization with NAC offers a potentially effective and feasible therapeutic strategy that warrants testing in patients with T-ALL. © 2014 John Wiley & Sons Ltd.

  17. Current challenges and opportunities in treating adult patients with Philadelphia-negative acute lymphoblastic leukaemia.

    Science.gov (United States)

    Wolach, Ofir; Amitai, Irina; DeAngelo, Daniel J

    2017-12-01

    Significant advances have been made in recent years in the field of Philadelphia-negative acute lymphoblastic leukaemia (ALL). New insights into the biology and genetics of ALL as well as novel clinical observations and new drugs are changing the way we diagnose, risk-stratify and treat adult patients with ALL. New genetic subtypes and alterations refine risk stratification and uncover new actionable therapeutic targets. The incorporation of more intensive, paediatric and paediatric-inspired approaches for young adults seem to have a positive impact on survival in this population. Minimal residual disease at different time points can assist in tailoring risk-adapted interventions for patients based on individual response. Finally, novel targeted approaches with monoclonal antibodies, immunotherapies and small molecules are moving through clinical development and entering the clinic. The aim of this review is to consolidate the abundance of emerging data and to review and revisit the concepts of risk-stratification, choice of induction and post-remission strategies as well as to discuss and update the approach to specific populations with ALL, such as young adult, elderly/unfit and relapsed/refractory patients with ALL. © 2017 John Wiley & Sons Ltd.

  18. A study on the predictability of acute lymphoblastic leukaemia response to treatment using a hybrid oncosimulator.

    Science.gov (United States)

    Ouzounoglou, Eleftherios; Kolokotroni, Eleni; Stanulla, Martin; Stamatakos, Georgios S

    2018-02-06

    Efficient use of Virtual Physiological Human (VPH)-type models for personalized treatment response prediction purposes requires a precise model parameterization. In the case where the available personalized data are not sufficient to fully determine the parameter values, an appropriate prediction task may be followed. This study, a hybrid combination of computational optimization and machine learning methods with an already developed mechanistic model called the acute lymphoblastic leukaemia (ALL) Oncosimulator which simulates ALL progression and treatment response is presented. These methods are used in order for the parameters of the model to be estimated for retrospective cases and to be predicted for prospective ones. The parameter value prediction is based on a regression model trained on retrospective cases. The proposed Hybrid ALL Oncosimulator system has been evaluated when predicting the pre-phase treatment outcome in ALL. This has been correctly achieved for a significant percentage of patient cases tested (approx. 70% of patients). Moreover, the system is capable of denying the classification of cases for which the results are not trustworthy enough. In that case, potentially misleading predictions for a number of patients are avoided, while the classification accuracy for the remaining patient cases further increases. The results obtained are particularly encouraging regarding the soundness of the proposed methodologies and their relevance to the process of achieving clinical applicability of the proposed Hybrid ALL Oncosimulator system and VPH models in general.

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

    Science.gov (United States)

    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. © The Author(s) 2015.

  20. Leukaemia in childhood | Kruger | Continuing Medical Education

    African Journals Online (AJOL)

    Leukaemia means white blood. It is a disease of the white blood cells and was first described by Virchow in 1845.1 Leukaemia can present as an acute disease, occurring more often in the younger age groups, or as a chronic disease, usually in the older age group. Acute leukaemia is rare, but about 1 in 2 000 people will ...

  1. The development of a three-dimensional scaffold for ex vivo biomimicry of human acute myeloid leukaemia.

    Science.gov (United States)

    Blanco, Teresa Mortera; Mantalaris, Athanasios; Bismarck, Alexander; Panoskaltsis, Nicki

    2010-03-01

    Acute myeloid leukaemia (AML) is a cancer of haematopoietic cells that develops in three-dimensional (3-D) bone marrow niches in vivo. The study of AML has been hampered by lack of appropriate ex vivo models that mimic this microenvironment. We hypothesised that fabrication and optimisation of suitable biomimetic scaffolds for culturing leukaemic cells ex vivo might facilitate the study of AML in its native 3-D niche. We evaluated the growth of three leukaemia subtype-specific cell lines, K-562, HL60 and Kasumi-6, on highly porous scaffolds fabricated from biodegradable and non-biodegradable polymeric materials, such as poly (L-lactic-co-glycolic acid) (PLGA), polyurethane (PU), poly (methyl-methacrylate), poly (D, L-lactade), poly (caprolactone), and polystyrene. Our results show that PLGA and PU supported the best seeding efficiency and leukaemic growth. Furthermore, the PLGA and PU scaffolds were coated with extracellular matrix (ECM) proteins, collagen type I (62.5 or 125 microg/ml) and fibronectin (25 or 50 microg/ml) to provide biorecognition signals. The 3 leukaemia subtype-specific lines grew best on PU scaffolds coated with 62.5 microg/ml collagen type I over 6 weeks in the absence of exogenous growth factors. In conclusion, PU-collagen scaffolds may provide a practical model to study the biology and treatment of primary AML in an ex vivo mimicry. Copyright (c) 2009 Elsevier Ltd. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. FISH Detection of PML-RARA Fusion in ins(15;17 Acute Promyelocytic Leukaemia Depends on Probe Size

    Directory of Open Access Journals (Sweden)

    Lynda J. Campbell

    2013-01-01

    Full Text Available The diagnosis of acute promyelocytic leukaemia (APL is usually confirmed by cytogenetics showing the characteristic t(15;17, but a minority of patients have a masked PML/RARA fusion. We report ten patients with APL and no evidence of the t(15;17, in whom the insertion of RARA into PML could not be demonstrated by initial FISH studies using a standard dual fusion probe but was readily identified using smaller probes. Given the need for rapid diagnosis of APL, it is important to be aware of the false negative rate for large PML/RARA FISH probes in the setting of masked rearrangements.

  4. Proteasome subunit expression analysis and chemosensitivity in relapsed paediatric acute leukaemia patients receiving bortezomib-containing chemotherapy

    Directory of Open Access Journals (Sweden)

    Denise Niewerth

    2016-09-01

    Full Text Available Abstract Background Drug combinations of the proteasome inhibitor bortezomib with cytotoxic chemotherapy are currently evaluated in phase 2 and 3 trials for the treatment of paediatric acute myeloid leukaemia (AML and acute lymphocytic leukaemia (ALL. Methods We investigated whether expression ratios of immunoproteasome to constitutive proteasome in leukaemic cells correlated with response to bortezomib-containing re-induction chemotherapy in patients with relapsed and refractory acute leukaemia, enrolled in two Children’s Oncology Group phase 2 trials of bortezomib for ALL (COG-AALL07P1 and AML (COG-AAML07P1. Expression of proteasome subunits was examined in 72 patient samples (ALL n = 60, AML n = 12 obtained before start of therapy. Statistical significance between groups was determined by Mann-Whitney U test. Results Ratios of immunoproteasome to constitutive proteasome subunit expression were significantly higher in pre-B ALL cells than in AML cells for both β5i/β5 and β1i/β1 subunits (p = 0.004 and p < 0.001. These ratios correlated with therapy response in AML patients; β1i/β1 ratios were significantly higher (p = 0.028 between patients who did (n = 4 and did not reach complete remission (CR (n = 8, although for β5i/β5 ratios, this did not reach significance. For ALL patients, the subunit ratios were also higher for patients who showed a good early response to therapy but this relation was not statistically significant. Overall, for this study, the patients were treated with combination therapy, so response was not only attributed to proteasome inhibition. Moreover, the leukaemic blast cells were not purified for these samples. Conclusions These first ex vivo results encourage further studies into relative proteasome subunit expression to improve proteasome inhibition-containing therapy and as a potential indicator of bortezomib response in acute leukaemia.

  5. Potentially avoidable hospital admissions in older patients with acute myeloid leukaemia in the USA: a retrospective analysis.

    Science.gov (United States)

    El-Jawahri, Areej; Keenan, Tanya; Abel, Gregory A; Steensma, David P; LeBlanc, Thomas W; Chen, Yi-Bin; Hobbs, Gabriela; Traeger, Lara; Fathi, Amir T; DeAngelo, Daniel J; Wadleigh, Martha; Ballen, Karen K; Amrein, Philip C; Stone, Richard M; Temel, Jennifer S

    2016-06-01

    Older adults (≥60 years of age) with acute myeloid leukaemia spend a substantial proportion of their life in hospital after diagnosis. We examined reasons for their hospital admissions and identified potentially avoidable hospital admissions (PAH) in this age group in the USA. In this retrospective analysis, we examined the reasons for hospital admissions in older patients diagnosed with and treated for acute myeloid leukaemia at two tertiary care hospitals in the USA. We included patients receiving intensive induction chemotherapy or non-intensive treatment. We excluded those with acute promyelocytic leukaemia, those seen only for a one-time consultation who received primary treatment elsewhere, and those who received supportive care alone. We identified the eligible cohort using the Dana-Farber Cancer Institute and Massachusetts General Hospital Leukemia Clinical Research Information Systems database. Practising oncologists used a consensus-driven medical record review process to identify the primary reason for each hospital admission and categorise it as potentially avoidable or not avoidable on the basis of an adaptation of Graham's criteria for PAH. We used multivariable logistic regression analyses to identify predictors of PAH. Between May 1, 2005, and Dec 23, 2011, we assessed 1040 hospital admissions (excluding initial admission for diagnosis) in 329 consecutively admitted patients. The most common primary reasons for hospital admissions were: fever or infection (396 [38%]), planned admission for chemotherapy or transplantation (391 [38%]), and uncontrolled symptoms (102 [10%]). We identified 172 (27%) of 649 unplanned hospital admissions as potentially avoidable; among these admissions, 82 (48%) were readmissions because of previous premature hospital discharge, 32 (19%) because of problems that could have been managed in the outpatient setting, and 26 (15%) because of failure of timely outpatient follow-up. In a mixed logistic regression model, higher

  6. Allogeneic stem cell transplantation in adult patients with acute myeloid leukaemia and 17p abnormalities in first complete remission: a study from the Acute Leukemia Working Party (ALWP) of the European Society for Blood and Marrow Transplantation (EBMT).

    Science.gov (United States)

    Poiré, Xavier; Labopin, Myriam; Maertens, Johan; Yakoub-Agha, Ibrahim; Blaise, Didier; Ifrah, Norbert; Socié, Gérard; Gedde-Dhal, Tobias; Schaap, Nicolaas; Cornelissen, Jan J; Vigouroux, Stéphane; Sanz, Jaime; Michaux, Lucienne; Esteve, Jordi; Mohty, Mohamad; Nagler, Arnon

    2017-01-18

    Acute myeloid leukaemia (AML) with 17p abnormalities (abn(17p)) carries a very poor prognosis due to high refractoriness to conventional chemotherapy, and allogeneic stem cell transplantation (allo-SCT) appears as the only potential curative option. To address outcomes after allo-SCT in patients with abn(17p), we retrospectively analysed de novo or secondary AML undergoing SCT between 2000 and 2013 from the EBMT registry. One hundred thirty-nine patients with confirmed abn(17p) have been selected. At the time of transplant, one hundred twenty-five were in first remission (CR1). Median age was 54 years old. Abn(17p) was associated with a monosomal karyotype in 83% of patients, complex karyotype in 91%, monosomy 5 or 5q deletion (-5/5q-) in 55%, monosomy 7 (-7) in 39% and both -5/5q and -7 in 27%. Seventy-three patients (59%) had a reduced-intensity conditioning regimen. The 2-year overall survival (OS) and leukaemia-free survival (LFS) were 28 and 24%, respectively. The 2-year non-relapse mortality (NRM) was 15%, and 2-year relapse incidence (RI) was 61%. The cumulative incidence of grade II to IV acute graft-versus-host disease (GvHD) was 24% and that of chronic GvHD was 21%. In multivariate analysis, the presence of a -5/5q- in addition to abn(17p) was significantly and independently associated with worse OS, LFS and higher RI. Age and donor types did not correlate with outcome. Conditioning intensity was not statistically associated with OS, LFS and NRM when adjusted for patients' age. In contrast to the dismal prognosis reported for AML patients harbouring abn(17p) undergoing conventional chemotherapy, allogeneic SCT provides responses in about 25% of those patients transplanted in CR1.

  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

    Energy Technology Data Exchange (ETDEWEB)

    Ringden, O. [Huddinge Hospital, Stockholm (Sweden). Dept. of Clinical Immunology; Labopin, M.; Gorin, N.C. [Hopital Saint-Antoine, Paris (France). Centre International Greffes de Moelle; Tura, S. [Orsola University Hospital, Bologna (Italy); Arcese, W. [University `La Sapienza`, Rome (Italy). Haematology; Iriondo, A. [Hospital National, Santander (Spain); Zittoun, R. [Hotel-Dieu, Paris (France). Service d`Hematologie; Sierra, J. [Hospital Clinic, Barcelona (Spain)

    1996-06-01

    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

    Energy Technology Data Exchange (ETDEWEB)

    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. Morphology of leukaemias

    Directory of Open Access Journals (Sweden)

    W. Ladines-Castro

    2016-04-01

    Full Text Available Acute leukaemias are characterised by uncontrolled proliferation of immature blood cells with lymphoid or myeloid lineage. Morphological classification is based on the identification of the leukaemia cell line and its stage of differentiation. The first microscopic descriptions dating from the 1930s pointed to 2 different types of leukaemia cells: lymphoid and myeloid. In 1976, the consensus that led to the French-American-British (FAB classification was achieved. This includes criteria for identifying myeloid and lymphoid leukaemias, and gives a list of morphological subtypes, describing how these affect the patient's prognosis. Today, despite new classifications based on sophisticated studies, FAB classification is widely used by experts due to its technical simplicity, good diagnostic reliability and cost-effectiveness.

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

    Directory of Open Access Journals (Sweden)

    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. Azacitidine: a review of its use in the management of myelodysplastic syndromes/acute myeloid leukaemia.

    Science.gov (United States)

    Keating, Gillian M

    2012-05-28

    Azacitidine (Vidaza®) is a pyrimidine nucleoside analogue of cytidine. This article reviews the clinical efficacy and tolerability of azacitidine in the treatment of patients with myelodysplastic syndromes (MDS)/acute myeloid leukaemia (AML), as well as summarizing its pharmacological properties. The randomized, multicentre Cancer and Leukemia Group B 9221 trial compared the efficacy of subcutaneous azacitidine with that of supportive care alone in patients with MDS fulfilling French-American-British (FAB) classification criteria. The overall response rate, the complete response rate and the complete plus partial response rate were significantly higher in patients receiving azacitidine than in those receiving supportive care alone. The randomized, open-label, multicentre AZA-001 trial compared the efficacy of subcutaneous azacitidine with that of conventional care in adults with higher-risk (i.e. International Prognostic Scoring System intermediate-2-risk or high-risk classification) MDS/AML. Prior to randomization, investigators preselected patients to the conventional care strategy considered most appropriate (i.e. best supportive care, low-dose cytarabine or intensive chemotherapy). The median duration of overall survival was significantly prolonged by 9.4 months in patients with higher-risk MDS receiving azacitidine versus those receiving conventional care. The survival benefit seen with azacitidine versus conventional care was maintained across various patient subgroups (e.g. in patients aged ≥75 years, in those who did not achieve complete remission and in patients with WHO-defined AML). The efficacy of subcutaneous or intravenous azacitidine was also shown in a noncomparative trial in Japanese patients with MDS fulfilling FAB classification criteria, and registry programmes in various countries support the efficacy of azacitidine in patients with MDS. Azacitidine was generally well tolerated in patients with MDS, including in the elderly. Across trials

  12. PCR-positivity in harvested bone marrow predicts relapse after transplantation with autologous purged bone marrow in children in second remission of precursor B-cell acute leukaemia

    NARCIS (Netherlands)

    Vervoordeldonk, S. F.; Merle, P. A.; Behrendt, H.; Steenbergen, E. J.; van den Berg, H.; van Wering, E. R.; von dem Borne, A. E.; van der Schoot, C. E.; van Leeuwen, E. F.; Slaper-Cortenbach, I. C.

    1997-01-01

    Purging of autologous bone marrow (BM) grafts of children in second remission after a relapse of precursor B acute lymphoblastic leukaemia (ALL) in the BM has been carried out in our laboratory since 1987, initially by complement mediated cell lysis. This protocol was extended by performing an

  13. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia: a time-dependent analysis

    NARCIS (Netherlands)

    Versluis, Jurjen; Hazenberg, Carin L. E.; Passweg, Jakob R.; van Putten, Wim L. J.; Maertens, Johan; Biemond, Bart J.; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C.; Pabst, Thomas; Löwenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J.; Meulendijks, Ine; Cornelisse, Petra; van Hooije, Christel; Biaggi, Christine; van der Holt, Bronno; Labopin, Myriam; de Bock, B.; Breems, D. A.; Zachee, P.; Ferrant, A.; Vekemans, M. C.; Mineur, P.; Delannoy, A.; Maertens, J.; Verhoef, G.; van Steenweghen, S.; Bosly, A.; Graux, C.; Jaeger, E.; Theobald, M.; Beck, J.; Fischer, Th; Gjertsen, B. T.; Bargetzi, M.; Wernli, M.; Passweg, J.; Gratwohl, A.; Leoncini-Francini, L.; Marini, G.; Fey, M. F.; Pabst, T.; Chapuis, B.; Chalandon, Y.; Herr, A.; Wuillemin, W. A.; Gregor, M.; Piquet, D.; Zimmerli-Schwab, B.; Hess, U.; Binder, D.; Kroner, Th; Mantz, M.; Jacky, E.; Schanz, U.; Wittebol, S.; van der Lelie, J.; Leeksma, O. C.; Janssen, J. J. W. M.; Ossenkoppele, G. J.; Huijgens, P. C.; Deenik, W.; Posthuma, W.; Wijermans, P. W.; Schaafsma, M. R.; Legdeur, M.; Huls, G.; Vellenga, E.; Daenen, S. M. G. J.; Voogt, P. J.; Joosten, P.; Schouten, H. C.; Laterveen, L.; Biesma, D. H.; de Weerdt, O.; Löwenberg, B.; Cornelissen, J. J.; Sonneveld, P.; Zijlmans, J.; Jongen-Lavrencic, M.; de Greef, G. E.; van Zaanen, H.; Verdonck, L. F.; Kuball, J.; van Marwijk Kooy, M.

    2015-01-01

    Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore, effective

  14. Post-remission treatment with allogeneic stem cell transplantation in patients aged 60 years and older with acute myeloid leukaemia : a time-dependent analysis

    NARCIS (Netherlands)

    Versluis, Jurjen; Hazenberg, Carin L. E.; Passweg, Jakob R.; van Putten, Wim L. J.; Maertens, Johan; Biemond, Bart J.; Theobald, Matthias; Graux, Carlos; Kuball, Jurgen; Schouten, Harry C.; Pabst, Thomas; Lowenberg, Bob; Ossenkoppele, Gert; Vellenga, Edo; Cornelissen, Jan J.

    2015-01-01

    Background Acute myeloid leukaemia mainly affects elderly people, with a median age at diagnosis of around 70 years. Although about 50-60% of patients enter first complete remission upon intensive induction chemotherapy, relapse remains high and overall outcomes are disappointing. Therefore,

  15. Various distinctive cytogenetic abnormalities in patients with acute myeloid leukaemia aged 60 years and older express adverse prognostic value : results from a prospective clinical trial

    NARCIS (Netherlands)

    van der Holt, Bronno; Breems, Dimitri A.; Beverloo, H. Berna; van den Berg, Eva; Burnett, Alan K.; Sonneveld, Pieter; Lowenberg, Bob

    Diagnostic cytogenetic abnormalities are considered important prognostic factors in patients with acute myeloid leukaemia (AML). However, the prognostic assessments have mainly been derived from patients with AML aged <60 years. Two recent studies of AML patients of 60 years and older proposed

  16. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

    Directory of Open Access Journals (Sweden)

    Virijevic Marijana

    2016-12-01

    Full Text Available Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2 genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK. The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up.

  17. Effectiveness of environmental control measures to decrease the risk of invasive aspergillosis in acute leukaemia patients during hospital building work.

    Science.gov (United States)

    Combariza, J F; Toro, L F; Orozco, J J

    2017-08-01

    Invasive aspergillosis (IA) is a significant problem in acute leukaemia patients. Construction work near hospital wards caring for immunocompromised patients is one of the main risk factors for developing invasive pulmonary aspergillosis (IPA). To assess the impact of environmental control measures used during hospital construction for the prevention of IA in acute leukaemia patients. A retrospective cohort study was developed to evaluate the IA incidence in acute leukaemia patients with different environmental control measures employed during hospital construction. We used European Organisation for the Research and Treatment of Cancer (EORTC) criterial diagnosis parameters for definition of IA. A total of 175 episodes of inpatient care were evaluated, 62 of which did not have any environmental control measures (when an outbreak occurred), and 113 that were subject to environmental control measures directed to preventing IA. The study showed an IA incidence of 25.8% for the group without environmental control measures vs 12.4% for those who did receive environmental control measures (P=0.024). The relative risk for IA was 0.595 (95% confidence interval: 0.394-0.897) for the group with environmental control measures. The current study suggests that the implementation of environmental control measures during a hospital construction has a positive impact for prevention of IA in patients hospitalized with acute leukaemia. Copyright © 2017 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  18. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology

    NARCIS (Netherlands)

    Hungate, Eric A.; Vora, Sapana R.; Gamazon, Eric R.; Moriyama, Takaya; Best, Timothy; Hulur, Imge; Lee, Younghee; Evans, Tiffany-Jane; Ellinghaus, Eva; Stanulla, Martin; Rudant, Jéremie; Orsi, Laurent; Clavel, Jacqueline; Milne, Elizabeth; Scott, Rodney J.; Pui, Ching-Hon; Cox, Nancy J.; Loh, Mignon L.; Yang, Jun J.; Skol, Andrew D.; Onel, Kenan

    2016-01-01

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3

  19. 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

    DEFF Research Database (Denmark)

    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...

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Science.gov (United States)

    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.

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

    International Nuclear Information System (INIS)

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

    2011-01-01

    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 CD33 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.

  3. 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

    International Nuclear Information System (INIS)

    Tang, Ruoping; Legrand, Ollivier; Marie, Jean-Pierre; Cohen, Simy; Perrot, Jean-Yves; Faussat, Anne-Marie; Zuany-Amorim, Claudia; Marjanovic, Zora; Morjani, Hamid; Fava, Fanny; Corre, Elise

    2009-01-01

    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 (IC 50 > 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Recent trends and concepts in the management of leukaemia ...

    African Journals Online (AJOL)

    Currently the treatment for Acute Leukaemia, which consists of Acute Myeloblastic Leukaemia (AML) and Acute Lymphoblastic Leukaemia (ALL), consists of the preventive and the definitive aspects of therapy. Recent trends that have been elucidated involve aspects of chemotherapy, radiotherapy, stem cell transplant, and ...

  6. Cyclooxygenase-2 (COX-2 Inhibition Constrains Indoleamine 2,3-Dioxygenase 1 (IDO1 Activity in Acute Myeloid Leukaemia Cells

    Directory of Open Access Journals (Sweden)

    Sergio Rutella

    2013-08-01

    Full Text Available Indoleamine 2,3-dioxygenase 1 (IDO1 metabolizes L-tryptophan to kynurenines (KYN, inducing T-cell suppression either directly or by altering antigen-presenting-cell function. Cyclooxygenase (COX-2, the rate-limiting enzyme in the synthesis of prostaglandins, is over-expressed by several tumours. We aimed at determining whether COX-2 inhibitors down-regulate the IFN-g-induced expression of IDO1 in acute myeloid leukaemia (AML cells. IFN-γ at 100 ng/mL up-regulated COX-2 and IDO1 in HL-60 AML cells, both at mRNA and protein level. The increased COX-2 and IDO1 expression correlated with heightened production of prostaglandin (PGE2 and kynurenines, respectively. Nimesulide, a preferential COX-2 inhibitor, down-regulated IDO1 mRNA/protein and attenuated kynurenine synthesis, suggesting that overall IDO inhibition resulted both from reduced IDO1 gene transcription and from inhibited IDO1 catalytic activity. From a functional standpoint, IFN-g-challenged HL-60 cells promoted the in vitro conversion of allogeneic CD4+CD25− T cells into bona fide CD4+CD25+FoxP3+ regulatory T cells, an effect that was significantly reduced by treatment of IFN-γ-activated HL-60 cells with nimesulide. Overall, these data point to COX-2 inhibition as a potential strategy to be pursued with the aim at circumventing leukaemia-induced, IDO-mediated immune dysfunction.

  7. Azole-based chemoprophylaxis of invasive fungal infections in paediatric patients with acute leukaemia: an internal audit.

    Science.gov (United States)

    Yunus, Sara; Pieper, Stephanie; Kolve, Hedwig; Goletz, Grazyna; Jürgens, Heribert; Groll, Andreas H

    2014-03-01

    Children and adolescents with acute myeloid leukaemia (AML) and recurrent acute leukaemias (RALs) are at high risk of life-threatening invasive fungal infections (IFIs). We analysed implementation, safety and efficacy of a standard operating procedure for oral, azole-based, mould-active antifungal prophylaxis. Patients with AML and RALs aged ≥13 years received 200 mg of posaconazole three times daily and patients aged 2-12 years received 200 mg of voriconazole two times daily from the completion of chemotherapy until haematopoietic recovery. Algorithms for fever or focal findings in all patients with haematological malignancies included blood cultures, high-resolution CT and other appropriate imaging, serial serum galactomannan, invasive diagnostics and pre-emptive therapy with change in class if on antifungal medication. From 2006 to 2010, 40 patients (0.8-17 years; 21 males) with newly diagnosed AML (n = 31) or RAL (n = 9) were admitted, of whom 36 received a total of 149 courses of chemotherapy (reasons for exclusion: contraindications and early death ≤3 days). Azole prophylaxis was given in 87.2% (n = 130/149) of episodes. Pre-emptive antifungal therapy for pulmonary infiltrates was initiated in 5/36 (13.9%) patients or 6/130 (4.6%) episodes for a duration of 3-22 days. No proven or probable IFIs occurred. Adverse events (AEs) were common but mostly low grade and reversible. Three courses (2.3%) were discontinued due to AEs. In simultaneously admitted new patients with acute lymphatic leukaemia (ALL; n = 101) and paediatric lymphomas (n = 29) not receiving standard antifungal prophylaxis, proven/probable IFIs occurred in 4 patients with ALL (4.0%) and 7/130 patients (5.4%) received pre-emptive therapy. Azole-based, mould-active antifungal prophylaxis in high-risk paediatric patients with AML and RALs was satisfactorily implemented, well tolerated and effective. The low rate of IFIs in patients with ALL/lymphoma supports the lack of a general indication for

  8. Feverfew: weeding out the root of leukaemia.

    Science.gov (United States)

    Guzman, Monica L; Jordan, Craig T

    2005-09-01

    Malignant stem cells are central to the pathogenesis and perpetuation of acute myelogenous leukaemia (AML). Despite their crucial role, standard chemotherapy often does not target these critical cells and, thus, the 'root' of leukaemic disease is not eradicated. To derive better therapies, unique molecular features of malignant stem cells have been characterised for AML and evaluated with regard to ablation of disease. In the course of such studies, the compound parthenolide, which is derived from the medicinal plant feverfew, has recently been shown to preferentially induce AML stem cells to undergo apoptosis. Importantly, parthenolide had no discernable effect on normal blood cells. Thus, this naturally occurring agent may provide new avenues of investigation for the treatment of leukaemia. In this article, characteristics of parthenolide are reviewed.

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

    International Nuclear Information System (INIS)

    Gonzalez, A.

    1993-01-01

    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

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

    DEFF Research Database (Denmark)

    Larsen, A M; Leinøe, E B; Johansson, P I

    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 biomarkers (s......OBJECTIVES: The beneficial effect of platelet transfusion on haemostasis is well established, but there is emerging evidence that platelet transfusion induces an inflammatory response in vascular endothelial cells. BACKGROUND: We investigated haemostatic function and endothelial biomarkers before......ICAM-1, syndecan-1, sThrombomodulin, sVE-Cadherin) and platelet activation biomarkers (sCD40L, TGF-beta) were investigated along with haematology/biochemistry analyses. RESULTS: Twenty-two patients were included. Despite continued low platelet counts, platelet transfusion normalised the median values...

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

    International Nuclear Information System (INIS)

    Jankovic, Momcilo; Masera, G.; Brouwers, Pim

    1994-01-01

    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)

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

    Science.gov (United States)

    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. A new Leukemia Prognostic Scoring System for refractory/relapsed adult acute myelogeneous leukaemia patients: a GOELAMS study.

    Science.gov (United States)

    Chevallier, P; Labopin, M; Turlure, P; Prebet, T; Pigneux, A; Hunault, M; Filanovsky, K; Cornillet-Lefebvre, P; Luquet, I; Lode, L; Richebourg, S; Blanchet, O; Gachard, N; Vey, N; Ifrah, N; Milpied, N; Harousseau, J-L; Bene, M-C; Mohty, M; Delaunay, J

    2011-06-01

    A simplified prognostic score is presented based on the multivariate analysis of 138 refractory/relapsed acute myeloid leukaemia (AML) patients (median age 55 years, range: 19-70) receiving a combination of intensive chemotherapy+Gemtuzumab as salvage regimen. Overall, 2-year event-free survival (EFS) and overall survival (OS) were 29±4% and 36±4%, respectively. Disease status (relapse Leukemia Prognostic Scoring System was then validated on an independent cohort of 111 refractory/relapsed AML patients. This new simplified prognostic score, using three clinical and biological parameters routinely applied, allow to discriminate around two third of the patients who should benefit from a salvage intensive regimen in the setting of refractory/relapsed AML patients. The other one third of the patients should receive investigational therapy.

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

    LENUS (Irish Health Repository)

    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.

  15. The subclonal complexity of STIL-TAL1+ T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Furness, Caroline L; Mansur, Marcela B; Weston, Victoria J; Ermini, Luca; van Delft, Frederik W; Jenkinson, Sarah; Gale, Rosemary; Harrison, Christine J; Pombo-de-Oliveira, Maria S; Sanchez-Martin, Marta; Ferrando, Adolfo A; Kearns, Pamela; Titley, Ian; Ford, Anthony M; Potter, Nicola E; Greaves, Mel

    2018-03-20

    Single-cell genetics were used to interrogate clonal complexity and the sequence of mutational events in STIL-TAL1+ T-ALL. Single-cell multicolour FISH was used to demonstrate that the earliest detectable leukaemia subclone contained the STIL-TAL1 fusion and copy number loss of 9p21.3 (CDKN2A/CDKN2B locus), with other copy number alterations including loss of PTEN occurring as secondary subclonal events. In three cases, multiplex qPCR and phylogenetic analysis were used to produce branching evolutionary trees recapitulating the snapshot history of T-ALL evolution in this leukaemia subtype, which confirmed that mutations in key T-ALL drivers, including NOTCH1 and PTEN, were subclonal and reiterative in distinct subclones. Xenografting confirmed that self-renewing or propagating cells were genetically diverse. These data suggest that the STIL-TAL1 fusion is a likely founder or truncal event. Therapies targeting the TAL1 auto-regulatory complex are worthy of further investigation in T-ALL.

  16. Asparaginase-associated pancreatitis in childhood acute lymphoblastic leukaemia: an observational Ponte di Legno Toxicity Working Group study.

    Science.gov (United States)

    Wolthers, Benjamin O; Frandsen, Thomas L; Baruchel, André; Attarbaschi, Andishe; Barzilai, Shlomit; Colombini, Antonella; Escherich, Gabriele; Grell, Kathrine; Inaba, Hiroto; Kovacs, Gábor; Liang, Der-Cherng; Mateos, Marion; Mondelaers, Veerle; Möricke, Anja; Ociepa, Tomasz; Samarasinghe, Sujith; Silverman, Lewis B; van der Sluis, Inge M; Stanulla, Martin; Vrooman, Lynda M; Yano, Michihiro; Zapotocka, Ester; Schmiegelow, Kjeld

    2017-09-01

    Survival for childhood acute lymphoblastic leukaemia surpasses 90% with contemporary therapy; however, patients remain burdened by the severe toxic effects of treatment, including asparaginase-associated pancreatitis. To investigate the risk of complications and risk of re-exposing patients with asparaginase-associated pancreatitis to asparaginase, 18 acute lymphoblastic leukaemia trial groups merged data for this observational study. Patient files from 26 trials run by 18 trial groups were reviewed on children (aged 1·0-17·9 years) diagnosed with t(9;22)-negative acute lymphoblastic leukaemia between June 1, 1996, and Jan 1, 2016, who within 50 days of asparaginase exposure developed asparaginase-associated pancreatitis. Asparaginase-associated pancreatitis was defined by at least two criteria: abdominal pain, pancreatic enzymes at least three times the upper limit of normal (ULN), and imaging compatible with pancreatitis. Patients without sufficient data for diagnostic criteria were excluded. Primary outcomes were defined as acute and persisting complications of asparaginase-associated pancreatitis and risk of re-exposing patients who suffered an episode of asparaginase-associated pancreatitis to asparaginase. Data were collected from Feb 2, 2015, to June 30, 2016, and analysed and stored in a common database at Rigshospitalet, Copenhagen, Denmark. Of 465 patients with asparaginase-associated pancreatitis, 33 (8%) of 424 with available data needed mechanical ventilation, 109 (26%) of 422 developed pseudocysts, acute insulin therapy was needed in 81 (21%) of 393, and seven (2%) of 458 patients died. Risk of assisted mechanical ventilation, need for insulin, pseudocysts, or death was associated with older age (median age for patients with complications 10·5 years [IQR 6·4-13·8] vs without complications 6·1 years [IQR 3·6-12·2], ppancreatitis, 31 (11%) of 275 patients still needed insulin or had recurrent abdominal pain or both. Both the risk of persisting

  17. FBXW7 and NOTCH1 mutations in childhood T cell acute lymphoblastic leukaemia and T cell non-Hodgkin lymphoma.

    Science.gov (United States)

    Park, Myoung-Ja; Taki, Tomohiko; Oda, Megumi; Watanabe, Tomoyuki; Yumura-Yagi, Keiko; Kobayashi, Ryoji; Suzuki, Nobuhiro; Hara, Junichi; Horibe, Keizo; Hayashi, Yasuhide

    2009-04-01

    Mutation analysis of FBXW7 and NOTCH1 genes was performed in 55 T cell acute lymphoblastic leukaemia (T-ALL) and 14 T cell non-Hodgkin lymphoma (T-NHL) patients who were treated on the Japan Association of Childhood Leukaemia Study (JACLS) protocols ALL-97 and NHL-98. FBXW7 and/or NOTCH1 mutations were found in 22 (40.0%) of 55 T-ALL and 7 (50.0%) of 14 T-NHL patients. FBXW7 mutations were found in 8 (14.6%) of 55 T-ALL and 3 (21.4%) of 14 T-NHL patients, and NOTCH1 mutations in 17 (30.9%) of 55 T-ALL and 6 (42.9%) of 14 T-NHL patients. Three (5.4%) T-ALL and two (1.4%) T-NHL patients had mutations in both FBXW7 and NOTCH1. FBXW7 mutations included one insertion, one deletion, one deletion/insertion and nine missense mutations. NOTCH1 mutations were detected in the heterodimerization domain (HD) in 15 cases, in the PEST domain in seven cases, and in both the HD and PEST domains in one case. Five-year event-free survival and overall survival for patients with FBXW7 and/or NOTCH1 mutations were 95.5% (95% CI, 71.9-99.4%) and 100% respectively, suggesting that T-ALL patients with FBXW7 and/or NOTCH1 mutation represent a good prognosis compared to those without FBXW7 and/or NOTCH1 mutations (63.6%, P = 0.007 and 78.8%, P = 0.023, respectively).

  18. Adapting a Vacuum Assisted Closure dressing to challenging wounds: negative pressure treatment for perineal necrotizing fasciitis with rectal prolapse in a newborn affected by acute myeloid leukaemia.

    Science.gov (United States)

    Negosanti, Luca; Aceti, Arianna; Bianchi, Tommaso; Corvaglia, Luigi; Negosanti, Francesca; Sgarzani, Rossella; Morselli, Paolo Giovanni; Cipriani, Riccardo; Negosanti, Massimino; Patrizi, Annalisa; Faldella, Giacomo

    2010-01-01

    We report the case of a newborn with acute myeloid leukaemia, who developed perineal necrotizing fasciitis due to Pseudomonas Aeruginosa, after twenty days of life. Following surgical debridement, she was effectively treated with topical negative pressure therapy (V.A.C.(R) device) with silver foam dressings, this achieved complete closure in thirteen days. Negative pressure therapy should be considered when conventional wound care fails to achieve complete wound closure, even in neonates.

  19. Antileukaemia effect of rapamycin alone or in combination with daunorubicin on Ph+ acute lymphoblastic leukaemia cell line.

    Science.gov (United States)

    Yang, Xi; Lin, Juan; Gong, Yuping; Ma, Hongbing; Shuai, Xiao; Zhou, Ruiqing; Guo, Yong; Shan, Qingqing; He, Guangcui

    2012-09-01

    The translocation (9;22) (q34;q11), known as the Philadelphia (Ph) chromosome and bcr-abl fusion gene, is the common cytogenetic abnormality and an unfavourable prognosis in adult acute lymphoblastic leukaemia (ALL). Although chemotherapeutic treatment produced high rates of complete response in approximately 70%-80% of newly diagnosed Ph+ ALL, the onset of resistance and clinical relapse is rapid. Therefore, the efficacy of treatment in Ph+ ALL is still to be determined. In this study, we aimed to assess the antileukemic activity of rapamycin (RAPA) (Sigma-Aldrich Corporation, MO, USA), a mammalian target of rapamycin inhibitor, alone and in combination with daunorubicin (DNR) (Pharmacia & Upjohn Company, Germany) in a Ph+ acute lymphoblastic cell line SUP-B15 and a primary Ph+ ALL sample in vitro. Here, we demonstrated that 50 nmol/L of RAPA significantly intensified the inhibition induced by DNR on both Ph+ ALL cell line and a primary Ph+ ALL sample. Notably, we reported that the consequence of DNR treatment induced the over expression of the components of mammalian target of rapamycin signalling pathway, whereas RAPA effectively eliminated this deleterious side effect of DNR, which might enhance DNR's ability to kill drug-resistant cancer. The synergistic effect was also associated with the increase in autophagy, blockage of cell cycle progression in the G1 phase. Altogether, our results suggest that DNR in combination with RAPA is more effective in the treatment of Ph+ ALL compared with DNR alone. Copyright © 2011 John Wiley & Sons, Ltd.

  20. DNA-thioguanine nucleotide concentration and relapse-free survival during maintenance therapy of childhood acute lymphoblastic leukaemia (NOPHO ALL2008)

    DEFF Research Database (Denmark)

    Nielsen, Stine Nygaard; Grell, Kathrine; Nersting, Jacob

    2017-01-01

    analysed data from centralised and blinded analyses of 6-mercaptopurine and methotrexate metabolites in blood samples from patients with non-high-risk childhood acute lymphoblastic leukaemia. Eligible patients were aged 1·0-17·9 years; had been diagnosed with non-high-risk precursor B-cell or T......-cell leukaemia; had been treated according to the Nordic Society of Pediatric Hematology and Oncology ALL2008 protocol; and had reached maintenance therapy in first remission. Maintenance therapy was (mercaptopurine 75 mg/m(2) once per day and methotrexate 20 mg/m(2) once per week, targeted to a leucocyte count...... Society, Childhood Cancer Foundation (Denmark), Childhood Cancer Foundation (Sweden), Nordic Cancer Union, Otto Christensen Foundation, University Hospital Rigshospitalet, and Novo Nordic Foundation....

  1. Analysis of ZAP70 expression in adult acute lymphoblastic leukaemia by real time quantitative PCR

    Directory of Open Access Journals (Sweden)

    Chakupurakal Geothy

    2012-05-01

    Full Text Available Abstract Background ZAP70 gene expression is associated with poor prognosis in B-cell lymphoproliferative disorders especially chronic lymphocytic leukaemia (CLL but its role in adult B-ALL has not been established. On diagnostic samples from 76 patients with adult ALL (65 with B-ALL and 11 with T-ALL ZAP70 mRNA expression levels were studied by real time-quantitative PCR (RT-qPCR analysis. Findings A broad distribution of ZAP70 expression was observed in ALL, ranging from 0.002 to 5.3 fold that of the ZAP70 positive Jurkat reference cell line. No association was observed between expression levels and the presence of specific cytogenetic abnormalities. Five cases, including one case of T-ALL, had ZAP70 expression above the level of the Jurkat reference cell line. Conclusions Our results confirm the frequent expression of ZAP70 in adult ALL. Limited comparisons made did highlight poor-risk patients with high ZAP70 expression, but due to lack of clinical information on patient samples we were unable to directly assess the impact on disease prognosis. ZAP-70 may be an important laboratory assay in adult ALL and further studies are warranted to study a potential correlation with cytogenetic and other genetic markers.

  2. In vitro testing of chemotherapeutic drug combinations in acute myelocytic leukaemia using the fluorometric microculture cytotoxicity assay (FMCA).

    Science.gov (United States)

    Larsson, R; Fridborg, H; Kristensen, J; Sundström, C; Nygren, P

    1993-05-01

    The fluorometric microculture cytotoxicity assay (FMCA) was employed for analysing the effect of different chemotherapeutic drug combinations and their single constituents in 44 cases of acute myelocytic leukaemia (AML). A large heterogeneity with respect to cell kill was observed for all combinations tested, the interactions ranging from antagonistic to synergistic in terms of the multiplicative concept for drug interactions. However, an 'additive' model provided a significantly better fit of the data compared to the effect of the most active single agent of the combination (Dmax) for several common antileukaemic drug combinations. When the two interaction models were related to treatment outcome 38% of the non-responders showed preference for the additive model whereas the corresponding figure for responders was 80%. Overall, in 248 of 290 (85%) tests performed with drug combinations, there was an agreement between the effect of the combination and that of the most active single component. Direct comparison of Dmax and the combination for correlation with clinical outcome demonstrated only minor differences in the ability to predict drug resistance. The results show that FMCA appear to report drug interactions in samples from patients with AML in accordance with clinical experience. Furthermore, testing single agents as a substitute for drug combinations may be adequate for detection of clinical drug resistance to combination therapy in AML.

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

    Directory of Open Access Journals (Sweden)

    Song Sarah

    2010-06-01

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

  4. A phase 1 clinical trial of vorinostat in combination with decitabine in patients with acute myeloid leukaemia or myelodysplastic syndrome.

    Science.gov (United States)

    Kirschbaum, Mark; Gojo, Ivana; Goldberg, Stuart L; Bredeson, Christopher; Kujawski, Lisa A; Yang, Allen; Marks, Peter; Frankel, Paul; Sun, Xing; Tosolini, Alessandra; Eid, Joseph E; Lubiniecki, Gregory M; Issa, Jean-Pierre

    2014-10-01

    Patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS) may respond to treatment with epigenetic-modifying agents. Histone deacetylase inhibitors may synergize with hypomethylating agents. This phase 1 dose-escalation study was designed to determine the maximum tolerated dose, recommended phase 2 dose, safety and tolerability of vorinostat plus decitabine in patients with relapsed/refractory AML, newly-diagnosed AML, or intermediate- to high-grade MDS. Thirty-four patients received concurrent therapy with decitabine plus vorinostat and 37 received sequential therapy with decitabine followed by vorinostat. Twenty-nine patients had relapsed/refractory AML, 31 had untreated AML and 11 had MDS. The target maximum administered dose (MAD) of decitabine 20 mg/m(2) daily for 5 d plus vorinostat 400 mg/d for 14 d was achieved for concurrent and sequential schedules, with one dose-limiting toxicity (Grade 3 QTc prolongation) reported in the sequential arm. Common toxicities were haematological and gastrointestinal. Responses were observed more frequently at the MAD on the concurrent schedule compared with the sequential schedule in untreated AML (46% vs. 14%), relapsed/refractory AML (15% vs. 0%) and MDS (60% vs. 0%). Decitabine plus vorinostat given concurrently or sequentially appears to be safe and well-tolerated. Concurrent therapy shows promising clinical activity in AML or MDS, warranting further investigation. © 2014 John Wiley & Sons Ltd.

  5. Sensitivity and resistance towards isoliquiritigenin, doxorubicin and methotrexate in T cell acute lymphoblastic leukaemia cell lines by pharmacogenomics.

    Science.gov (United States)

    Youns, Mahmoud; Fu, Yu-Jie; Zu, Yuan-Gang; Kramer, Anne; Konkimalla, V Badireenath; Radlwimmer, Bernhard; Sültmann, Holger; Efferth, Thomas

    2010-09-01

    The development of drug resistance in cancer cells necessitates the identification of novel agents with improved activity towards cancer cells. In the present investigation, we compared the cytotoxicity of the chalcone flavonoide, isoliquiritigenin (ISL), with that of doxorubicin (DOX) and methotrexate (MTX) in five T cell acute lymphoblastic leukaemia (T-ALL) cell lines (Jurkat, J-Jhan, J16, HUT78 and Karpas 45). To gain insight into the molecular mechanisms which determine the response of T-ALL cells towards ISL, DOX and MTX, we applied array-based matrix comparative genomic hybridisation and microarray-based mRNA expression profiling and compared the genomic and transcriptomic profiles of the cell lines with their 50% inhibition (IC(50)) values for these three drugs. The IC(50) values for ISL did not correlate with those for DOX or MTX, indicating that ISL was still active in DOX- or MTX-unresponsive cell lines. Likewise, the genomic imbalances of chromosomal clones and mRNA expression profile significantly correlating with IC(50) values for ISL were different from thoses correlating with IC(50) values for DOX and MTX. In conclusion, ISL represents a cytotoxic natural product with activity towards T-ALL cell lines. There was no cross-resistance between ISL and DOX or MTX, and the genomic and transcriptomic profiles pointed to different molecular modes of action of ISL as compared to DOX and MTX, indicating that ISL may be a valuable adjunct for cancer therapy to treat otherwise drug-resistant tumours.

  6. Occurrence of graft-versus-host disease increases mortality after umbilical cord blood transplantation for acute myeloid leukaemia: a report from Eurocord and the ALWP of the EBMT.

    Science.gov (United States)

    Baron, F; Ruggeri, A; Beohou, E; Labopin, M; Mohty, M; Sanz, J; Vigouroux, S; Furst, S; Bosi, A; Chevallier, P; Cornelissen, J J; Michallet, M; Sierra, J; Karakasis, D; Savani, B N; Gluckman, E; Nagler, A

    2018-02-01

    The efficacy of umbilical cord blood transplantation (UCBT) as treatment for acute myeloid leukaemia (AML) relies on immune-mediated graft-versus-leukaemia effects. Previous studies have suggested a strong association between graft-versus-host disease (GVHD) occurrence and graft-versus-leukaemia effects after allogeneic hematopoietic cell transplantation. Here, we evaluated the kinetics of relapse rate in correlation with GVHD occurrence after UCBT. The kinetics of relapse rate over time in correlation to GVHD occurrence were assessed by calculating the relapse rate per patient-year within sequential 90-day intervals. The impact of GVHD on relapse and mortality was further studied in multivariate Cox models handling GVHD as a time-dependent covariate. The study included data from 1068 patients given single (n = 567) or double (n = 501) UCBT. The proportion of patients with grade II, III and IV acute GVHD was 20%, 7% and 4%, respectively. At 2 years, the cumulative incidence of chronic GVHD was 42%, the cumulative incidence of relapse was 32%, and overall survival was 32% as well. Relapse rates declined gradually over time during the first 30 months after transplantation. There was a possible suggestion that grade II-IV acute (HR = 0.8, P = 0.1) and chronic (HR = 0.65, P = 0.1) GVHD decreased relapse risk. However, grade II-IV acute GVHD significantly increased early (the first 18 months after UCBT) mortality (HR = 1.3, P = 0.02), whilst chronic GVHD increased each early (HR = 2.7, P chronic GVHD each increases overall mortality after UCBT for AML mitigating the possible graft-versus-leukemia effect of GVHD. © 2017 The Association for the Publication of the Journal of Internal Medicine.

  7. Use of arsenic trioxide in remission induction and consolidation therapy for acute promyelocytic leukaemia in the Australasian Leukaemia and Lymphoma Group (ALLG) APML4 study: a non-randomised phase 2 trial.

    Science.gov (United States)

    Iland, Harry J; Collins, Marnie; Bradstock, Ken; Supple, Shane G; Catalano, Alberto; Hertzberg, Mark; Browett, Peter; Grigg, Andrew; Firkin, Frank; Campbell, Lynda J; Hugman, Amanda; Reynolds, John; Di Iulio, Juliana; Tiley, Campbell; Taylor, Kerry; Filshie, Robin; Seldon, Michael; Taper, John; Szer, Jeff; Moore, John; Bashford, John; Seymour, John F

    2015-09-01

    Initial treatment of acute promyelocytic leukaemia traditionally involves tretinoin (all-trans retinoic acid) combined with anthracycline-based risk-adapted chemotherapy, with arsenic trioxide being the treatment of choice at relapse. To try to reduce the relapse rate, we combined arsenic trioxide with tretinoin and idarubicin in induction therapy, and used arsenic trioxide with tretinoin as consolidation therapy. Patients with previously untreated genetically confirmed acute promyelocytic leukaemia were eligible for this study. Eligibilty also required Eastern Cooperative Oncology Group performance status 0-3, age older than 1 year, normal left ventricular ejection fraction, Q-Tc interval less than 500 ms, absence of serious comorbidity, and written informed consent. Patients with genetic variants of acute promyelocytic leukaemia (fusion of genes other than PML with RARA) were ineligible. Induction comprised 45 mg/m(2) oral tretinoin in four divided doses daily on days 1-36, 6-12 mg/m(2) intravenous idarubicin on days 2, 4, 6, and 8, adjusted for age, and 0·15 mg/kg intravenous arsenic trioxide once daily on days 9-36. Supportive therapy included blood products for protocol-specified haemostatic targets, and 1 mg/kg prednisone daily as prophylaxis against differentiation syndrome. Two consolidation cycles with tretinoin and arsenic trioxide were followed by maintenance therapy with oral tretinoin, 6-mercaptopurine, and methotrexate for 2 years. The primary endpoints of the study were freedom from relapse and early death (within 36 days of treatment start) and we assessed improvement compared with the 2 year interim results. To assess durability of remission we compared the primary endpoints and disease-free and overall survival at 5 years in APML4 with the 2 year interim APML4 data and the APML3 treatment protocol that excluded arsenic trioxide. This study is registered with the Australian New Zealand Clinical Trials Registry, number ACTRN12605000070639. 124

  8. Impact of hydrochloric acid instillation on salvage of infected central venous catheters in children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Madsen, Mette; Rosthøj, Steen

    2013-01-01

    Bacteraemia associated with indwelling central venous catheters (CVC) causes significant morbidity in children with cancer. Hydrochloric acid (HCl) instillations have been reported to salvage CVCs with antibiotic-refractory infection. We implemented this treatment in 2002. The impact on the survival of CVCs has been evaluated in a retrospective cohort study of children with acute lymphoblastic leukaemia (ALL). Children with newly diagnosed ALL during 1999-2005 having their first CVC inserted before (n = 16) and after (n = 24) the introduction of the procedure were studied. All bacteraemic episodes were reviewed, recording bacteriological findings and treatment, and the time to premature or planned removal of the CVC was determined. In the comparison cohort, 31.0% (9/29) of bacteraemic episodes led to removal of the CVC, compared to 5.5% (2/36) in the intervention cohort (p = 0.01). Thus, the rate of catheter loss due to infection fell from 56.3% (9/16) to 8.3% (2/24) after introducing HCl treatment (p = 0.0025). Overall, the premature catheter removal rate fell from 75.0% (12/16) to 45.8% (11/24) (p = 0.10). Analysed in a CUSUM plot the reduced frequency of premature CVC removal evidently coincided with the introduction of the procedure. In a subgroup analysis of 21 monobacterial infections with coagulase-negative staphylococci, a decrease in systemic and lock antibiotic therapy was found. No adverse events were noted. HCl instillations significantly reduced the need to remove and replace CVCs. The procedure is practical, appears to be safe, and may reduce the consumption of antibiotics.

  9. Outcome of Childhood Acute Lymphoblastic Leukaemia after Induction Therapy --- Three-Year Experience in a Tertiary Care Hospital in Bangladesh

    Directory of Open Access Journals (Sweden)

    M Belayet Hossain

    2017-01-01

    Full Text Available Background: The incidence of different malignancies is increasing among the world populations. Acute lymphoblastic leukaemia (ALL is the most common of all the paediatric malignancies. Response to induction therapy is one of the most important predictors of long term outcome of ALL. Objective: To see the immediate outcome of paediatric ALL patients following induction therapy. Materials and Methods: This retrospective study was conducted from January 2013 to December 2015. Total 221 paediatric ALL patients were included in this study. Diagnosis was based on history, examination, blast cells count on peripheral blood film and bone marrow study, CSF study and immunophenotyping of peripheral blood/bone marrow aspirate in patients who were financially capable. Among them, parents of 40 (18% patients did not agree to start chemotherapy. According to Modified UK ALL 2003 protocol (Regimen A & B 181 patients were given induction therapy (vincristine, prednisolone, L-asparaginase, and daunomycin in high risk patients. Among them 14 patients discontinued, 10 patients died during chemotherapy and rest 157 patients completed induction phase. Bone marrow study was repeated after completion of induction therapy and remission pattern was seen. Results: Out of 157 chemotherapy completed patients, 137 (87% went into complete remission (25% blast cells in the bone marrow. Ten (5.5% patients died due to bleeding, febrile neutropenia and sepsis during the course of induction therapy. Conclusion: ALL in children is curable with effective chemotherapy. Poverty, ignorance and misconception regarding outcome are responsible for refusal and discontinuation of chemotherapy in third world countries like Bangladesh. Mortality and treatment cost can be reduced with the improvement of the facilities for isolation, barrier nursing and supportive treatment, and by creating awareness.

  10. Label-free imaging and identification of typical cells of acute myeloid leukaemia and myelodysplastic syndrome by Raman microspectroscopy.

    Science.gov (United States)

    Vanna, R; Ronchi, P; Lenferink, A T M; Tresoldi, C; Morasso, C; Mehn, D; Bedoni, M; Picciolini, S; Terstappen, L W M M; Ciceri, F; Otto, C; Gramatica, F

    2015-02-21

    In clinical practice, the diagnosis and classification of acute myeloid leukaemia (AML) and myelodysplastic syndrome (MDS) start from the manual examination of stained smears of bone marrow (BM) and peripheral blood (PB) by using an optical microscope. This step is subjective and scarcely reproducible. Therefore, the development of subjective and potentially automatable methods for the recognition of typical AML/MDS cells is necessary. Here we have used Raman spectroscopy for distinguishing myeloblasts, promyelocytes, abnormal promyelocytes and erhytroblasts, which have to be counted for a correct diagnosis and morphological classification of AML and MDS. BM samples from patients affected by four different AML subtypes, mostly characterized by the presence of the four subpopulations selected for this study, were analyzed. First, each cell was scanned by acquiring 4096 spectra, thus obtaining Raman images which demonstrate an accurate description of morphological features characteristic of each subpopulation. Raman imaging coupled with hierarchical cluster analysis permitted the automatic discrimination and localization of the nucleus, the cytoplasm, myeloperoxidase containing granules and haemoglobin. Second, the averaged Raman fingerprint of each cell was analysed by multivariate analysis (principal component analysis and linear discriminant analysis) in order to study the typical vibrational features of each subpopulation and also for the automatic recognition of cells. The leave-one-out cross validation of a Raman-based classification model demonstrated the correct classification of myeloblasts, promyelocytes (normal/abnormal) and erhytroblasts with an accuracy of 100%. Normal and abnormal promyelocytes were distinguished with 95% accuracy. The overall classification accuracy considering the four subpopulations was 98%. This proof-of-concept study shows that Raman micro-spectroscopy could be a valid approach for developing label-free, objective and automatic

  11. Acute myeloid leukaemia: expression of MYC protein and its association with cytogenetic risk profile and overall survival.

    Science.gov (United States)

    Mughal, Muhammad Kashif; Akhter, Ariz; Street, Lesley; Pournazari, Payam; Shabani-Rad, Meer-Taher; Mansoor, Adnan

    2017-09-01

    Acute myeloid leukaemia (AML) is a clinically aggressive disease with marked genetic heterogeneity. Cytogenetic abnormalities provide the basis for risk stratification into clinically favourable, intermediate, and unfavourable groups. There are additional genetic mutations, which further influence the prognosis of patients with AML. Most of these result in molecular aberrations whose downstream target is MYC. It is therefore logical to study the relationship between MYC protein expression and cytogenetic risk groups. We studied MYC expression by immunohistochemistry in a large cohort (n = 199) of AML patients and correlated these results with cytogenetic risk profile and overall survival (OS). We illustrated differential expression of MYC protein across various cytogenetic risk groups (p = 0.03). Highest expression of MYC was noted in AML patients with favourable cytogenetic risk group. In univariate analysis, MYC expression showed significant negative influence of OS in favourable and intermediate cytogenetic risk group (p = 0.001). Interestingly, MYC expression had a protective effect in the unfavourable cytogenetic risk group. In multivariate analysis, while age and cytogenetic risk group were significant factors influencing survival, MYC expression by immunohistochemistry methods also showed some marginal impact (p = 0.069). In conclusion, we have identified differential expression of MYC protein in relation to cytogenetic risk groups in AML patients and documented its possible impact on OS in favourable and intermediate cytogenetic risk groups. These preliminary observations mandate additional studies to further investigate the routine clinical use of MYC protein expression in AML risk stratification. Copyright © 2016 John Wiley & Sons, Ltd. Copyright © 2016 John Wiley & Sons, Ltd.

  12. Smoking and subsequent risk of acute myeloid leukaemia: A pooled analysis of 9 cohort studies in Japan.

    Science.gov (United States)

    Ugai, Tomotaka; Matsuo, Keitaro; Oze, Isao; Ito, Hidemi; Wakai, Kenji; Wada, Keiko; Nagata, Chisato; Nakayama, Tomio; Liu, Rong; Kitamura, Yuri; Tamakoshi, Akiko; Tsuji, Ichiro; Sugawara, Yumi; Sawada, Norie; Sadakane, Atsuko; Tanaka, Keitaro; Mizoue, Tetsuya; Inoue, Manami; Tsugane, Shoichiro; Shimazu, Taichi

    2018-02-01

    Smoking has been identified as a significant risk factor for acute myeloid leukaemia (AML). However, epidemiological evidence for the effect of smoking on the risk of AML among Asians is scarce. Here, we investigated the impact of smoking habits on the risk of AML by conducting a pooled analysis of 9 population-based prospective cohort studies in Japan. We analysed original data on smoking habits at baseline from 9 cohort studies. Hazard ratios (HRs) in the individual studies were calculated using a Cox proportional hazard model adjusted for potential confounders and combined using a random-effects model. During 4 808 175 person-years of follow-up for a total of 344 676 participants (165 567 men and 179 109 women), 245 AML cases (139 men and 106 women) were identified. For both sexes combined, current smokers had a marginally significant increased risk of AML compared to never smokers (HR = 1.44, 95% confidence interval [CI], 0.97-2.14). Ever smokers with more than 30 pack-years had a statistically significant increased risk of AML compared to never smokers among both sexes combined (HR = 1.66, 95% CI, 1.06-2.63). By sex, this significant association was observed only among men, with an HR of 1.69 (95% CI, 1.00-2.87) for ever smokers with more than 30 pack-years relative to never smokers. In conclusion, this study confirmed that cigarette smoking increases the risk of AML in Japanese. This study provides important evidence that smoking increases the risk of AML among Asians, which has already been shown in Western populations. Copyright © 2017 John Wiley & Sons, Ltd.

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

    Science.gov (United States)

    Jiménez-Hernández, Elva; Jaimes-Reyes, Ethel Zulie; Arellano-Galindo, José; García-Jiménez, Xochiketzalli; Tiznado-García, Héctor Manuel; Sánchez-Jara, Berenice; Bekker-Méndez, Vilma Carolina; Ortíz-Torres, María Guadalupe; Ortíz-Fernández, Antonio; Marín-Palomares, Teresa; Mejía-Aranguré, Juan Manuel

    2015-01-01

    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. PMID:25922837

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

    DEFF Research Database (Denmark)

    Forestier, Erik; Heyman, Mats; Andersen, Mette K

    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...

  15. Randomized trial of two schedules of low-dose gemtuzumab ozogamicin as induction monotherapy for newly diagnosed acute myeloid leukaemia in older patients not considered candidates for intensive chemotherapy. A phase II study of the EORTC and GIMEMA leukaemia groups (AML-19).

    NARCIS (Netherlands)

    Amadori, S.; Suciu, S.; Selleslag, D.; Stasi, R.; Alimena, G.; Baila, L.; Rizzoli, V.; Borlenghi, E.; Gaidano, G.; Magro, D.; Torelli, G.; Muus, P.; Venditti, A.; Cacciola, E.; Lauria, F; Vignetti, M.; Witte, T.J.M. de

    2010-01-01

    This study compared two schedules of low-dose gemtuzumab ozogamicin (GO) as induction monotherapy for untreated acute myeloid leukaemia in older patients unfit for intensive chemotherapy, to identify the more promising regimen for further study. Patients were randomized to receive either best

  16. Acute leukaemia with a pure erythroid phenotype: under-recognized morphological and cytogenetic signatures associated universally with primary refractory disease and a dismal clinical outcome.

    Science.gov (United States)

    Park, David C; Ozkaya, Neval; Lovitch, Scott B

    2017-08-01

    Pure erythroid leukaemia (PEL) is an extremely rare and aggressive subtype of acute myeloid leukaemia defined by the World Health Organization (WHO) as a neoplastic proliferation of immature cells committed exclusively to the erythroid lineage, comprising >80% of bone marrow cells and not meeting the criteria of other well-defined myeloid neoplasms. The aim of this study was to describe the clinicopathological features of acute leukaemias with a pure erythroid phenotype (ALPEP) irrespective of their WHO classification and to determine if ALPEP represents a distinct clinicopathological entity. We identified seven cases of ALPEP, in which immature cells fulfilled WHO morphological and immunophenotypical criteria for PEL. All patients except one were male, with a median age of 60 years. Three cases represented de novo PEL, three were therapy-related myeloid neoplasms and one was a blast phase of a myeloproliferative neoplasm. Extensive tumour necrosis was present in five cases (71%). Five cases with available modal karyotypes all demonstrated a complex karyotype involving the TP53 gene locus, with three cases (60%) also showing a monosomy 5 or deletion 5q and additional material on chromosome 19q13. All patients died of their disease, with a mean overall survival of 189 and 64.7 days in cases without and with necrosis on the initial biopsy, respectively. We describe previously unreported but relatively common findings of extensive tumour necrosis and recurring cytogenetic abnormalities in ALPEP. Our findings suggest strongly that ALPEP represents a distinct clinicopathological entity regardless of its WHO classification. © 2017 John Wiley & Sons Ltd.

  17. 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).

    Science.gov (United States)

    Panagopoulos, Ioannis; Kerndrup, Gitte; Carlsen, Niels; Strömbeck, Bodil; Isaksson, Margareth; Johansson, Bertil

    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 in leukaemias; however, it encodes a protein that specifically interacts with SET, fused to NUP214 in a case of acute undifferentiated leukaemia.

  18. Secondary cancers among children with acute lymphoblastic leukaemia treated by the Tokyo Children's Cancer Study Group protocols: a retrospective cohort study.

    Science.gov (United States)

    Ishida, Yasushi; Maeda, Miho; Urayama, Kevin Y; Kiyotani, Chikako; Aoki, Yuki; Kato, Yoko; Goto, Shoko; Sakaguchi, Sachi; Sugita, Kenichi; Tokuyama, Mika; Nakadate, Naoya; Ishii, Eizaburo; Tsuchida, Masahiro; Ohara, Akira

    2014-01-01

    With improvement in survival, it is important to evaluate the impact of treatment on secondary cancers in acute lymphoblastic leukaemia (ALL) survivors. A retrospective cohort study comprising 2918 children diagnosed with ALL and enrolled on Tokyo Children's Cancer Study Group (TCCSG) protocols between 1984 and 2005 was conducted to evaluate the incidence of secondary cancers and associated factors including treatment protocol, cranial irradiation and other characteristics of the primary ALL. Thirty-seven patients developed secondary cancers, including acute myeloid leukaemia (n = 11), myelodysplastic syndrome (n = 5), non-Hodgkin lymphoma (n = 2), brain tumours (n = 13) and other solid carcinomas (n = 6) within a median follow-up duration of 9·5 years. The cumulative incidence of any secondary cancers was 1·0% (95% confidence interval (CI), 0·7-1·4%) at 10 years and 2·4% (95% CI, 1·5-3·7%) at 20 years, respectively. Standardized incidence rate ratio of secondary cancers was 9·3 (95% CI, 6·5-12·8). Multivariate analyses showed an increased risk of secondary cancers associated with the recent treatment protocol and cranial irradiation. There was no evidence of a reduction in secondary cancer incidence despite marked decreases in cranial irradiation use in the recent protocols. © 2013 John Wiley & Sons Ltd.

  19. Oxindole alkaloids from Uncaria tomentosa induce apoptosis in proliferating, G0/G1-arrested and bcl-2-expressing acute lymphoblastic leukaemia cells.

    Science.gov (United States)

    Bacher, Nicole; Tiefenthaler, Martin; Sturm, Sonja; Stuppner, Hermann; Ausserlechner, Michael J; Kofler, Reinhard; Konwalinka, Günther

    2006-03-01

    Natural products are still an untapped source of promising lead compounds for the generation of antineoplastic drugs. Here, we investigated for the first time the antiproliferative and apoptotic effects of highly purified oxindole alkaloids, namely isopteropodine (A1), pteropodine (A2), isomitraphylline (A3), uncarine F (A4) and mitraphylline (A5) obtained from Uncaria tomentosa, a South American Rubiaceae, on human lymphoblastic leukaemia T cells (CCRF-CEM-C7H2). Four of the five tested alkaloids inhibited proliferation of acute lymphoblastic leukaemia cells. Furthermore, the antiproliferative effect of the most potent alkaloids pteropodine (A2) and uncarine F (A4) correlated with induction of apoptosis. After 48 h, 100 micromol/l A2 or A4 increased apoptotic cells by 57%. CEM-C7H2 sublines with tetracycline-regulated expression of bcl-2, p16ink4A or constitutively expressing the cowpox virus protein crm-A were used for further studies of the apoptosis-inducing properties of these alkaloids. Neither overexpression of bcl-2 or crm-A nor cell-cycle arrest in G0/G1 phase by tetracycline-regulated expression of p16INK4A could prevent alkaloid-induced apoptosis. Our results show the strong apoptotic effects of pteropodine and uncarine F on acute leukaemic lymphoblasts and recommend the alkaloids for further studies in xenograft models.

  20. The relationship between pain, fatigue, sleep disorders and quality of life in adult patients with acute leukaemia: During the first year after diagnosis.

    Science.gov (United States)

    Miladinia, Mojtaba; Baraz, Shahram; Ramezani, Monir; Malehi, Amal Saki

    2018-01-01

    The aim of this study was to investigate the relationship between pain, fatigue, sleep disorders and quality of life and assess the most powerful predictor of quality of life in patients with acute leukaemia. In this cross-sectional multicentre study, 406 patients were recruited. Data were collected using the Iranian Short-Form 36-item Health Survey, the Pittsburgh Sleep Quality Index, and the Numeric Rating Scale for Pain and Fatigue Intensity. It was found that pain and fatigue had direct relationship with sleep disorders. Statistically significant relationships were reported between pain, fatigue, sleep disorders and QoL. Also, a statistically significant relationship was found between pain and QoL (p sleep disorders in total had the predictive power for quality of life (R 2  = 36%). The most powerful predictor of quality of life was pain. It is suggested that healthcare professionals note the importance of patients' symptoms in clinical investigations and take appropriate measures for their management. The assessment of pain as the most powerful predictor of quality of life can be considered a basis for the improvement of quality of life, fatigue and sleep quality in patients with acute leukaemia. © 2017 John Wiley & Sons Ltd.

  1. A review of therapy-related myelodysplastic syndromes and acute myeloid leukaemia (t-MDS/AML) in Irish patients: a single centre experience.

    Science.gov (United States)

    Maung, Su W; Burke, Cathie; Hayde, Jennifer; Walshe, Janice; McDermott, Ray; Desmond, Ronan; McHugh, Johnny; Enright, Helen

    2017-07-01

    To demonstrate the incidence, characteristics, treatment and outcomes of patients with therapy-related myelodysplastic syndromes and therapy-related acute myeloid leukaemia (t-MDS/AML) in a tertiary referral centre. Patients meeting the diagnostic criteria for t-MDS/AML from 2003 to 2014 were reviewed to analyse their diagnostic features, details of antecedent disorder and treatment, approach to management and survival. 39 patients who developed t-MDS/AML were identified with incidence of 8.7%. Median age and gender distribution were similar to de novo MDS but t-MDS/AML patients had greater degree of cytopenia and adverse karyotypes. Time to development of t-MDS/AML was shortest for patients with antecedent haematological malignancy compared to solid tumours and autoimmune disorders (46, 85 and 109 months). Patients with prior acute leukaemia had the shortest latency and poor overall survival. Treatment options included best supportive care (56%), Azacitidine (31%) or intensive chemotherapy/allogeneic transplant (13%). Median OS of all patients was 14 months. Survival declined markedly after two years and 5-year OS was 13.8%. Longer survival was associated with blast count MDS/AML patients showed unique characteristics which influenced their treatment and outcomes. IPSS-R may be useful in risk-adapted treatment approaches and can predict outcomes. Survival remains poor but improved outcomes were seen with allogeneic transplantation. Azacitidine may be effective in patients unfit for intensive therapies.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    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 heter......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 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...... follow-up. Two patients relapsed, and both were MRD positive in BM after first induction course. A total of three relapses occurred, and they were detected by RT-qPCR 3 wks before haematological relapse was diagnosed. CONCLUSION: This MLL-MLLT3 RT-qPCR assay could be useful in MRD monitoring of a group...

  3. Population pharmacokinetics of cytarabine, etoposide and daunorubicin in the treatment of acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Krogh-Madsen, Mikkel; Bender, B.; Jensen, M. K.

    2012-01-01

    insights into the PK of this combination treatment. METHODS: A prospective population PK study of twenty-three patients with acute myeloid leukemia was undertaken. Plasma concentrations of patients were determined by high-pressure liquid chromatography. PK models were developed with NONMEM......PURPOSE: Interpatient variability in the pharmacokinetics (PK) of cytarabine, etoposide, and daunorubicin following body surface area-adjusted doses calls for studies that point to other covariates to explain this variability. The purpose of this study was to investigate such relationships and give......(®); for daunorubicin, PK information from a prior study was utilized. RESULTS: Baseline white blood cell count (bWBC) influenced the PK for all drugs. A small, statistically insignificant improvement in model fit was achieved when a relationship between bWBC and daunorubicin central volume of distribution was included...

  4. The TEL-AML1 real-time quantitative polymerase chain reaction (PCR) might replace the antigen receptor-based genomic PCR in clinical minimal residual disease studies in children with acute lymphoblastic leukaemia

    NARCIS (Netherlands)

    de Haas, V.; Breunis, W. B.; dee, R.; Verhagen, O. J. H. M.; Kroes, W.; van Wering, E. R.; van Dongen, J. J. M.; van den Berg, H.; van der Schoot, C. E.

    2002-01-01

    Prospective studies in children with B-precursor acute lymphoblastic leukaemia (ALL) have shown that polymerase chain reaction (PCR)-based detection of minimal residual disease (MRD) using immunoglobin (Ig) and T-cell receptor (TCR) gene rearrangements as targets can be used to identify patients

  5. Hyperleucocytosis in paediatric acute myeloid leukaemia - the challenge of white blood cell counts above 200 × 10(9) /l. The NOPHO experience 1984-2014

    DEFF Research Database (Denmark)

    Zeller, Bernward; Glosli, Heidi; Forestier, Erik

    2017-01-01

    Hyperleucocytosis in paediatric acute myeloid leukaemia (AML) is associated with increased morbidity and mortality. We studied hyperleucocytosis in 890 patients with AML aged 0-18 years registered in the Nordic Society of Paediatric Haematology and Oncology (NOPHO) registry, with special focus on...

  6. Expression of co-stimulatory and adhesion molecules and chemokine or apoptosis receptors on acute myeloid leukaemia : high CD40 and CD11a expression correlates with poor prognosis

    NARCIS (Netherlands)

    Brouwer, RE; Hoefnagel, J; van der Burg, BB; Jedema, [No Value; Zwinderman, KH; Starrenburg, ICW; Kluin-Nelemans, HC; Barge, RMY; Willemze, R; Falkenburg, JHF

    2001-01-01

    The expression of adhesion and co-stimulatory molecules. and chemokine and death receptors such as tumour necrosis factor (TNF) and FAS on acute myeloid leukaemia (AML) may influence the biology of the disease and response to chemotherapy and immunotherapy. In this study, we analysed the expression

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

    Directory of Open Access Journals (Sweden)

    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.

  8. Lymphatic Leukaemia* In Acute

    African Journals Online (AJOL)

    S. Afr. Med. J., 45, 867 (1971). Pneumocystis carinii is an organism which causes a diffuse pulmonary alveolar infestation in man. The organism was recognized and classified as a protozoan 60 years ago by. Chagas and CariniY This rare and usually fatal disease occurs in young babies;" or in individuals whose capacity.

  9. 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

    DEFF Research Database (Denmark)

    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...... was unmethylated in 10/10 bone marrow and 7/7 blood samples from healthy individuals, the gene was hypermethylated in 43% of the AML patients. The RARbeta2 degree of promoter methylation differed between and within individuals, and the mRNA transcription levels of the gene varied inter-individually by a factor...... of 4000. A significant inverse correlation between promoter hypermethylation and gene expression could be established (t-test, P = 0.019). Comparison of methylation data with a series of other molecular alterations in the same patient materials revealed a correlation between hypermethylation...

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

    DEFF Research Database (Denmark)

    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...... was a major concomitant factor for death. No significant associations between CHIT1 polymorphism and sepsis (P = 0.85) or death caused by sepsis (P = 0.14) were found. Furthermore, no significant associations between MBL2 polymorphism and sepsis (P = 0.76) or death caused by sepsis (P = 0.24) were observed...... in children with AML, and polymorphism in the MBL-coding gene (MBL2) seems to modify the risk of infections in several patient groups. The purpose of this study was to investigate the possible associations between polymorphisms in CHIT1, MBL2 and sepsis in adult patients treated with high-dose chemotherapy...

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

    DEFF Research Database (Denmark)

    Tierens, Anne; Bjørklund, Elizabeth; Siitonen, Sanna

    2016-01-01

    Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society...... of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after...... first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively (P consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively (P

  12. Guadecitabine (SGI-110) in treatment-naive patients with acute myeloid leukaemia: phase 2 results from a multicentre, randomised, phase 1/2 trial.

    Science.gov (United States)

    Kantarjian, Hagop M; Roboz, Gail J; Kropf, Patricia L; Yee, Karen W L; O'Connell, Casey L; Tibes, Raoul; Walsh, Katherine J; Podoltsev, Nikolai A; Griffiths, Elizabeth A; Jabbour, Elias; Garcia-Manero, Guillermo; Rizzieri, David; Stock, Wendy; Savona, Michael R; Rosenblat, Todd L; Berdeja, Jesus G; Ravandi, Farhad; Rock, Edwin P; Hao, Yong; Azab, Mohammad; Issa, Jean-Pierre J

    2017-10-01

    The hypomethylating drugs azacitidine and decitabine have shown efficacy in myelodysplastic syndromes and acute myeloid leukaemia, but complete tumour responses are infrequent and of short duration, possibly because of the short half-lives and suboptimal bone marrow exposure of the drugs. Guadecitabine, a next-generation hypomethylating drug, has a longer half-life and exposure than its active metabolite decitabine. A phase 1 study established 60 mg/m 2 guadecitabine for 5 days as an effective treatment schedule. In this phase 2 study, we aimed to assess the safety and activity of two doses and schedules of guadecitabine in older (≥65 years) patients with treatment-naive acute myeloid leukaemia who were not candidates for intensive chemotherapy. We did a multicentre, randomised, open-label, phase 1/2 study of guadecitabine in cohorts of patients with treatment-naive acute myeloid leukaemia, relapsed or refractory acute myeloid leukaemia, and myelodysplastic syndromes; here we report the phase 2 results from the cohort of treatment-naive patients with acute myeloid leukaemia. We included patients aged at least 65 years from 14 US medical centres (hospitals and specialist cancer clinics) who were not candidates for intensive chemotherapy and randomly assigned them (1:1) using a computer algorithm (for dynamic randomisation) to guadecitabine 60 or 90 mg/m 2 on days 1-5 (5-day schedule) of a 28-day treatment cycle. Treatment allocation was not masked. We also assigned additional patients to guadecitabine 60 mg/m 2 in a 10-day schedule in a 28-day treatment cycle after a protocol amendment. The primary endpoint was composite complete response (complete response, complete response with incomplete platelet recovery, or complete response with incomplete neutrophil recovery regardless of platelets). Response was assessed in all patients (as-treated) who received at least one dose of guadecitabine. We present the final analysis, although at the time of the database lock

  13. Leukaemia risks and exposure to ionizing radiations. ASN seminar, Tuesday, June 9, 2015, report

    International Nuclear Information System (INIS)

    Niel, Jean-Christophe; Samain, Jean-Paul; Colonna, Marc; Maynadie, Marc; Richardson, David; Bey, Pierre; Leuraud, Klervi; Laurier, Dominique; Hemon, Denis; Spycher, Ben; Kosti, Ourania; Bouville, Andre; Grosche, Bernd; Ziegelberger, Gunde; Kesminiene, Ausrele; Clavel, Jacqueline; Smeesters, Patrick; Murith, Christophe

    2015-08-01

    This seminar aims at proposing a review of present knowledge on leukaemia risks for children and adults associated with ionizing radiations, and at sharing knowledge between experts. After an introduction which outlined the interest of the ASN in research issues, and the importance awarded by the ASN to the variety of points of view, a first session addressed leukaemia and exposures to ionizing radiations. The contributions addressed some general aspects (an overview of leukaemia in France, the different types of adult and child leukaemia), leukaemia and acute exposures to ionizing radiations (ionizing radiation and leukaemia among Japanese bomb survivors, risks of leukaemia after radiotherapy), leukaemia and chronic exposures to ionizing radiations (assessment of epidemiological studies for adult chronic exposures). The second session addressed childhood leukaemia and ionizing radiations. The contributions of this second session more particularly addressed the following topics: childhood leukaemia and natural radioactivity (French studies, synthesis of international studies and a new Swiss study), childhood leukaemia and proximity of nuclear base installations (assessment of national and international studies, analysis of cancer risks in populations near nuclear facilities in the US, calculation of dose at the medulla as example of dosimetry of ionizing radiations and leukaemia, conclusions of the 2012 MELODI workshop), childhood leukaemia and scanner (recent results and perspectives), childhood leukaemia and other risk factors (etiology of childhood leukaemia - presentation of French studies initiated by the INSERM, and presentation of studies initiated by BfS)

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  15. Nuclear power and leukaemia

    International Nuclear Information System (INIS)

    Grimston, M.

    1991-03-01

    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)

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

    Directory of Open Access Journals (Sweden)

    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.

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

    DEFF Research Database (Denmark)

    Marklund, Maria; Rostgaard, Klaus; Hjalgrim, Lisa

    2013-01-01

    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...

  18. Meeting Report: Institute for Social Security and Services for State Workers (ISSSTE on Acute Lymphoblastic Leukaemia, Mexico City, Mexico, 3rd to 4th October 2016

    Directory of Open Access Journals (Sweden)

    Alvarado Ibarra Martha

    2017-06-01

    Full Text Available From October 3 to 4, 2016, the fourth meeting of haematologists who belonged to the institute for social security and services for state workers (ISSSTE was held, the meeting was held in Mexico City, Mexico. Attending this working meeting, medical fellows of the specialty of Haematology and Paediatric Haematology, as well as attached doctors of both specialties that work in different hospitals in Mexico City and the rest of the country, the purpose of the attendees to this consensus was discuss, update, and homogenize the protocols of diagnostic and therapeutic approach in patients with acute lymphoblastic leukaemia of all ages. All participants appreciated the opportunity to participate in one of the most important cooperation projects of the ISSSTE and to be able to offer updated treatment protocols to this population or, failing that, to send them a Medical Center that can provide hospital care as soon as possible. Physicians took advantage of this meeting for the scientific exchange, the discussion on projects in course and were planned the development of other consensuses being the closest the one of lymphomas. As in the previous consensuses that were published in a National magazine. The coordinator of this project raised to the attendees the possibility of a publication in magazines of greater prestige international since in countries like Mexico the cooperative work is not frequent and the group of haematologists belonging to ISSSTE are working towards this goal. This consensus was considered as a very well-organized platform to support the research of young fellows in the specialty to stimulate the team work in protocols of the different haematological pathologies and to inform the world the results achieved in a population of patients attended by the ISSSTE. In agreement with the main objective of this consensus on acute lymphoblastic leukaemia once finished and discussed throughout the haematological group, the coordinator for the

  19. The pyrrolo-1,5-benzoxazepine, PBOX-15, enhances TRAIL-induced apoptosis by upregulation of DR5 and downregulation of core cell survival proteins in acute lymphoblastic leukaemia cells

    Science.gov (United States)

    NATHWANI, SEEMA-MARIA; GREENE, LISA M.; BUTINI, STEFANIA; CAMPIANI, GIUSEPPE; WILLIAMS, D. CLIVE; SAMALI, AFSHIN; SZEGEZDI, EVA; ZISTERER, DANIELA M.

    2016-01-01

    Apoptotic defects are frequently associated with poor outcome in pediatric acute lymphoblastic leukaemia (ALL) hence there is an ongoing demand for novel strategies that counteract apoptotic resistance. The death ligand TRAIL (tumour necrosis factor-related apoptosis-inducing ligand) and its selective tumour receptor system has attracted exceptional clinical interest. However, many malignancies including ALL are resistant to TRAIL monotherapy. Tumour resistance can be overcome by drug combination therapy. TRAIL and its agonist antibodies are currently undergoing phase II clinical trials with established chemotherapeutics. Herein, we present promising therapeutic benefits in combining TRAIL with the selective anti-leukaemic agents, the pyrrolo-1,5-benzoxazepines (PBOXs) for the treatment of ALL. PBOX-15 synergistically enhanced apoptosis induced by TRAIL and a DR5-selective TRAIL variant in ALL-derived cells. PBOX-15 enhanced TRAIL-induced apoptosis by dual activation of extrinsic and intrinsic apoptotic pathways. The specific caspase-8 inhibitor, Z-IETD-FMK, identified the extrinsic pathway as the principal mode of apoptosis. We demonstrate that PBOX-15 can enhance TRAIL-induced apoptosis by upregulation of DR5, reduction of cellular mitochondrial potential, activation of the caspase cascade and downregulation of PI3K/Akt, c-FLIP, Mcl-1 and IAP survival pathways. Of note, the PI3K pathway inhibitor LY-294002 significantly enhanced the apoptotic potential of TRAIL and PBOX-15 validating the importance of Akt downregulation in the TRAIL/PBOX-15 synergistic combination. Considering the lack of cytotoxicity to normal cells and ability to downregulate several survival pathways, PBOX-15 may represent an effective agent for use in combination with TRAIL for the treatment of ALL. PMID:27176505

  20. Detection of BCR-ABL and E2A-PBX1 fusion genes by RT-PCR in acute lymphoblastic leukaemia with failed or normal cytogenetics.

    Science.gov (United States)

    Devaraj, P E; Foroni, L; Kitra-Roussos, V; Secker-Walker, L M

    1995-02-01

    To evaluate the use of molecular analysis as a complement to karyotypic analysis in the detection of specific chromosomal abnormalities, the occurrence of t(1;19)(q23;p13) and t(9;22)(q34;q11) was investigated by RT-PCR in 43 diagnostic acute lymphoblastic leukaemia cases in whom cytogenetic investigations had failed (32 cases) or showed only a normal karyotype (> or = 20 normal metaphases, 11 cases). One child (aged 14 years) and five adults (aged 18-60 years) were BCR-ABL positive on first round for M-BCR-ABL (one case) or m-BCR-ABL (one case), or on nested PCR for m-BCR-ABL (three cases). Co-expression of M-BCR-ABL (first-round PCR) and m-BCR-ABL (nested PCR was seen in one case. One m-BCR-ABL-positive case also expressed the E2A-PBX1 fusion transcript. Patients positive for the transcript(s) were older, had higher white blood cell counts and a significantly poorer event-free survival (P < 0.001) than those negative for the transcript.

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

    International Nuclear Information System (INIS)

    Ippolito, D.; Masetto, A.; Franzesi, C.T.; Bonaffini, P.A.; Sironi, S.; Sala, A.; Biondi, A.

    2016-01-01

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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

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

    Science.gov (United States)

    Ippolito, D; Masetto, A; Franzesi, C Talei; Bonaffini, P A; Sala, A; Biondi, A; Sironi, S

    2016-04-01

    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.

  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

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  5. A prospective phase II randomized study of deferasirox to prevent iatrogenic iron overload in patients undertaking induction/consolidation chemotherapy for acute myeloid leukaemia.

    Science.gov (United States)

    Kennedy, Glen A; Morris, Kirk L; Subramonpillai, Elango; Curley, Cameron; Butler, Jason; Durrant, Simon

    2013-06-01

    This prospective randomized phase II study aimed to determine the safety and efficacy of deferasirox in preventing iatrogenic iron overload in patients receiving induction/consolidation chemotherapy for acute myeloid leukaemia (AML) ize. Serum ferritin, transferrin saturation and CRP were measured pre-, mid- and post- each chemotherapy cycle. Patients were randomized to receive either therapy with deferasirox vs. no deferasirox therapy once serum ferritin increased to >500 μg/l. The trial was stopped prematurely due to excess gastrointestinal (GI) and infectious toxicity demonstrable in the deferasirox arm, after 10 patients had been randomized to deferasirox and 6 patients to the control arm. Overall, deferasirox was poorly tolerated, with median maximum tolerated dose only 13·8 mg/kg/d and no patient able to tolerate doses >20 mg/kg/d. Median duration of deferasirox therapy was only 72 d (range 19-130 d), with 9/10 patients requiring unplanned dose interruptions and 4/10 patients unable to continue the drug predominantly due to GI effects. Although all 3 treatment-related deaths occurred in the deferasirox arm (P = 0·25), median overall survival was similar between treatment arms. Use of deferasirox to prevent iatrogenic iron overload in AML patients undertaking induction/consolidation is poorly tolerated and appears to be associated with excess GI and infectious toxicity. © 2013 John Wiley & Sons Ltd.

  6. Pevonedistat (MLN4924), a First-in-Class NEDD8-activating enzyme inhibitor, in patients with acute myeloid leukaemia and myelodysplastic syndromes: a phase 1 study.

    Science.gov (United States)

    Swords, Ronan T; Erba, Harry P; DeAngelo, Daniel J; Bixby, Dale L; Altman, Jessica K; Maris, Michael; Hua, Zhaowei; Blakemore, Stephen J; Faessel, Hélène; Sedarati, Farhad; Dezube, Bruce J; Giles, Francis J; Medeiros, Bruno C

    2015-05-01

    This trial was conducted to determine the dose-limiting toxicities (DLTs) and maximum tolerated dose (MTD) of the first in class NEDD8-activating enzyme (NAE) inhibitor, pevonedistat, and to investigate pevonedistat pharmacokinetics and pharmacodynamics in patients with acute myeloid leukaemia (AML) and myelodysplastic syndromes (MDS). Pevonedistat was administered via a 60-min intravenous infusion on days 1, 3 and 5 (schedule A, n = 27), or days 1, 4, 8 and 11 (schedule B, n = 26) every 21-days. Dose escalation proceeded using a standard '3 + 3' design. Responses were assessed according to published guidelines. The MTD for schedules A and B were 59 and 83 mg/m(2) , respectively. On schedule A, hepatotoxicity was dose limiting. Multi-organ failure (MOF) was dose limiting on schedule B. The overall complete (CR) and partial (PR) response rate in patients treated at or below the MTD was 17% (4/23, 2 CRs, 2 PRs) for schedule A and 10% (2/19, 2 PRs) for schedule B. Pevonedistat plasma concentrations peaked after infusion followed by elimination in a biphasic pattern. Pharmacodynamic studies of biological correlates of NAE inhibition demonstrated target-specific activity of pevonedistat. In conclusion, administration of the first-in-class agent, pevonedistat, was feasible in patients with MDS and AML and modest clinical activity was observed. © 2015 John Wiley & Sons Ltd.

  7. 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

    Science.gov (United States)

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

    2018-01-01

    SUMMARY The optimal management of asparaginase-associated thrombotic complications is not well-defined. We report the features, management, and outcome of paediatric (ages 0–18 years) and adult (18–50 years) 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 >30 years 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. 30 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

  8. Treatment of acute lymphoblastic leukaemia with the second generation of CD19 CAR-T containing either CD28 or 4-1BB.

    Science.gov (United States)

    Li, Shiqi; Zhang, Jiasi; Wang, Meiling; Fu, Gang; Li, Yunyan; Pei, Li; Xiong, Zhouxing; Qin, Dabing; Zhang, Rui; Tian, Xiaobo; Wei, Zhihao; Chen, Run; Chen, Xuejiao; Wan, Jia; Chen, Jun; Wei, Xia; Xu, Yanmin; Zhang, Pei; Wang, Ping; Peng, Xi; Yang, Sainan; Shen, Junjie; Yang, Zhi; Chen, Jieping; Qian, Cheng

    2018-04-10

    T cells modified with anti-CD19 chimeric antigen receptor (CAR) containing either CD28 or 4-1BB (also termed TNFRSF9, CD137) costimulatory signalling have shown great potential in the treatment of acute lymphoblastic leukaemia (ALL). However, the difference between CD28 and 4-1BB costimulatory signalling in CAR-T treatment has not been well elucidated in clinical trials. In this study, we treated 10 relapsed or refractory ALL patients with the second generation CD19 CAR-T. The first 5 patients were treated with CD28-CAR and the other 5 patients were treated with 4-1BB CAR-T. All the 10 patients were response-evaluable. Three patients achieved complete remission and 1 patient with extramedullary disease achieved partial response after CD28-CAR-T treatment. In the 4-1BB CAR-T treatment group, 3 patients achieved complete remission. Furthermore, FLT-3 ligand (FLT3LG) was highly correlated with response time and may serve as a prognosis factor. No severe adverse events were observed in these 10 treated patients. Our study showed that both CD28 CAR-T and 4-1BB CAR-T both worked for response but they differed in response pattern (peak reaction time, reaction lasting time and reaction degree), adverse events, cytokine secretion and immune-suppressive factor level. © 2018 John Wiley & Sons Ltd.

  9. A variant at 9p21.3 functionally implicates CDKN2B in paediatric B-cell precursor acute lymphoblastic leukaemia aetiology.

    Science.gov (United States)

    Hungate, Eric A; Vora, Sapana R; Gamazon, Eric R; Moriyama, Takaya; Best, Timothy; Hulur, Imge; Lee, Younghee; Evans, Tiffany-Jane; Ellinghaus, Eva; Stanulla, Martin; Rudant, Jéremie; Orsi, Laurent; Clavel, Jacqueline; Milne, Elizabeth; Scott, Rodney J; Pui, Ching-Hon; Cox, Nancy J; Loh, Mignon L; Yang, Jun J; Skol, Andrew D; Onel, Kenan

    2016-02-12

    Paediatric B-cell precursor acute lymphoblastic leukaemia (BCP-ALL) is the most common cancer of childhood, yet little is known about BCP-ALL predisposition. In this study, in 2,187 cases of European ancestry and 5,543 controls, we discover and replicate a locus indexed by rs77728904 at 9p21.3 associated with BCP-ALL susceptibility (Pcombined=3.32 × 10(-15), OR=1.72) and independent from rs3731217, the previously reported ALL-associated variant in this region. Of correlated SNPs tagged by this locus, only rs662463 is significant in African Americans, suggesting it is a plausible causative variant. Functional analysis shows that rs662463 is a cis-eQTL for CDKN2B, with the risk allele associated with lower expression, and suggests that rs662463 influences BCP-ALL risk by regulating CDKN2B expression through CEBPB signalling. Functional analysis of rs3731217 suggests it is associated with BCP-ALL by acting within a splicing regulatory element determining CDKN2A exon 3 usage (P=0.01). These findings provide new insights into the critical role of the CDKN2 locus in BCP-ALL aetiology.

  10. A risk score including microdeletions improves relapse prediction for standard and medium risk precursor B-cell acute lymphoblastic leukaemia in children.

    Science.gov (United States)

    Sutton, Rosemary; Venn, Nicola C; Law, Tamara; Boer, Judith M; Trahair, Toby N; Ng, Anthea; Den Boer, Monique L; Dissanayake, Anuruddhika; Giles, Jodie E; Dalzell, Pauline; Mayoh, Chelsea; Barbaric, Draga; Revesz, Tamas; Alvaro, Frank; Pieters, Rob; Haber, Michelle; Norris, Murray D; Schrappe, Martin; Dalla Pozza, Luciano; Marshall, Glenn M

    2018-02-01

    To prevent relapse, high risk paediatric acute lymphoblastic leukaemia (ALL) is treated very intensively. However, most patients who eventually relapse have standard or medium risk ALL with low minimal residual disease (MRD) levels. We analysed recurrent microdeletions and other clinical prognostic factors in a cohort of 475 uniformly treated non-high risk precursor B-cell ALL patients with the aim of better predicting relapse and refining risk stratification. Lower relapse-free survival at 7 years (RFS) was associated with IKZF1 intragenic deletions (P 5 × 10 -5 (P < 0·0001) and High National Cancer Institute (NCI) risk (P < 0·0001). We created a predictive model based on a risk score (RS) for deletions, MRD and NCI risk, extending from an RS of 0 (RS0) for patients with no unfavourable factors to RS2 +  for patients with 2 or 3 high risk factors. RS0, RS1, and RS2 +  groups had RFS of 93%, 78% and 49%, respectively, and overall survival (OS) of 99%, 91% and 71%. The RS provided greater discrimination than MRD-based risk stratification into standard (89% RFS, 96% OS) and medium risk groups (79% RFS, 91% OS). We conclude that this RS may enable better early therapeutic stratification and thus improve cure rates for childhood ALL. © 2017 John Wiley & Sons Ltd.

  11. 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

    International Nuclear Information System (INIS)

    Rijn, Rick R. van; Wittenberg, Rianne; Boot, Annemieke; Sluis, Inge M. van der; MuinckKeizer-Schrama, Sabine M.P.F. de; Heuvel-Eibrink, Marry M. van den; Lequin, Maarten H.; Kuijk, Cornelis Van

    2006-01-01

    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.)

  12. Inclusion of chemotherapy in addition to anthracycline in the treatment of acute promyelocytic leukaemia does not improve outcomes: results of the MRC AML15 trial.

    Science.gov (United States)

    Burnett, A K; Hills, R K; Grimwade, D; Jovanovic, J V; Craig, J; McMullin, M F; Kell, J; Wheatley, K; Yin, J A L; Hunter, A; Milligan, D; Russell, N H

    2013-04-01

    Two hundred eighty-five patients, median age 42, with PML-RARα-positive acute promyelocytic leukaemia were randomised to Ara-C-containing 'Medical Research Council (MRC) Chemotherapy'+ATRA (All-trans-retinoic acid) or anthracycline+ATRA (modified 'Spanish') therapy. MRC treatment comprised four courses with ATRA in courses 1-2. Spanish treatment comprised four anthracycline-based courses with ATRA in courses 1-3. In course 3 patients were randomised to gemtuzumab ozogamicin (GO) or not. The Spanish arm received 24-month maintenance. Patients were sequentially molecularly monitored. Quality of life was assessed at baseline, 3, 6, 9, 12, 24 months. Remission rates were similar in both arms (93%): cumulative incidence of haematological relapse (CIHR) was 6% at 5 years; 5 patients relapsed molecularly. Survival post relapse was 80%. There were more deaths in remission in the MRC arm (4% vs 10%: P=0.2). The overall 5-year relapse-free and overall survival was similar between arms (81% vs 82% and 84% vs 83%, respectively). More supportive care and hospitalisation (81.8 vs 63 days, PMRC arm. GO did not provide benefit. High white blood cell count (>10 × 10(9)/l) was not prognostic overall, or within treatment arms. Both approaches deliver similar results with minor differences in quality of life. MRC treatment required more hospitalisation. This suggests that additional chemotherapy, Ara-C in particular, is not required.

  13. Urinary apolipoprotein M as a biomarker of acute kidney injury in children undergoing heart surgery

    DEFF Research Database (Denmark)

    Svarrer, Eva Martha Madsen; Andersen, Henrik Ørbæk; Helvind, Morten

    2016-01-01

    AIM: To investigate whether apoM is excreted in urine of children undergoing heart surgery and the potential of apoM as early biomarker of acute kidney injury (AKI). MATERIALS & METHODS: Urine was collected in children undergoing heart surgery. ApoM was measured with ELISA. U-apoM was characterized.......018). Sensitivity was 0.71 and specificity was 0.68 at a cutoff level at 1.45 nmol/l. CONCLUSION: ApoM is excreted in the urine of children after cardiac surgery. Its potential as biomarker of AKI deserves exploration....

  14. Blood Transfusion and the Risk of Acute Kidney Injury Among Patients With Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention.

    Science.gov (United States)

    Karrowni, Wassef; Vora, Amit Navin; Dai, David; Wojdyla, Daniel; Dakik, Habib; Rao, Sunil V

    2016-09-01

    Acute kidney injury (AKI) complicating percutaneous coronary intervention (PCI) is associated with adverse clinical outcomes. To date, no studies have evaluated the association of blood transfusion with AKI in patients undergoing PCI. We used a retrospective cohort study of all patients with acute coronary syndrome undergoing PCI from CathPCI Registry (n=1 756 864). The primary outcome was AKI defined as the rise in serum creatinine post procedure ≥0.5 mg/dL or ≥25% above baseline values. AKI developed in 9.0% of study sample. Patients with AKI were older, more often women, and had high prevalence of comorbidities, including diabetes mellitus, hypertension, and advanced stages of chronic kidney disease at baseline. Blood transfusion was utilized in 2.2% of patients. In the overall sample, AKI developed in 35.1% of patients who received transfusion versus 8.4% of patients without transfusion (adjusted odds ratio, 4.87 [4.71-5.04]). In the subgroup of patients who sustained bleeding event and received transfusion, the rate of AKI was significantly increased across all preprocedure hemoglobin levels versus no blood transfusion. Similar findings were seen in the subgroup of patients with no bleeding event. Blood transfusion is strongly associated with AKI in patients with acute coronary syndrome undergoing PCI. Further investigation is needed to determine whether a restrictive blood transfusion strategy might improve PCI outcomes by reducing the risk of AKI. © 2016 American Heart Association, Inc.

  15. Somatic mutations of isocitrate dehydrogenases 1 and 2 are prognostic and follow-up markers in patients with acute myeloid leukaemia with normal karyotype

    Science.gov (United States)

    Karan-Djurasevic, Teodora; Marjanovic, Irena; Tosic, Natasa; Mitrovic, Mirjana; Djunic, Irena; Colovic, Natasa; Vidovic, Ana; Suvajdzic-Vukovic, Nada; Tomin, Dragica; Pavlovic, Sonja

    2016-01-01

    Abstract Background Mutations in the isocitrate dehydrogenase 1 and 2 (IDH1 and IDH2) genes are frequent molecular lesions in acute myeloid leukaemia with normal karyotype (AML-NK). The effects of IDH mutations on clinical features and treatment outcome in AML-NK have been widely investigated, but only a few studies monitored these mutations during follow-up. Patients and methods In our study samples from 110 adult de novo AML-NK were studied for the presence of IDH1 and IDH2 mutations, their associations with other prognostic markers and disease outcome. We also analyzed the stability of these mutations during the course of the disease in complete remission (CR) and relapse. Results IDH mutations were found in 25 (23%) patients. IDH+ patients tend to have lower CR rate compared to IDH-patients (44% vs 62.2%, p = 0.152), and had slightly lower disease free survival (12 months vs 17 months; p = 0.091). On the other hand, the presence of IDH mutations had significant impact on overall survival (2 vs 7 months; p = 0.039). The stability of IDH mutations were studied sequentially in 19 IDH+ patients. All of them lost the mutation in CR, and the same IDH mutations were detected in relapsed samples. Conclusions Our study shows that the presence of IDH mutations confer an adverse effect in AML-NK patients, which in combination with other molecular markers can lead to an improved risk stratification and better treatment. Also, IDH mutations are very stable during the course of the disease and can be potentially used as markers for minimal residual disease detection. PMID:27904446

  16. C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: effect on methotrexate-related toxicity in adult acute lymphoblastic leukaemia.

    Science.gov (United States)

    Eissa, Deena Samir; Ahmed, Tamer Mohamed

    2013-03-01

    Methylenetetrahydrofolate reductase (MTHFR) is a key enzyme involved in folate metabolism. Two polymorphisms, C677T and A1298C, were described leading to reduced enzyme activity. Methotrexate (MTX) is an antifolate agent of consolidation and maintenance therapy of acute lymphoblastic leukaemia (ALL). Despite its clinical success, MTX can be associated with serious toxicities resulting in treatment interruption or discontinuation, impacting disease outcome. There is evidence that MTX toxicity can be affected by polymorphisms in genes encoding for drug-metabolizing enzymes such as MTHFR. Therefore, we aimed to investigate the influence of MTHFR C677T and A1298C polymorphisms on the frequency of MTX-related toxicity, disease outcome and patients' survival. MTHFR polymorphisms were assessed in 50 adult patients with de novo ALL using real-time PCR. Patients were followed-up for the development of haematologic and/or nonhaematologic toxicity and assessment of clinical outcome. Frequency of C677T polymorphisms was 42% for TT, 24% for CT and 34% for CC; A1298C polymorphisms were 28, 6 and 66% for CC, AC and AA, respectively. MTX therapy was significantly associated with neutropaenia, hepatic and gastrointestinal toxicities, unfavourable response at day 14 of induction therapy, increased relapse and mortality rates and shorter survival in patients with 677 TT genotype than in those with CC and CT, whereas 1298 CC genotype patients had lower frequency of neutropaenia, hepatic toxicity and relapse than in those with AA and AC. Our study suggests MTHFR polymorphism as an attractive predictor of MTX-related toxicity in adult ALL, considering it a potential prognostic factor influencing disease outcome.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

  18. Cognitive, behaviour, and academic functioning in adolescent and young adult survivors of childhood acute lymphoblastic leukaemia: a report from the Childhood Cancer Survivor Study.

    Science.gov (United States)

    Jacola, Lisa M; Edelstein, Kim; Liu, Wei; Pui, Ching-Hon; Hayashi, Robert; Kadan-Lottick, Nina S; Srivastava, Deokumar; Henderson, Tara; Leisenring, Wendy; Robison, Leslie L; Armstrong, Gregory T; Krull, Kevin R

    2016-10-01

    Survivors of childhood acute lymphoblastic leukaemia (ALL) are at risk for neurocognitive deficits that affect development in adolescence and young adulthood, and influence educational attainment and future independence. We examined a large and diverse cohort of survivors to identify risk predictors and modifiers of these outcomes. In this cohort study, cognitive and behaviour symptoms were assessed via a standardised parent questionnaire for 1560 adolescent survivors of ALL diagnosed between 1970 and 1999. Clinically significant symptoms (≥90th percentile) and learning problems were compared between survivors and a sibling cohort. Multivariable regression models were used to examine associations with demographic and treatment characteristics. Models were adjusted for inverse probability of sampling weights to reflect undersampling of ALL survivors in the expansion cohort. In a subset of survivors with longitudinal data (n=925), we examined associations between adolescent symptoms or problems and adult educational attainment. Compared with siblings, survivors treated with chemotherapy only were more likely to demonstrate headstrong behaviour (155 [19%] of 752 survivors vs 88 [14%] of 610 siblings, p=0·010), inattention-hyperactivity (15 [19%] vs 86 [14%], plearning problems (191 [28%] vs 76 [14%], p4·3 g/m 2 ) conferred increased risk of inattention-hyperactivity (relative risk [RR] 1·53, 95% CI 1·13-2·08). Adolescent survivors with cognitive or behaviour problems and those with learning problems were less likely to graduate from college as young adults than adolescent survivors without cognitive or behaviour problems. Although modern therapy for childhood ALL has eliminated the use of cranial radiation therapy, adolescent survivors treated with chemotherapy only remain at increased risk for cognitive, behaviour, and academic problems that adversely affect adult education outcomes. National Cancer Institute, American Lebanese-Syrian Associated Charities

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

    Directory of Open Access Journals (Sweden)

    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.

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

    Directory of Open Access Journals (Sweden)

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

    Science.gov (United States)

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

    2016-08-01

    Early response after induction is a prognostic factor for disease outcome in childhood acute myeloid leukaemia (AML). Residual disease (RD) detection by multiparameter flow cytometry (MFC) was performed at day 15 and before consolidation therapy in 101 patients enrolled in the Nordic Society of Paediatric Haemato-Oncology AML 2004 study. A multicentre laboratory approach to RD analysis was used. Event-free survival (EFS) and overall survival (OS) was significantly different in patients with and without RD at both time points, using a 0·1% RD cut-off level. RD-negative and -positive patients after first induction showed a 5-year EFS of 65 ± 7% and 22 ± 7%, respectively (P < 0·001) and an OS of 77 ± 6% (P = 0·025) and 51 ± 8%. RD-negative and -positive patients at start of consolidation therapy had a 5-year EFS of 57 ± 7% and 11 ± 7%, respectively (P < 0·001) and an OS of 78 ± 6% and 28 ± 11%) (P < 0·001). In multivariate analysis only RD was significantly correlated with survival. RD before consolidation therapy was the strongest independent prognostic factor for EFS [hazard ratio (HR):5·0; 95% confidence interval (CI):1·9-13·3] and OS (HR:7·0; 95%CI:2·0-24·5). In conclusion, RD before consolidation therapy identifies patients at high risk of relapse in need of intensified treatment. In addition, RD detection can be performed in a multicentre setting and can be implemented in future trials. © 2016 John Wiley & Sons Ltd.

  2. Genetic variation of the gene coding for microRNA-204 (miR-204) is a risk factor in acute myeloid leukaemia.

    Science.gov (United States)

    Butrym, Aleksandra; Łacina, Piotr; Kuliczkowski, Kazimierz; Bogunia-Kubik, Katarzyna; Mazur, Grzegorz

    2018-01-30

    MicroRNAs (miRNAs or miRs) are small molecules known to be involved in post-transcriptional gene expression. Many of them have been shown to influence risk for various diseases. Recent studies suggest that lower expression of miR-204, a gene coding for miRNA-204, is correlated with shorter survival in patients with acute myeloid leukaemia (AML). This observation prompted us to analyse the effect of two polymorphisms of the miR-204 gene, one in the upstream flanking region (rs718447 A > G) and the other inside the gene itself (rs112062096 A > G), both also in intron 3 of the TRPM3 gene. The study was conducted on DNA samples isolated from AML patients (n = 95) and healthy individuals (n = 148), who were genotyped using the Light SNiP assays. The miR-204 rs718447 GG homozygosity was found to constitute a risk factor associated with susceptibility to AML (73/95 vs 92/148, AML patients vs healthy controls, OR = 2.020, p = 0.017). Additionally, this genotype was more frequent in patients with subtypes M0-M1 in the French-American-British (FAB) classification as compared to patients with subtypes M2-M7 (23/25 vs 39/57, p = 0.026). We also found that presence of allele A was linked to longer survival of AML patients. Our results show that polymorphism in miR-204 flanking region may constitute a risk and prognostic factor in AML.

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

    DEFF Research Database (Denmark)

    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...

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Multidisciplinary perioperative protocol in patients undergoing acute high-risk abdominal surgery

    DEFF Research Database (Denmark)

    Tengberg, L. T.; Bay-Nielsen, M.; Bisgaard, T.

    2017-01-01

    Background: Acute high-risk abdominal (AHA) surgery carries a very high risk of morbidity and mortality and represents a massive healthcare burden. The aim of the present study was to evaluate the effect of a standardized multidisciplinary perioperative protocol in patients undergoing AHA surgery...... = 0·004). Conclusion: The introduction of a multidisciplinary perioperative protocol was associated with a significant reduction in postoperative mortality in patients undergoing AHA surgery. NCT01899885 (http://www.clinicaltrials.gov).......Background: Acute high-risk abdominal (AHA) surgery carries a very high risk of morbidity and mortality and represents a massive healthcare burden. The aim of the present study was to evaluate the effect of a standardized multidisciplinary perioperative protocol in patients undergoing AHA surgery...... after initiation of the AHA protocol as standard care. The intervention cohort was compared with a predefined, consecutive historical cohort of patients from the same department. The protocol involved continuous staff education, consultant-led attention and care, early resuscitation and high...

  6. Treatment reduction for children and young adults with low-risk acute lymphoblastic leukaemia defined by minimal residual disease (UKALL 2003): a randomised controlled trial.

    Science.gov (United States)

    Vora, Ajay; Goulden, Nick; Wade, Rachel; Mitchell, Chris; Hancock, Jeremy; Hough, Rachael; Rowntree, Clare; Richards, Sue

    2013-03-01

    Minimal residual disease (MRD) is the most sensitive and specific predictor of relapse risk in children with acute lymphoblastic leukaemia (ALL) during remission. We assessed whether treatment intensity could be adjusted for children and young adults according to MRD risk stratification. Between Oct 1, 2003 and June 30, 2011, consecutive children and young adults (aged 1-25 years) with ALL from the UK and Ireland were recruited. Eligible patients were categorised into clinical standard, intermediate, and high risk groups on the basis of a combination of National Cancer Institute (NCI) criteria, cytogenetics, and early response to induction therapy, which was assessed by bone marrow blast counts taken at days 8 (NCI high-risk patients) and 15 (NCI standard-risk patients) after induction began. Clinical standard-risk and intermediate-risk patients were assessed for MRD. Those classified as MRD low risk (undetectable MRD at the end of induction [day 29] or detectable MRD at day 29 that became undetectable by week 11) were randomly assigned to receive one or two delayed intensification courses. Patients had received induction, consolidation, and interim maintenance therapy before they began delayed intensification. Delayed intensification consisted of pegylated asparaginase on day 4; vincristine, dexamethasone (alternate weeks), and doxorubicin for 3 weeks; and 4 weeks of cyclophosphamide and cytarabine. Computer randomisation was done with stratification by MRD result and balancing for sex, age, and white blood cell count at diagnosis by method of minimisation. Patients, clinicians, and data analysts were not masked to treatment allocation. The primary outcome was event-free survival (EFS), which was defined as time to relapse, secondary tumour, or death. Our aim was to rule out a 7% reduction in EFS in the group given one delayed intensification course relative to that given two delayed intensification courses. Analyses were by intention to treat. This trial is

  7. An acute pain service improves postoperative pain management for children undergoing selective dorsal rhizotomy.

    Science.gov (United States)

    Frigon, Chantal; Loetwiriyakul, Witthaya; Ranger, Manon; Otis, Annik

    2009-12-01

    A continuous epidural infusion of morphine is the pain treatment modality for children undergoing selective dorsal rhizotomy (SDR) in our institution. The aim of the study was to evaluate the impact of having an organized acute pain service (APS) on postoperative pain management of these children. We conducted a retrospective cohort study using anesthetic records and the APS database to compare the postoperative pain management of children undergoing SDR before and after the introduction of the APS at the Montreal Children's Hospital in April 2001. Ninety-two consecutive children who had their surgery between January 1997 and July 2006 were included. We collected data regarding postoperative pain, opioid-induced side effects, complications (sedation, desaturations improvements in general postoperative care and in length of stay, our study did show that having an organized APS allowed to significantly decrease the incidence of postoperative oxygen desaturation and to decrease the hospital length of stay by 1 day.

  8. Central nervous system leukemia in a patient with concurrent nasopharyngeal carcinoma and acute myeloid leukaemia: A case report.

    Science.gov (United States)

    Liu, Jun-Qing; Mai, Wen-Yuan; Wang, Si-Ben; Lou, Yin-Jun; Yan, Sen-Xiang; Jin, Jie; Xu, Wei-Lai

    2017-12-01

    Concurrent case of nasopharyngeal carcinoma (NPC) and acute myeloid leukemia (AML) has not been reported. Here, we report a case of NPC, who was concurrently suffered from AML one mother after the NPC diagnosis. The patient was a 45-year-old male who presented with a mass on his right side neck. The patient was diagnosed with Epstein-Barr virus negative type-2 non-keratinizing carcinoma with clivus involvement and unilateral metastasis to the cervical lymph node. He was treated with one cycle of cisplatin and 69.76 Gy of concurrent external-beam radiation. Three months after completion of chemo-radiotherapy, the patient was diagnosed as acute myeloid leukemia, which achieved complete remission after one course induction chemotherapy. Two months later, however, the patient was diagnosed as central nervous system leukemia. He ultimately died of relapsed leukemia. The overall survival of the patient was 10 months. The co-occurrence of NPC and AML is rare and prognosis is poor. Radiotherapy in NPC can disrupt the blood-brain barrier, which may contribute to the pathogenesis of central nervous system leukemia. Early alert and prevention of central nervous system leukemia following radiotherapy in NPC patient is recommended. Copyright © 2017 The Authors. Published by Wolters Kluwer Health, Inc. All rights reserved.

  9. Prevalence and outcome of patients with cancer and acute coronary syndrome undergoing percutaneous coronary intervention: a BleeMACS substudy

    NARCIS (Netherlands)

    Iannaccone, Mario; D'Ascenzo, Fabrizio; Vadalà, Paolo; Wilton, Stephen B.; Noussan, Patrizia; Colombo, Francesco; Raposeiras Roubín, Sergio; Abu Assi, Emad; González-Juanatey, José Ramón; Henriques, Jose Paulo Simao; Saucedo, Jorge; Kikkert, Wouter J.; Nuñez-Gil, Iván; Ariza-Sole, Albert; Song, Xian-Tao; Alexopoulos, Dimitrios; Liebetrau, Christoph; Kawaji, Tetsuma; Moretti, Claudio; Garbo, Roberto; Huczek, Zenon; Nie, Shao-Ping; Fujii, Toshiharu; Correia, Luis Cl; Kawashiri, Masa-Aki; García Acuña, José María; Southern, Danielle; Alfonso, Emilio; Terol, Belén; Garay, Alberto; Zhang, Dongfeng; Chen, Yalei; Xanthopoulou, Ioanna; Osman, Neriman; Möllmann, Helge; Shiomi, Hiroki; Giordana, Francesca; Kowara, Michal; Filipiak, Krzysztof; Wang, Xiao; Yan, Yan; Fan, Jing-Yao; Ikari, Yuji; Nakahashi, Takuya; Sakata, Kenji; Gaita, Fiorenzo; Yamagishi, Masakazu; Kalpak, Oliver; Kedev, Sasko

    2017-01-01

    The prevalence and outcome of patients with cancer that experience acute coronary syndrome (ACS) have to be determined. The BleeMACS project is a multicentre observational registry enrolling patients with acute coronary syndrome undergoing percutaneous coronary intervention worldwide in 15

  10. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Directory of Open Access Journals (Sweden)

    Mohammed Al Huneini

    2013-05-01

    Full Text Available We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA for the treatment of acute promyelocytic leukemia (APL. Between October 2007 and March 2010, three males and one female (age range 19-35 years were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted.

  11. Genital Ulcer Development in Patients with Acute Promyelocytic Leukaemia Treated with All-Trans Retinoic Acid: A Case Series

    Science.gov (United States)

    Al Huneini, Mohammed; Wasim, Fauzia; Al Farsi, Khalil; Al-Khabori, Murtadha; Al Kindi, Salam

    2013-01-01

    We report here four cases of genital ulcers that developed after the administration of all-trans retinoic acid (ATRA) for the treatment of acute promyelocytic leukemia (APL). Between October 2007 and March 2010, three males and one female (age range 19-35 years) were identified to have genital ulcers after being prescribed all-trans retinoic acid (ATRA) as a part of chemotherapy for APL. This is the first series of cases describing genital ulcers, as a unique and rare complication of ATRA used for treatment of APL in these patients, with no other cause identified. Following temporary cessation of ATRA for a few days in these three cases, improvement of the ulcers was noted. PMID:23772289

  12. Leukaemia in East Suffolk

    International Nuclear Information System (INIS)

    Bush, M.F.H.

    1983-09-01

    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.)

  13. Are survival and mortality rates associated with recruitment to clinical trials in teenage and young adult patients with acute lymphoblastic leukaemia? A retrospective observational analysis in England.

    Science.gov (United States)

    Hough, Rachael; Sandhu, Sabrina; Khan, Maria; Moran, Anthony; Feltbower, Richard; Stiller, Charles; Stevens, Mike C G; Rowntree, Clare; Vora, Ajay; McCabe, Martin G

    2017-10-05

    Participation rates in clinical trials are low in teenagers and young adults (TYA) with cancer. Whilst the importance of clinical trials in informing best practice is well established, data regarding individual patient benefit are scarce. We have investigated the association between overall survival and trial recruitment in TYA patients with acute lymphoblastic leukaemia (ALL). Retrospective. National (England) TYA patients treated for ALL. 511 patients aged 15-24 years diagnosed with ALL between 2004 and 2010 inclusive, of whom 239 (46.7%) participated in the UKALL2003 trial. Patients were identified using National Clinical Trial (UKALL2003) and Cancer Registry (National Cancer Data Repository, English National Cancer Online Registration Environment) Databases. Relative survival rates were calculated for trial and non-trial patients and observed differences were modelled using a multiple regression approach. The numbers and percentages of deaths in those patients included in the survival analysis were determined for each 3-month period, p values were calculated using the two-tailed z-test for difference between proportions and 95% CIs for percentage deaths were derived using the binomial distribution based on the Wilson Score method. Patients treated on the trial had a 17.9% better 2-year survival (85.4% vs 67.5%, p<0.001) and 8.9% better 1-year survival (90.8% vs 81.9%, p=0.004) than those not on the trial. 35 (14.6%) patients recruited to the trial died in the 2 years following diagnosis compared with 86 (32.6%) of those not recruited (p<0.001). TYA patients recruited to the clinical trial UKALL 2003 in England had a lower risk of mortality and a higher overall survival than contemporaneous non-trial patients. These data underline the potential for individual patient benefit in participating in a clinical trial and the importance of international efforts to increase trial participation in the TYA age group. ISRCTN07355119. © Article author(s) (or their

  14. Haematopoietic cell transplantation with and without sorafenib maintenance for patients with FLT3-ITD acute myeloid leukaemia in first complete remission.

    Science.gov (United States)

    Brunner, Andrew M; Li, Shuli; Fathi, Amir T; Wadleigh, Martha; Ho, Vincent T; Collier, Kerry; Connolly, Christine; Ballen, Karen K; Cutler, Corey S; Dey, Bimalangshu R; El-Jawahri, Areej; Nikiforow, Sarah; McAfee, Steven L; Koreth, John; Deangelo, Daniel J; Alyea, Edwin P; Antin, Joseph H; Spitzer, Thomas R; Stone, Richard M; Soiffer, Robert J; Chen, Yi-Bin

    2016-11-01

    We performed a retrospective study analysing the effect of sorafenib, an oral fms-Like Tyrosine Kinase 3 (FLT3)/multikinase inhibitor, as post-transplant maintenance in adult patients with FLT3-internal tandem duplication (ITD) acute myeloid leukaemia (AML). We identified consecutive patients with FLT3-ITD AML diagnosed between 2008 and 2014 who received haematopoietic cell transplantation (HCT) in first complete remission (CR1). Post-HCT initiation of sorafenib (yes/no) was evaluated as a time-varying covariate in the overall survival/progression-free survival (OS/PFS) analysis and we performed a landmark analysis of controls alive without relapse at the median date of sorafenib initiation. We identified 26 sorafenib patients and 55 controls. Median follow-up was 27·2 months post-HCT for sorafenib survivors, and 38·4 months for controls (P = 0·021). The median time to initiating sorafenib was 68 days post-HCT; 43 controls were alive without relapse at this cut-off. Sorafenib patients had improved 2-year OS in the d+68 landmark analysis (81% vs. 62%, P = 0·029). Sorafenib was associated with improved 2-year PFS (82% vs. 53%, P = 0·0081) and lower 2-year cumulative incidence of relapse (8·2% vs. 37·7%, P = 0·0077). In multivariate analysis, sorafenib significantly improved OS [Hazard ratio (HR) 0·26, P = 0·021] and PFS (HR 0·25, P = 0·016). There was no difference in 2-year non-relapse mortality (9·8% vs. 9·3%, P = 0·82) or 1-year chronic graft-versus-host disease (55·5% vs. 37·2%, P = 0·28). These findings suggest potential benefit of post-HCT sorafenib in FLT3-ITD AML, and support further evaluation of post-HCT FLT3 inhibition. © 2016 John Wiley & Sons Ltd.

  15. FBXW7 regulates glucocorticoid response in T-cell acute lymphoblastic leukaemia by targeting the glucocorticoid receptor for degradation.

    Science.gov (United States)

    Malyukova, A; Brown, S; Papa, R; O'Brien, R; Giles, J; Trahair, T N; Dalla Pozza, L; Sutton, R; Liu, T; Haber, M; Norris, M D; Lock, R B; Sangfelt, O; Marshall, G M

    2013-04-01

    Loss of function mutation in FBXW7, an E3 ubiquitin ligase, is associated with good prognosis and early glucocorticoid treatment response in childhood T-cell acute lymphoblastic leukemia (T-ALL) by unknown mechanisms. Here, we show that FBXW7 targets the glucocorticoid receptor α (GRα) for ubiquitylation and proteasomal degradation in a manner dependent on glycogen synthase kinase 3 β-mediated phsophorylation. FBXW7 inactivation caused elevated GRα levels, and enhanced the transcriptional response to glucocorticoids. There was significant enhancement of GR transcriptional responses in FBXW7-deficient cell lines and primary T-ALL samples, in particular, for those pro-apoptotic regulatory proteins, BIM and PUMA. Reduced FBXW7 expression or function promoted glucocorticoid sensitivity, but not sensitivity to other chemotherapeutic agents used in T-ALL. Moreover, this was a general feature of different cancer cell types. Taken together, our work defines GRα as a novel FBXW7 substrate and demonstrates that favorable patient prognosis in T-ALL is associated with FBXW7 mutations due to enhanced GRα levels and steroid sensitivity. These findings suggest that inactivation of FBXW7, a putative tumor suppressor protein, may create a synthetic lethal state in the presence of specific anticancer therapies.

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Factors associated with mortality in a population with acute kidney injury undergoing hemodialysis in Peru

    Directory of Open Access Journals (Sweden)

    Percy Herrera-Añazco

    Full Text Available Abstract Introduction: Patients with acute kidney injury (AKI in developing countries are described in a profile of young age, with less comorbidities, with unifactorial, and with a lower mortality compared to patients in developed countries. Objective: To assess mortality in patients with acute kidney injury undergoing hemodialysis (HD and its associated factors in a developing country setting. Methods: Retrospective study. Demographic, clinical, and mortality variables were collected from patients who presented AKI and underwent HD between January 2014 and December 2015 at a national reference hospital in Lima, Peru. Risk ratios (RR and 95% confidence intervals (95%CI were estimated through Poisson regressions. Results: Data from 72 patients with AKI that underwent HD were analyzed, 66.7% of them were 8.9 mg/dL. The adjusted analysis showed that having had a creatinine level of > 8.9 mg/dL, compared to a creatinine level of < 5.2 mg/dL at the time of initiating HD, was associated with 74% less probability of death. Conclusion: Four out of every ten AKI patients undergoing HD die. Higher levels of creatinine were associated with lower probability of mortality.

  18. Effects of stem cell factor on hypoxia-inducible factor 1 alpha accumulation in human acute myeloid leukaemia and LAD2 mast cells.

    Directory of Open Access Journals (Sweden)

    Bernhard F Gibbs

    Full Text Available Stem cell factor (SCF is a hematopoietic growth factor that exerts its activity by signalling through the tyrosine kinase receptor known as Kit or CD117. SCF-Kit signalling is crucial for the survival, proliferation and differentiation of hematopoietic cells of myeloid lineage. Furthermore, since myeloid leukaemia cells express the Kit receptor, SCF may play an important role in myeloid leukaemia progression too. However, the mechanisms of this pathophysiological effect remain unclear. Recent evidence shows that SCF triggers accumulation of the inducible alpha subunit of hypoxia-inducible factor 1 (HIF-1 in hematopoietic cells--a transcription complex that plays a pivotal role in cellular adaptation to low oxygen availability. However, it is unknown how SCF impacts on HIF-1α accumulation in human myeloid leukaemia and mast cells. Here we show that SCF induces HIF-1α accumulation in THP-1 human myeloid leukaemia cells but not in LAD2 mast cells. We demonstrated that LAD2 cells have a more robust glutathione (GSH-dependent antioxidative system compared to THP-1 cells and are therefore protected against the actions of ROS generated in an SCF-dependent manner. BSO-induced GSH depletion led to a significant decrease in HIF-1α prolyl hydroxylase (PHD activity in THP-1 cells and to near attenuation of it in LAD2 cells. In THP-1 cells, SCF-induced HIF-1α accumulation is controlled via ERK, PI3 kinase/PKC-δ/mTOR-dependent and to a certain extent by redox-dependent mechanisms. These results demonstrate for the first time an important cross-talk of signalling pathways associated with HIF-1 activation--an important stage of the myeloid leukaemia cell life cycle.

  19. Side effects and late sequelae of combined irradiation- and chemotherapy of the neurocranium in children with acute lymphoblastic leukaemia

    International Nuclear Information System (INIS)

    Zippel, R.M.

    1978-01-01

    Therapeutical procedures are not only judged according to their efficacy, but also with respect to their affection to the patient. For acute side effects as headaches, nausea, tiredness and fever, which occurred in several children, cranial irradiation and intrathecal MTX injections have to be considered as responsible factors. These accompanying symptoms, for example also alopecia, have to be tolerated with respect to the successful course of phase II, i.e. the prevention of a leukaemic meningo-encephalitis. The somnolence syndrome can be observed also after cerebral irradiation with a different indication; in several patients the occurrence of this syndrome has to be expected. Up to the present no secondary damages caused by this syndrome have been observed. Severe neurologic disorders only rarely appear within the course of the ALL; nevertheless it is necessary to determine at the earliest possible date also more subtle disturbances in the neurologic and psychic development of the children by neurologic examinations, regular ECG registrations, and psychologic tests. A delineation of late damages of ZNS therapy is only possible on the basis of the cerebral post-mortem findings. Since the dose of the brain irradiations of phase II are within the limits of the generally accepted tolerance range, a late necrosis induced by irradiation, has not to be expected. Single cases of leukoencephalopathies are ascribed to the ALL therapy. Growth retardations - which in the most cases are reversible - are found in children treated with ALL therapy; as possibly damaging agent also neurocranial irradiation might be considered as responsible. Regular control examinations of the length show a possibly occuring growth reduction, which should be accessible by hormone therapy if necessary. (orig./MG) [de

  20. Acute intraoperative effect of intravenous amiodarone on right ventricular function in patients undergoing valvular surgery.

    Science.gov (United States)

    Denault, André Y; Beaulieu, Yanick; Couture, Pierre; Haddad, Francois; Shi, Yanfen; Pagé, Pierre; Levesque, Sylvie; Tardif, Jean-Claude; Lambert, Jean

    2015-08-01

    Amiodarone is commonly used in the acute care setting. However the acute hemodynamic and echocardiographic effect of intravenous amiodarone administered intraoperatively on right ventricular (RV) systolic and diastolic function using transesophageal echocardiography (TEE) has not been described. The study design was a randomized controlled trial in elective cardiac surgical patients undergoing valvular surgery. Patients received an intravenous loading dose of 300 mg of either amiodarone or placebo in the operating room, followed by an infusion of 15 mg/kg for two days. Hemodynamic profiles, echocardiographic measurement of RV and left ventricular (LV) dimensions, Doppler interrogation of tricuspid and mitral valve, hepatic and pulmonary venous flow combined with tissue Doppler imaging of the tricuspid and mitral valve annulus were obtained before and after bolus. Although more patients in the placebo group had chronic obstructive lung disease (14 vs 6, p=0.05) and diabetes (14 vs 5; p=0.0244), there was no difference in terms of baseline hemodynamic, 2D and Doppler variables. After bolus, a significant increase in pulmonary artery pressure, central venous pressure and pulmonary vascular resistance index (pAcute administration of amiodarone is associated with alteration in RV diastolic properties and has minimal negative inotropic effect on RV systolic function in cardiac surgical patients with valvular disease. © The European Society of Cardiology 2014.

  1. Children’s pain and distress while undergoing an acute radiographic examination

    International Nuclear Information System (INIS)

    Björkman, B.; Nilsson, S.; Sigstedt, B.; Enskär, K.

    2012-01-01

    Pain has been highlighted as a main concern for children in conjunction with an acute radiographic examination. The aim of this study was to further investigate children’s pain and distress while undergoing an acute radiographic examination. The study comprised 29 participants with an age range of 5–15 years who were injured and submitted to an acute radiographic examination of the upper or lower extremity when the question at issue was fracture. The Coloured Analogue Scale (CAS) and the Facial Affective Scale (FAS) were used as self-reporting scales to measure the children’s pain and distress. The Face, Legs, Activity, Cry and Consolability Behavioural scale (FLACC) was used as an observation tool to assess behaviours associated with pain in children. Descriptive statistics were used when analysing the scores, and the results showed that children experience pain and distress in conjunction with a radiographic examination after an injury. Spearman’s correlation was used to compare variables, and significant correlations were obtained between the self-reported pain and the observed pain behaviour. Fischer’s Exact test was used to compare groups, and when using the cut-off 3.0 on the self-reporting scale no significant correlation was found concerning the pain reported by children diagnosed with and without a fracture. No significant correlations were found concerning the self-reported distress and pain either, regardless of whether it was a first-time visit and whether a parent was near during the examination.

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

    International Nuclear Information System (INIS)

    Metz, O.; Stoll, W.; Plenert, W.; Deckert, H.; Doege, H.; Doerffel, W.; Mittler, U.; Redemann, H.; Roenisch, P.; Zastrow, J.

    1982-01-01

    Intrathecal 198 Au 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 198 Au colloid and methotrexate. (orig.) [de

  3. Translocation t(6;9) in acute non-lymphocytic leukaemia results in the formation of a DEK-CAN fusion gene

    NARCIS (Netherlands)

    von Lindern, M.; Fornerod, M.; Soekarman, N.; van Baal, S.; Jaegle, M.; Hagemeijer, A.; Bootsma, D.; Grosveld, G.

    1992-01-01

    The t(6;9) that characterizes a specific subtype of ANLL fuses the 3' part of a gene located on chromosome 9q34, CAN, to the 5' part of a gene located on chromosome 6p23, DEK. On the 6p- chromosome, the resulting DEK-CAN fusion gene is transcribed into a leukaemia-specific 5.5 kb chimaeric mRNA that

  4. HOXA9 is critical in the proliferation, differentiation, and malignancy of leukaemia cells both in vitro and in vivo.

    Science.gov (United States)

    Chen, Shibing; Yu, Juan; Lv, Xin; Zhang, Lijuan

    2017-10-01

    Progress in the understanding of the molecular mechanism for acute myeloid leukaemia is of great significance to generate new potential targets for treatment. Recent studies showed that HOXA9, a homeodomain-containing transcription factor, is commonly deregulated in acute leukaemia. In this study, we elucidated the direct correlation between HoxA9 expression and progression of leukaemia using 2 different types of leukaemia cells HL-60 and MOLT-3. The HoxA9 expression level was decreased in leukaemia cells with the treatment of all-trans retinoic acid or arsenic trioxide (As 2 O 3 ). Downregulation of HoxA9 could impair the proliferation and promote the leukaemia cell death. HoxA9 silencing also potentiated the differentiation of leukaemia cells, and in vivo studies demonstrated that HoxA9 downregulation could interfere the tumour growth. Interestingly, HoxA9 silencing also led to the alteration in miRNA expression, mediating the promoting effect on the leukaemia cell differentiation. Therefore, this work provided a promising and potentially efficient target to leukaemia treatment, indicating that HoxA9 is likely to be an ideal candidate in the gene therapy against acute myeloid leukaemia. In this study, we elucidated the critical role of HoxA9 in the proliferation and differentiation of leukaemia cells both in vitro and in vivo. The effect of HoxA9 modulation was correlated with the clinical effect of all-trans retinoic acid and As 2 O 3 . Furthermore, HoxA9 also regulated the miRNA expression, controlling the leukaemia cell differentiation. Therefore, this work provided new insights into molecular mechanism underlying the leukaemia treatment, potentially putting forward a brand new target to the gene therapy against leukaemia. Copyright © 2017 John Wiley & Sons, Ltd.

  5. Risk Factors of Contrast-induced Acute Kidney Injury in Patients Undergoing Emergency Percutaneous Coronary Intervention.

    Science.gov (United States)

    Yuan, Ying; Qiu, Hong; Hu, Xiao-Ying; Luo, Tong; Gao, Xiao-Jin; Zhao, Xue-Yan; Zhang, Jun; Wu, Yuan; Yan, Hong-Bing; Qiao, Shu-Bin; Yang, Yue-Jin; Gao, Run-Lin

    Previous studies of contrast-induced acute kidney injury (CI-AKI) were mostly based on selective percutaneous coronary intervention (PCI) cases, and risk factors of CI-AKI after emergency PCI are unclear. The aim of this study was to explore the risk factors of CI-AKI in a Chinese population undergoing emergency PCI. A total of 1061 consecutive patients undergoing emergency PCI during January 2013 and June 2015 were enrolled and divided into CI-AKI and non-CI-AKI group. Univariable and multivariable analyses were used to identify the risk factors of CI-AKI in emergency PCI patients. CI-AKI was defined as an increase in serum creatinine ≥25% or ≥0.5 mg/dl (44.2 μmol/L) above baseline within 3 days after exposure to contrast medium. The incidence of CI-AKI in patients undergoing emergency PCI was 22.7% (241/1061). Logistic multivariable analysis showed that body surface area (BSA) (odds ratio [OR] 0.213, 95% confidence interval [CI]: 0.075-0.607, P= 0.004), history of myocardial infarction (MI) (OR 1.642, 95% CI: 1.079-2.499, P= 0.021), left ventricular ejection fraction (LVEF) (OR 0.969, 95% CI: 0.944-0.994, P= 0.015), hemoglobin (Hb) (OR 0.988, 95% CI: 0.976-1.000, P= 0.045), estimated glomerular filtration rate (OR 1.027, 95% CI: 1.018-1.037, P < 0.001), left anterior descending (LAD) stented (OR 1.464, 95% CI: 1.000-2.145, P= 0.050), aspirin (OR 0.097, 95%CI: 0.009-0.987, P= 0.049), and diuretics use (OR 1.850, 95% CI: 1.233-2.777, P= 0.003) were independent predictors of CI-AKI in patients undergoing emergency PCI. History of MI, low BSA, LVEF and Hb level, LAD stented, and diuretics use are associated with increased risk of CI-AKI in patients undergoing emergency PCI.

  6. Pattern of Leukaemia Patients Admitted in Ayub Teaching Hospital Abbottabad

    International Nuclear Information System (INIS)

    Khan, T. M.

    2016-01-01

    Background: Any tissue of the body can give rise to cancer. However, those tissues which multiply rapidly are at high risk of developing cancer and haematopoietic system is one of them. Neoplasms of this system are known as leukaemia and lymphoma, according to the types of white cells involved.Study of cancer patterns in different societies, however can contribute a substantial knowledge about the aetiology of cancer. The present Study was designed and aimed to estimate the frequency of different types of leukaemia in patients admitted in Ayub Teaching hospital Abbottabad. Methods: Data from the patients admitted at oncology Department of Ayub Teaching Hospital Abbottabad from 2010 to 2015 was collected and analysed to calculate cumulative and year-wise frequency of leukaemia and its major types. Frequency distribution with reference to gender and age was also calculated. Results: In our analysis about 16 percent patients had acute myelocytic leukaemia and 32 percent patients had acute lymphocytic leukaemia; while chronic myeloid leukaemia outnumbered chronic lymphocytic leukaemia (11 percent and 3 percent); Hodgkin lymphoma was seen in 18 percent cases while Non Hodgkin lymphoma (NHL) was present in 20 percent cases. Out of the total, 150 cases (75 percent) belonged to mountainous areas of Hazara, i.e., 40 cases belonged to Kohistan, another 40 cases were residents of Battagram, 45 cases belonged to hilly areas of Mansehra and 25 cases to Kaghan valley, while only 50 (25 percent) cases were from the plain areas of Abbottabad and Haripur districts, i.e., 20 and 30 cases respectively. Conclusion: Leukaemia is more common in hilly areas of Hazara, since majority of the cases belonged to well-known mountainous regions of Kohistan, Battagram, Kaghan or Mansehra and only few cases belonged to the plain areas of Abbottabad and Haripur districts. (author)

  7. Two acute kidney injury risk scores for critically ill cancer patients undergoing non-cardiac surgery.

    Science.gov (United States)

    Xing, Xue-Zhong; Wang, Hai-Jun; Huang, Chu-Lin; Yang, Quan-Hui; Qu, Shi-Ning; Zhang, Hao; Wang, Hao; Gao, Yong; Xiao, Qing-Ling; Sun, Ke-Lin

    2012-01-01

    Several risk scoures have been used in predicting acute kidney injury (AKI) of patients undergoing general or specific operations such as cardiac surgery. This study aimed to evaluate the use of two AKI risk scores in patients who underwent non-cardiac surgery but required intensive care. The clinical data of patients who had been admitted to ICU during the first 24 hours of ICU stay between September 2009 and August 2010 at the Cancer Institute, Chinese Academy of Medical Sciences & Peking Union Medical College were retrospectively collected and analyzed. AKI was diagnosed based on the acute kidney injury network (AKIN) criteria. Two AKI risk scores were calculated: Kheterpal and Abelha factors. The incidence of AKI was 10.3%. Patients who developed AKI had a increased ICU mortality of 10.9% vs. 1.0% and an in-hospital mortality of 13.0 vs. 1.5%, compared with those without AKI. There was a significant difference between the classification of Kheterpal's AKI risk scores and the occurrence of AKI (PAbelha's AKI risk scores and the occurrence of AKI (P=0.499). Receiver operating characteristic curves demonstrated an area under the curve of 0.655±0.043 (P=0.001, 95% confidence interval: 0.571-0.739) for Kheterpal's AKI risk score and 0.507±0.044 (P=0.879, 95% confidence interval: 0.422-0.592) for Abelha's AKI risk score. Kheterpal's AKI risk scores are more accurate than Abelha's AKI risk scores in predicting the occurrence of AKI in patients undergoing non-cardiac surgery with moderate predictive capability.

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

    Energy Technology Data Exchange (ETDEWEB)

    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

  9. 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)

    DEFF Research Database (Denmark)

    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...

  10. 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

    Energy Technology Data Exchange (ETDEWEB)

    Uderzo, C. [Milan Univ. (Italy); Rondelli, R.; Dini, G. [Bologna Univ. (Italy)] [and others

    1995-04-01

    We investigated the feasibility and efficacy of high-dose vincristine (4 mg/m{sup 2} 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).

  11. Evaluation of acute normovolemic hemodilution and autotransfusion in neurosurgical patients undergoing excision of intracranial meningioma.

    Science.gov (United States)

    Naqash, Imtiaz A; Draboo, M A; Lone, Abdul Qayoom; Nengroo, Showkat H; Kirmani, Altaf; Bhat, Abdul Rashid

    2011-01-01

    Several blood conservation strategies have been tried with the purpose of reducing homologons blood transfusion. PATIENTS #ENTITYSTARTX00026; In a prospective randomized study, the potential benefits of acute normovolemic hemodilution (ANH) with autologous transfusion were investigated as a blood conservation technique in surgical excision of intracranial meningioma. Over a period of 2 years, 40 patients undergoing excision of intracranial meningioma were randomly assigned to two groups of 20 patients each. Group I (Control Group) received conventional homologous blood intraoperatively and were not subjected to ANH. In Group II (ANH Group), Acute Normovolemic Hemodilution was initiated to a target hematocrit of 30% after induction of anesthesia. Parameters studied included changes in hemoglobin, hematocrit and hemodynamic parameters. The mean value of blood withdrawn in ANH group was 802.5 ± 208 ml. This was replaced simultaneously with an equal volume of 6% Hydroxyethyl starch to maintain normovolemia. There was no statistically significant variation in mean hemoglobin levels between the two groups at various stages of study. Hematocrit decreased significantly in both the groups at various stages as compared to preoperative values , the decrease being more but insignificant in group II. Changes in heart rate and mean blood pressure were similar and without statistically significant differences in either group at various stages of study. The amount of surgical blood loss in group I was 835.29 ± 684.37 ml, as compared to 865 + 409.78 ml in group II. The difference was statistically insignificant (p>0.05). The mean volume of homologous blood transfused in group I was 864.71 ± 349.89 ml, as compared to 165 ± 299.6 ml in group II which was statistically significant (p<0.05). In group II (ANH Group) only 5 patients (25%) required homologous blood whereas in group I I all patients (100%) needed homologous blood. We conclude that acute normovolemic hemodilution up to

  12. Evaluation of acute normovolemic hemodilution and autotransfusion in neurosurgical patients undergoing excision of intracranial meningioma

    Directory of Open Access Journals (Sweden)

    Imtiaz A Naqash

    2011-01-01

    Full Text Available Background : Several blood conservation strategies have been tried with the purpose of reducing homologons blood transfusion. Patients & Methods : In a prospective randomized study, the potential benefits of acute normovolemic hemodilution (ANH with autologous transfusion were investigated as a blood conservation technique in surgical excision of intracranial meningioma. Over a period of 2 years, 40 patients undergoing excision of intracranial meningioma were randomly assigned to two groups of 20 patients each. Group I (Control Group received conventional homologous blood intraoperatively and were not subjected to ANH. In Group II (ANH Group, Acute Normovolemic Hemodilution was initiated to a target hematocrit of 30% after induction of anesthesia. Parameters studied included changes in hemoglobin, hematocrit and hemodynamic parameters. Results : The mean value of blood withdrawn in ANH group was 802.5 ± 208 ml. This was replaced simultaneously with an equal volume of 6% Hydroxyethyl starch to maintain normovolemia. There was no statistically significant variation in mean hemoglobin levels between the two groups at various stages of study. Hematocrit decreased significantly in both the groups at various stages as compared to preoperative values , the decrease being more but insignificant in group II. Changes in heart rate and mean blood pressure were similar and without statistically significant differences in either group at various stages of study. The amount of surgical blood loss in group I was 835.29 ± 684.37 ml, as compared to 865 + 409.78 ml in group II. The difference was statistically insignificant (p>0.05. The mean volume of homologous blood transfused in group I was 864.71 ± 349.89 ml, as compared to 165 ± 299.6 ml in group II which was statistically significant (p<0.05. In group II (ANH Group only 5 patients (25% required homologous blood whereas in group I I all patients (100% needed homologous blood. Conclusion : We conclude

  13. Postoperative acute kidney injury in high-risk patients undergoing major abdominal surgery.

    Science.gov (United States)

    Romagnoli, Stefano; Zagli, Giovanni; Tuccinardi, Germana; Tofani, Lorenzo; Chelazzi, Cosimo; Villa, Gianluca; Cianchi, Fabio; Coratti, Andrea; De Gaudio, Angelo Raffaele; Ricci, Zaccaria

    2016-10-01

    Acute kidney injury (AKI) is a frequent complication in high-risk patients undergoing major surgery and is associated with longer hospital stay, increased risk for nosocomial infection and significantly higher costs. A prospective observational study exploring the incidence of AKI (AKIN classification at any stage) in high-risk patients within 48 hours after major abdominal surgery was conducted. Patients' preoperative characteristics, intraoperative management, and outcome were evaluated for associations with AKI using a logistic regression model. Data from 258 patients were analyzed. Thirty-one patients (12%) developed AKI, reaching the AKIN stage 1. No patient reached an AKIN stage higher than 1. AKI patients were older (75.2 vs 70.2 years; P = 0.0113) and had a higher body mass index (26.5 vs 25.1 kg/m(2)). In addition, AKI patients had a significantly longer ICU length of stay (3.4 vs 2.4 days; P= .0017). Creatinine levels of AKI patients increased significantly compared to the preoperative levels at 24 (P= .0486), 48 (P= .0011) and 72 hours (P= .0055), while after 72 hours it showed a downwards trend. At ICU discharge, 28 out of 31 patients (90.3%) recovered preoperative levels. Multivariate analysis identified age (OR 1.088; P= .002) and BMI (OR 1.124; P= .022) as risk factors for AKI development. Moreover, AKI development was an independent risk factor for ICU stays longer than 48 hours (OR 2.561; P= .019). Mild AKI is a not rare complication in high-risk patients undergoing major abdominal surgery. Although in almost the totality of cases, the indicators of renal function recovered to preoperative levels, post-operative AKI represents a primary risk factor for a prolonged ICU stay. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Urinary protein profiles in ketorolac-associated acute kidney injury in patients undergoing orthopedic day surgery

    Directory of Open Access Journals (Sweden)

    Mariano F

    2017-09-01

    Full Text Available Filippo Mariano,1 Chiara Cogno,1 Fulvia Giaretta,2,3 Ilaria Deambrosis,2,3 Simona Pozza,4 Maurizio Berardino,5 Giuseppe Massazza,6 Luigi Biancone1,3 1Department of General and Specialist Medicine, Nephrology, Dialysis and Transplantation Unit, City of Health and Science, CTO Hospital, Turin, 2Department of General and Specialist Medicine, Laboratory of Nephrology and Immunopathology, City of Health and Science, Molinette Hospital, Turin, 3Department of Medical Sciences, University of Turin, Turin, 4Department of Radiology and Radiotherapy, CTO Radiology, City of Health and Science, CTO Hospital, Turin, 5Department of Anesthesiology and Intensive Care, Anesthesiology and Intensive Care 5, City of Health and Science, CTO Hospital, Turin, 6Department of Orthopedics and Traumatology, Week Hospital Unit, City of Health and Science, CTO Hospital, and University of Turin, Turin, Italy Background: Parenteral administration of ketorolac is very effective in controlling postoperative pain for orthopedic surgery. Ketorolac can induce clinically relevant renal alterations in elderly patients, whereas its short course is considered safe for young adults with normal preoperative renal function. In this study, of a cohort of young adults undergoing elective orthopedic day surgery, we sought cases complicated by readmission due to acute kidney injury (AKI.Patients and methods: Among 1397 young adults, aged 18–32 years who were admitted to undergo orthopedic day surgery from 2013 to 2015, four patients (0.29%, three males/one female treated in postprocedure with ketorolac (from 60 to 90 mg/day for 1–2 days were readmitted for suspected severe AKI. We evaluated functional outcome, urinary protein profiles and kidney biopsy (1 patient.Results: After day surgery discharge, they experienced gastrointestinal disturbances, flank pain and fever. Readmitted on post-surgery days 3–4, they presented with oliguric AKI (creatinine range 158.4–466.4 µmol/L and

  15. Screening microarrays of novel monoclonal antibodies for binding to T-, B- and myeloid leukaemia cells.

    Science.gov (United States)

    Belov, Larissa; Huang, Pauline; Chrisp, Jeremy S; Mulligan, Stephen P; Christopherson, Richard I

    2005-10-20

    We have developed a microarray (DotScan) that enables rapid immunophenotyping and classification of leukaemias and lymphomas by measuring the capture of cells by immobilized dots of 82 CD antibodies [Belov, L., de la Vega, O., dos Remedios, C.G., Mulligan, S.P., 2001. Immunophenotyping of leukemia using a cluster of differentiation antibody microarray. Cancer Res. 61, 4483; Belov, L., Huang, P., Barber, N., Mulligan, S.P., Christopherson, R.I., 2003. Identification of repertoires of surface antigens on leukemias using an antibody microarray. Proteomics 3, 2147]. The DotScan technology has been used to investigate the properties of 498 new antibodies submitted to the HLDA8 Workshop. These antibodies have been applied as 10 nl dots to a film of nitrocellulose on a microscope slide to make an HLDA8 microarray. After blocking the remaining nitrocellulose surface, individual arrays were incubated with each of 7 cell types from a human leukaemia cell panel consisting of three cell lines, CCRF-CEM (a T-cell acute lymphocytic leukaemia), MEC-1 (derived from B-cell chronic lymphocytic leukaemia) and HL-60 (a promyelocytic leukaemia), and four leukaemias from patients: a T-cell prolymphocytic leukaemia, a B-cell chronic lymphocytic leukaemia, and two acute myeloid leukaemias. Leukaemia cells were captured by those immobilized antibodies for which they expressed the corresponding surface molecule. Unbound cells were gently washed off, bound cells were fixed to the arrays and dot patterns were recorded using a DotScan array reader and quantified using DotScan data analysis software. The data obtained show the unique expression profiles of the 7 cell types in the leukaemia cell panel obtained with the DotScan microarray, and the differential capture patterns for these 7 cell types screened against the 498 antibodies in the HLDA8 microarray constructed for this study.

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

    International Nuclear Information System (INIS)

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

    1989-01-01

    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

  17. New leukaemia link

    International Nuclear Information System (INIS)

    Roche, P.

    1993-01-01

    A new study around the Aldermaston and Burghfield nuclear weapons establishments published in the British Medical Journal has found a similar association between the risk of childhood leukaemia and employment in the nuclear industry to that found by Professor Gardner in 1990 at Sellafield. It suggests that occupational exposure to radiation prior to conception increases the risk of a subsequent child developing leukaemia by 9 times. It is clear that working at Aldermaston or Burghfield does not explain the entire excess of cancers -there must be another factor at work. The one factor that Aldermaston, Burghfield, Sellafield and Dounreay where a similar pattern is found, have in common is plutonium. Whilst further studies are important to determine the role played by plutonium, it should be declared 'guilty until proven innocent'. The production and use of plutonium should cease immediately. (author)

  18. High PRDM16 expression identifies a prognostic subgroup of pediatric acute myeloid leukaemia correlated to FLT3-ITD, KMT2A-PTD, and NUP98-NSD1: the results of the Japanese Paediatric Leukaemia/Lymphoma Study Group AML-05 trial.

    Science.gov (United States)

    Shiba, Norio; Ohki, Kentaro; Kobayashi, Tohru; Hara, Yusuke; Yamato, Genki; Tanoshima, Reo; Ichikawa, Hitoshi; Tomizawa, Daisuke; Park, Myoung-Ja; Shimada, Akira; Sotomatsu, Manabu; Arakawa, Hirokazu; Horibe, Keizo; Adachi, Souichi; Taga, Takashi; Tawa, Akio; Hayashi, Yasuhide

    2016-02-01

    Recent reports described the NUP98-NSD1 fusion as an adverse prognostic marker for acute myeloid leukaemia (AML) and PRDM16 (also known as MEL1) as the representative overexpressed gene in patients harbouring NUP98-NSD1 fusion. PRDM16 gene expression levels were measured via real-time polymerase chain reaction in 369 paediatric patients with de novo AML, of whom 84 (23%) exhibited PRDM16 overexpression (PRDM16/ABL1 ratio ≥0·010). The frequencies of patients with high or low PRDM16 expression differed widely with respect to each genetic alteration, as follows: t(8;21), 4% vs. 96%, P NUP98-NSD1, 100% vs. 0%, P < 0·001. The overall survival (OS) and event-free survival (EFS) among PRDM16-overexpressing patients were significantly worse than in patients with low PRDM16 expression (3-year OS: 51% vs. 81%, P < 0·001, 3-year EFS: 32% vs. 64%, P < 0·001) irrespective of other cytogenetic alterations except for NPM1. PRDM16 gene expression was particularly useful for stratifying FLT3-internal tandem duplication-positive AML patients (3-year OS: high = 30% vs. low = 70%, P < 0·001). PRDM16 overexpression was highly recurrent in de novo paediatric AML patients with high/intermediate-risk cytogenetic profiles and was independently associated with an adverse outcome. © 2015 John Wiley & Sons Ltd.

  19. Antithrombin III is associated with acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support.

    Science.gov (United States)

    Hoefer, Judith; Ulmer, Hanno; Kilo, Juliane; Margreiter, Raimund; Grimm, Michael; Mair, Peter; Ruttmann, Elfriede

    2017-06-01

    There are few data on the role of liver dysfunction in patients with end-stage heart failure supported by mechanical circulatory support. The aim of our study was to investigate predictors for acute liver failure in patients with end-stage heart failure undergoing mechanical circulatory support. A consecutive 164 patients with heart failure with New York Heart Association class IV undergoing mechanical circulatory support were investigated for acute liver failure using the King's College criteria. Clinical characteristics of heart failure together with hemodynamic and laboratory values were analyzed by logistic regression. A total of 45 patients (27.4%) with heart failure developed subsequent acute liver failure with a hospital mortality of 88.9%. Duration of heart failure, cause, cardiopulmonary resuscitation, use of vasopressors, central venous pressure, pulmonary capillary wedge pressure, pulmonary pulsatility index, cardiac index, and transaminases were not significantly associated with acute liver failure. Repeated decompensation, atrial fibrillation (P failure in univariate analysis only. In multivariable analysis, decreased antithrombin III was the strongest single measurement indicating acute liver failure (relative risk per %, 0.84; 95% confidence interval, 0.77-0.93; P = .001) and remained an independent predictor when adjustment for the Model for End-Stage Liver Disease score was performed (relative risk per %, 0.89; 95% confidence interval, 0.80-0.99; P = .031). Antithrombin III less than 59.5% was identified as a cutoff value to predict acute liver failure with a corresponding sensitivity of 81% and specificity of 87%. In addition to the Model for End-Stage Liver Disease score, decreased antithrombin III activity tends to be superior in predicting acute liver failure compared with traditionally thought predictors. Antithrombin III measurement may help to identify patients more precisely who are developing acute liver failure during mechanical

  20. Molecular genetics, natural history and the demise of childhood leukaemia.

    Science.gov (United States)

    Greaves, M

    1999-12-01

    The patterns of genetic change, clonal evolution, natural history and latency are very different in the paediatric leukaemias compared with adult epithelial cancers but are similar to those in other childhood cancers of mesenchymal stem cell origin. This distinction has a biological logic in the context of the selective pressures for clonal emergence in different developmental and cellular contexts and has a major impact on curability. Most childhood leukaemias and some other mesenchymal stem cell tumours are of fetal origin and can metastasize without corruption of restraints on cell proliferation or bypassing apoptosis. In marked contrast to most invasive or metastatic epithelial carcinomas in adults, these former cancers then retain sensitivity to therapeutic apoptosis. Moreover, their abbreviated and less complex evolutionary status is associated with less genetic diversity and instability, minimising opportunity for clonal selection for resistance. A minority of leukaemias in children and a higher fraction in adults do, however, have genetic alterations that bypass cell cycle controls and apoptosis imposition. These are the 'bad news' genotypes. The cellular and molecular diversity of acute leukaemia impacts also on aetiology. Paediatric acute leukaemias can be initiated prenatally by illegitimate recombination and fusion gene formation in fetal haemopoiesis. For acute lymphoblastic leukaemia (ALL) in children, twin studies suggest that a secondary postnatal molecular event is also required. This may be promoted by an abnormal or delayed response to common infections. Even for a classic case of a cancer that is intrinsically curable by systematic chemotherapy i.e. childhood ALL, prevention may turn out to be the preferred option.

  1. Associations of novel genetic variations in the folate-related and ARID5B genes with the pharmacokinetics and toxicity of high-dose methotrexate in paediatric acute lymphoblastic leukaemia.

    Science.gov (United States)

    Csordas, Katalin; Lautner-Csorba, Orsolya; Semsei, Agnes F; Harnos, Andrea; Hegyi, Marta; Erdelyi, Daniel J; Eipel, Oliver T; Szalai, Csaba; Kovacs, Gabor T

    2014-08-01

    High-dose methotrexate (HD-MTX) plays an important role in the consolidation therapy of acute lymphoblastic leukaemia (ALL) in many treatment regimens worldwide. However, there is a large interpatient variability in the pharmacokinetics and toxicity of the drug. We investigated the influence of single nucleotide polymorphisms (SNPs) in genes of the folate metabolic pathway, transporter molecules and transcription proteins on the pharmacokinetics and toxicity of MTX and 7-hydroxy-methotrexate (7-OH-MTX). 63 SNPs of 14 genes were genotyped and a total of 463 HD-MTX courses (administered according to the ALL-BFM 95 and ALL IC-BFM 2002 protocols) were analysed. Haematological, hepatic and renal toxicities, estimated by routine laboratory parameters were evaluated. Random forest and regression trees were used for variable selection and model building. Linear mixed models were established to prove the significance of the selected variables. SNPs (rs4948502, rs4948496, rs4948487) of the ARID5B gene were associated with the serum levels of MTX (P < 0·02), serum levels and area under the curve of 7-OH-MTX (P < 0·02) and with hypoproteinaemia (P = 0·004). SLCO1B1 rs4149056 also showed a significant association with serum MTX levels (P < 0·001). Our findings confirm the association of novel genetic variations in folate-related and ARID5B genes with the serum MTX levels and acute toxicity. © 2014 John Wiley & Sons Ltd.

  2. Temporal and Other Exposure Aspects of Residential Magnetic Fields Measurement in Relation to Acute Lymphoblastic Leukaemia in Children: The National Cancer Institute Children's Cancer Group Study (invited paper)

    International Nuclear Information System (INIS)

    Baris, D.; Linet, M.; Auvinen, A.; Kaune, W.T.; Wacholder, S.; Kleinerman, R.; Hatch, E.; Robison, L.; Niwa, S.; Haines, C.; Tarone, R.E.

    1999-01-01

    Case-control studies have used a variety of measurements to evaluate the relationship of children's exposure to magnetic fields (50 or 60 Hz) with childhood leukaemia and other childhood cancers. In the absence of knowledge about which exposure metrics may be biologically meaningful, studies during the past 10 years have often used time-weighted average (TWA) summaries of home measurements. Recently, other exposure metrics have been suggested, usually based on theoretical considerations or limited laboratory data. In this paper, the rationale and associated preliminary studies undertaken are described as well as feasibility and validity issues governing the choice of the primary magnetic field exposure assessment methods and summary metric used to estimate children's exposure in the National Cancer Institute/Children's Cancer Group (NCI/CCG) case-control study. Also provided are definitions and discussion of the strengths and weaknesses of the various exposure metrics used in exploratory analyses of the NCI/CCG measurement data. Exposure metrics evaluated include measures of central tendency (mean, median, 30th to 70th percentiles), peak exposures (90th and higher percentiles, peak values of the 24 h measurements), and measurements of short-term temporal variability (rate of change). This report describes correlations of the various metrics with the time-weighted average for the 24 h period (TWA-24-h). Most of the metrics were found to be positively and highly correlated with TWA-24-h, but lower correlations of TWA-24-h with peak exposure and with rate of change were observed. To examine further the relation between TWA and alternative metrics, similar exploratory analysis should be considered for existing data sets and for forthcoming measurement investigations of residential magnetic fields and childhood leukaemia. (author)

  3. [Multimodal distraction to relieve pain in children undergoing acute medical procedures].

    Science.gov (United States)

    Miller, Kate; Rodger, Sylvia; Bucolo, Sam; Wang, Xue-Qing; Kimble, Roy M

    2009-10-01

    Non-pharmacological approaches to pain management have been used by therapists for decades to reduce the anxiety and pain experienced by children during burn care procedures. With a greater understanding of pain and the principles behind what causes a child to be distracted, combined with access to state of the art technology, we have developed an easy to use, hand held multimodal distraction device (MMD). MMD is an interactive device that prepares the child for a procedure and uses developmentally appropriate distraction stories and games during the procedures to alleviate anxiety and pain. This paper summarizes the results of three randomized control trials. The trials aimed to understand the effectiveness of MMD as a distraction and preparation tool in reducing anxiety and pain in children undergoing burns and non-burns medical procedures compared to pure pharmacological approaches Standard Distraction (SD) and off the shelf video games (VG). Three separate prospective randomized control trials involving 182 children having 354 dressing changes were conducted in the burns and orthopedic departments at Royal Children's Hospital, Brisbane, Australia, to address the above aims. Pain and anxiety scores were completed for the child, caregiver and nursing staff according to the Modified Faces, Legs, Activity, Cry and Consolability Scale, Faces Pain Scale-Revised, Visual Analogue Scale and Wong-Baker Faces Pain Rating Scale. Procedural length was recorded. MMD as a preparation and distraction tool were shown to have a significant impact on child, parent and nursing staff reported anxiety and pain during procedures compared to standard care and video games (P < 0.01). The MMD had a positive effect on clinical time and was shown to sustain its impact on pain and time with further dressing changes. MMD is more effective in reducing the pain and anxiety experienced by children in acute medical procedures as compared with SD and VG. MMD is continuing to be trialed and is

  4. Granulocytic sarcoma in a patient with chronic myeloid leukaemia in complete haematological, cytogenetic and molecular remission.

    Science.gov (United States)

    Kittai, Adam; Yu, Eun-Mi; Tabbara, Imad

    2014-12-23

    Granulocytic sarcoma, also known as myeloid sarcoma, is an extramedullary tumour composed of immature myeloid cells. Granulocytic sarcoma is typically found in patients with acute myeloid leukaemia, accelerated phase or blast crisis of chronic myeloid leukaemia, myelodysplastic syndrome, or as an isolated event without bone marrow involvement. We present a case of granulocytic sarcoma in a patient with chronic myeloid leukaemia in the setting of complete haematological, molecular and cytogenetic remission. Our patient was first treated with imatinib for chronic-phase chronic myeloid leukaemia. After maintaining remission for 42 months, he developed a granulocytic sarcoma in his spine. In this case report, we describe our case, along with the three other cases reported in the literature. In addition to being a rare diagnosis, this case demonstrates the importance of being vigilant in diagnosing the cause of back pain and atypical symptoms in patients with a history of leukaemia. 2014 BMJ Publishing Group Ltd.

  5. Low dose irradiation and risk of leukaemia: A case-control study

    International Nuclear Information System (INIS)

    Chobanova, N.; Bayrakova, A.

    1997-01-01

    The effect of low dose irradiation (medical X-ray diagnostic) on the developing of leukaemias in adults is investigated. The influence of non-radiation agents (occupational exposure to chemical carcinogens, past viral infections, family aggregations) to leukaemias are considered also. During this retrospective study 228 patients have been examined with the following diagnosis: acute myeloid leukaemia, chronic myelogenous leukaemias, myelodisplastic syndrome and non-Hodgkin lymphoma (diagnosed between 1991-1993). Each case has been matched with two controls. Statistically significant increase has been found in the risk of developing leukaemias after X-ray diagnostic irradiation (OR = 1.98, 95% CI = 1.14 ./. 3.46). Exposure to chemical agents is also associated with significant increase in the risk (OR = 1.98, 95% CI = 1.25 ./. 2.86). (author)

  6. Comparative outcome of reduced intensity and myeloablative conditioning regimen in HLA identical sibling allogeneic haematopoietic stem cell transplantation for patients older than 50 years of age with acute myeloblastic leukaemia: a retrospective survey from the Acute Leukemia Working Party (ALWP) of the European group for Blood and Marrow Transplantation (EBMT).

    Science.gov (United States)

    Aoudjhane, M; Labopin, M; Gorin, N C; Shimoni, A; Ruutu, T; Kolb, H-J; Frassoni, F; Boiron, J M; Yin, J L; Finke, J; Shouten, H; Blaise, D; Falda, M; Fauser, A A; Esteve, J; Polge, E; Slavin, S; Niederwieser, D; Nagler, A; Rocha, V

    2005-12-01

    Results of reduced intensity conditioning regimen (RIC) in the HLA identical haematopoietic stem cell transplantation (HSCT) setting have not been compared to those after myeloablative (MA) regimen HSCT in patients with acute myeloblastic leukaemia (AML) over 50 years of age. With this aim, outcomes of 315 RIC were compared with 407 MA HSCT recipients. The majority of RIC was fludarabine-based regimen associated to busulphan (BU) (53%) or low-dose total body irradiation (24%). Multivariate analyses of outcomes were used adjusting for differences between both groups. The median follow-up was 13 months. Cytogenetics, FAB classification, WBC count at diagnosis and status of the disease at transplant were not statistically different between the two groups. However, RIC patients were older, transplanted more recently, and more frequently with peripheral blood allogeneic stem cells as compared to MA recipients. In multivariate analysis, acute GVHD (II-IV) and transplant-related mortality were significantly decreased (P=0.01 and P<10(-4), respectively) and relapse incidence was significantly higher (P=0.003) after RIC transplantation. Leukaemia-free survival was not statistically different between the two groups. These results may set the grounds for prospective trials comparing RIC with other strategies of treatment in elderly AML.

  7. Nuclear DNA as Predictor of Acute Kidney Injury in Patients Undergoing Coronary Artery Bypass Graft: A Pilot Study.

    Science.gov (United States)

    Likhvantsev, Valery V; Landoni, Giovanni; Grebenchikov, Oleg A; Skripkin, Yuri V; Zabelina, Tatiana S; Zinovkina, Liudmila A; Prikhodko, Anastasia S; Lomivorotov, Vladimir V; Zinovkin, Roman A

    2017-12-01

    To measure the release of plasma nuclear deoxyribonucleic acid (DNA) and to assess the relationship between nuclear DNA level and acute kidney injury occurrence in patients undergoing cardiac surgery. Cardiovascular anesthesiology and intensive care unit of a large tertiary-care university hospital. Prospective observational study. Fifty adult patients undergoing cardiac surgery. Nuclear DNA concentration was measured in the plasma. The relationship between the level of nuclear DNA and the incidence of acute kidney injury after coronary artery bypass grafting was investigated. Cardiac surgery leads to significant increase in plasma nuclear DNA with peak levels 12 hours after surgery (median [interquartile range] 7.0 [9.6-22.5] µg/mL). No difference was observed between off-pump and on-pump surgical techniques. Nuclear DNA was the only predictor of acute kidney injury between baseline and early postoperative risk factors. The authors found an increase of nuclear DNA in the plasma of patients who had undergone coronary artery bypass grafting, with a peak after 12 hours and an association of nuclear DNA with postoperative acute kidney injury. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Traffic-related air pollution and risk for leukaemia of an adult population.

    Science.gov (United States)

    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. © 2015 UICC.

  9. Leukaemia near british nuclear installations

    International Nuclear Information System (INIS)

    Hubert, D.

    1991-01-01

    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 [fr

  10. Acute megakaryoblastic leukaemia: a national clinical and biological study of 53 adult and childhood cases by the Groupe Français d'Hématologie Cellulaire (GFHC).

    Science.gov (United States)

    Duchayne, Eliane; Fenneteau, Odile; Pages, Marie-Pierre; Sainty, Danielle; Arnoulet, Christine; Dastugue, Nicole; Garand, Richard; Flandrin, Georges

    2003-01-01

    Since the WHO classification of haematological malignancies recommended the description of global entities, we performed a national M7-AML study to correlate morphological, immunological and cytogenetic features, and to find new clinically relevant M7 entities. This study is based on accurate morphological and immunological study to select pure megakaryoblastic proliferations and to eliminate megakaryocytic participation in haemopathies. We collected 53 cases: 23 adults and 30 children. We confirm the wide heterogeneity of adult M7. In adults, the cytogenetic abnormalities are frequently those of secondary leukaemia while a few patients have a previous history and morphological features of dyshaematopoiesis; their outcome is very poor. Among children, besides the well-known Down syndrome M7, we in particular, studied ten t(1;22) M7 and one OTT-MAL transcript positive case with normal karyotype presenting specific features. We were already aware of their younger age, female and tumoral presentation, but we also found a lower percentage of bone marrow blasts, sometimes without any megakaryoblastic bone marrow involvement, but always, with a dysmegakaryocytopoiesis associated with micromegakaryocytes. They are generally good responders to intensive AML chemotherapy with very long disease-free survivals (DFS). Accordingly, OTT-MAL transcript study, in infant M7 with normal karyotype, is recommended and we feel that this entity should be added to the WHO AML classification.

  11. 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)

    Energy Technology Data Exchange (ETDEWEB)

    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.

  12. The incidence of and mortality from leukaemias in the UK: a general population-based study

    OpenAIRE

    Bhayat, Fatima; Das-Gupta, Emma; Smith, Chris; McKeever, Tricia; Hubbard, Richard

    2009-01-01

    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 leuk...

  13. [A patient with acute Philadelphia-chromosome-positive mixed phenotype leukemia developing ecthyma gangrenosum while undergoing combined imatinib mesylate chemotherapy].

    Science.gov (United States)

    Suzuki, Kei; Sekine, Takao

    2014-05-01

    A 67-year-old woman with acute Philadelphia-chromosome-positive mixed phenotype leukemia developed bilateral periorbital ecthyma gangrenousum (EG) subsequent to periorbital edema while undergoing combined imatinib mesylate (imatinib) chemotherapy. Although initial periorbital edema was considered an imatinib side effect, the lesion deteriorated rapidly with high fever in the neutropenic phase, and the woman died of septic shock. Cultures from blood and exudative fluid grew Pseudomonas aeruginosa, after which EG was diagnosed. EG is a well-recognized emergent cutaneous infection most commonly associated with Pseudomonas aeruginosa bactremia. Because some patients present with EG a few days prior to developing life-threatening septicemia, it is important that EG be diagnosed correctly. Imatinib side effects such as edema are usually tolerable, and imatinib is widely used to treat Philadelphia-chromosome-positive leukemia, particularly in those with acute lymphoblastic leukemia, and neutropenic patients undergoing imatinib therapy are expected to increase in number. Delay in initiating appropriate therapy is correlated with poor outcome, so drug side effects and EG must be carefully differentiated when skin edema with surrounding erythema is noted in neutropenic patients undergoing imatinib therapy.

  14. Childhood leukaemia and lymphoma: African experience supports a role for environmental factors in leukaemogenesis

    Science.gov (United States)

    Williams, Christopher KO; Foroni, Letizia; Luzzatto, Lucio; Saliu, Idris; Levine, Arthur; Greaves, Mel F

    2014-01-01

    Major differences exist in the nature of leukaemia and lymphoma in low-income African children compared to those in the high-income countries. These include the absence of the peak incidence of acute lymphoblastic leukaemia (ALL) in under-five-year olds that characterizes the disease in high-income countries. Conversely, chloroma association with acute myelogenous leukaemia (CA-AML/AMML) and Burkitt’s lymphoma (BL) are rare in the high-income countries. This report describes clinical and laboratory as well as epidemiological features of childhood leukaemia and lymphoma reported betwen 1982 and 1984 in the city of Ibadan, Nigeria. The observed pattern of distribution of childhood haematological malignancies in the city is more consistent with the observations of Ludwik Gross’s experiments on environmental influences, such as malnutrition and infections, animal leukaemogenesis, and mirroring the consequences of the primordial pressures that have shaped human genetics and pathophysiology. PMID:25435906

  15. Childhood leukaemia and lymphoma: African experience supports a role for environmental factors in leukaemogenesis.

    Science.gov (United States)

    Williams, Christopher Ko; Foroni, Letizia; Luzzatto, Lucio; Saliu, Idris; Levine, Arthur; Greaves, Mel F

    2014-01-01

    Major differences exist in the nature of leukaemia and lymphoma in low-income African children compared to those in the high-income countries. These include the absence of the peak incidence of acute lymphoblastic leukaemia (ALL) in under-five-year olds that characterizes the disease in high-income countries. Conversely, chloroma association with acute myelogenous leukaemia (CA-AML/AMML) and Burkitt's lymphoma (BL) are rare in the high-income countries. This report describes clinical and laboratory as well as epidemiological features of childhood leukaemia and lymphoma reported betwen 1982 and 1984 in the city of Ibadan, Nigeria. The observed pattern of distribution of childhood haematological malignancies in the city is more consistent with the observations of Ludwik Gross's experiments on environmental influences, such as malnutrition and infections, animal leukaemogenesis, and mirroring the consequences of the primordial pressures that have shaped human genetics and pathophysiology.

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

    DEFF Research Database (Denmark)

    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 risks and radon

    International Nuclear Information System (INIS)

    Wolff, S.P.

    1991-01-01

    A correlation has been established between domestic radon exposure and mutation in peripheral T lymphocytes. Some caution must be exercised, however, in interpreting this result as evidence that levels of domestically encountered radon are sufficient to cause leukaemogenic chromosomal alterations. Radon may simply be acting as a surrogate for some other mutagenic factor. Correlations with Local Authority statistics collected in the United Kingdom 1981 Census appear to show that lower domestic radon levels reflect relatively greater socioeconomic deprivation whereas higher levels reflect greater prosperity. The relative risk of lymphoproliferative disease correlates with the same factors that determine domestic radon levels at the county level. Putative relationships between domestic radon exposure and cancer thus need to be controlled for socioeconomic status and associated factors, at least at the county level. (The correlations may not apply to smaller areas.) Similarly, the causative factors underlying the relationships between higher regional socioeconomic status and leukaemia require closer examination. (author)

  18. Acute pulmonary edema caused by takotsubo cardiomyopathy in a pregnant woman undergoing transvaginal cervical cerclage

    OpenAIRE

    Lee, Jae-Young; Kwon, Hyun-Jung; Park, Sang-Wook; Lee, Yu-Mi

    2017-01-01

    Abstract Background: The physiological changes associated with pregnancy may predispose pregnant women to pulmonary edema. Other known causes of pulmonary edema during pregnancy include tocolytic drugs, preeclampsia, eclampsia, and peripartum cardiomyopathy. Methods: We describe a rare case of pulmonary edema caused by takotsubo cardiomyopathy in a pregnant woman at 14 weeks of gestation who was undergoing emergency transvaginal cervical cerclage. Results: Intraoperative chest radiography rev...

  19. Thiamine pyrophosphate effect and normalized erythrocyte transketolase activity ratio in Wernicke-Korsakoff patients and acute alcoholics undergoing detoxification.

    Science.gov (United States)

    Rooprai, H K; Pratt, O E; Shaw, G K; Thomson, A D

    1996-09-01

    Thiamine deficiency may be assessed clinically by an abnormally low specific erythrocyte transketolase activity and/or by abnormally large activation by thiamine diphosphate in vitro (or 'TPP effect'). In the present investigation, we report erythrocyte transketolase activation by TPP in acute alcoholics and Wernicke-Korsakoff patients undergoing detoxification. A new age-dependent parameter was used to improve the reliability of transketolase activity as an indicator of marginal thiamine deficiency. Thus normalized transketolase activity ratio (NTKZ), primary activation ratio (PAR) and further activation ratio (FAR) were measured in 29 acute alcoholics and 12 Wernicke-Korsakoff patients upon admission, and also on 47 control subjects. It was possible to follow up 14 of the 29 acute alcoholics after 7 days of treatment. Twenty-one per cent of the acute alcoholics and 33% of the Wernicke-Korsakoff patients, on admission to the detoxification Unit, had NTKZ values beyond the defined critical conditions for thiamine deficiency, whereas 7% of the former and 25% of the latter had PAR values beyond these critical conditions. Furthermore, all three parameters were significantly different in the Wernicke-Korsakoff patients compared to the other groups. The pattern of improvement of the different parameters on follow-up varied considerably and is difficult to explain, as only the NTKZ was statistically significant. Hence, only eight out of 14 acute alcoholics showed improvement in NTKZ, seven showed improvement of PAR and six showed improvement of FAR after treatment. Five patients showed improvement of both NTKZ and PAR and none of the patients showed improvement of all three parameters. We conclude that our findings confirm previous reports and that this modified transketolase activation test improves its reliability as an indicator of marginal thiamine deficiency.

  20. The Complexity of Targeting PI3K-Akt-mTOR Signalling in Human Acute Myeloid Leukaemia: The Importance of Leukemic Cell Heterogeneity, Neighbouring Mesenchymal Stem Cells and Immunocompetent Cells

    Directory of Open Access Journals (Sweden)

    Annette K. Brenner

    2016-11-01

    Full Text Available Therapeutic targeting of PI3K-Akt-mTOR is considered a possible strategy in human acute myeloid leukaemia (AML; the most important rationale being the proapoptotic and antiproliferative effects of direct PI3K/mTOR inhibition observed in experimental studies of human AML cells. However, AML is a heterogeneous disease and these effects caused by direct pathway inhibition in the leukemic cells are observed only for a subset of patients. Furthermore, the final effect of PI3K-Akt-mTOR inhibition is modulated by indirect effects, i.e., treatment effects on AML-supporting non-leukemic bone marrow cells. In this article we focus on the effects of this treatment on mesenchymal stem cells (MSCs and monocytes/macrophages; both these cell types are parts of the haematopoietic stem cell niches in the bone marrow. MSCs have unique membrane molecule and constitutive cytokine release profiles, and mediate their support through bidirectional crosstalk involving both cell-cell contact and the local cytokine network. It is not known how various forms of PI3K-Akt-mTOR targeting alter the molecular mechanisms of this crosstalk. The effect on monocytes/macrophages is also difficult to predict and depends on the targeted molecule. Thus, further development of PI3K-Akt-mTOR targeting into a clinical strategy requires detailed molecular studies in well-characterized experimental models combined with careful clinical studies, to identify patient subsets that are likely to respond to this treatment.

  1. Effects of Sigh on Regional Lung Strain and Ventilation Heterogeneity in Acute Respiratory Failure Patients Undergoing Assisted Mechanical Ventilation.

    Science.gov (United States)

    Mauri, Tommaso; Eronia, Nilde; Abbruzzese, Chiara; Marcolin, Roberto; Coppadoro, Andrea; Spadaro, Savino; Patroniti, Nicolo'; Bellani, Giacomo; Pesenti, Antonio

    2015-09-01

    In acute respiratory failure patients undergoing pressure support ventilation, a short cyclic recruitment maneuver (Sigh) might induce reaeration of collapsed lung regions, possibly decreasing regional lung strain and improving the homogeneity of ventilation distribution. We aimed to describe the regional effects of different Sigh rates on reaeration, strain, and ventilation heterogeneity, as measured by thoracic electrical impedance tomography. Prospective, randomized, cross-over study. General ICU of a single university-affiliated hospital. We enrolled 20 critically ill patients intubated and mechanically ventilated with PaO2/FIO2 up to 300 mm Hg and positive end-expiratory pressure at least 5 cm H2O (15 with acute respiratory distress syndrome), undergoing pressure support ventilation as per clinical decision. Sigh was added to pressure support ventilation as a 35 cm H2O continuous positive airway pressure period lasting 3-4 seconds at different rates (no-Sigh vs 0.5, 1, and 2 Sigh(s)/min). All study phases were randomly performed and lasted 20 minutes. In the last minutes of each phase, we measured arterial blood gases, changes in end-expiratory lung volume of nondependent and dependent regions, tidal volume reaching nondependent and dependent lung (Vtnondep and Vtdep), dynamic intratidal ventilation heterogeneity, defined as the average ratio of Vt reaching nondependent/Vt reaching dependent lung regions along inspiration (VtHit). With Sigh, oxygenation improved (p ventilation heterogeneity. Our study generates the hypothesis that in ventilated acute respiratory failure patients, Sigh may enhance regional lung protection.

  2. Dermatoglyphics in childhood leukaemia: a guide to prognosis and aetiology?

    Science.gov (United States)

    Till, M.; Larrauri, S.; Smith, P. G.

    1978-01-01

    The results of analysis of the dermatoglyphics of 152 children with acute lymphoblastic leukaemia (ALL) (and the first-degree relatives of 54 of them) contrast with those of 31 children with acute myeloblastic leukaemia (AML) (and the first-degree relatives of 25 of them). In ALL our findings suggest that neither genetic susceptibility nor an environmental factor, effective during the early antenatal period, is of aetiological importance; but the response to treatment, assessed as length of first remission, was found to be related to the amount of fingertip pattern. This may have clinical application. In AML there is evidence of a genetically determined factor carrying a high risk of the development of the disease, in that a member of each of 5 different families of the 25 studied bore a rare hypothenar pattern, compared with none in 75 control families. No dermatoglyphic features were of prognostic significance in AML. PMID:277206

  3. Silencing of HMGA2 reverses retardance of cell differentiation in human myeloid leukaemia.

    Science.gov (United States)

    Tan, Li; Xu, Hongfa; Chen, Guoshu; Wei, Xiaoping; Yu, Baodan; Ye, Jingmei; Xu, Lihua; Tan, Huo

    2018-02-06

    High-mobility group AT-hook 2 (HMGA2) may serve as an architectural transcription factor, and it can regulate a range of normal biological processes including proliferation and differentiation. Upregulation of HMGA2 expression is correlated to the undifferentiated phenotype of immature leukaemic cells. However, the underlying mechanism of HMGA2-dependent myeloid differentiation blockage in leukaemia is unknown. To reveal the role and mechanism of HMGA2 in differentiation arrest of myeloid leukaemia cells, the quantitative expression of HMGA2 and homeobox A9 (HOXA9) was analysed by real-time PCR (qRT-PCR). The regulatory function of HMGA2 in blockage of differentiation in human myeloid leukaemia was investigated through in vitro assays (XTT assay, May-Grünwald-Giemsa, flow cytometry analysis and western blot). We found that the expression of HMGA2 and HOXA9 was reduced during the process of granulo-monocytic maturation of acute myeloid leukaemia (AML) cells, knockdown of HMGA2 promotes terminal (granulocytic and monocytic) differentiation of myeloid leukaemia primary blasts and cell lines, and HOXA9 was significantly downregulated in leukaemic cells with knockdown of HMGA2. Downregulation of HOXA9 in myeloid leukaemia cells led to increased differentiation capacity in vitro. Our data suggest that increased expression of HMGA2 represents a possible new mechanism of myeloid differentiation blockage of leukaemia. Aberrant expression of HMGA2 may enhance HOXA9-dependent leukaemogenesis and myeloid leukaemia phenotype. Disturbance of the HMGA2-HOXA9 pathway is probably a therapeutic strategy in myeloid leukaemia.

  4. In vivo dosimetry and acute toxicity in breast cancer patients undergoing intraoperative radiotherapy as boost

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Jason Joon Bock; Choi, Jin Hyun; Lee, Ik Jae; Park, Kwang Woo; Kim, Kang Pyo; Kim, Jun Won [Dept. of Radiation Oncology, Yonsei University College of Medicine, Seoul (Korea, Republic of); Ahn, Sung Gwe; Jeong, Joon [Dept. of Surgery, Gangnam Severance Hospital, Yonsei University College of Medicine, Seoul (Korea, Republic of)

    2017-06-15

    To report the results of a correlation analysis of skin dose assessed by in vivo dosimetry and the incidence of acute toxicity. This is a phase 2 trial evaluating the feasibility of intraoperative radiotherapy (IORT) as a boost for breast cancer patients. Eligible patients were treated with IORT of 20 Gy followed by whole breast irradiation (WBI) of 46 Gy. A total of 55 patients with a minimum follow-up of 1 month after WBI were evaluated. Optically stimulated luminescence dosimeter (OSLD) detected radiation dose delivered to the skin during IORT. Acute toxicity was recorded according to the Common Terminology Criteria for Adverse Events v4.0. Clinical parameters were correlated with seroma formation and maximum skin dose. Median follow-up after IORT was 25.9 weeks (range, 12.7 to 50.3 weeks). Prior to WBI, only one patient developed acute toxicity. Following WBI, 30 patients experienced grade 1 skin toxicity and three patients had grade 2 skin toxicity. Skin dose during IORT exceeded 5 Gy in two patients: with grade 2 complications around the surgical scar in one patient who received 8.42 Gy. Breast volume on preoperative images (p = 0.001), ratio of applicator diameter and breast volume (p = 0.002), and distance between skin and tumor (p = 0.003) showed significant correlations with maximum skin dose. IORT as a boost was well-tolerated among Korean women without severe acute complication. In vivo dosimetry with OSLD can help ensure safe delivery of IORT as a boost.

  5. Whole body perfusion in patients undergoing frozen elephant trunk for type A acute aortic dissections.

    Science.gov (United States)

    Cappabianca, Giangiuseppe; Roscitano, Claudio; Bichi, Samuele; Cricco, Antonio; Parrinello, Matteo; Beghi, Cesare; Albano, Giovanni; Esposito, Giampiero

    2017-03-01

    The Frozen Elephant Trunk (FET) can be adopted in selected type A acute aortic dissections (TAAAD). During FET, a prolonged distal circulatory arrest exposes the spine and visceral organs to potential ischemic injuries. Antegrade distal aortic perfusion (ADAP) could minimize this risk: we describe the technical aspects of the simultaneous use of antegrade cerebral perfusion (ACP) and ADAP achieving a "Whole Body Perfusion" (WBP) during FET.

  6. Treatment for myeloid leukaemia of Down syndrome: population-based experience in the UK and results from the Medical Research Council AML 10 and AML 12 trials.

    NARCIS (Netherlands)

    Rao, A.; Hills, R.K.; Stiller, C.; Gibson, B.E.; Graaf, S.S.N. de; Hann, I.M.; O'Marcaigh, A.; Wheatley, K.; Webb, D.K.

    2006-01-01

    Down syndrome (DS) children are at an increased risk of developing myelodysplasia and acute myeloid leukaemia (AML). We retrospectively analysed the population-based data on 81 children with myeloid leukaemia of Down syndrome (ML-DS) from the UK National Registry of Childhood Tumours and experience

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

    Directory of Open Access Journals (Sweden)

    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. Association of renal insufficiency with in-hospital mortality among Japanese patients with acute myocardial infarction undergoing percutaneous coronary interventions.

    Science.gov (United States)

    Hirakawa, Yoshihisa; Masuda, Yuichiro; Kuzuya, Masafumi; Iguchi, Akihisa; Kimata, Takaya; Uemura, Kazumasa

    2006-09-01

    It is not yet clear whether a difference in in-hospital morality between patients with and without renal insufficiency undergoing percutaneous coronary intervention (PCI) exists. Therefore, the aim of the present study was to investigate if such as association exists in Japan. Data from the Tokai Acute Myocardial Infarction Study II were used. This was a prospective study of all 3274 patients admitted with acute myocardial infarction (AMI) to the 15 participating hospitals from 2001 to 2003. We abstracted the baseline and procedural characteristics as well as in-hospital mortality from detailed chart reviews. Patients were stratified into 2 groups according to the estimated creatinine clearance on admission. The creatinine clearance values were available in 2116, 107 of whom had renal insufficiency. The patients with renal insufficiency were more likely to be older, female, not independent in their daily activities, have lower body mass index and higher heart rate values on admission, lower prevalences of hypercholesterolemia and peptic ulcers, greater prevalences of diabetes, angina, previous heart failure, previous renal failure, previous cerebrovascular disease, aortic aneurysm, worse clinical course such as bleeding, and a multivessel coronary disease. Vasopressors, an intra-aortic balloon pump, and mechanical ventilation were frequently used in the patients with renal insufficiency, while thrombolytics were used less frequently. The patients with renal insufficiency had a higher in-hospital mortality rate than those without. Multivariate analysis identified renal insufficiency as an independent predictor of in-hospital death. The results suggest that renal insufficiency is an independent predictor of in-hospital death among AMI patients undergoing PCI.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    International Nuclear Information System (INIS)

    Parikh, Puja B.; Prakash, Sheena; Tahir, Usman; Kort, Smadar; Gruberg, Luis; Jeremias, Allen

    2014-01-01

    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. N-acetylcysteine for prevention of acute renal failure in patients with chronic renal insufficiency undergoing cardiac surgery: a prospective, randomized, clinical trial.

    Science.gov (United States)

    Sisillo, Erminio; Ceriani, Roberto; Bortone, Franco; Juliano, Glauco; Salvi, Luca; Veglia, Fabrizio; Fiorentini, Cesare; Marenzi, Giancarlo

    2008-01-01

    To assess the preventive effect of the antioxidant N-acetylcysteine on postoperative acute renal failure in patients with renal insufficiency undergoing cardiac surgery. Randomized, placebo-controlled, prospective study. University cardiology center. Two hundred fifty-four consecutive patients with chronic renal insufficiency (estimated creatinine clearance acute renal failure (> 25% increase in serum creatinine from baseline) and the in-hospital clinical course were evaluated. Acute renal failure occurred in 46% of patients and was associated with increased in-hospital mortality (7% vs. 0.7%; p = .024). It occurred in 52% of control patients and 40% of N-acetylcysteine-treated patients (p = .06). In-hospital mortality and need for renal replacement therapy were not affected by N-acetylcysteine, but a lower percentage of N-acetylcysteine-treated patients required mechanical ventilation prolonged for > 48 hrs (3% vs. 18%; p 4 days (13% vs. 33%; p acute renal failure in patients with renal insufficiency undergoing cardiac surgery.

  12. Effect of technique and timing of tracheostomy in patients with acute traumatic spinal cord injury undergoing mechanical ventilation

    Science.gov (United States)

    Ganuza, Javier Romero; Forcada, Angel Garcia; Gambarrutta, Claudia; De La Lastra Buigues, Elena Diez; Gonzalez, Victoria Eugenia Merlo; Fuentes, Fátima Paz; Luciani, Alejandro A.

    2011-01-01

    Objective To assess the effect of timing and techniques of tracheostomy on morbidity, mortality, and the burden of resources in patients with acute traumatic spinal cord injuries (SCIs) undergoing mechanical ventilation. Design Review of a prospectively collected database. Setting Intensive and intermediate care units of a monographic hospital for the treatment of SCI. Participants Consecutive patients admitted to the intensive care unit (ICU) during their first inpatient rehabilitation for cervical and thoracic traumatic SCI. A total of 323 patients were included: 297 required mechanical ventilation and 215 underwent tracheostomy. Outcome measures Demographic data, data relevant to the patients’ neurological injuries (level and grade of spinal cord damage), tracheostomy technique and timing, duration of mechanical ventilation, length of stay at ICU, incidence of pneumonia, incidence of perioperative and early postoperative complications, and mortality. Results Early tracheostomy (tracheostomy was performed in 101 patients (47%) and late (≥7 days) in 114 (53%). Surgical tracheostomy was employed in 119 cases (55%) and percutaneous tracheostomy in 96 (45%). There were 61 complications in 53 patients related to all tracheostomy procedures. Two were qualified as serious (tracheoesophageal fistula and mediastinal abscess). Other complications were mild. Bleeding was moderate in one case (late, percutaneous tracheostomy). Postoperative infection rate was low. Mortality of all causes was also low. Conclusion Early tracheostomy may have favorable effects in patients with acute traumatic SC. Both techniques, percutaneous and surgical tracheostomy, can be performed safely in the ICU. PMID:21528630

  13. A case-control study of risk of leukaemia in relation to mobile phone use.

    Science.gov (United States)

    Cooke, R; Laing, S; Swerdlow, A J

    2010-11-23

    Mobile phone use is now ubiquitous, and scientific reviews have recommended research into its relation to leukaemia risk, but no large studies have been conducted. In a case-control study in South East England to investigate the relation of acute and non-lymphocytic leukaemia risk to mobile phone use, 806 cases with leukaemia incident 2003-2009 at ages 18-59 years (50% of those identified as eligible) and 585 non-blood relatives as controls (provided by 392 cases) were interviewed about mobile phone use and other potentially aetiological variables. No association was found between regular mobile phone use and risk of leukaemia (odds ratio (OR)=1.06, 95% confidence interval (CI)=0.76, 1.46). Analyses of risk in relation to years since first use, lifetime years of use, cumulative number of calls and cumulative hours of use produced no significantly raised risks, and there was no evidence of any trends. A non-significantly raised risk was found in people who first used a phone 15 or more years ago (OR=1.87, 95% CI=0.96, 3.63). Separate analyses of analogue and digital phone use and leukaemia subtype produced similar results to those overall. This study suggests that use of mobile phones does not increase leukaemia risk, although the possibility of an effect after long-term use, while biologically unlikely, remains open.

  14. Extramedullary Myeloid Cell Tumour Presenting As Leukaemia Cutis

    Directory of Open Access Journals (Sweden)

    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.

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

    Science.gov (United States)

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

    1997-02-01

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

  16. [Prognostic factors for in-hospital mortality in patients with acute kidney injury requiring continuous renal replacement therapy undergoing surgery for acute Stanford type A aortic dissection].

    Science.gov (United States)

    Jiao, R; Liu, N

    2017-04-01

    Objective: To evaluate prognostic factors for in-hospital mortality in patients with acute kidney injury (AKI) requiring continuous renal replacement therapy (CRRT) undergoing surgery for acute Stanford type A aortic dissection. Methods: Retrospective analysis were conducted for 60 patients diagnosed with AKI requiring CRRT undergoing surgery for acute Stanford type A aortic dissection at Beijing Anzhen Hospital, Capital Medical University from March 2015 to September 2016. There were 43 male and 17 female patients with an mean age of (50±14) years. Demographic characteristics, diagnosis, perioperative periodrelated data, clinical parameters during CRRT were collected to set up a database. The patients were divided into survival group and non-survival group according to in-hospital mortality. The prognostic factors of mortality in-hospital after AKI requiring CRRT were analyzed by multivariate Logistic regression analysis regression. Results: In the 60 adult patients who had received CRRT, 21 patients (35.0%) died. There were significant differences between died and survival patients on proportion of age>60 years (χ(2)=6.851, P =0.003), lactic acid levels at 12-hour after CRRT ( t =-3.631, P =0.004), lactic acid levels at 24 hours after CRRT ( t =-2.986, P =0.032), proportion of body mass index >25 kg/m(2) (χ(2)=5.660, P =0.041), cardiopulmonary bypass time ( t =-2.720, P =0.001). Multivariate Logistic regression analysis revealed that age≥60 years ( OR =16.450, 95% CI: 2.172 to 84.589); high lactic acid levels at 12-hour after CRRT ( OR =1.719, 95% CI: 1.998 to 2.960) and long cardiopulmonary bypass time ( OR =1.028, 95% CI: 1.004 to 1.052) (all P acid levels at 12-hour after CRRT and long cardiopulmonary bypass time were independent prognostic factors of patients with AKI requiring CRRT after aortic surgery. Proper identification and management shall improve the prognosis of patients.

  17. Association of methylenetetrahytrofolate reductase (MTHFR) C677T and A1298C polymorphisms with the susceptibility of childhood acute lymphoblastic leukaemia (ALL) in Chinese population.

    Science.gov (United States)

    Li, Xiaolei; Liao, Qingchuan; Zhang, Shunguo; Chen, Minling

    2014-01-29

    The aim of this study was to investigate the relationship between the polymorphisms of the methylenetetrahytrofolate reductase (MTHFR) gene and susceptibility to childhood acute lymphoblastic leukemia (ALL). A case-control study was conducted among 98 children with ALL and 93 age- and sex- matched non-ALL controls. Genotyping of MTHFR C677T and A1298C polymorphisms was performed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). The odds ratios (ORs) of MTHFR genotypes were used to assess the associations of these polymorphisms with childhood ALL susceptibility. No significant differences were observed for frequencies of the 677CC, 677CT and 677TT genotypes between patients and controls. Frequencies of the 1298AA, 1298 AC and 1298CC genotypes between the two groups were significantly different. The risk of ALL with the 1298C allele carriers (AC + CC) was elevated by 1.1 times compared with the AA genotype [OR = 2.100; 95% CI (1.149; 3.837); P = 0.015]. The MTHFR A1298C polymorphism is associated with susceptibility to childhood ALL in the Chinese population.

  18. The association between serum levels of oxLDL-lgG and oxLDL-lgM autoantibody with adult acute myeloblastic leukaemia.

    Science.gov (United States)

    Li, Hao; Diao, Yu Tao; Li, Hui Qing; Ma, Qing; Cui, Jia; Zhou, Ying Zhi; Li, Dong

    2010-01-31

    To evaluate the relationship between serum antibodies against ox-LDL levels and adult acute myeloblastic leukemia (AML). Forty three patients with AML and 52 normal controls were enrolled in this study in the Department of Hematology, Tumor Center of Qilu Hospital of Shandong University from Feb. 2008 to Mar.2009. Serum lgG and lgM antibodies versus the oxLDL levels were evaluated by ELISA method. Data was analyzed by covariance and binary Logistic regression. Serum mean levels of oxLDL-lgG in patients (38.92 +/- 21.1259 ug/ml) were significantly lower than in control subjects (78.88 +/- 9.3705 ug/ml); Meanwhile, Serum mean levels of oxLDL-lgM in patients (20.53 +/- 10.2990 IU/L) were significantly higher than in control subjects (10.29 +/- 10.5771 IU/L). Binary logistic regression showed the odds ratios of association of oxLD-lgG and oxLD-lgM with adult AML were 0.72(95%CI: 0.55-0.94) and 1.11(95%CI: 1.01-1.21) respectively after adjusted for potential confounders. In the preliminary investigation we found a descensive oxLDL- lgG and an elevated oxLDL-lgM serum levels for the adult AML. Future studies need to confirm the hypothesis whether they related to the development and progression of adult AML.

  19. Role of regulatory T cells in acute myeloid leukemia patients undergoing relapse-preventive immunotherapy.

    Science.gov (United States)

    Sander, Frida Ewald; Nilsson, Malin; Rydström, Anna; Aurelius, Johan; Riise, Rebecca E; Movitz, Charlotta; Bernson, Elin; Kiffin, Roberta; Ståhlberg, Anders; Brune, Mats; Foà, Robin; Hellstrand, Kristoffer; Thorén, Fredrik B; Martner, Anna

    2017-11-01

    Regulatory T cells (T regs ) have been proposed to dampen functions of anti-neoplastic immune cells and thus promote cancer progression. In a phase IV trial (Re:Mission Trial, NCT01347996, http://www.clinicaltrials.gov ) 84 patients (age 18-79) with acute myeloid leukemia (AML) in first complete remission (CR) received ten consecutive 3-week cycles of immunotherapy with histamine dihydrochloride (HDC) and low-dose interleukin-2 (IL-2) to prevent relapse of leukemia in the post-consolidation phase. This study aimed at defining the features, function and dynamics of Foxp3 + CD25 high CD4 + T regs during immunotherapy and to determine the potential impact of T regs on relapse risk and survival. We observed a pronounced increase in T reg counts in peripheral blood during initial cycles of HDC/IL-2. The accumulating T regs resembled thymic-derived natural T regs (nT regs ), showed augmented expression of CTLA-4 and suppressed the cell cycle proliferation of conventional T cells ex vivo. Relapse of AML was not prognosticated by T reg counts at onset of treatment or after the first cycle of immunotherapy. However, the magnitude of T reg induction was diminished in subsequent treatment cycles. Exploratory analyses implied that a reduced expansion of T regs in later treatment cycles and a short T reg telomere length were significantly associated with a favorable clinical outcome. Our results suggest that immunotherapy with HDC/IL-2 in AML entails induction of immunosuppressive T regs that may be targeted for improved anti-leukemic efficiency.

  20. The incidence of and mortality from leukaemias in the UK: a general population-based study

    Directory of Open Access Journals (Sweden)

    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 association between serum levels of oxLDL-lgG and oxLDL-lgM autoantibody with adult acute myeloblastic leukaemia

    Directory of Open Access Journals (Sweden)

    Cui Jia

    2010-01-01

    Full Text Available Abstract Aim To evaluate the relationship between serum antibodies against ox-LDL levels and adult acute myeloblastic leukemia (AML. Methods Forty three patients with AML and 52 normal controls were enrolled in this study in the Department of Hematology, Tumor Center of Qilu Hospital of Shandong University from Feb. 2008 to Mar.2009. Serum lgG and lgM antibodies versus the oxLDL levels were evaluated by ELISA method. Data was analyzed by covariance and binary Logistic regression. Results Serum mean levels of oxLDL-lgG in patients (38.92 ± 21.1259 ug/ml were significantly lower than in control subjects (78.88 ± 9.3705 ug/ml; Meanwhile, Serum mean levels of oxLDL-lgM in patients (20.53 ± 10.2990 IU/L were significantly higher than in control subjects (10.29 ± 10.5771 IU/L. Binary logistic regression showed the odds ratios of association of oxLD-lgG and oxLD-lgM with adult AML were 0.72(95%CI: 0.55-0.94 and 1.11(95%CI: 1.01-1.21 respectively after adjusted for potential confounders. Conclusion In the preliminary investigation we found a descensive oxLDL- lgG and an elevated oxLDL-lgM serum levels for the adult AML. Future studies need to confirm the hypothesis whether they related to the development and progression of adult AML.

  2. Hepatic adverse event profile of inotuzumab ozogamicin in adult patients with relapsed or refractory acute lymphoblastic leukaemia: results from the open-label, randomised, phase 3 INO-VATE study.

    Science.gov (United States)

    Kantarjian, Hagop M; DeAngelo, Daniel J; Advani, Anjali S; Stelljes, Matthias; Kebriaei, Partow; Cassaday, Ryan D; Merchant, Akil A; Fujishima, Naohito; Uchida, Toshiki; Calbacho, Maria; Ejduk, Anna A; O'Brien, Susan M; Jabbour, Elias J; Zhang, Hui; Sleight, Barbara J; Vandendries, Erik R; Marks, David I

    2017-08-01

    The INO-VATE study demonstrated efficacy and safety of inotuzumab ozogamicin versus standard care in adults with relapsed or refractory B-cell acute lymphoblastic leukaemia. Here, we report the frequency of, and potential risk factors for, hepatotoxicity in patients in this trial and after treatment and subsequent haemopoietic stem-cell transplantation (HSCT). In this open-label, phase 3, multicentre, international study, adults with relapsed or refractory, CD22-positive, Philadelphia chromosome (Ph)-positive or Ph-negative B-cell acute lymphoblastic leukaemia who were due to receive first or second salvage treatment were randomly assigned (1:1) via an interactive voice response system to receive inotuzumab ozogamicin (starting dose 1·8 mg/m 2 per cycle [0·8 mg/m 2 on day 1; 0·5 mg/m 2 on days 8 and 15 of a 21-28 day cycle for ≤6 cycles]) or standard care (either fludarabine plus cytarabine plus granulocyte colony-stimulating factor, mitoxantrone plus cytarabine, or high-dose cytarabine). Stratification factors at randomisation were duration of first remission (<12 months vs ≥12 months), salvage treatment phase (first vs second), and age (<55 years vs ≥55 years). We present data up to March 8, 2016. At this cutoff date, all patients had been discontinued from treatment but 54 patients were continuing in long-term follow-up. Long-term follow-up has now been completed, with the final patient's last visit on Jan 4, 2017. This prespecified safety analysis describes investigator-assessed treatment-emergent hepatotoxicity, including sinusoidal obstruction syndrome (also known as veno-occlusive disease) in patients during study treatment or thereafter (without follow-up HSCT) and after study treatment and subsequent HSCT, for all patients who received at least one dose of study treatment. This study is registered with ClinicalTrials.gov, number NCT01564784. Between Aug 27, 2012, and and the data cutoff of March 8, 2016, 326 patients were randomly assigned to

  3. Comparison of effective radiation doses in patients undergoing unenhanced MDCT and excretory urography for acute flank pain

    Energy Technology Data Exchange (ETDEWEB)

    Eikefjord, E.N.; Thorsen, F.; Rorvik, J. [Haukeland University Hospital, Bergen (Norway). Dept. of Radiology

    2007-07-15

    Objective: The purpose of this study was to measure and compare the effective radiation dose in patients undergoing unenhanced MDCT and excretory urography for acute flank pain, and to explore technical and practical factors affecting the effective dose. Subjects and methods: One hundred nineteen patients with acute flank pain were included. All patients were examined using both MDCT and excretory urography. CT involved one acquisition from the upper kidney margin to the symphysis pubis. The only protocol variation was in the tube current (mAs), which was made according to patient body mass. The excretory urography protocol consisted of three images, with more when supplementary images were needed. Effective radiation doses were computer-simulated using dosimetry programs for CT and conventional radiography, based on Norwegian Radiological Protection Board dose data sets. Mean and SDs of measured patient doses were calculated and compared. Further analyses of dose variations in body mass categories (body mass index) were conducted, as were analyses concerning the number of images taken. Results: The mean effective doses were 7.7 mSv with MDCT and 3.63 mSv with excretory urography. The effective dose varied both in and between techniques but could be predicted. Radiation risk decreased significantly with increased patient weight. Conclusion: The average effective dose with MDCT was more than double that with excretory urography. However, the appropriate dose could be strongly predicted by the patient's body mass index and by procedure. An optimum low-dose protocol should be considered before initiating unenhanced MDCT for ureteral colic in order to minimize the radiation-induced cancer risk and to secure adequate image quality. (author)

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

    Science.gov (United States)

    2017-03-27

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

  5. Vancomycin pharmacokinetic parameters in patients with acute brain injury undergoing controlled normothermia, therapeutic hypothermia, or pentobarbital infusion.

    Science.gov (United States)

    Morbitzer, Kathryn A; Jordan, J Dedrick; Rhoney, Denise H

    2015-04-01

    Therapeutic strategies that cause an alteration in patient temperature, such as controlled normothermia (CN), therapeutic hypothermia (TH), and pentobarbital infusion (PI), are often used to manage complications caused by acute brain injury. The purpose of this study was to evaluate pharmacokinetic (PK) parameters of vancomycin in patients with acute brain injury undergoing temperature modulation. This was a retrospective cohort study of adult patients with acute brain injury admitted between May 2010 and March 2014 who underwent CN, TH, or PI and received vancomycin. Predicted PK parameters based on population data were compared with calculated PK parameters based on serum concentrations. Seventeen CN patients and 10 TH/PI patients met inclusion criteria. Traumatic brain injury and aneurysmal subarachnoid hemorrhage accounted for the majority of admitting diagnoses. In the CN group, the median dose was 16.7 (15.5-18.4) mg/kg. The median calculated elimination rate constant [0.155 (0.108-0.17) vs. 0.103 (0.08-0.142) hr(-1); p = 0.04] was significantly higher than the predicted value. The median measured trough concentration [8.9 (7.7-11.1) vs. 17.1 (10.8-22.3) υg/mL; p = 0.004] was significantly lower than predicted. In the TH/PI group, the median dose was 15.4 (14.7-17.2) mg/kg. No significant differences were found between the median calculated and predicted elimination rate constant [0.107 (0.097-0.109) vs. 0.112 (0.102-0.127) hr(-1); p = 0.41] and median measured and predicted trough concentration [14.2 (12.7-17.1) vs. 13.1 (11-17.8) υg/mL; p = 0.71]. Patients who underwent TH/PI did not exhibit PK alterations when compared to predicted PK parameters based on population data, while patients who underwent CN experienced PK alterations favoring an increased elimination of vancomycin.

  6. Childhood leukaemia around nuclear facilities

    International Nuclear Information System (INIS)

    Wojcik, Andrzej; Feychting, Maria

    2010-06-01

    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

  7. Summary curves for patients transplanted for chronic myeloid leukaemia salvaged by a donor lymphocyte infusion: the current leukaemia-free survival curve

    DEFF Research Database (Denmark)

    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...

  8. Feasibility of neuropsychological assessment in leukaemia patients shortly after diagnosis: directions for future prospective research

    NARCIS (Netherlands)

    Jansen, NC; Kingma, A; Tellegen, P; van Dommelen, RI; Bouma, A; Veerman, A; Kamps, WA

    Aims: To study neuropsychological functioning of newly diagnosed children with acute lymphoblastic leukaemia (ALL) within two weeks after diagnosis in order to determine the feasibility of a sibling controlled prospective study design. Methods: Fifty consecutive patients (median age at testing 6.6

  9. Florid radiological appearance of megakaryoblastic leukaemia - an aid to earlier diagnosis

    Energy Technology Data Exchange (ETDEWEB)

    Moody, A.; Shaw, D.; Simpson, E.

    1989-07-01

    Accurate diagnosis of leukaemia is essential to enable appropriate treatment. The diagnosis is made by cytological and cytochemical techniques but radiology may, however, serve a very useful role in first suggesting a diagnosis. We present here four cases of megakaryoblastic leukaemia (AML FAB classification M7), three of which have strikingly similar unusual radiological changes. A review of the literature suggests this condition has previously been diagnosed as acute or malignant myelofibrosis, and the megakaryoblastic nature of the disease was not recognised. The presence of these radiological features may therefore prompt specific immunocytochemical testing, in a disease that is otherwise difficult to diagnose early. (orig.).

  10. Dose Escalation of Total Marrow Irradiation With Concurrent Chemotherapy in Patients With Advanced Acute Leukemia Undergoing Allogeneic Hematopoietic Cell Transplantation

    Energy Technology Data Exchange (ETDEWEB)

    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

  11. Childhood acute lymphoblastic leukaemia and birthweight

    DEFF Research Database (Denmark)

    Roman, Eve; Lightfoot, Tracy; Smith, Alexandra G

    2013-01-01

    using the UK study which accessed birth registrations of participants and non-participants. Odds ratios (OR) and 95% confidence intervals (CIs) were estimated using unconditional logistic regression models. RESULTS: Children with ALL were, on average, heavier than controls at all gestations...

  12. Neuropenic enterocolitis complicating acute lymphoblastic leukaemia

    African Journals Online (AJOL)

    ... modalities allows earlier diagnosis and can expedite the management of these severely ill patients. We describe the clinico-radiological features of this condition in the following case report, as well as a brief management approach to this rare, but increasingly recognised condition. South African Journal of Radiology Vol.

  13. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

    -based gene-lookup webservices, called HemaExplorer and BloodSpot. These web-services support the aim of making data and analysis of haematopoietic cells from mouse and human accessible for researchers without bioinformatics expertise. Finally, in order to aid the analysis of the very limited number...

  14. Body mass index is inversely associated with mortality in patients with acute kidney injury undergoing continuous renal replacement therapy

    Directory of Open Access Journals (Sweden)

    Hyoungnae Kim

    2017-03-01

    Full Text Available Background: Many epidemiologic studies have reported on the controversial concept of the obesity paradox. The presence of acute kidney injury (AKI can accelerate energy-consuming processes, particularly in patients requiring continuous renal replacement therapy (CRRT. Thus, we aimed to investigate whether obesity can provide a survival benefit in this highly catabolic condition. Methods: We conducted an observational study in 212 patients who had undergone CRRT owing to various causes of AKI between 2010 and 2014. The study end point was defined as death that occurred within 30 days after the initiation of CRRT. Results: Patients were categorized into three groups according to tertiles of body mass index (BMI. During ≥30 days after the initiation of CRRT, 39 patients (57.4% in the highest tertile died, as compared with 58 patients (78.4% in the lowest tertile (P = 0.02. In a multivariable analysis adjusted for cofounding factors, the highest tertile of BMI was significantly associated with a decreased risk of death (hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.37–0.87; P = 0.01. This significant association remained unaltered for 60-day (HR, 0.64; 95% CI, 0.43–0.94; P = 0.03 and 90-day mortality (HR, 0.66; 95% CI, 0.44–0.97; P = 0.03. Conclusion: This study showed that a higher BMI confer a survival benefit over a lower BMI in AKI patients undergoing CRRT.

  15. Use of Multifrequency Bioimpedance Analysis in Male Patients with Acute Kidney Injury Who Are Undergoing Continuous Veno-Venous Hemodiafiltration.

    Science.gov (United States)

    Rhee, Harin; Jang, Keum Sook; Shin, Min Ji; Lee, Jang Won; Kim, Il Young; Song, Sang Heon; Lee, Dong Won; Lee, Soo Bong; Kwak, Ihm Soo; Seong, Eun Young

    2015-01-01

    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.

  16. [THE RISK OF ACUTE RENAL LESIONS AND ITS PROGNOSTIC SIGNIFICANCE IN PATIENTS WITH CHRONIC RENAL DISEASE UNDERGOING CARDIAC SURGICAL INTERVENTION].

    Science.gov (United States)

    Iskenderov, B G; Sisina, O N; Budagovskaia, Z M

    2015-01-01

    to determine the frequency and risk factors of acute renal lesions (ARL) and their prognostic significance in patients with chronic renal disease (CRD) undergoing surgical intervention. The study included 1122 patients (586 men and 536 women) aged 32-68 (mean 62.3 ± 5.2) years who underwent correction of valvular defects, aortocoronary bypass surgery or their combination). Initial glomerular filtration rate was higher than 90 ml/min/l.73 m2 in 656 patients (group 1) and 89-60 ml/min/l/73 m2 in 470 ones (group 2). ARL were diagnosed based on the serum creatinine level using RIFLE criteria. In the early postoperative period, ARL were diagnosed in 23.9% of the patients in group I and 38.7% of those in group 2 (p < 0.001). Intra-hospital lethality in group 1 was 4.9% (14.1% in patients with ARL) and 12.1% in group 2 (18.1% iin patients with ARL). In group 2, 47.9% of the patients with ARL experienced regress of renal dysfunction during 12 months compared with 56.9% ones without ARL. The progress of CRD was documented in 11% of group 2 patients with ARL and in (4.5% without AR (p = 0.013). 5.7% of the patients in group 1 developed CRD after ARL. 4.9% of the patients in group 2 needed programmed hemodialysis. The development of ARL in patients with CRD is associated with unfvouravle cardiovascular prognosis following cardiosurgery.

  17. Use of Multifrequency Bioimpedance Analysis in Male Patients with Acute Kidney Injury Who Are Undergoing Continuous Veno-Venous Hemodiafiltration.

    Directory of Open Access Journals (Sweden)

    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.

  18. Leukaemia incidence among workers in the shoe and boot manufacturing industry: a case-control study

    Directory of Open Access Journals (Sweden)

    Forand Steven P

    2004-08-01

    Full Text Available Abstract Background Previous reports have indicated an excess of leukaemia in Broome County, New York, particularly in the Town of Union. Surveillance of cancer incidence data indicates that a large proportion of these cases occurred among males ages 65 and older. Shoe and boot manufacturing has been the largest single industry in this area throughout much of the past century. Occupational studies from Europe suggest a link between leukaemia and employment in the shoe and boot manufacturing industry. However, researchers have not found a positive association between leukaemia and employment in the shoe industry among workers in the United States. Methods A matched case-control study was conducted to investigate the association between leukaemia incidence among males 65 and older and employment in the shoe and boot manufacturing industry. Thirty-six cases of leukaemia occurring between 1981–1990; among males age 65 and older; residing in the town of Union met the study case criteria. Death certificates were obtained for each of the cases. These were matched to death certificates of 144 controls on date of death and date of birth +/- 1 year. Death certificates were then examined to determine the employer and occupation of each study subject. Conditional logistic regression was used to determine the risk of leukaemia among those working in the industry. Results The risk of both leukaemia (OR = 1.47; 95% CI 0.70, 3.09 and acute myeloid leukaemia (OR = 1.19; 95% CI 0.33, 4.28 were elevated among those employed in the shoe and boot manufacturing industry, however neither was statistically significant. Conclusion The results, though suggestive of an association between leukaemia and employment in the shoe and boot manufacturing industry, were not statistically conclusive due mainly to limited study power. Several additional limitations may also have prevented the observance of more conclusive findings. Better exposure assessment, information on

  19. Child leukaemia and low frequency electromagnetic fields

    International Nuclear Information System (INIS)

    Clavel, J.

    2009-01-01

    The author discusses the possible causes of child leukaemia: exposure to natural ionizing radiation (notably radon), to pesticides, and to hydrocarbons emitted by road traffic. Some studies suggested that an inadequate reaction of the immune system to an ordinary infection could result in leukaemia. Other factors are suspected, notably extremely low frequency electromagnetic fields, the influence of which is then discussed by the author. She evokes and discusses results of different investigations on this topic which have been published since the end of the 1970's. It appears that a distance less than 50 meters from high voltage lines or the vicinity of transformation stations may double the risk of child leukaemia

  20. Childhood leukaemia and nuclear power

    International Nuclear Information System (INIS)

    Berry, R.J.; Wakeford, R.

    1992-01-01

    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

  1. Recruitment of childhood leukaemia patients to clinical trials in Great Britain during 1980-2007: variation by birth weight, congenital malformation, socioeconomic status and ethnicity.

    Science.gov (United States)

    Shah, Anjali; Diggens, Nicole; Stiller, Charles; Richards, Sue; Stevens, Michael C G; Murphy, Michael F G

    2014-05-01

    To assess recruitment of children to national clinical trials for acute lymphoblastic leukaemia (ALL) and acute myeloid leukaemia (AML) in Great Britain during 1980-2007 and describe variation by some factors that might influence trial entry. Records of leukaemia patients aged 0-14 years at diagnosis were identified in the National Registry of Childhood Tumours and linked to birth registrations, Children's Cancer and Leukaemia Group records, Hospital Episode Statistics and Medical Research Council clinical trial registers. Trial entry rates were compared between categories of birth weight, congenital malformation, socioeconomic status and ethnicity. 9147 ALL and 1466 AML patients were eligible for national clinical trials during 1980-2007. Overall recruitment rates were 81% and 60% respectively. For ALL, rates varied significantly with congenital malformation (Down syndrome 61%, other malformations 80%, none 82%; p4000 g 67%; p=0.001) and congenital malformation (Down syndrome 28%, other malformations 56%, none 63%; pcongenital malformations.

  2. Similar Survival for Patients Undergoing Reduced-Intensity Total Body Irradiation (TBI) Versus Myeloablative TBI as Conditioning for Allogeneic Transplant in Acute Leukemia

    Energy Technology Data Exchange (ETDEWEB)

    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

  3. Rapid-Onset Acute Respiratory Distress Syndrome (ARDS in a Patient Undergoing Metastatic Liver Resection: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Thorsten Brenner

    2010-01-01

    Full Text Available Metastatic liver resection following cytoreductive chemotherapy is an accepted treatment for oligometastatic tumor diseases. Although pulmonary complications are frequently reported in patients undergoing liver surgery including liver transplantation, life-threatening acute respiratory failures in the absence of aspiration, embolism, transfusion-related acute lung injury (TRALI, pulmonary infection, or an obvious source of systemic sepsis are rare. We performed an extensive clinical review of a patient undergoing metastatic liver resection who had a clinical course compatible to an acute respiratory distress syndrome (ARDS without an obvious cause except for the surgical procedure and multiple preoperative chemotherapies. We hypothesize that either the surgical procedure mediated by cytokines and tumor necrosis factor or possible toxic effects of oxygen applied during general anesthesia were associated with life-threatening respiratory failure in the patient. Discrete and subclinical inflammated alveoli (probably due to multiple preoperative chemotherapies with substances at potential risk for interstitial pneumonitis as well as chest radiation might therefore be considered as risk factors.

  4. Coffee and tea consumption and risk of leukaemia in an adult population: A reanalysis of the Italian multicentre case-control study.

    Science.gov (United States)

    Parodi, Stefano; Merlo, Domenico Franco; Stagnaro, Emanuele

    2017-04-01

    Coffee and tea are the most frequently consumed beverages in the world. Their potential effect on the risk of developing different types of malignancies has been largely investigated, but studies on leukaemia in adults are scarce. The present investigation is aimed at evaluating the potential role of regular coffee and tea intake on the risk of adult leukaemia by reanalysing a large population based case-control study carried out in Italy, a country with a high coffee consumption and a low use of green tea. Interviewed subjects, recruited between 1990 and 1993 in 11 Italian areas, included 1771 controls and 651 leukaemia cases. Association between Acute Myeloid Leukaemia (AML), Acute Lymphoid Leukaemia, Chronic Myeloid Leukaemia, Chronic Lymphoid Leukaemia, and use of coffee and tea was evaluated by standard logistic regression. Odds Ratios (OR) were estimated adjusting for the following potential confounders: gender, age, residence area, smoking habit, educational level, previous chemotherapy treatment, alcohol consumption and exposure to electromagnetic fields, radiation, pesticides and aromatic hydrocarbons. No association was observed between regular use of coffee and any type of leukaemia. A small protective effect of tea intake was found among myeloid malignancies, which was more evident among AML (OR=0.68, 95%CI: 0.49-0.94). However, no clear dose-response relation was found. The lower risk of leukaemia among regular coffee consumers, reported by a few of previous small studies, was not confirmed. The protective effect of tea on the AML risk is only partly consistent with results from other investigations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Normal Tissue Complication Probability Analysis of Acute Gastrointestinal Toxicity in Cervical Cancer Patients Undergoing Intensity Modulated Radiation Therapy and Concurrent Cisplatin

    International Nuclear Information System (INIS)

    Simpson, Daniel R.; Song, William Y.; Moiseenko, Vitali; Rose, Brent S.; Yashar, Catheryn M.; Mundt, Arno J.; Mell, Loren K.

    2012-01-01

    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 (V 45 ) using the logistic model. Results: Twenty-three patients (46%) had Grade ≥2 GI toxicity. The mean (SD) V 45 was 143 mL (99). The mean V 45 values for patients with and without Grade ≥2 GI toxicity were 176 vs. 115 mL, respectively. Twenty patients (40%) had V 45 >150 mL. The proportion of patients with Grade ≥2 GI toxicity with and without V 45 >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 V 45 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 V 45 is correlated with increased GI toxicity in cervical cancer patients undergoing IMRT and concurrent cisplatin. Reducing bowel V 45 could reduce the risk of Grade ≥2 GI toxicity by approximately 50% per 100 mL of bowel spared.

  6. Acute inflammatory reaction following placement of sodium hyaluronate-carboxymethylcellulose barrier in a young woman undergoing gynecologic surgery: a case report.

    Science.gov (United States)

    Temkin, Sarah M; Turner, Jerrold R; Lengyel, Ernst R

    2011-01-01

    Hyaluronate-carboxymethylcellulose (HA-CMC) is commonly used to inhibit adhesion formation in women undergoing gynecologic surgery. A 38-year old woman underwent a bilateral salpingo-oophorectomy for the indication of persistent pelvic pain following a hysterectomy, an ovarian cyst and endometriosis. HA-CMC was placed at the time of surgery. The patient returned to the operating room on postoperative day 3 with an acute inflammatory reaction and small bowel obstruction. A mast cell infiltrate and acute serosal damage was observed on final histopathology of the resection portion of small bowel. Few case reports describing adverse events with the use of HA-CMC have been published. This patient appears to have had a paradoxical inflammatory reaction to this adhesion barrier.

  7. Epidemiological patterns of leukaemia in 184 countries: a population-based study.

    Science.gov (United States)

    Miranda-Filho, Adalberto; Piñeros, Marion; Ferlay, Jacques; Soerjomataram, Isabelle; Monnereau, Alain; Bray, Freddie

    2018-01-01

    Leukaemia is a heterogeneous group of haemopoietic cancers that comprises a number of diverse and biologically distinct subgroups. We examine the leukaemia burden worldwide and highlight the distinct incidence patterns in order to elucidate explanatory factors that may support preventive measures and health resource planning. We aimed to estimate the global burden of leukaemia incidence according to the four major subtypes stratified by age and sex. In this population-based study, we assessed leukaemia incidence for the major subtypes using the Cancer Incidence in Five Continents Volume X (CI5-X), which includes data from 290 cancer registries in 68 countries covering the diagnostic period 2003-07, for all ages and both sexes. We then extracted counts and incidence rates in 184 countries for the year 2012 from IARC's GLOBOCAN database of national estimates. We calculated age-specific incidence rates per 100 000 person-years and age-standardised rates (ASRs) using the world standard population by country, sex, age group, and where applicable, by major subtypes. We excluded from all analyses registries for which the total number of leukaemia cases was less than 100 or the proportion of microscopically verified (MV%) cases was less than 80% (2572 cases). 717 863 cases between 2003-07 were included in this analysis. More than 350 000 new leukaemia cases were estimated in 2012. We observed substantial variation in incidence between and within world regions. The highest leukaemia incidence rates for both sexes were estimated in Australia and New Zealand (ASR per 100 000 11·3 in males and 7·2 in females), Northern America (10·5 in males and 7·2 in females), and western Europe (9·6 in males and 6·0 in females), and the lowest was in in western Africa (1·4 in males and 1·2 in females). Rates were generally higher in males than females with an overall male to female ratio of 1·4. In children, acute lymphoblastic leukaemia was the main subtype in all studied

  8. THE OCCURRENCE OF HIGH-LEVELS OF ACUTE BEHAVIORAL DISTRESS IN CHILDREN AND ADOLESCENTS UNDERGOING ROUTINE VENIPUNCTURES

    NARCIS (Netherlands)

    HUMPHREY, GB; BOON, CMJ; VANDENHEUVELL, GFECV; VANDEWIEL, HBM

    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

  9. An investigation into childhood leukaemia in Northamptonshire

    International Nuclear Information System (INIS)

    1996-01-01

    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

  10. Breastfeeding and early infection in the aetiology of childhood leukaemia in Down syndrome

    OpenAIRE

    Flores-Lujano, J; Perez-Saldivar, M L; Fuentes-Panan?, E M; Gorodezky, C; Bernaldez-Rios, R; Del Campo-Martinez, M A; Martinez-Avalos, A; Medina-Sanson, A; Paredes-Aguilera, R; De Diego-Flores Chapa, J; Bolea-Murga, V; Rodriguez-Zepeda, M C; Rivera-Luna, R; Palomo-Colli, M A; Romero-Guzman, L

    2009-01-01

    Background: For a child to develop acute leukaemia (AL), environmental exposure may not be sufficient: interaction with a susceptibility factor to the disease, such as Down syndrome (DS), may also be necessary. We assessed whether breastfeeding and early infection were associated with the risk of developing AL in children with DS. Methods: Children with DS in Mexico City, and either with or without AL, were the cases (N=57) and controls (N=218), respectively. Population was divided in childre...

  11. Impact of triple antithrombotic therapy in patients with acute coronary syndrome undergoing percutaneous coronary intervention in real-world practice

    NARCIS (Netherlands)

    Yan, Yan; Wang, Xiao; Fan, Jing-Yao; Nie, Shao-Ping; Raposeiras-Roubín, Sergio; Abu-Assi, Emad; Henriques, Jose P. Simao; D'Ascenzo, Fabrizio; Saucedo, Jorge; González-Juanatey, José R.; Wilton, Stephen B.; Kikkert, Wouter J.; Nuñez-Gil, Iván; Ariza-Sole, Albert; Song, Xian-Tao; Alexopoulos, Dimitrios; Liebetrau, Christoph; Kawaji, Tetsuma; Moretti, Claudio; Huczek, Zenon; Fujii, Toshiharu; Correia, Luis Cl; Kawashiri, Masa-Aki; Kedev, Sasko

    2017-01-01

    The optimal antithrombotic regimen for patients on oral anticoagulation (OAC) after acute coronary syndrome (ACS) and percutaneous coronary intervention (PCI) remains debated. This study sought to evaluate the efficacy and safety of OAC plus clopidogrel with or without aspirin in a real-world

  12. Antibodies to HTLV-I in Nigerian blood-donors, their relatives and patients with leukaemias, lymphomas and other diseases.

    Science.gov (United States)

    Fleming, A F; Maharajan, R; Abraham, M; Kulkarni, A G; Bhusnurmath, S R; Okpara, R A; Williams, E; Akinsete, I; Schneider, J; Bayer, H

    1986-12-15

    Antibodies to HTLV-I have been detected in sera from 15 (2.0%) of 736 adult blood-donors in Nigeria, in 4 (20.0%) of 20 patients with chronic lymphatic leukaemia, 3 (10.0%) of 30 with non-Hodgkin's lymphoma, one of 12 with Burkitt's lymphoma and one of 7 with acute lymphoblastic leukaemia. The frequency of positivity was higher (3.6%) in the blood-donors from the guinea and wooded savanna of northern Nigeria than in those from the rain-forest and mangrove swamps of southern Nigeria (1.8% in Lagos and 0.7% in Calabar). Two of the 3 seropositive patients with lymphoma had clinical presentation and courses similar to those of Japanese and Caribbean patients with adult T-cell leukaemia/lymphoma.

  13. The effect of TIcagrelor administered through a nasogastric tube to COMAtose patients undergoing acute percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Ratcovich, Hanna; Sadjadieh, Golnaz; Andersson, Hedvig B

    2017-01-01

    AIMS: Patients in a coma after cardiac arrest may have adversely affected drug absorption and metabolism. This study, the first of its kind, aimed to investigate the early pharmacokinetic and pharmacodynamic effects of ticagrelor administered through a nasogastric tube (NGT) to patients......-8) hours (Multiplate). CONCLUSIONS: Ticagrelor, administered as crushed tablets through a nasogastric tube, leads to sufficient platelet inhibition after 12 hours, and in many cases earlier, in the vast majority of patients undergoing pPCI and subsequent intensive care management after an OHCA....

  14. Image-Guided Total-Marrow Irradiation Using Helical Tomotherapy in Patients With Multiple Myeloma and Acute Leukemia Undergoing Hematopoietic Cell Transplantation

    International Nuclear Information System (INIS)

    Wong, Jeffrey Y.C.; Rosenthal, Joseph; Liu An; Schultheiss, Timothy; Forman, Stephen; Somlo, George

    2009-01-01

    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

  15. Evaluation of acute and chronic toxicity of DSS and LAS surfactants undergoing the irradiation with electron beam

    International Nuclear Information System (INIS)

    Romanelli, Maria Fernanda

    2004-01-01

    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)

  16. Acute pulmonary edema caused by takotsubo cardiomyopathy in a pregnant woman undergoing transvaginal cervical cerclage: A case report.

    Science.gov (United States)

    Lee, Jae-Young; Kwon, Hyun-Jung; Park, Sang-Wook; Lee, Yu-Mi

    2017-01-01

    The physiological changes associated with pregnancy may predispose pregnant women to pulmonary edema. Other known causes of pulmonary edema during pregnancy include tocolytic drugs, preeclampsia, eclampsia, and peripartum cardiomyopathy. We describe a rare case of pulmonary edema caused by takotsubo cardiomyopathy in a pregnant woman at 14 weeks of gestation who was undergoing emergency transvaginal cervical cerclage. Intraoperative chest radiography revealed severe pulmonary edema and echocardiography indicated moderate left ventricular dysfunction with akinesia of the mid to apical left ventricular wall segment, which is reflective of takotsubo cardiomyopathy. With early detection and appropriate management, the patient was stabilized in a relatively short period of time. Based on her clinical signs and symptoms, we suspect that the pulmonary edema was caused by takotsubo cardiomyopathy.

  17. Use of prasugrel vs clopidogrel and outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention in contemporary clinical practice: Results from the PROMETHEUS study.

    Science.gov (United States)

    Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna; Kapadia, Samir; Weiss, Sandra; Strauss, Craig; Muhlestein, J Brent; Toma, Catalin; Rao, Sunil V; DeFranco, Anthony; Poddar, Kanhaiya L; Chandrasekhar, Jaya; Weintraub, William; Henry, Timothy D; Bansilal, Sameer; Baker, Brian A; Marrett, Elizabeth; Keller, Stuart; Effron, Mark; Pocock, Stuart; Mehran, Roxana

    2017-06-01

    We sought to determine the frequency of use and association between prasugrel and outcomes in acute coronary syndrome patients undergoing percutaneous coronary intervention (PCI) in clinical practice. PROMETHEUS was a multicenter observational registry of acute coronary syndrome patients undergoing PCI from 8 centers in the United States that maintained a prospective PCI registry for patient outcomes. The primary end points were major adverse cardiovascular events at 90days, a composite of all-cause death, nonfatal myocardial infarction, stroke, or unplanned revascularization. Major bleeding was defined as any bleeding requiring hospitalization or blood transfusion. Hazard ratios (HRs) were generated using multivariable Cox regression and stratified by the propensity to treat with prasugrel. Of 19,914 patients (mean age 64.4years, 32% female), 4,058 received prasugrel (20%) and 15,856 received clopidogrel (80%). Prasugrel-treated patients were younger with fewer comorbid risk factors compared with their counterparts receiving clopidogrel. At 90days, there was a significant association between prasugrel use and lower major adverse cardiovascular event (5.7% vs 9.6%, HR 0.58, 95% CI 0.50-0.67, P<.0001) and bleeding (1.9% vs 2.9%, HR 0.65, 95% CI 0.51-0.83, P<.001). After propensity stratification, associations were attenuated and no longer significant for either outcome. Results remained consistent using different approaches to adjusting for potential confounders. In contemporary clinical practice, patients receiving prasugrel tend to have a lower-risk profile compared with those receiving clopidogrel. The lower ischemic and bleeding events associated with prasugrel use were no longer evident after accounting for these baseline differences. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Temporal evolution of antithrombotic therapy use in patients with acute coronary syndromes undergoing percutaneous coronary intervention in Italy: comparison between the EYESHOT and SCOPE registries].

    Science.gov (United States)

    De Luca, Leonardo; Pennacchi, Mauro; Musumeci, Giuseppe; D'Ascenzo, Fabrizio; Gallo, Pamela; Rigattieri, Stefano; Granatelli, Antonino; Berti, Sergio; Gulizia, Michele Massimo; De Servi, Stefano; Bolognese, Leonardo

    2018-02-01

    Few data exist on temporal evolution of antithrombotic agent use in patients with acute coronary syndromes (ACS) undergoing percutaneous coronary intervention (PCI) in Italy. We sought to compare data from the most recent prospective, multicenter, nationwide registries conducted in Italy, namely EYESHOT and SCOPE. EYESHOT enrolled 2585 consecutive ACS patients, both ST-segment elevation myocardial infarction (STEMI) and non-ST elevation ACS (NSTE-ACS), admitted to 203 Italian coronary care units over a 3-week period (2-22 Dec 2013 and 27 Jan-16 Feb 2014). Among patients enrolled in EYESHOT, 1755 (67.9%) underwent PCI (52.6% with STEMI and 47.4% with NSTE-ACS). In the SCOPE registry, a total of 1363 patients undergoing PCI were enrolled over 3 months (15 Feb-15 Apr 2016) in 39 Italian cath lab centers at medium to high PCI volume: 331 (24.3%) with a diagnosis of STEMI and 1032 (75.7%) with a diagnosis of NSTE-ACS. Over 2 years, the use of clopidogrel in the cath lab significantly decreased (from 11% to 8% in STEMI; p=0.06 and from 9% to 5% in NSTE-ACS; p=0.0002), while the administration of ticagrelor dramatically increased (from 14% to 37%; pSCOPE registries, a significant increase in the use of novel P2Y12 receptor inhibitors was observed, both at the time of PCI and at discharge.

  19. Conscious Sedation versus General Anesthesia for Patients with Acute Ischemic Stroke Undergoing Endovascular Therapy: A Systematic Review and Meta-Analysis

    Directory of Open Access Journals (Sweden)

    Ren Jing

    2018-01-01

    Full Text Available The aim of this study is to compare the effect of conscious sedation (CS with general anesthesia (GA on clinical outcomes in patients with acute ischemic stroke (AIS undergoing endovascular therapy (EVT. MEDLINE, EMBASE, and Cochrane Central Registers of Controlled Trials (from inception to July 2017 were searched for reports on CS and GA of AIS undergoing EVT. Two reviewers assessed the eligibility of the identified studies and extracted data. Data were analyzed using the fixed-effects model, and the sources of heterogeneity were explored by sensitive analysis. Trial sequential analysis was conducted to monitor boundaries for the limitation of global type I error, and GRADE system was demonstrated to evaluate the quality of evidence. A total of thirteen studies were finally identified. Pooled analysis of the incidence of mRS score ≦ 2 after hospital discharge and one or three months in the CS group was higher than that in the GA group. The all-causing mortality of AIS patients in the CS group was lower than that in the GA group. There were no differences in the proportion of IA rtPA and thrombolysis between the two groups. Compared with AIS patients receiving GA, the all-causing mortality in the AIS patients receiving CS was decreased, while incidence of mRS score ≦ 2 at hospital discharge and one or three months was increased.

  20. History of consolidation is prognostic in acute myeloid leukemia patients undergoing allogeneic hematopoietic cell transplantation in minimal residual disease-negative first complete remission.

    Science.gov (United States)

    Rashidi, Armin; Linden, Michael A; DeFor, Todd E; Warlick, Erica; Bejanyan, Nelli; Yohe, Sophia; Weisdorf, Daniel J; Ustun, Celalettin

    2017-10-01

    Prognostic factors among acute myeloid leukemia (AML) patients undergoing allogeneic hematopoietic cell transplantation (allo-HCT) in minimal residual disease (MRD)-negative first complete remission (CR1) are unknown. We retrospectively attempted to answer the following question: In AML patients undergoing allo-HCT in MRD-negative CR1, does a history of prior consolidation provide additional prognostic information? The inclusion criteria were: (i) Age > 18 years, (ii) AML in CR1 after 1-2 cycles of intensive induction chemotherapy, with or without consolidation, (iii) Allo-HCT between 1/2003 and 4/2016 at our institution, (iv) Available standard-sensitivity 4-color flow cytometry results from a bone marrow aspiration at diagnosis and after completion of all previous chemotherapy within one month prior to HCT, (v) Flow cytometry-based MRD-negative status at the time of HCT. A history of prior consolidation was associated with favorable overall survival (Hazard Ratio [95% Confidence Interval]: 0.59 [0.35-0.99], P = .046), relapse-free survival (0.60 [0.37-0.96], P = .036), and relapse (0.50 [0.27-0.92], P = .025). Analysis of potential sources of bias was unrevealing. In AML patients undergoing allo-HCT in MRD-negative CR1, a history of prior consolidation was associated with favorable outcomes. If the path to pre-HCT MRD negativity includes consolidation, it may identify patients with improved prognosis following HCT in MRD-negative state. These results warrant validation in larger cohorts. © 2017 Wiley Periodicals, Inc.

  1. Neurological Complications Of Chronic Myeloid Leukaemia: Any ...

    African Journals Online (AJOL)

    Of the five, two (40%) patients presented with bilateral hearing impairment, each beginning with the left ear; one (20%) presented with left ear hearing loss; one ... pathogenetic mechanisms underlying these complications with a view to finding specific treatment measures for worrisome chronic myeloid leukaemia-related ...

  2. ABSTRACT CHRONIC MYELOID LEUKAEMIA IN CENTRAL ...

    African Journals Online (AJOL)

    hi-tech

    2003-09-09

    , USA. .... anaemia (Hb ≤ 9.4g/dl recorded in 86 (57.3%) patients and ..... J.M. Chronic myeloid leukaemia. In. Haematology, Basic Principles and Practice 2nd edn., (ed.), R. Hoffman. Churchill Livingstone, New York, USA.

  3. Splenic irradiation for hairy cell leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Al-Moundhri, A.; Graham, P.H. [St George Hospital, Kogarah, NSW, (Australia). Department of Radiation Oncology

    1997-11-01

    Splenic irradiation in the management of hairy cell leukaemia is previously unreported. A case is presented here to illustrate that splenic irradiation may be a useful addition to systemic therapies. It achieved local splenic and blood picture response and remission similar to splenectomy without any significant toxicity. (authors). 7 refs., 2 figs.

  4. Safety and efficacy of thrombectomy in patients undergoing primary percutaneous coronary intervention for Acute ST elevation MI: A Meta-Analysis of Randomized Controlled Trials

    Directory of Open Access Journals (Sweden)

    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.

  5. A New Model for Predicting Acute Mucosal Toxicity in Head-and-Neck Cancer Patients Undergoing Radiotherapy With Altered Schedules

    International Nuclear Information System (INIS)

    Strigari, Lidia; Pedicini, Piernicola; D’Andrea, Marco; Pinnarò, Paola; Marucci, Laura; Giordano, Carolina; Benassi, Marcello

    2012-01-01

    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.

  6. Long-term survival and functional outcome of unselected patients undergoing percutaneous coronary intervention for acute myocardial infarction.

    Science.gov (United States)

    Anabitarte, Pablo; Kurz, David J; Stettler, Irene; Naegeli, Barbara; Bertel, Osmund; Frielingsdorf, Juergen; Maurer, Dominik; Straumann, Edwin

    2009-10-31

    Percutaneous coronary intervention (PCI) is the most effective reperfusion modality in patients with acute myocardial infarction (MI). Data concerning long-term survival and functional outcome are sparse. One thousand consecutive patients treated by emergency PCI were systematically ana-lysed in a single-centre registry. Multivariate predictors of in-hospital mortality, post-discharge mortality and late functional capacity were identified. Follow-up was completed for 978 patients. The median clinical follow-up length was 3.2 years. In-hospital and post-discharge mortality were 7.6% and 7.3%, respectively. Annualised post-discharge mortality remained stable over time at 2% per year. Independent predictors of in-hospital death were cardiogenic shock, TIMI flow 6 h. Independent predictors of post-discharge mortality were TIMI flow after PCI <3, prior MI, elevated glucose levels at admission, and increasing age. In contrast, cardiogenic shock, time to patent artery and left ventricular ejection fraction <40% were not independently associated with post-hospital death. At late follow-up, 47% of patients had normal functional capacity and 49.1% were in New York Heart Association functional class II. Predictors of impaired functional capacity at follow-up were age, gender, smoking habits and multivessel coronary disease. Post-discharge mortality after PCI for acute MI was 2% per year. Significant differences exist between predictors of in-hospital and post-discharge mortality. The functional capacity of surviving patients was remarkably good, even when presented in cardiogenic shock.

  7. Trends and territorial inequalities of incidence and survival of childhood leukaemia and their relations to socioeconomic status in Hungary, 1971-2015.

    Science.gov (United States)

    Jakab, Zsuzsanna; Juhasz, Attila; Nagy, Csilla; Schuler, Dezso; Garami, Miklos

    2017-09-01

    The Hungarian Childhood Cancer Registry, a population-based national registry of the Hungarian Paediatric Haemato-Oncology Network founded in 1971, monitors the incidence and mortality of childhood cancer. Our aims were to carry out a longitudinal study to investigate the trends and spatial inequalities of incidence and survival of leukaemia, and the association between survival and deprivation in Hungary. All cases of childhood leukaemia and myelodysplasia were analysed (3157 cases, 1971-2015, age: 0-14 years). Time trends and the annual percentage change in direct standardized incidence and mortality were assessed. Survival and association with deprivation were assessed using the Kaplan-Meier method and Cox regression. Incidence rates of leukaemia (23.5-56.0/million) increased with an average annual percent change (AAPC) of 1%, determined by an increase in the incidence of acute lymphoblastic leukaemia (14.6-39.2/million, AAPC: 1.25%). Kaplan-Meier analysis showed a significant improvement in overall survival over the study period. Starting from 25% of cases surviving 5 years in the 70s; the overall 5-year survival reached 80% by 2010. Survival differences were observed with sex, leukaemia type and age at diagnosis. A reverse association was found in the survival probability of leukaemia by degree of deprivation. The Cox proportional hazards model verified a significant reverse association with deprivation [hazard ratio=1.08 (1.04-1.12)]. This is the first nationwide study to confirm the prognostic role of deprivation on the basis of a large cohort of patients with childhood leukaemia during a 45-year period. To maintain further improvement in treatment results, it is important to detect inequalities. Our results showed that deprivation may also be important in the survival of leukaemia.

  8. Worsening Renal Function in Acute Heart Failure Patients Undergoing Aggressive Diuresis is Not Associated with Tubular Injury.

    Science.gov (United States)

    Ahmad, Tariq; Jackson, Keyanna; Rao, Veena S; Tang, W H Wilson; Brisco-Bacik, Meredith A; Chen, Horng H; Felker, G Michael; Hernandez, Adrian F; O'Connor, Christopher M; Sabbisetti, Venkata S; Bonventre, Joseph V; Wilson, F Perry; Coca, Steven G; Testani, Jeffrey M

    2018-01-19

    Background -Worsening renal function (WRF) in the setting of aggressive diuresis for acute heart failure (AHF) treatment may reflect renal tubular injury or simply indicate a hemodynamic or functional change in glomerular filtration. Well-validated tubular injury biomarkers-NAG, NGAL, and KIM-1- are now available that can quantify the degree of renal tubularinjury. The ROSE-AHF trial provides an experimental platform for the study of mechanisms of WRF during aggressive diuresis for AHF, as the ROSE-AHF protocol dictated high dose loop diuretic therapy in all patients. We sought to determine whether tubular injury biomarkers are associated with WRF in the setting of aggressive diuresis and its association with prognosis. Methods -Patients in the multicenter ROSE-AHF trial with baseline and 72-hour urine tubular injury biomarkers were analyzed ( N =283). WRF was defined as a ≥20% decrease in glomerular filtration rate estimated using cystatin C. Results -Consistent with protocol driven aggressive dosing of loop diuretics, participants received a median 560 mg of IV furosemide equivalents (IQR 300-815 mg) which induced a urine output of 8425 mL (IQR 6341-10528 ml) over the 72-hour intervention period. Levels of NAG and KIM-1 did not change with aggressive diuresis ( P >0.59, both), whereas levels of NGAL decreased slightly [-8.7 ng/mg (-169, 35 ng/mg), P renal tubular injury: NGAL ( P =0.21), NAG ( P =0.46), or KIM-1 ( P =0.22). Increases in NGAL, NAG, and KIM-1 were paradoxically associated with improved survival (adjusted HR: 0.80 per 10 percentile increase, 95% CI: 0.69-0.91; P =0.001). Conclusions -Kidney tubular injury does not appear to have an association with WRF in the context of aggressive diuresis of AHF patients. These findings reinforce the notion that the small to moderate deteriorations in renal function commonly encountered with aggressive diuresis are dissimilar from traditional causes of acute kidney injury.

  9. Microalbuminuria indicates long-term vascular risk in patients after acute stroke undergoing in-patient rehabilitation

    Directory of Open Access Journals (Sweden)

    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.

  10. Functional exhaustion of CD4+T cells induced by co-stimulatory signals from myeloid leukaemia cells.

    Science.gov (United States)

    Ozkazanc, Didem; Yoyen-Ermis, Digdem; Tavukcuoglu, Ece; Buyukasik, Yahya; Esendagli, Gunes

    2016-12-01

    To cope with immune responses, tumour cells implement elaborate strategies such as adaptive resistance and induction of T-cell exhaustion. T-cell exhaustion has been identified as a state of hyporesponsiveness that arises under continuous antigenic stimulus. Nevertheless, contribution of co-stimulatory molecules to T-cell exhaustion in cancer remains to be better defined. This study explores the role of myeloid leukaemia-derived co-stimulatory signals on CD4 + T helper (Th) cell exhaustion, which may limit anti-tumour immunity. Here, CD86 and inducible T-cell co-stimulator ligand (ICOS-LG) co-stimulatory molecules that are found on myeloid leukaemia cells supported Th cell activation and proliferation. However, under continuous stimulation, T cells co-cultured with leukaemia cells, but not with peripheral blood monocytes, became functionally exhausted. These in vitro-generated exhausted Th cells were defined by up-regulation of programmed cell death 1 (PD-1), cytotoxic T-lymphocyte antigen 4 (CTLA-4), lymphocyte activation gene 3 (LAG3) and T-cell immunoglobulin and mucin domain-containing protein 3 (TIM-3) inhibitory receptors. They were reluctant to proliferate upon re-stimulation and produced reduced amounts of interleukin-2 (IL-2), tumour necrosis factor-α (TNF-α) and interferon-γ (IFN-γ). Nonetheless, IL-2 supplementation restored the proliferation capacity of the exhausted Th cells. When the co-stimulation supplied by the myeloid leukaemia cells were blocked, the amount of exhausted Th cells was significantly decreased. Moreover, in the bone marrow aspirates from patients with acute myeloid leukaemia (AML) or myelodysplastic syndrome (MDS), a subpopulation of Th cells expressing PD-1, TIM-3 and/or LAG3 was identified together with CD86 + and/or ICOS-LG + myeloid blasts. Collectively, co-stimulatory signals derived from myeloid leukaemia cells possess the capacity to facilitate functional exhaustion in Th cells. © 2016 John Wiley & Sons Ltd.

  11. Enteral Nutrition Is a Risk Factor for Airway Complications in Subjects Undergoing Noninvasive Ventilation for Acute Respiratory Failure.

    Science.gov (United States)

    Kogo, Mariko; Nagata, Kazuma; Morimoto, Takeshi; Ito, Jiro; Sato, Yuki; Teraoka, Shunsuke; Fujimoto, Daichi; Nakagawa, Atsushi; Otsuka, Kojiro; Tomii, Keisuke

    2017-04-01

    Early enteral nutrition is recommended for mechanically ventilated patients in several studies and guidelines. In contrast, the effects of early enteral nutrition on noninvasive ventilation (NIV) have not been investigated extensively. The lack of an established method of airway protection suggests that enteral nutrition administration to these patients could increase airway complications and worsen outcomes. Between January 2007 and January 2015, 150 patients were admitted to our respiratory department for acute respiratory failure and received NIV for >48 h. Of these, 107 subjects incapable of oral intake were retrospectively analyzed. Clinical background and complications were compared in subjects who did and did not receive enteral nutrition. Sixty of the 107 subjects (56%) incapable of oral intake who received NIV also received enteral nutrition. Serum albumin concentration was significantly lower in subjects who received enteral nutrition than in those who did not (mean 2.7 ± 0.68 mg/dL vs 3.0 ± 0.75 mg/dL, P = .048). The rate of airway complications was significantly higher (53% [32/60] vs 32% [15/47], P = .03), and median NIV duration was significantly longer (16 [interquartile range 7-43] d vs 8 [5-20] d, P = .02) in subjects who received enteral nutrition than in those who did not. Multivariate analysis showed that enteral nutrition was unrelated to in-hospital mortality. Among subjects receiving NIV, enteral nutrition was associated with increased risk of airway complications but did not affect mortality. Enteral nutrition should be carefully considered in these patients. Copyright © 2017 by Daedalus Enterprises.

  12. Impact of the ASPECT scores and distribution on outcome among patients undergoing thrombectomy for acute ischemic stroke.

    Science.gov (United States)

    Spiotta, Alejandro M; Vargas, Jan; Hawk, Harris; Turner, Raymond; Chaudry, M Imran; Battenhouse, Holly; Turk, Aquilla S

    2015-08-01

    This study investigates whether the Alberta Stroke Program Early CT Score (ASPECTS) quantification is associated with outcome following mechanical thrombectomy. To determine whether preintervention non-perfect ASPECT scores involving cortical or subcortical regions and the side of the non-perfect ASPECT score affects outcomes. A retrospective review of a prospectively maintained database of patients with acute ischemic stroke involving the anterior circulation who underwent thrombectomy between May 2008 and August 2012 at a single tertiary care center. The device for mechanical thrombectomy used was the penumbra aspiration system (Penumbra Inc, Alameda, California, USA) and the Solitaire stent retriever (ev3, Irvine, California, USA). A 'blinded' neuroradiologist obtained ASPECTS quantification and noted each region demonstrating early changes. 149 patients (51.7% female, mean age 66.1±15.1 years) were included with an average National Institutes of Health Stroke Scale of 16.2±6.7. Patients with non-perfect ASPECT scores on pretreatment imaging were more likely to have a hemorrhagic conversion (p=0.04) evident on post-procedure CT. However, functional outcomes were the same. Patients with both cortical and basal ganglia non-perfect ASPECT scores were more likely to be in a persistent vegetative state or expire. No differences were identified in outcome among patients with left- versus right-sided infarcts affecting the basal ganglia or cortical regions. These findings support a strategy of selecting candidacy for thrombectomy that does not exclude patients with non-perfect ASPECT scores involving either the basal ganglia or cortical regions. Outcomes were identical among patients with no non-perfect ASPECT scores and those with cortical or subcortical infarcts, despite a higher incidence of hemorrhagic conversion found among those with non-perfect ASPECT scores. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted

  13. Analgesic effect of bupivacaine eluting porcine small intestinal submucosa (SIS) in ferrets undergoing acute abdominal hernia defect surgery.

    Science.gov (United States)

    Johnson, Brenda M; Ko, Jeff C; Hall, Paul J; Saunders, Alan T; Lantz, Gary C

    2011-05-15

    Porcine small intestinal submucosa (SIS) is used as a biological implant for abdominal wall hernia repair to facilitate wound healing and augment local tissue strength. This prospective, randomized, blinded study evaluated local pain control provided by bupivacaine adsorbed to SIS for repair of acutely created abdominal wall full thickness muscle/fascial defects in ferrets. Eighteen healthy ferrets were randomly and equally assigned to three groups: (1) SIS with bupivacaine subjected to surgery, (2) SIS with no bupivacaine subjected to surgery, and (3) anesthesia only control group. Ferrets in groups 1 and 2 were anesthetized with butorphanol and sevoflurane for the surgery. Control ferrets were anesthetized in the same fashion for the same duration without surgery. Behavior and pain were evaluated in all ferrets by behavioral observation, algometer, and palpometer measurements, and heart and respiratory rates each obtained before surgery and at various intervals for 96 h after surgery. When pain reached a predetermined threshold, buprenorphine was used as a rescue analgesic. The serum and combined tissue concentrations of bupivacaine were analyzed. Overall, the palpometer testing was better tolerated in the bupivacaine treated SIS group than by the untreated SIS group (P = 0.04). There was an observed physiologically significant difference in algometer and other palpometer readings as well as heart and respiratory rates. All ferrets in the untreated SIS group were rescued while 33% of the SIS-bupivacaine groups were rescued (P pain relief over 2-4 days with no clinical adverse effects observed in the ferrets. Copyright © 2011 Elsevier Inc. All rights reserved.

  14. [Renal insufficiency and clinical outcomes in patients with acute coronary syndrome undergoing percutaneous coronary intervention: a multi-centre study].

    Science.gov (United States)

    Huo, Yong; Ho, Wa

    2007-12-18

    To investigate the association of renal insufficiency and clinical outcomes in patients with acute coronary syndrome(ACS). The study was a multi-centre register study including 3,589 ACS patients coming from 39 centers across China who had received percutaneous coronary intervention(PCI) prior to 1st February, 2007. Estimated glomerular filtration rate (eGFR) was calculated for all patients using the 4-variable MDRD equation with the serum creatinine obtained before angiography. The association between renal insufficiency and clinical outcomes and the presence of in-hospital death and bleeding was studied by Fisher's exact test. Multi-variable analysis on the risk factors of in-hospital bleeding was done by logistic regression test. The mean age of the study population was (61.74+/-11.37) years (ranging from 23 years to 92 years)and 76.5% (2,746/3,589) of the population was male. Only 90 patients (2.51%) were known to have chronic kidney disease at the time of admission and 144 patients(4.01%) had serum creatinine levels above 133 micromol/L. However, after the evaluation of renal status by the MDRD equation, 2,250 patients (63.1%)showed a reduction in eGFR of less than 90 mL/min, of whom, 472 (13.1%) even reached the level of moderate renal insufficiency (eGFRchronic total occlusion lesions(CTO) and eight (0.22%) needed shift to coronary artery bypass grafting (CABG) after angiography. Both the presence of CTO lesions and CABG were proved to be associated with decrease of renal function through Fisher's exact test (P= 0.005 8 and 0.041, respectively). The in-hospital mortality rate was 0.47%(17/3 589) which was associated with the degree of renal insufficiency (P=0.001 3). A total of 75 patients(2.09%) of in-hospital bleeding were recorded with 26 patients(0.72%) diagnosed as major bleeding events. 92% (69/75) of the bleeding events occurred after PCI. Bleeding was found to be associated with the degree of renal insufficiency in every type of antithrombotic

  15. 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.

    Science.gov (United States)

    Zakkar, Mustafa; Bruno, Vito D; Guida, Gustavo; Angelini, Gianni D; Chivasso, Pierpaulo; Suleiman, M Sadeeh; Bryan, Alan J; Ascione, Raimondo

    2016-07-01

    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). 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, failure, loss, and end-stage (RIFLE) criteria. Health outcome measures included the rate of in-hospital AKI and all-cause 30-day and long-term mortality, using data from the United Kingdom's Office of National Statistics. Propensity score matching, as well as logistic regression analyses, were used. The impact of postoperative AKI at different time points was related to survival. In patients with redo CABG, the occurrence of postoperative AKI was associated with in-hospital mortality (odds ratio [OR], 3.74; 95% confidence interval [CI], -1.3 to 10.5; P < .01], high Euroscore (OR, 1.27; 95% CI, 1.07-1.52; P < .01), use of IABP (OR, 6.9; 95% CI, 2.24-20.3; P < .01), and reduced long-term survival (hazard ratio [HR], 2.42; 95% CI, 1.63-3.6; P = .01). Overall survival at 5 and 10 years was lower in AKI patients with AKI compared with those without AKI (64% vs 85% at 5 years; 51% vs 68% at 10 years). On 1:1 propensity score matching analysis, postoperative AKI was independently associated with reduced long term survival (HR, 2.8; 95% CI, 1.15-6.7). In patients undergoing redo CABG, the occurrence of postoperative AKI is associated with increased 30-day mortality and major complications and with reduced long-term survival. Copyright © 2016 The American Association for Thoracic Surgery. Published by Elsevier Inc. All rights reserved.

  16. Renal resistive index by transesophageal and transparietal echo-doppler imaging for the prediction of acute kidney injury in patients undergoing major heart surgery.

    Science.gov (United States)

    Regolisti, Giuseppe; Maggiore, Umberto; Cademartiri, Carola; Belli, Loredana; Gherli, Tiziano; Cabassi, Aderville; Morabito, Santo; Castellano, Giuseppe; Gesualdo, Loreto; Fiaccadori, Enrico

    2017-04-01

    Acute kidney injury (AKI) following major heart surgery (MHS) is associated with early decrease in renal blood flow and worsened prognosis. Doppler-derived renal resistive index (RRI), which reflects renal vascular resistance, may predict the development of AKI in patients undergoing MHS. We studied 60 consecutive patients (mean age 69.5 years, range 30-88, 41 males) undergoing MHS. We measured RRI, both at the renal sinus and intraparenchymally, by transesophageal echo-Doppler ultrasound (TE-ED us ) at anesthesia induction and at the end of surgery in all patients. Additionally, we measured RRI by external transparietal echo-Doppler ultrasound (TP-ED us ) at the following time points: anesthesia induction, end of surgery, 4 and 24 h from cardiopulmonary bypass (CPB) start. We also measured serum neutrophil gelatinase associated lipocalin (NGAL) at the same time points. AKI [serum creatinine (sCr) increase ≥0.3 mg/dl vs. baseline within 72 h] developed in 23/60 (38.3 %) patients, with two requiring dialysis. Systemic hemodynamic parameters were similar in the patients who developed AKI (AKI+) and in those who did not (AKI-). Intraparenchymal RRI at end-surgery was significantly higher in AKI+ compared to AKI- patients, both at TE-ED us and TP-ED us (TE-ED us mean difference, p = 0.004; TP-ED us mean difference, p = 0.013; difference between TE-ED us and TP-ED us results, p = 0.066), although the predictive performance was limited with both methods (area under the curve [AUC] of the receiver-operator characteristics: 0.71 and 0.70 for TE-ED us and TP-ED us , respectively). Serum NGAL values were higher in AKI + than in AKI- patients (anesthesia induction, p = 0.037; end-surgery, p = 0.007; 4 h from CPB start, p = 0.093; 24 h from CPB start, p = 0.024. However, combining RRI with serum NGAL at end-surgery did not provide a clear-cut advantage in predicting AKI. In patients undergoing MHS, increased echo-Doppler ultrasound-derived RRI at end

  17. Associations Between Complex PCI and Prasugrel or Clopidogrel Use in Patients With Acute Coronary Syndrome Who Undergo PCI: From the PROMETHEUS Study.

    Science.gov (United States)

    Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Aquino, Melissa; Kini, Annapoorna S; Rao, Sunil; Weintraub, William; Henry, Timothy D; Farhan, Serdar; Vogel, Birgit; Sorrentino, Sabato; Ge, Zhen; Kapadia, Samir; Muhlestein, Joseph B; Weiss, Sandra; Strauss, Craig; Toma, Catalin; DeFranco, Anthony; Effron, Mark B; Keller, Stuart; Baker, Brian A; Pocock, Stuart; Dangas, George; Mehran, Roxana

    2018-03-01

    Potent P2Y 12 inhibitors might offer enhanced benefit against thrombotic events in complex percutaneous coronary intervention (PCI). We examined prasugrel use and outcomes according to PCI complexity, as well as analyzing treatment effects according to thienopyridine type. PROMETHEUS was a multicentre observational study that compared clopidogrel vs prasugrel in acute coronary syndrome patients who underwent PCI (n = 19,914). Complex PCI was defined as PCI of the left main, bifurcation lesion, moderate-severely calcified lesion, or total stent length ≥ 30 mm. Major adverse cardiac events (MACE) were a composite of death, myocardial infarction, stroke, or unplanned revascularization. Outcomes were adjusted using multivariable Cox regression for effect of PCI complexity and propensity-stratified analysis for effect of thienopyridine type. The study cohort included 48.9% (n = 9735) complex and 51.1% (n = 10,179) noncomplex patients. Second generation drug-eluting stents were used in 70.1% complex and 66.2% noncomplex PCI patients (P < 0.0001). Complex PCI was associated with greater adjusted risk of 1-year MACE (hazard ratio [HR], 1.29; 95% confidence interval [CI], 1.20-1.39; P < 0.001). Prasugrel was prescribed in 20.7% of complex and 20.1% of noncomplex PCI patients (P = 0.30). Compared with clopidogrel, prasugrel significantly decreased adjusted risk for 1-year MACE in complex PCI (HR, 0.79; 95% CI, 0.68-0.92) but not noncomplex PCI (HR, 0.91; 95% CI, 0.77-1.08), albeit there was no evidence of interaction (P interaction = 0.281). Despite the use of contemporary techniques, acute coronary syndrome patients who undergo complex PCI had significantly higher rates of 1-year MACE. Adjusted magnitude of treatment effects with prasugrel vs clopidogrel were consistent in complex and noncomplex PCI without evidence of interaction. Copyright © 2018. Published by Elsevier Inc.

  18. Outcomes and changes in code status of patients with acute myeloid leukemia undergoing induction chemotherapy who were transferred to the intensive care unit.

    Science.gov (United States)

    Ahmed, Tamjeed; Koch, Abby L; Isom, Scott; Klepin, Heidi D; Bishop, Jonathan M; Ellis, Leslie R; Berenzon, Dmitriy; Howard, Dianna; Lyerly, Susan; Powell, Bayard L; Pardee, Timothy S

    2017-11-01

    Patients with Acute Myeloid Leukemia (AML) have compromised marrow function and chemotherapy causes further suppression. As a result complications are frequent, and patients may require admission to the intensive care unit (ICU). How codes status changes when these events occur and how those changes influence outcome are largely unknown. Outcomes for adult patients with AML, undergoing induction chemotherapy, and transferred to the ICU between January 2000 and December 2013 were analyzed. 94 patients were included. Median survival was 1.3 months. At 3 and 6 months overall survival (OS) was 27% and 18% respectively. Respiratory failure was the most common reason for transfer to ICU (88%), with 63% requiring mechanical ventilation at transfer. Other reasons included: cardiac arrest (18%), septic shock (17%), hypotension (9%), and acute renal failure (9%). The most frequent interventions were mechanical ventilation in 85%, vasopressors in 62%, and hemodialysis in 30%. Following transfer 55 patients (58%) had a change in code status. Overall, 46 patients (49%) changed from Full Code (FC) to Comfort Care (CC), 7 (7%) from FC to Do Not Resuscitate (DNR), and 2 (2%) from DNR to CC. For the entire cohort, ICU mortality (IM) was 61% and hospital mortality (HM) was 71%. For FC or DNR patients, IM was 30% and HM was 41%. For CC patients, IM was 90% and HM was 100%. Overall, 27 patients (29%) survived to discharge. Of those discharged, 22 (81%) were alive at 3 months and 17 (63%) were alive at 6 months. In conclusion, patients that required ICU admission during induction chemotherapy have a poor prognosis. Code status changed during the ICU stay for the majority of patients and always to a less aggressive status. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction undergoing emergent PCI.

    Science.gov (United States)

    Yang, Wu-Xiao; Lai, Chun-Lin; Chen, Fu-Heng; Wang, Ji-Rong; Ji, You-Rui; Wang, Dong-Xia

    2017-06-01

    The value of Sonoclot detection technology to guide the clinical medication of the perioperative anticoagulation and antiplatelet therapy in patients with acute myocardial infarction (AMI) undergoing emergent percutaneous coronary intervention (PCI) was estimated. One hundred and twenty-eight patients were randomly divided into control group and observation group with 64 cases in each group. Control group adopted routine blood coagulation indexes, including prothrombin time, activated partial thromboplastin time, fibrinogen and plasma thrombin time, platelet count and platelet aggregation turbidity analysis; observation group adopted Sonoclot detection technology, including activated clotting time, coagulation rate and platelet function. Anticoagulant therapy selected was of low molecular weight heparin calcium perioperatively, intraoperative unfractionated heparin, and clopidogrel (75 mg) combined with aspirin enteric-coated tablets (100 mg) as antiplatelet drugs. The therapy was administered in accordance with blood coagulation results. The blood coagulation time, postoperative creatine kinase isoenzyme MB, cardiac troponin I and B-type natriuretic peptide levels in the observation group are significantly lower than those in the control group (P0.05). The incidence of recurrent myocardial infarction, microembolism, acute and subacute thrombosis and bleeding events in the observation group are significantly lower than those in the control group (P0.05). Whereas, in the observation group, there is significant difference in coagulation indexes of the patients with thrombosis events or bleeding events or no event (P<0.05). In conclusion, Sonoclot detection technology instructs emergent PCI treatment in AMI patients to shorten the detection time of blood coagulation, reduce the degree of myocardial injury, reduce the incidence of perioperative thrombosis and bleeding events. Furthermore, it has great value in guiding the clinical medication of anticoagulation and

  20. Ocular manifestations of leukaemia in Ethiopians.

    Science.gov (United States)

    Alemayehu, W; Shamebo, M; Bedri, A; Mengistu, Z

    1996-10-01

    A prospective ophthalmic evaluation of 74 newly diagnosed and 34 old (on follow-up) leukaemic patients, carried out from March 1990 to December 1995 is described. Primary ocular involvement, that is leukaemic retinal infiltrates, were detected in 32% of the newly diagnosed. In contrast, none of the old leukaemic patients had this lesion. In 69% of the new and 21% of the old cases, secondary ocular manifestations of leukaemia were observed. The major secondary ocular manifestation of leukaemia in both groups was intra-retinal haemorrhage. A variety of miscellaneous ocular findings, such as cataract, pterygium, pingeculae, etc. were detected in 36% of all leukemics. These findings indicate the importance of a complete ophthalmologic evaluation in the diagnosis, follow-up and management of leukaemic patients.

  1. Recent advances in the pathogenesis and treatment of juvenile myelomonocytic leukaemia.

    Science.gov (United States)

    Loh, Mignon L

    2011-03-01

    Myeloid neoplasms derive from the pathological clonal expansion of an abnormal stem cell and span a diverse spectrum of phenotypes including acute myeloid leukaemia (AML), myeloproliferative neoplasms (MPN) and myelodysplastic syndromes (MDS). Expansion of myeloid blasts with suppression of normal haematopoiesis is the hallmark of AML, whereas MPN is associated with over-proliferation of one or more lineages that retain the capacity to differentiate, and MDS is characterized by cytopenias and aberrant differentiation. MPD and MDS can progress to AML, which is likely due to the acquisition of cooperative mutations. Juvenile myelomonocytic leukaemia (JMML) is an aggressive myeloid neoplasm of childhood that is clinically characterized by overproduction of monocytic cells that can infiltrate organs, including the spleen, liver, gastrointestinal tract, and lung. JMML is categorized as an overlap MPN/MDS by the World Health Organization and also shares some clinical and molecular features with chronic myelomonocytic leukaemia, a similar disease in adults. While the current standard of care for patients with JMML relies on allogeneic haematopoietic stem cell transplant (HSCT), relapse is the most frequent cause of treatment failure. This review outlines our understanding of the genetic underpinnings of JMML with a recent update on the discovery of novel CBL mutations, as well as a brief review on current therapeutic approaches. © 2011 Blackwell Publishing Ltd.

  2. The Time Profile of Pentraxin 3 in Patients with Acute ST-Elevation Myocardial Infarction and Stable Angina Pectoris Undergoing Percutaneous Coronary Intervention

    Directory of Open Access Journals (Sweden)

    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.

  3. Assessing the cardiology community position on transradial intervention and the use of bivalirudin in patients with acute coronary syndrome undergoing invasive management: results of an EAPCI survey.

    Science.gov (United States)

    Adamo, Marianna; Byrne, Robert A; Baumbach, Andreas; Haude, Michael; Windecker, Stephan; Valgimigli, Marco

    2016-10-20

    Our aim was to report on a survey initiated by the European Association of Percutaneous Cardiovascular Interventions (EAPCI) collecting the opinion of the cardiology community on the invasive management of acute coronary syndrome (ACS), before and after the MATRIX trial presentation at the American College of Cardiology (ACC) 2015 Scientific Sessions. A web-based survey was distributed to all individuals registered on the EuroIntervention mailing list (n=15,200). A total of 572 and 763 physicians responded to the pre- and post-ACC survey, respectively. The radial approach emerged as the preferable access site for ACS patients undergoing invasive management with roughly every other responder interpreting the evidence for mortality benefit as definitive and calling for a guidelines upgrade to class I. The most frequently preferred anticoagulant in ACS patients remains unfractionated heparin (UFH), due to higher costs and greater perceived thrombotic risks associated with bivalirudin. However, more than a quarter of participants declared the use of bivalirudin would increase after MATRIX. The MATRIX trial reinforced the evidence for a causal association between bleeding and mortality and triggered consensus on the superiority of the radial versus femoral approach. The belief that bivalirudin mitigates bleeding risk is common, but UFH still remains the preferred anticoagulant based on lower costs and thrombotic risks.

  4. A cytogenetic model predicts relapse risk and survival in patients with acute myeloid leukemia undergoing hematopoietic stem cell transplantation in morphologic complete remission.

    Science.gov (United States)

    Rashidi, Armin; Cashen, Amanda F

    2015-01-01

    Up to 30% of patients with acute myeloid leukemia (AML) and abnormal cytogenetics have persistent cytogenetic abnormalities (pCytAbnl) at morphologic complete remission (mCR). We hypothesized that the prognostic significance of pCytAbnl in patients undergoing allogeneic hematopoietic stem cell transplantation (HSCT) in mCR varies with cytogenetic risk group. We analyzed the data on 118 patients with AML and abnormal cytogenetics who underwent HSCT in mCR, and developed a risk stratification model based on pCytAbnl and cytogenetic risk group. The model distinguished three groups of patients (Pcytogenetics (n=25) had the shortest median time to relapse (TTR; 5 months), relapse-free survival (RFS; 3 months), and overall survival (OS; 7 months). The group with favorable/intermediate risk cytogenetics and without pCytAbnl (n=43) had the longest median TTR (not reached), RFS (57 months), and OS (57 months). The group with pCytAbnl and favorable/intermediate risk cytogenetics, or, without pCytAbnl but with unfavorable risk cytogenetics (n=50) experienced intermediate TTR (18 months), RFS (9 months), and OS (18 months). In conclusion, a cytogenetic risk model identifies patients with AML in mCR with distinct rates of relapse and survival following HSCT. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. Residential exposures to pesticides and childhood leukaemia

    International Nuclear Information System (INIS)

    Metayer, C.; Buffler, P. 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 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)

  6. 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.

    Science.gov (United States)

    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 risk of MACEs increased with increasing RDW content (p value of combining RDW content and GRACE risk score was significantly improved, also shown by the net reclassification improvement (NRI = 0.352, p 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.

  7. Sex-related differences in outcomes among men and women under 55 years of age with acute coronary syndrome undergoing percutaneous coronary intervention: Results from the PROMETHEUS study.

    Science.gov (United States)

    Chandrasekhar, Jaya; Baber, Usman; Sartori, Samantha; Faggioni, Michela; Aquino, Melissa; Kini, Annapoorna; Weintraub, William; Rao, Sunil; Kapadia, Samir; Weiss, Sandra; Strauss, Craig; Toma, Catalin; Muhlestein, Brent; DeFranco, Anthony; Effron, Mark; Keller, Stuart; Baker, Brian; Pocock, Stuart; Henry, Timothy; Mehran, Roxana

    2017-03-01

    Young women undergoing percutaneous coronary intervention (PCI) for acute coronary syndrome (ACS) experience greater adverse events than men, potentially due to under-treatment. We sought to compare the 1-year outcomes by sex in patients ≤55 years of age from a contemporary PCI cohort. PROMETHEUS was a retrospective multicenter observational US study comparing outcomes in clopidogrel and prasugrel treated patients following ACS PCI. MACE was defined as a composite of death, myocardial infarction, stroke or unplanned revascularization. Clinically significant bleeding was defined as bleeding requiring transfusion or hospitalization. Hazard ratios were generated using multivariable Cox proportional hazards regression. The study cohort included 4,851 patients of which 1,162 (24.0%) were women and 3,689 (76.0%) were men. In this cohort, the prevalence of diabetes (41.0 vs. 27.9%) and chronic kidney disease (12.7 vs. 7.2%) was higher among women compared with men. Irrespective of sex, prasugrel was used in less than one-third of patients (31.8% in men vs. 28.1% in women, P = 0.01). Unadjusted, 1-year MACE (21.1% vs. 16.2%, P < 0.001) and bleeding (3.6% vs. 2.2%, P = 0.01) was significantly higher in women compared with men, but these results were no longer significant after adjustment for risk (HR 1.13, 95% CI 0.94-1.36 for MACE and HR 1.31, 95% CI 0.85-2.04 for bleeding). Women ≤ 55 years of age undergoing ACS PCI have significantly greater comorbidities than young men. Despite a higher risk clinical phenotype in women, prasugrel use was significantly lower in women than men. Female sex was associated with a significantly higher risk of 1-year MACE and bleeding than male sex, findings that are attributable to baseline differences. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  8. The pathogenesis of radiation leukaemia and its significance for the pathogenesis of spontaneous leukaemias

    International Nuclear Information System (INIS)

    Ludwig, F.C.

    1985-01-01

    There is no radiation leukaemia per se, there is just a spontaneous disposition to this disease owing to irradiation. Weakened immunity is one component of the preleukaemic condition. Changes in organs with tumour-virus-sensitive cells should not be disregarded. Preleukaemic condition involves the release of tumour viruses and the increased occurrence of cells which can react with tumour viruses. (DG) [de

  9. Long-term results and quality of life of patients undergoing sequential surgical treatment for severe acute pancreatitis complicated by infected pancreatic necrosis.

    Science.gov (United States)

    Cinquepalmi, Lorenza; Boni, Luigi; Dionigi, Gianlorenzo; Rovera, Francesca; Diurni, Mario; Benevento, Angelo; Dionigi, Renzo

    2006-01-01

    Infected pancreatic necrosis (IPN) is one of the most severe complications of acute pancreatitis (AP). Sequential surgical debridement represents one of the most effective treatments in terms of morbidity and mortality. The aim of this paper is to describe the quality of life and long-term results (e.g., nutritional, muscular, and pancreatic function) of patients treated by sequential necrosectomy at the Department of Surgery of the University of Insubria (Varese, Italy). Data were collected on patients undergoing sequential surgical debridement as treatment for IPN. The severity of AP was evaluated using the Ranson criteria, the Acute Physiology and Chronic Health Evaluation (APACHE II) Score, and the Sepsis Score, as well as the extent of necrosis. The surgical approach was through a midline or subcostal laparotomy, followed by exploration of the peritoneal cavity, wide debridement, and peritoneal lavage. The abdomen was either left open or closed partially with a surgical zipper, with multiple re-laparotomies scheduled until debridement of necrotic tissue was complete. The long-term evaluation focused on late morbidity, performance status, and abdominal wall function. In the majority of patients (68%), mixed flora were isolated. Pseudomonas aeruginosa was the microorganism identified most commonly (59%), often associated with Candida albicans or C. glabrata. The mean total hospital stay was 71+/-38 days (range 13-146 days), of which 24+/-19 days (range 0-66 days) were in the intensive care unit. Eight patients died, the deaths being caused by multiple organ dysfunction syndrome in seven patients and hemorrhage from the splenic artery in one. Normal exocrine and endocrine pancreatic function was observed in 28 patients (88%). At discharge, four patients had steatorrhea, which was temporary. Eight patients (23%) developed pancreatic pseudocysts, and in six, cystogastostomy was performed. Most patients (29/32, 91%) developed a post-operative hernia, but only five

  10. Cytogenetic risk grouping by the monosomal karyotype classification is superior in predicting the outcome of acute myeloid leukemia undergoing allogeneic stem cell transplantation in complete remission.

    Science.gov (United States)

    Hemmati, Philipp G; Schulze-Luckow, Anthea; Terwey, Theis H; le Coutre, Philipp; Vuong, Lam G; Dörken, Bernd; Arnold, Renate

    2014-02-01

    We retrospectively analyzed the impact of cytogenetic abnormalities grouped according to the monosomal karyotype (MK) classification or the Southwest Oncology/Eastern Cooperative Oncology Group (SWOG/ECOG) definition in 263 patients with acute myeloid leukemia (AML) who underwent allogeneic stem cell transplantation (alloSCT) in complete remission (CR) at our center. Risk grouping using the MK criteria shows a highly significant difference in 5-yr overall survival (OS) ranging between 67%, for the most favorable, and 32%, for the poorest risk group (P = 0.001). Although similarly precise in predicting OS, the MK scheme better separates patients with respect to relapse incidence as compared to the SWOG/ECOG grouping (P = 0.0001 vs. P = 0.01). Notably, patients displaying non-MK abnormalities (MK-) had a 5-yr relapse incidence identical to those cytogenetically normal (CN), that is 24%. Multivariate analysis revealed that the MK classification is an independent prognosticator and superior in predicting OS (hazard ratios, HR 3.74, P = 0.01) and relapse incidence (HR 3.74, P = 0.005) as compared to the SWOG/ECOG criteria. Finally, subgroup analysis revealed that the prognostic capacity of the MK classification is highly significant in patients treated with standard myeloablative conditioning prior to alloSCT (P = 0.0011 for OS, P = 0.0007 for relapse). In contrast, the MK grouping failed to predict OS or relapse incidence in patients treated with reduced intensity conditioning. Taken together, these results indicate that the MK classification is superior in predicting the overall outcome of patients with AML undergoing alloSCT in CR. Furthermore, our data suggest that the genetic risk profile of MK- and CN patients is mostly overlapping in this setting. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  11. Estimation of current cumulative incidence of leukaemia-free patients and current leukaemia-free survival in chronic myeloid leukaemia in the era of modern pharmacotherapy.

    Science.gov (United States)

    Pavlík, Tomáš; Janoušová, Eva; Pospíšil, Zdeněk; Mužík, Jan; Záčková, Daniela; Ráčil, Zdeněk; Klamová, Hana; Cetkovský, Petr; Trněný, Marek; Mayer, Jiří; Dušek, Ladislav

    2011-10-11

    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. 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. 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. Two quantities for the evaluation of the efficacy of current CML therapy that may be estimated with standard nonparametric methods have been proposed in this paper. Both quantities reliably illustrate a patient's disease

  12. 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.

    Directory of Open Access Journals (Sweden)

    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.

  13. Nuclear power and leukaemia in children

    International Nuclear Information System (INIS)

    Charles, M.W.; Harte, G.A.

    1985-01-01

    A summary is given of a session entitled ''Nuclear Power and Leukaemia in children'' held at a meeting of the Royal Statistical Society and the Society for Social Medicine in June 1985. The first part of the session was devoted to summarising the principal findings of the Black Report on the Investigation of the Possible Increased Incidence of Cancer in West Cumbria'', and to a description and critical review of the main evidence presented to the Committee. Later, further epidemiological studies arising out of and related to the Report were described. The meeting was useful in identifying areas of uncertainty in environmental modelling, radiobiology and epidemiology. (U.K.)

  14. 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

    Directory of Open Access Journals (Sweden)

    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.

  15. Impact of FAB classification on predicting outcome in acute myeloid leukemia, not otherwise specified, patients undergoing allogeneic stem cell transplantation in CR1: An analysis of 1690 patients from the acute leukemia working party of EBMT.

    Science.gov (United States)

    Canaani, Jonathan; Beohou, Eric; Labopin, Myriam; Socié, Gerard; Huynh, Anne; Volin, Liisa; Cornelissen, Jan; Milpied, Noel; Gedde-Dahl, Tobias; Deconinck, Eric; Fegueux, Nathalie; Blaise, Didier; Mohty, Mohamad; Nagler, Arnon

    2017-04-01

    The French, American, and British (FAB) classification system for acute myeloid leukemia (AML) is extensively used and is incorporated into the AML, not otherwise specified (NOS) category in the 2016 WHO edition of myeloid neoplasm classification. While recent data proposes that FAB classification does not provide additional prognostic information for patients for whom NPM1 status is available, it is unknown whether FAB still retains a current prognostic role in predicting outcome of AML patients undergoing allogeneic stem cell transplantation. Using the European Society of Blood and Bone Marrow Transplantation registry we analyzed outcome of 1690 patients transplanted in CR1 to determine if FAB classification provides additional prognostic value. Multivariate analysis revealed that M6/M7 patients had decreased leukemia free survival (hazard ratio (HR) of 1.41, 95% confidence interval (CI), 1.01-1.99; P = .046) in addition to increased nonrelapse mortality (NRM) rates (HR, 1.79; 95% CI, 1.06-3.01; P = .028) compared with other FAB types. In the NPM1 wt AML, NOS cohort, FAB M6/M7 was also associated with increased NRM (HR, 2.17; 95% CI, 1.14-4.16; P = .019). Finally, in FLT3-ITD + patients, multivariate analyses revealed that specific FAB types were tightly associated with adverse outcome. In conclusion, FAB classification may predict outcome following transplantation in AML, NOS patients. © 2017 Wiley Periodicals, Inc.

  16. Self-Esteem and Academic Difficulties in Preadolescents and Adolescents Healed from Paediatric Leukaemia.

    Science.gov (United States)

    Tremolada, Marta; Taverna, Livia; Bonichini, Sabrina; Basso, Giuseppe; Pillon, Marta

    2017-05-24

    Adolescents with cancer may demonstrate problems in their self-esteem and schooling. This study aims to screen the preadolescents and adolescents more at risk in their self-esteem perception and schooling difficulties post-five years from the end of therapy. Twenty-five paediatric ex-patients healed from leukaemia were recruited at the Haematology-Oncologic Clinic (University of Padua). The mean age of the children was 13.64 years (Standard Deviation (SD)) = 3.08, range = 10-19 years), most were treated for acute lymphoblastic leukaemia (ALL) (84%) and relatively equally distributed by gender. They filled in the Multidimensional Self-Esteem Test, while parents completed a questionnaire on their child's schooling. Global self-esteem was mostly below the 50 percentile (58.5%), especially regarding interpersonal relationships (75%). An independent sample t -test showed significant mean differences on the emotionality scale ( t = 2.23; degree of freedom (df) = 24; p = 0.03) and in the bodily experience scale ( t = 3.02; df = 24; p = 0.006) with survivors of Acute Myeloid Leukaemia (AML) having lower scores. An Analysis of Variance (ANOVA ) showed significant mean differences in the bodily experience scale ( F = 12.31; df = 2, p = 0.0001) depending on the survivors' assigned risk band. The parent reports showed that 43.5% of children had difficulties at school. Childhood AML survivors with a high-risk treatment were more at risk in their self-esteem perceptions. Preventive interventions focusing on self-esteem and scholastic wellbeing are suggested in order to help their return to their normal schedules.

  17. HLA-DPβ1 Asp84-Lys69 antigen-binding signature predicts event-free survival in childhood B-cell precursor acute lymphoblastic leukaemia: results from the MRC UKALL XI childhood ALL trial.

    Science.gov (United States)

    Taylor, G M; Wade, R; Hussain, A; Thompson, P; Hann, I; Gibson, B; Eden, T; Richards, S

    2012-07-01

    We previously reported that children in the UKALL XI ALL trial with HLA-DP 1 and -DP 3 supertypes had significantly worse event-free survival (EFS) than children with other DP supertypes. As DP 1 and DP 3 share two of four key antigen-binding amino-acid polymorphisms (aspartic acid84-lysine69), we asked whether Asp84-Lys69 or Asp84 alone were independent prognostic indicators in childhood acute lymphoblastic leukemia (ALL). We analysed EFS in 798 UKALL XI patients, stratified by Asp84-Lys69 vs non-Asp84-Lys69, for a median follow-up of 12.5 years. Asp84-Lys69 was associated with a significantly worse EFS than non-Asp84-Lys69 (5-year EFS: Asp84-Lys69: 58.8% (95% CI (confidence of interval): 52.7-64.9%); non-Asp84-Lys69: 67.3% (63.4-71.2%); 2P=0.007). Post-relapse EFS was 10% less in Asp84-Lys69 than non-Asp84-Lys69 patients. EFS was significantly worse (P=0.03) and post-relapse EFS marginally worse (P=0.06) in patients with Asp84 compared with Gly84. These results suggest that Asp84-Lys69 predicted adverse EFS in the context of UKALL XI because of Asp84, and may have influenced post-relapse EFS. We speculate that this may be due to the recruitment of Asp84-Lys69-restricted regulatory T cells in the context of this regimen, leading to the re-emergence of residual disease. However, functional and molecular studies of the prognostic value of this and other HLA molecular signatures in other childhood ALL trials are needed.

  18. Leucocyte classification for leukaemia detection using image processing techniques.

    Science.gov (United States)

    Putzu, Lorenzo; Caocci, Giovanni; Di Ruberto, Cecilia

    2014-11-01

    The counting and classification of blood cells allow for the evaluation and diagnosis of a vast number of diseases. The analysis of white blood cells (WBCs) allows for the detection of acute lymphoblastic leukaemia (ALL), a blood cancer that can be fatal if left untreated. Currently, the morphological analysis of blood cells is performed manually by skilled operators. However, this method has numerous drawbacks, such as slow analysis, non-standard accuracy, and dependences on the operator's skill. Few examples of automated systems that can analyse and classify blood cells have been reported in the literature, and most of these systems are only partially developed. This paper presents a complete and fully automated method for WBC identification and classification using microscopic images. In contrast to other approaches that identify the nuclei first, which are more prominent than other components, the proposed approach isolates the whole leucocyte and then separates the nucleus and cytoplasm. This approach is necessary to analyse each cell component in detail. From each cell component, different features, such as shape, colour and texture, are extracted using a new approach for background pixel removal. This feature set was used to train different classification models in order to determine which one is most suitable for the detection of leukaemia. Using our method, 245 of 267 total leucocytes were properly identified (92% accuracy) from 33 images taken with the same camera and under the same lighting conditions. Performing this evaluation using different classification models allowed us to establish that the support vector machine with a Gaussian radial basis kernel is the most suitable model for the identification of ALL, with an accuracy of 93% and a sensitivity of 98%. Furthermore, we evaluated the goodness of our new feature set, which displayed better performance with each evaluated classification model. The proposed method permits the analysis of blood cells

  19. Impact of elevated serum glycated albumin levels on contrast-induced acute kidney injury in diabetic patients with moderate to severe renal insufficiency undergoing coronary angiography.

    Science.gov (United States)

    Ding, Feng Hua; Lu, Lin; Zhang, Rui Yan; Zhu, Tian Qi; Pu, Li Jin; Zhang, Qi; Chen, Qiu Jing; Hu, Jian; Yang, Zhen Kun; Shen, Wei Feng

    2013-07-31

    Glycated albumin (GA) has been shown to be a better indicator than glycosylated hemoglobin A1c (HbA1c) in terms of severity of renal impairment in patients with type 2 diabetes mellitus (T2DM). This study aimed to determine whether elevated serum GA levels are associated with an increased risk for contrast-induced acute kidney injury (CI-AKI) and worse clinical outcome in patients with T2DM and at least moderate renal insufficiency (RI) undergoing coronary angiography. Serum levels of fasting blood glucose (FBG), HbA1c and GA were measured in 1030 patients with T2DM and moderate to severe RI (eGFR 15-59 mL/min/1.73 m(2)). CI-AKI was defined as ≥ 25% increase in serum creatinine within 72 h after the procedure. Receiver-operating characteristic curve was constructed to assess the predictive value of GA, HbA1c and FBG for CI-AKI. Multivariable logistic regression model was developed to identify risk factors for CI-AKI, and Kaplan-Meier curve analysis was used to compare the rates of dialysis and major adverse cardiac events (MACE) during one-year follow-up. The overall rate of CI-AKI was 11.1%. GA was significantly higher in patients with CI-AKI than in those without, and correlated positively with changes of renal function after the procedure. After adjusting for age, sex, left ventricular ejection fraction, multi-vessel disease, type and volume of contrast media, FBG, and HbA1c, GA remained an independent risk factor for CI-AKI. GA ≥ 21% was associated with increased rates of dialysis and MACE during one-year follow-up in patients with or without CI-AKI. Increased GA level serves as a valuable risk factor for CI-AKI and indicates poor one-year clinical outcome in patients with T2DM and moderate to severe RI. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  20. Impact of benazepril on contrast-induced acute kidney injury for patients with mild to moderate renal insufficiency undergoing percutaneous coronary intervention.

    Science.gov (United States)

    Li, Xi-ming; Cong, Hong-liang; Li, Ting-ting; He, Li-jun; Zhou, Yu-jie

    2011-07-01

    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. 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. 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 (ΔeGFR) 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, ΔeGFR in benazepril group was slightly lower than that in the control group, but the difference was not statistically significant. Benazepril has a protective effect on mild to moderate impairment of renal function

  1. Atypical chronic myeloid leukaemia: A case of an orphan disease-A multicenter report by the Polish Adult Leukemia Group.

    Science.gov (United States)

    Drozd-Sokołowska, Joanna; Mądry, Krzysztof; Waszczuk-Gajda, Anna; Biecek, Przemysław; Szwedyk, Paweł; Budziszewska, Katarzyna; Raźny, Magdalena; Dutka, Magdalena; Obara, Agata; Wasilewska, Ewa; Lewandowski, Krzysztof; Piekarska, Agnieszka; Bober, Grażyna; Krzemień, Helena; Stella-Hołowiecka, Beata; Kapelko-Słowik, Katarzyna; Sawicki, Waldemar; Paszkowska-Kowalewska, Małgorzata; Machowicz, Rafał; Dwilewicz-Trojaczek, Jadwiga

    2018-03-07

    Atypical chronic myeloid leukaemia (aCML) belongs to myelodysplastic/myeloproliferative neoplasms. Because of its rarity and changing diagnostic criteria throughout subsequent classifications, data on aCML are very scarce. Therefore, we at the Polish Adult Leukemia Group performed a nationwide survey on aCML. Eleven biggest Polish centres participated in the study. Altogether, 45 patients were reported, among whom only 18 patients (40%) fulfilled diagnostic criteria. Among misdiagnosed patients, myelodysplastic/myeloproliferative syndrome unclassifiable and chronic myelomonocytic leukaemia were the most frequent diagnoses. Thirteen patients were male, median age 64.6 years (range 40.4-80.9). The median parameters at diagnosis were as follows: white blood cell count 97 × 10 9 /L (23.8-342) with immature progenitors amounting at 27.5% (12-72), haemoglobin 8.6 g/dL (3.9-14.9), and platelet count 66 × 10 9 /L (34-833). Cytoreductive treatment was used in all patients, and 2 patients underwent allogeneic hematopoietic stem cell transplantation. The median overall survival was 14.1 months (95% CI, 7.2), with median acute myeloid leukaemia-free survival of 13.3 months (95% CI, 3.6-22.6). Cumulative incidence of acute myeloid leukaemia transformation after 1 year in aCML group was 12.5% (95% CI, 0%-29.6%). To conclude, aCML harbours a poor prognosis. Treatment options are limited, with allogeneic hematopoietic stem cell transplantation being the only curative method at present, although only a minority of patients are transplant eligible. Educational measures are needed to improve the quality of diagnoses. Copyright © 2018 John Wiley & Sons, Ltd.

  2. Childhood leukaemia around Canadian nuclear facilities. Phase 1

    International Nuclear Information System (INIS)

    Clarke, E.A.; McLaughlin, J.; Anderson, T.W.

    1989-05-01

    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

  3. Clinicopathological features of transient myeloproliferative syndrome and congenital leukaemia

    International Nuclear Information System (INIS)

    Sajid, N.; Ahmed, N.; Mahmood, S.

    2010-01-01

    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)

  4. Childhood leukaemia and socioeconomic status: What is the evidence?

    International Nuclear Information System (INIS)

    Adam, M.; Rebholz, C. E.; Egger, M.; Zwahlen, M.; Kuehni, C. E.

    2008-01-01

    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)

  5. Leukaemia clusters around Sellafield and Dounreay. Dosimetry and epidemiology

    International Nuclear Information System (INIS)

    Wakeford, R.

    2003-01-01

    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.) [de

  6. Minimal residual disease in chronic lymphocytic leukaemia.

    Science.gov (United States)

    García Vela, José Antonio; García Marco, José Antonio

    2018-02-23

    Minimal residual disease (MRD) assessment is an important endpoint in the treatment of chronic lymphocytic leukaemia (CLL). It is highly predictive of prolonged progression-free survival (PFS) and overall survival and could be considered a surrogate for PFS in the context of chemoimmunotherapy based treatment. Evaluation of MRD level by flow cytometry or molecular techniques in the era of the new BCR and Bcl-2 targeted inhibitors could identify the most cost-effective and durable treatment sequencing. A therapeutic approach guided by the level of MRD might also determine which patients would benefit from an early stop or consolidation therapy. In this review, we discuss the different MRD methods of analysis, which source of tumour samples must be analysed, the future role of the detection of circulating tumour DNA, and the potential role of MRD negativity in clinical practice in the modern era of CLL therapy. Copyright © 2017 Elsevier España, S.L.U. All rights reserved.

  7. Endoplasmic reticulum calcium transport ATPase expression during differentiation of colon cancer and leukaemia cells

    International Nuclear Information System (INIS)

    Papp, Bela; Brouland, Jean-Philippe; Gelebart, Pascal; Kovacs, Tuende; Chomienne, Christine

    2004-01-01

    The calcium homeostasis of the endoplasmic reticulum (ER) is connected to a multitude of cell functions involved in intracellular signal transduction, control of proliferation, programmed cell death, or the synthesis of mature proteins. Calcium is accumulated in the ER by various biochemically distinct sarco/endoplasmic reticulum calcium transport ATPase isoenzymes (SERCA isoforms). Experimental data indicate that the SERCA composition of some carcinoma and leukaemia cell types undergoes significant changes during differentiation, and that this is accompanied by modifications of SERCA-dependent calcium accumulation in the ER. Because ER calcium homeostasis can also influence cell differentiation, we propose that the modulation of the expression of various SERCA isoforms, and in particular, the induction of the expression of SERCA3-type proteins, is an integral part of the differentiation program of some cancer and leukaemia cell types. The SERCA content of the ER may constitute a new parameter by which the calcium homeostatic characteristics of the organelle are adjusted. The cross-talk between ER calcium homeostasis and cell differentiation may have some implications for the better understanding of the signalling defects involved in the acquisition and maintenance of the malignant phenotype

  8. [Relapse of acute promyelocytic leukemia in the central nervous system revealed by isolated dementia].

    Science.gov (United States)

    Colin, O; Julian, A; Puyade, M; Bouyer, S; Meurin, E; Blondeau, S; Houeto, J L; Neau, J P

    2016-12-01

    Approximately 1.5% of dementia is due to curable aetiology. We report an isolated dementia syndrome due to a meningeal relapse of acute promyelocytic leukaemia with favourable outcome after appropriate treatment. A 72-year-old woman, in remission of an acute promyelocytic leukaemia, presented a loss of autonomy for several months due to corticosubcortical dementia. Lumbar puncture showed blast cells indicating meningeal relapse of leukaemia. Intrathecal chemotherapy and arsenic trioxide obtained biological and molecular remission as well as restoration of normal cognitive functions. In patients with hematologic past history such as acute promyelocytic leukaemia, an isolated cognitive impairment should alert physicians to search for an isolated neuromeningeal relapse. Copyright © 2016 Société nationale française de médecine interne (SNFMI). Published by Elsevier SAS. All rights reserved.

  9. Proteomic profile of acute myeloid leukaemia: A review update ...

    African Journals Online (AJOL)

    Tropical Journal of Pharmaceutical Research ... This review draws attention to the progress and advancements in cancer proteomics technology with the aim of simplifying the understanding of the mechanisms underlying the disease and to contribute to detection of biomarkers in addition to the development of novel ...

  10. Cytoplasmic nucleophosmin (cNPM) in acute myeloid leukaemia ...

    African Journals Online (AJOL)

    Amani H. Kazem

    2011-08-26

    Aug 26, 2011 ... cytoplasmic positivity for NPM was significantly correlated with increased survival and better out- come after cycles of chemotherapy. .... Statistical Package for Social Science (SPSS) version 17 format and data explore was carried out. ..... ACT cytogenetics laboratory manual. The Association of. Cytogenetic ...

  11. The nutritional management of a patient with acute myeloid leukaemia

    African Journals Online (AJOL)

    The risk of malnutrition is compounded further when treatment is initiated. A micronutrient deficiency is possible in most cancer patients who consume. 10 days. Vomiting and diarrhoea further contribute to the loss of micronutrients. Adequate nutrition intervention and care can ...

  12. an unusual presentation of acute lymphoblastic leukaemia with peri ...

    African Journals Online (AJOL)

    2013-06-11

    Jun 11, 2013 ... history and progression was later reported by Chia et al in 1973, (12). In this case we have presented, peri-cardial effusion did not reoccur most likely because of prednisone which was incorporated in the initial treatment after she presented with tamponade. In conclusion, we report a very unusual case of.

  13. Childhood vaccinations and risk of acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Søegaard, Signe Holst; Rostgaard, Klaus; Schmiegelow, Kjeld

    2017-01-01

    ) diphtheria, tetanus and inactivated polio (HR, 1.14; 95% CI, 0.42-3.13). Analyses conducted according to ALL subtypes defined by immunopheno- and karyotypes showed no association with childhood vaccination.Conclusions: This nationwide cohort study provides no support of the proposed protective effect...

  14. Antioxidant Levels of Acute Leukaemia Patients in Nigeria

    African Journals Online (AJOL)

    ABSTRACT. The incorporation of nutritional screening and comprehensive assessments of oxidative stress is increasingly recognised as imperative in the development of standards for quality care in oncology. This study evaluated the levels of nitric oxide (NO), some essential trace metals (Zn, Cu, Fe, and Se), superoxide ...

  15. Application of the pMHC Array to Characterise Tumour Antigen Specific T Cell Populations in Leukaemia Patients at Disease Diagnosis.

    Directory of Open Access Journals (Sweden)

    Suzanne E Brooks

    Full Text Available Immunotherapy treatments for cancer are becoming increasingly successful, however to further improve our understanding of the T-cell recognition involved in effective responses and to encourage moves towards the development of personalised treatments for leukaemia immunotherapy, precise antigenic targets in individual patients have been identified. Cellular arrays using peptide-MHC (pMHC tetramers allow the simultaneous detection of different antigen specific T-cell populations naturally circulating in patients and normal donors. We have developed the pMHC array to detect CD8+ T-cell populations in leukaemia patients that recognise epitopes within viral antigens (cytomegalovirus (CMV and influenza (Flu and leukaemia antigens (including Per Arnt Sim domain 1 (PASD1, MelanA, Wilms' Tumour (WT1 and tyrosinase. We show that the pMHC array is at least as sensitive as flow cytometry and has the potential to rapidly identify more than 40 specific T-cell populations in a small sample of T-cells (0.8-1.4 x 10(6. Fourteen of the twenty-six acute myeloid leukaemia (AML patients analysed had T cells that recognised tumour antigen epitopes, and eight of these recognised PASD1 epitopes. Other tumour epitopes recognised were MelanA (n = 3, tyrosinase (n = 3 and WT1(126-134 (n = 1. One of the seven acute lymphocytic leukaemia (ALL patients analysed had T cells that recognised the MUC1(950-958 epitope. In the future the pMHC array may be used provide point of care T-cell analyses, predict patient response to conventional therapy and direct personalised immunotherapy for patients.

  16. Deciphering KRAS and NRAS mutated clone dynamics in MLL-AF4 paediatric leukaemia by ultra deep sequencing analysis.

    Science.gov (United States)

    Trentin, Luca; Bresolin, Silvia; Giarin, Emanuela; Bardini, Michela; Serafin, Valentina; Accordi, Benedetta; Fais, Franco; Tenca, Claudya; De Lorenzo, Paola; Valsecchi, Maria Grazia; Cazzaniga, Giovanni; Kronnie, Geertruy Te; Basso, Giuseppe

    2016-10-04

    To induce and sustain the leukaemogenic process, MLL-AF4+ leukaemia seems to require very few genetic alterations in addition to the fusion gene itself. Studies of infant and paediatric patients with MLL-AF4+ B cell precursor acute lymphoblastic leukaemia (BCP-ALL) have reported mutations in KRAS and NRAS with incidences ranging from 25 to 50%. Whereas previous studies employed Sanger sequencing, here we used next generation amplicon deep sequencing for in depth evaluation of RAS mutations in 36 paediatric patients at diagnosis of MLL-AF4+ leukaemia. RAS mutations including those in small sub-clones were detected in 63.9% of patients. Furthermore, the mutational analysis of 17 paired samples at diagnosis and relapse revealed complex RAS clone dynamics and showed that the mutated clones present at relapse were almost all originated from clones that were already detectable at diagnosis and survived to the initial therapy. Finally, we showed that mutated patients were indeed characterized by a RAS related signature at both transcriptional and protein levels and that the targeting of the RAS pathway could be of beneficial for treatment of MLL-AF4+ BCP-ALL clones carrying somatic RAS mutations.

  17. Childhood leukaemia around Canadian nuclear facilities. Phase 2

    International Nuclear Information System (INIS)

    Clarke, E.A.; McLaughlin, J.; Anderson, T.W.

    1991-06-01

    Prompted by findings of increased occurrence of childhood leukaemia in the vicinity of some nuclear facilities in the United Kingdom, this study aimed to investigate whether the frequency of leukaemia among children born to mothers living near nuclear facilities in Ontario differed from the provincial average. The Ontario Cancer Registry was used to identify 1894 children aged 0 to 14 years who died from leukaemia between 1950 and 1987, and 1814 children who were diagnosed with leukaemia between 1964 and 1986. Residence at birth and death was obtained from birth and death certificates. Analyses were performed separately for nuclear research and development facilities; uranium mining, milling and refining facilities; and, nuclear generating stations; and for areas within the same county as the facility and 'nearby' - within a 25-km radius of the facility. Risk estimates were calculated as the ratio of the observed (O) number of events over the expected (E) number. In the vicinity of nuclear research and development facilities the rate of leukaemia was less than expected and within the bound of chance variation. In the areas around the uranium mining, milling and refining facilities and nuclear power plants leukaemia occurred slightly more frequently than expected, but due to small frequencies these differences may have arisen due to chance. Large differences between observed and expected rates were not detected around any of the Ontario facilities. This study was large enough to detect excess risks of the magnitude reported in the United Kingdom, but it was not large enough to discriminate between the observed relative risks and a chance finding. Levels of leukaemia detected near nuclear generating stations indicate the need for further investigation. (20 tabs., 15 figs., 32 refs.)

  18. Translating microarray data for diagnostic testing in childhood leukaemia

    International Nuclear Information System (INIS)

    Hoffmann, Katrin; Firth, Martin J; Beesley, Alex H; Klerk, Nicholas H de; Kees, Ursula R

    2006-01-01

    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. The MI SYNTAX score for risk stratification in patients undergoing primary percutaneous coronary intervention for treatment of acute myocardial infarction: A substudy of the COMFORTABLE AMI trial

    NARCIS (Netherlands)

    Magro, Michael; Räber, Lorenz; Heg, Dik; Taniwaki, Masanori; Kelbaek, Henning; Ostojic, Miodrag C.; Baumbach, Andreas; Tüller, David; von Birgelen, Clemens; Roffi, Marco; Pedrazzini, Giovanni; Kornowski, Ran; Weber, Klaus; Meier, Bernard; Lüscher, Thomas F.; Serruys, Patrick W.; Jüni, Peter; Windecker, Stephan

    2014-01-01

    Background To investigate the performance of the MI Sxscore in a multicentre randomised trial of patients undergoing primary percutaneous coronary intervention (PPCI). Methods and results The MI Sxscore was prospectively determined among 1132 STEMI patients enrolled into the COMFORTABLE AMI trial,

  20. Potential additional effect of omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in grade III obese patients undergoing laparoscopic Roux-en-Y gastric bypass: a randomized trial.

    Science.gov (United States)

    Herrera, Miguel F; Pantoja, Juan Pablo; Velázquez-Fernández, David; Cabiedes, Javier; Aguilar-Salinas, Carlos; García-García, Eduardo; Rivas, Alfredo; Villeda, Christian; Hernández-Ramírez, Diego F; Dávila, Andrea; Zaraín, Aarón

    2010-07-01

    To assess the additional effect of sudden visceral fat reduction by omentectomy on metabolic syndrome, acute-phase reactants, and inflammatory mediators in patients with grade III obesity (G-III O) undergoing laparoscopic Roux-en-Y gastric bypass (LRYGB). Twenty-two patients were randomized into two groups, LRYGB alone or with omentectomy. Levels of interleukin-6, C-reactive protein, tumor necrosis factor-alpha, leptin, adiponectin, glucose, total cholesterol, HDL cholesterol, LDL cholesterol, and triglycerides, as well as clinical characteristics, were evaluated before surgery and at 1, 3, 6, and 12 months after surgery. Results were compared between groups. Baseline characteristics were comparable in both groups. Mean operative time was significantly higher in the group of patients who underwent omentectomy (P acute-phase reactants, and inflammatory mediators. Omentectomy does not have an ancillary short-term significant impact on the components of metabolic syndrome and does not induce important changes in the inflammatory mediators in patients undergoing LRYGB. Operative time is more prolonged when omentectomy is performed.

  1. Metaphyseal impaction fractures in acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Manson, D.; Cockshott, W.P.; Martin, R.F.

    1989-01-01

    Patients with acute lymphatic leukaemia frequently are osteoporotic. A small subset of these develop disabling metaphyseal transverse fractures, usually bilateral and in the lower limb. These impaction fractures have a characteristic appearance and develop in recently laid down bone. They may develop ab initio of during therapy, Magnesium deficiency is found in these patients.

  2. The risk of childhood leukaemia near nuclear establishments

    International Nuclear Information System (INIS)

    Stather, J.W.; Clarke, R.H.; Duncan, K.P.

    1988-01-01

    Childhood leukaemia has been reported to be increased in communities living near a number of nuclear sites in the United Kingdom. The National Radiological Protection Board has, over the last three and a half years, published the results of a series of studies giving radiation doses and risks calculated for some of these populations. The studies have all indicated that it is most unlikely that radiation doses arising from releases of radioactive materials into the environment could have contributed to any increase in the leukaemia incidence in local communities. In the absence of any other obvious causative agent, however, there remains some concern that the radiation doses and risks of leukaemia have been underestimated. This report, therefore, summarises the methods used in the analyses by the Board, examines possible sources of uncertainty in the calculations, and considers the extent to which more information is required. (author)

  3. Age- and sex-based resource utilisation and costs in patients with acute chest pain undergoing cardiac CT angiography. Pooled evidence from ROMICAT II and ACRIN-PA trials

    International Nuclear Information System (INIS)

    Bamberg, Fabian; Hoffmann, Udo; Mayrhofer, Thomas; Ferencik, Maros; Bittner, Daniel O.; Hallett, Travis R.; Janjua, Sumbal; Schlett, Christopher L.; Nagurney, John T.; Udelson, James E.; Truong, Quynh A.; Woodard, Pamela K.; Hollander, Judd E.; Litt, Harold

    2018-01-01

    To determine resource utilisation according to age and gender-specific subgroups in two large randomized diagnostic trials. We pooled patient-specific data from ACRIN-PA 4005 and ROMICAT II that enrolled subjects with acute chest pain at 14 US sites. Subjects were randomized between a standard work-up and a pathway utilizing cardiac computed tomography angiography (CCTA) and followed for the occurrence of acute coronary syndrome (ACS) and resource utilisation during index hospitalisation and 1-month follow-up. Study endpoints included diagnostic accuracy of CCTA for the detection of ACS as well as resource utilisation. Among 1240 patients who underwent CCTA, negative predictive value of CCTA to rule out ACS remained very high (≥99.4%). The proportion of patients undergoing additional diagnostic testing and cost increased with age for both sexes (p < 0.001), and was higher in men as compared to women older than 60 years (43.1% vs. 23.4% and $4559 ± 3382 vs. $3179 ± 2562, p < 0.01; respectively). Cost to rule out ACS was higher in men (p < 0.001) and significantly higher for patients older than 60 years ($2860-5935 in men, p < 0.001). CCTA strategy in patients with acute chest pain results in varying resource utilisation according to age and gender-specific subgroups, mandating improved selection for advanced imaging. (orig.)

  4. The risk of childhood leukaemia near nuclear establishments

    International Nuclear Information System (INIS)

    Fry, F.A.

    1997-01-01

    The author concentrates on an epidemiological investigation on the increased incidence of leukaemia in young people of age 0∼24 years old in the years of 1963∼1992 in Seascale, a Village near the BNFL reprocessing plant at Sellafield on the north-west coast of England. A comparison of this incidence is made with that revealed in regions of other similar nuclear establishments. It has been concluded that the increased incidence of leukaemia in young people in Seascale can not be imputed to any single factor, but interaction between different factor cannot be ruled out

  5. Parental reports of behavioural outcome among paediatric leukaemia survivors in Malaysia: a single institution experience.

    Science.gov (United States)

    Hamidah, Alias; Sham Marina, Mohd; Tamil, Azmi M; Loh, C-Khai; Zarina, Latiff A; Jamal, Rahman; Tuti Iryani, Mohd Daud; Ratnam, Vijayalakshmi C

    2014-10-01

    To determine the behavioural impact of chemotherapy in survivors of acute lymphoblastic leukaemia (ALL) treated with chemotherapy only and to identify treatment-related or sociodemography-related factors that might be associated with behavioural outcome. We examined 57 survivors of childhood ALL, who were off treatment for at least 2 years and were in remission, aged 4-18 years, and 221 unrelated healthy controls. The Child Behaviour Checklist (CBCL) parent report was used either in English or in Bahasa Malaysia (the national language of Malaysia) to assess the behavioural outcome. Childhood ALL survivors had significantly higher scores on externalising behaviour on the CBCL parent report than did controls. Higher problem scores were found in ALL survivors with single parents on 'total problems' (P = 0.03) and subscales 'withdrawn' (P = 0.03), 'social problems' (P design the most appropriate remedy for problem behaviours detected in this multi-ethnic population. © 2014 John Wiley & Sons Ltd.

  6. TREATMENT OF PRIMARY PLASMA CELL LEUKAEMIA

    Directory of Open Access Journals (Sweden)

    Peter Černelč

    2003-04-01

    Full Text Available Background. The author describes long-term survival in 3 patients with primary plasma cell leukaemia (PL after different therapeutic regimen and maintenance treatment with interferon alpha (INF.Patients and treatment. In a 52-year-old male patient, a partial remission of PL was achieved after 6 months of treatment with melphalan and prednisone. The patient did not consent to stem cell transplantation (SCT. An 86-year-old female patient with PL achieved a complete remission after 6 months of treatment with vincristine, doxorubicin and dexamethasone. A 31-year-old male patient experienced a complete remission of PL after 6 months of treatment with cyclophosphamide, vincristine, doxorubicin, methilprednisone, followed by autologous SCT. All three patients were placed on maintenance therapy with INF-2b (Intron A 3 × 106 IU given subcutaneously on two days per week. In the 52-year-old man, the remission lasted 9 months and in the woman 23 months, whereupon they developed a relapse with signs of disseminated plasmacytoma. In both patients the former chemotherapy was applied again, resulting in a slight improvement. The man died 37 months and the woman 43 months after the diagnosis of PL, while the youngest patient has been in complete remission for 82 months.Conclusions. Long remission achieved in our patients confirmed the favourable effect of INF in terms of prolongation of the remission duration in this patients. The effect of maintenance treatment with INF is usually directly dependent on the degree of remission induced by different therapeutic regimen.

  7. Differentiating intraparenchymal hemorrhage from contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients undergoing endovascular treatment

    International Nuclear Information System (INIS)

    Payabvash, Seyedmehdi; Qureshi, Mushtaq H.; Khan, Shayaan M.; Khan, Mahnoor; Majidi, Shahram; Pawar, Swaroop; Qureshi, Adnan I.

    2014-01-01

    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.)

  8. Differentiating intraparenchymal hemorrhage from contrast extravasation on post-procedural noncontrast CT scan in acute ischemic stroke patients undergoing endovascular treatment

    Energy Technology Data Exchange (ETDEWEB)

    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.)

  9. Increased mortality associated with low use of clopidogrel in patients with heart failure and acute myocardial infarction not undergoing percutaneous coronary intervention

    DEFF Research Database (Denmark)

    Bonde, Lisbeth; Sorensen, Rikke; Fosbøl, Emil Loldrup

    2010-01-01

    OBJECTIVES: We studied the association of clopidogrel with mortality in acute myocardial infarction (AMI) patients with heart failure (HF) not receiving percutaneous coronary intervention (PCI). BACKGROUND: Use of clopidogrel after AMI is low in patients with HF, despite the fact that clopidogrel......-up of 1.50 years (SD = 1.2), 709 (28.1%) and 812 (32.2%) deaths occurred in patients receiving and not receiving clopidogrel treatment, respectively (p = 0.002). The corresponding numbers for patients without HF (n = 6,092), with a mean follow-up of 2.05 years (SD = 1.3), were 285 (9.4%) and 294 (9...

  10. Study of the possible medical and medication explanatory factors of angiographic outcomes in patients with acute ST elevation myocardial infarction undergoing primary percutaneous intervention

    Directory of Open Access Journals (Sweden)

    Azadeh

    2014-01-01

    Full Text Available Background: Myocardial blush grade (MBG, thrombolysis in myocardial infarction (TIMI and corrected TIMI frame count (cT F C are indices of successful angiographic reperfusion. This study sought to determine the predictors of angiographically successful reperfusion including demographic, clinical and angiographic factors in patients with ST elevation myocardial infarction (STEMI undergoing primary percutaneous coronary intervention (pPCI. Materials and Methods: A cross-sectional study of patients with a confirmed diagnosis of STEMI undergoing pPCI was designed. Eligible patients referring to a university heart center were enrolled in the study from March 2012 to December 2012. Successful epicardial reperfusion was defned as TIMI flow grade 3 or cTFC<= 28 frames and successful myocardial reperfusion as MBG 2 or 3. Results: The study population consisted of 100 patients, including 74 males and 26 females, with mean ± standard deviation age of 58.27 ± 11.60 years. Achieving open microvasculature (MBG 2/3 was positively associated with a history of nitrate intake (P = 0.03 and history of calcium channel blocker (CCB intake (P = 0.005. Hyperglycemia was inversely associated with achieving a final cTFC ≤ 28 frames (r = −0.32, P = 0.001. Conclusions: Our findings suggest that patients with a history of nitrate and CCB intake had a higher likelihood of successful PCI. In addition, patients with a higher blood glucose level on admission may have a reduced rate of reperfusion success. Future studies with a larger sample size are recommended to investigate the significant relationships observed in this study.

  11. Environmental factors and leukaemia risks of children: an overview

    International Nuclear Information System (INIS)

    Schuez, Joachim

    2008-01-01

    Leukaemia is the most common malignancy in childhood, with an incidence rate in Germany of 5.5 per 100,000 children aged 0 to 14 years per year. Overall, epidemiological studies suggest a rather minor role of environmental factors in the development of childhood leukaemia. Ionising radiation is the only established risk factor; however, it is currently unclear at which doses effects occur. Low doses from terrestrial exposures or related to living close to a nuclear power plant show weak associations in recent epidemiological studies, but the findings can at present not be explained with mechanistic models from radiation biology. The consistent association observed in epidemiological studies between extremely low-frequency magnetic fields and childhood leukaemia risk also lacks a good explanation and it is still not known whether this observation displays an artefact or a causal link. Some pesticides appear to be carcinogenic in experiments, but the results from epidemiological studies are inconsistent. No substantial risk appears to be related to air pollution from road traffic. Recent research focused on working hypotheses related to patterns of infections, in particular that an isolation from infectious stimulation in infancy leads to an immature immune system reacting inappropriately to later common infections. While children being at day care at an early age appear to have a reduced risk of childhood leukaemia, more work needs to be done to clearly identify the agents involved in a putative mechanism. (orig.)

  12. Complications of lumbar puncture in a child treated for leukaemia

    Energy Technology Data Exchange (ETDEWEB)

    Staebler, Melanie; Delpierre, Isabelle; Damry, Nash; Christophe, Catherine [Children' s University Hospital Queen Fabiola, Department of Medical Imaging, Brussels (Belgium); Azzi, Nadira [Children' s University Hospital Queen Fabiola, Haematology-Oncology Unit, Brussels (Belgium); Sekhara, Tayeb [Children' s University Hospital Queen Fabiola, Department of Neurology, Brussels (Belgium)

    2005-11-01

    Lumbar puncture may lead to neurological complications. These include intracranial hypotension, cervical epidural haematomas, and cranial and lumbar subdural haematomas. MRI is the modality of choice to diagnose these complications. This report documents MRI findings of such complications in a child treated for leukaemia. (orig.)

  13. Priapism as an initial presentation of chronic myeloid leukaemia ...

    African Journals Online (AJOL)

    ... the idiopathic types are believed to be associated with an initial prolonged sexual stimulation. Two case reports illustrating the possibility of such cases being the first presentation of myeloproliferative disorder are thus presented. Keywords: Chronic myeloid leukaemia, Priapism, Presentation Sahel Medical Journal Vol.

  14. Oxidative Stress Responses and NRF2 in Human Leukaemia

    Directory of Open Access Journals (Sweden)

    Amina Abdul-Aziz

    2015-01-01

    Full Text Available 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 intracellular ROS levels is required for cancer cell function, growth, and survival. Nuclear factor (erythroid-derived 2-like 2 (NRF2 transcription factor plays a dual role in cancer. Primarily, NRF2 is a transcription factor functioning to protect nonmalignant cells from malignant transformation and oxidative stress through transcriptional activation of detoxifying and antioxidant enzymes. However, once malignant transformation has occurred within a cell, NRF2 functions to protect the tumour from oxidative stress and chemotherapy-induced cytotoxicity. Moreover, inhibition of the NRF2 oxidative stress pathway in leukaemia cells renders them more sensitive to cytotoxic chemotherapy. Our improved understanding of NRF2 biology in human leukaemia may permit mechanisms by which we could potentially improve future cancer therapies. This review highlights the mechanisms by which leukaemic cells exploit the NRF2/ROS response to promote their growth and survival.

  15. Defective monocyte function in Legionnaires' disease complicating hairy cell leukaemia

    DEFF Research Database (Denmark)

    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 leukaem...

  16. Tuberculosis complicating imatinib treatment for chronic myeloid leukaemia

    NARCIS (Netherlands)

    Daniels, J. M. A.; Vonk-Noordegraaf, A.; Janssen, J. J. W. M.; Postmus, P. E.; van Altena, R.

    Although imatinib is not considered a predisposing factor for tuberculosis (TB), the present case report describes three patients in whom imatinib treatment for chronic myeloid leukaemia was complicated by TB. This raises the question of whether imatinib increases susceptibility to TB. There are

  17. Complications of lumbar puncture in a child treated for leukaemia

    International Nuclear Information System (INIS)

    Staebler, Melanie; Delpierre, Isabelle; Damry, Nash; Christophe, Catherine; Azzi, Nadira; Sekhara, Tayeb

    2005-01-01

    Lumbar puncture may lead to neurological complications. These include intracranial hypotension, cervical epidural haematomas, and cranial and lumbar subdural haematomas. MRI is the modality of choice to diagnose these complications. This report documents MRI findings of such complications in a child treated for leukaemia. (orig.)

  18. Hypothyroidism and hyponatremia: data from a series of patients with iatrogenic acute hypothyroidism undergoing radioactive iodine therapy after total thyroidectomy for thyroid cancer.

    Science.gov (United States)

    Vannucci, L; Parenti, G; Simontacchi, G; Rastrelli, G; Giuliani, C; Ognibene, A; Peri, A

    2017-01-01

    The aim of the present study was to evaluate the role of hypothyroidism as a cause of hyponatremia in a clinical model of iatrogenic acute hypothyroidism due to thyroid hormone withdrawal prior to ablative radioactive iodine (RAI) therapy after total thyroidectomy. The study group consisted of 101 differentiated thyroid cancer (DTC) patients (77 women and 24 men). Plasma concentration of thyroid-stimulating hormone ([TSH]) and sodium ([Na + ]) was evaluated before total thyroidectomy (pre[TSH] and pre[Na + ]) and on the day of RAI therapy (post[TSH] and post[Na + ]). The frequency of hypothyroidism-associated hyponatremia was 4 % (4/101). Pre[Na + ] was significantly higher than post[Na + ] (140.7 ± 1.6 vs 138.7 ± 2.3 mEq/L, p = 0.012). Moreover, a linear correlation was identified between pre[Na + ] and post[Na + ]. Iatrogenic acute hypothyroidism-related hyponatremia is uncommon. However, because of the significant reduction of [Na + ] in the transition from euthyroidism to iatrogenic hypothyroidism, the value of pre[Na + ] should be viewed as a parameter to be considered. Since it acts as an independent risk factor for the development of hyponatremia, patients with a pre[Na + ] close to the lower limit of normal range may deserve a closer monitoring of [Na + ].

  19. Chronic Subdural Hematoma development in Accelerated phase of Chronic Myeloid Leukaemia presenting with seizure and rapid progression course with fatal outcome

    Directory of Open Access Journals (Sweden)

    Raheja Amol

    2015-06-01

    Full Text Available Occurrence of chronic subdural hematoma (CSDH in leukemia is rare, and most reported cases occurred in relation with acute myeloid leukaemia; however, occurrence is extremely rare in accelerated phase of chronic myelogenous leukaemia (CML. Seizure as presentation of SDH development in CML cases is not reported in literature. Authors report an elderly male, who was diagnosed as CML, accelerated phase of developing SDH. Initially presented to local physician with seizure; urgent CT scan head was advised, but ignored and sensorium rapidly worsened over next day and reported to our emergency department in deeply comatose state, where imaging revealed chronic subdural hematoma with hypoxic brain injury with fatal outcome. Seizure, progressive worsening of headache, vomiting and papilloedema are harbinger of intracranial space occupying lesion and requires CT head in emergency medical department for exclusion, who are receiving treatment of haematological malignancy

  20. Epigenetic regulation of microRNA-128a expression contributes to the apoptosis-resistance of human T-cell leukaemia jurkat cells by modulating expression of fas-associated protein with death domain (FADD).

    Science.gov (United States)

    Yamada, Nami; Noguchi, Shunsuke; Kumazaki, Minami; Shinohara, Haruka; Miki, Kohei; Naoe, Tomoki; Akao, Yukihiro

    2014-03-01

    Increased expression of miR-128a is often observed in acute lymphoblastic leukaemia (ALL) compared with its expression in acute myeloid leukaemia (AML). The objective of this study was to investigate the role of miR-128a, especially that in the Fas-signalling pathway, in T-cell leukaemia cells. The role of miR-128a in Fas-mediated apoptosis was examined by using Fas-activating antibody (CH-11)-susceptible Jurkat cells and -resistant Jurkat/R cells. Whereas ectopic expression of miR-128a conferred Fas-resistance on Jurkat cells by directly targeting Fas-associated protein with death domain (FADD), antagonizing miR-128a expression sensitized Jurkat/R cells to the Fas-mediated apoptosis through derepression of FADD expression. Myeloid leukaemia HL60 and K562 cells were also CH-11-resistant, sharing a similar resistant mechanism with Jurkat/R cells. Furthermore, CH-11 induced demethylation of the promoter region of miR-128a with resultant up-regulation of miR-128a expression in Jurkat/R cells, which was shown to be a mechanism for the resistance ofJurkat/R cells to Fas-mediated apoptosis. Our results indicate that the induction of miR-128a expression by DNA demethylation is a novel mechanism of resistance to Fas-mediated apoptosis.

  1. Post-procedural hemodiafiltration in acute coronary syndrome patients with associated renal and cardiac dysfunction undergoing urgent and emergency coronary angiography.

    Science.gov (United States)

    Marenzi, Giancarlo; Mazzotta, Gianfranco; Londrino, Francesco; Gistri, Roberto; Moltrasio, Marco; Cabiati, Angelo; Assanelli, Emilio; Veglia, Fabrizio; Rombolà, Giuseppe

    2015-02-15

    We investigated the use of a 3-hr treatment with hemodiafiltration, initiated soon after emergency or urgent coronary angiography in acute coronary syndrome (ACS) patients with associated severe renal and cardiac dysfunction. Patients with ACS and severe combined renal and cardiac dysfunction have a particularly high mortality risk. In them, the ideal strategy to both optimize treatment of coronary disease and minimize renal injury risk is currently unknown. This was an interventional study. ACS patients (STEMI and NSTEMI) with associated severe renal (eGFR ≤30 ml/min/1.73 m(2) ) and cardiac (LVEF ≤40%) dysfunction, admitted at La Spezia Hospital renal replacement therapy during hospitalization (7% vs. 27%; P = 0.04). Our pilot study suggests that, in ACS patients with severe renal and cardiac insufficiency, treatment with an aggressive prophylactic hemodiafiltration session after urgent or emergency coronary angiography seems to be associated with a relevant improvement in survival. © 2014 Wiley Periodicals, Inc.

  2. Development and validation of an acute kidney injury risk index for patients undergoing general surgery: results from a national data set.

    Science.gov (United States)

    Kheterpal, Sachin; Tremper, Kevin K; Heung, Michael; Rosenberg, Andrew L; Englesbe, Michael; Shanks, Amy M; Campbell, Darrell A

    2009-03-01

    The authors sought to identify the incidence, risk factors, and mortality impact of acute kidney injury (AKI) after general surgery using a large and representative national clinical data set. The 2005-2006 American College of Surgeons-National Surgical Quality Improvement Program participant use data file is a compilation of outcome data from general surgery procedures performed in 121 US medical centers. The primary outcome was AKI within 30 days, defined as an increase in serum creatinine of at least 2 mg/dl or acute renal failure necessitating dialysis. A variety of patient comorbidities and operative characteristics were evaluated as possible predictors of AKI. A logistic regression full model fit was used to create an AKI model and risk index. Thirty-day mortality among patients with and without AKI was compared. Of 152,244 operations reviewed, 75,952 met the inclusion criteria, and 762 (1.0%) were complicated by AKI. The authors identified 11 independent preoperative predictors: age 56 yr or older, male sex, emergency surgery, intraperitoneal surgery, diabetes mellitus necessitating oral therapy, diabetes mellitus necessitating insulin therapy, active congestive heart failure, ascites, hypertension, mild preoperative renal insufficiency, and moderate preoperative renal insufficiency. The c statistic for a simplified risk index was 0.80 in the derivation and validation cohorts. Class V patients (six or more risk factors) had a 9% incidence of AKI. Overall, patients experiencing AKI had an eightfold increase in 30-day mortality. Approximately 1% of general surgery cases are complicated by AKI. The authors have developed a robust risk index based on easily identified preoperative comorbidities and patient characteristics.

  3. Phosphate is a potential biomarker of disease severity and predicts adverse outcomes in acute kidney injury patients undergoing continuous renal replacement therapy.

    Directory of Open Access Journals (Sweden)

    Su-Young Jung

    Full Text Available Hyperphosphatemia is associated with mortality in patients with chronic kidney disease, and is common in critically ill patients with acute kidney injury (AKI; however, its clinical implication in these patients is unknown. We conducted an observational study in 1144 patients (mean age, 63.2 years; male, 705 [61.6%] with AKI who received continuous renal replacement therapy (CRRT between January 2009 and September 2016. Phosphate levels were measured before (0 h and 24 h after CRRT initiation. We assessed disease severity using various clinical parameters. Phosphate at 0 h positively correlated with the Acute Physiology and Chronic Health Evaluation II (APACHE II; P < 0.001 and Sequential Organ Failure Assessment (SOFA; P < 0.001 scores, and inversely with mean arterial pressure (MAP; P = 0.02 and urine output (UO; P = 0.01. In a fully adjusted linear regression analysis for age, sex, Charlson comorbidity index (CCI, MAP, and estimated glomerular filtration rate (eGFR, higher 0 h phosphate level was significantly associated with high APACHE II (P < 0.001 and SOFA (P = 0.04 scores, suggesting that phosphate represents disease severity. A multivariable Cox model also showed that hyperphosphatemia was significantly associated with increased 28-day (HR 1.05, 95% CI 1.02-1.08, P = 0.001 and 90-day (HR 1.05, 95% CI 1.02-1.08, P = 0.001 mortality. Furthermore, patients with increased phosphate level during 24 h were at higher risk of death than those with stable or decreased phosphate levels. Finally, c-statistics significantly increased when phosphate was added to a model that included age, sex, CCI, body mass index, eGFR, MAP, hemoglobin, serum albumin, C-reactive protein, and APACHE II score. This study shows that phosphate is a potential biomarker that can reflect disease severity and predict mortality in critically ill patients receiving CRRT.

  4. Erythrocyte-Rich Thrombus Is Associated with Reduced Number of Maneuvers and Procedure Time in Patients with Acute Ischemic Stroke Undergoing Mechanical Thrombectomy

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    Kota Maekawa

    2018-01-01

    Full Text Available Background: Only few studies have investigated the relationship between the histopathology of retrieved thrombi and clinical outcomes. This study aimed to evaluate thrombus composition and its association with clinical, laboratory, and neurointerventional findings in patients treated by mechanical thrombectomy due to acute large vessel occlusion. Methods: At our institution, 79 patients were treated by mechanical thrombectomy using a stent retriever and/or aspiration catheter between August 2015 and August 2016. The retrieved thrombi were quantitatively analyzed to quantify red blood cells, white blood cells, and fibrin by area. We divided the patients into two groups – a fibrin-rich group and an erythrocyte-rich group – based on the predominant composition in the thrombus. The groups were compared for imaging, clinical, and neurointerventional data. Results: The retrieved thrombi from 43 patients with acute stroke from internal carotid artery, middle cerebral artery, or basilar artery occlusion were histologically analyzed. Erythrocyte-rich thrombi were present in 18 cases, while fibrin-rich thrombi were present in 25 cases. A cardioembolic etiology was significantly more prevalent among the patients with fibrin-rich thrombi than among those with erythrocyte-rich thrombi. Attenuation of thrombus density as shown on computed tomography images was greater in patients with erythrocyte-rich thrombi than in those with fibrin-rich thrombi. All other clinical and laboratory characteristics remained the same. Patients with erythrocyte-rich thrombi had a smaller number of recanalization maneuvers, shorter procedure times, a shorter time interval between arrival and recanalization, and a higher percentage of stent retrievers in the final recanalization procedure. The occluded vessels did not differ significantly. Conclusions: In this study, erythrocyte-rich thrombus was associated with noncardioembolic etiology, higher thrombus density, and reduced

  5. Ticagrelor and Eptifibatide Bolus Versus Ticagrelor and Eptifibatide Bolus With 2-Hour Infusion in High-Risk Acute Coronary Syndromes Patients Undergoing Early Percutaneous Coronary Intervention.

    Science.gov (United States)

    Marian, Moazez J; Alli, Oluseun; Al Solaiman, Firas; Brott, Brigitta C; Sasse, Mark; Leesar, Tara; Prabhu, Sumanth D; Leesar, Massoud A

    2017-06-13

    In patients with non-ST-segment elevation acute coronary syndromes, inhibition of platelet aggregation (IPA) with a potent P2Y 12 inhibitor, ticagrelor, was inferior to tirofiban infusion at 2 hours, indicating that glycoprotein IIb/IIIa inhibitors are still needed. Ticagrelor and eptifibatide bolus only may maximally inhibit platelet aggregation and decrease bleeding, but IPA with ticagrelor and eptifibatide bolus versus 2-hour infusion is unknown. A total of 70 P2Y 12 -naïve patients, with high-risk non-ST-segment elevation acute coronary syndromes, were randomized to ticagrelor and eptifibatide bolus (group 1) versus ticagrelor and eptifibatide bolus with 2-hour infusion (group 2). Levels of IPA with ADP, thrombin receptor-activating peptide, collagen, and high on-treatment platelet reactivity were measured by light transmission aggregometry at baseline and at 2, 6, and 24 hours after percutaneous coronary intervention in both groups. The primary end point, IPA with ADP 20 μmol/L at 2 hours, was 99.59±0.43% in group 1 versus 99.88±1.0% in group 2 ( P zero at 2, 6, and 24 hours in both groups. IPA levels with ADP, thrombin receptor-activating peptide, and collagen were significantly higher at 2 and 6 hours than at 24 hours in both groups. Periprocedural myocardial infarction was not significantly different between the groups. Hemoglobin level was significantly less at 24 hours versus baseline in group 2 (13.35±1.8 versus 12.38±1.8 g/dL, respectively; P hours, which was associated with no significant hemoglobin drop after percutaneous coronary intervention. This obviates the need for eptifibatide 2-hour infusion and might decrease bleeding complications. URL: http://www.clinicaltrials.gov. Unique identifier: NCT01919723. © 2017 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  6. Genetic Variants in CD44 and MAT1A Confer Susceptibility to Acute Skin Reaction in Breast Cancer Patients Undergoing Radiation Therapy

    International Nuclear Information System (INIS)

    Mumbrekar, Kamalesh Dattaram; Bola Sadashiva, Satish Rao; Kabekkodu, Shama Prasada; Fernandes, Donald Jerard; Vadhiraja, Bejadi Manjunath; Suga, Tomo; Shoji, Yoshimi; Nakayama, Fumiaki; Imai, Takashi; Satyamoorthy, Kapaettu

    2017-01-01

    Purpose: Heterogeneity in radiation therapy (RT)-induced normal tissue toxicity is observed in 10% of cancer patients, limiting the therapeutic outcomes. In addition to treatment-related factors, normal tissue adverse reactions also manifest from genetic alterations in distinct pathways majorly involving DNA damage–repair genes, inflammatory cytokine genes, cell cycle regulation, and antioxidant response. Therefore, the common sequence variants in these radioresponsive genes might modify the severity of normal tissue toxicity, and the identification of the same could have clinical relevance as a predictive biomarker. Methods and Materials: The present study was conducted in a cohort of patients with breast cancer to evaluate the possible associations between genetic variants in radioresponsive genes described previously and the risk of developing RT-induced acute skin adverse reactions. We tested 22 genetic variants reported in 18 genes (ie, NFE2L2, OGG1, NEIL3, RAD17, PTTG1, REV3L, ALAD, CD44, RAD9A, TGFβR3, MAD2L2, MAP3K7, MAT1A, RPS6KB2, ZNF830, SH3GL1, BAX, and XRCC1) using TaqMan assay-based real-time polymerase chain reaction. At the end of RT, the severity of skin damage was scored, and the subjects were dichotomized as nonoverresponders (Radiation Therapy Oncology Group grade <2) and overresponders (Radiation Therapy Oncology Group grade ≥2) for analysis. Results: Of the 22 single nucleotide polymorphisms studied, the rs8193 polymorphism lying in the micro-RNA binding site of 3′-UTR of CD44 was significantly (P=.0270) associated with RT-induced adverse skin reactions. Generalized multifactor dimensionality reduction analysis showed significant (P=.0107) gene–gene interactions between MAT1A and CD44. Furthermore, an increase in the total number of risk alleles was associated with increasing occurrence of overresponses (P=.0302). Conclusions: The genetic polymorphisms in radioresponsive genes act as genetic modifiers of acute normal tissue toxicity

  7. Childhood leukaemia incidence below the age of 5 years near French nuclear power plants

    International Nuclear Information System (INIS)

    Laurier, D; Hemon, D; Clavel, J

    2008-01-01

    A recent study indicated an excess risk of leukaemia among children under the age of 5 years living in the vicinity of nuclear power plants in Germany. We present results relating to the incidence of childhood leukaemia in the vicinity of nuclear power plants in France for the same age range. These results do not indicate an excess risk of leukaemia in young children living near French nuclear power plants. (note)

  8. Irradiation of FDG-PET–Defined Active Bone Marrow Subregions and Acute Hematologic Toxicity in Anal Cancer Patients Undergoing Chemoradiation

    International Nuclear Information System (INIS)

    Rose, Brent S.; Jee, Kyung-Wook; Niemierko, Andrzej; Murphy, Janet E.; Blaszkowsky, Lawrence S.; Allen, Jill N.; Lee, Leslie K.; Wang, Yingbing; Drapek, Lorraine C.; Hong, Theodore S.; Wo, Jennifer Y.

    2016-01-01

    Purpose: Irradiation of pelvic bone marrow (BM) has been correlated with hematologic toxicity (HT) in patients undergoing chemoradiation for anal cancer. We hypothesized that irradiation of hematologically active bone marrow (ABM) subregions defined by fluorodeoxyglucose (FDG) positron emission tomography (PET) is a principal cause of radiation-associated HT. Methods and Materials: The cohort included 45 patients with nonmetastatic anal cancer who underwent FDG-PET imaging prior to definitive chemoradiation with mitomycin-C and 5-fluorouracil. Total bone marrow (TBM) was defined as the external contour of the pelvic bones from the top of lumbar 5 (L5) to the bottom of the ischial tuberosity. Standardized uptake values (SUV) for all voxels within the TBM were quantified and normalized by comparison to normal liver SUV. Subvolumes of the TBM that exhibited the highest and lowest 50% of the SUVs were designated ABM 50 and IBM 50 , respectively. The primary endpoint was the absolute neutrophil count (ANC) nadir during or within 2 weeks of completion of treatment. Multivariate linear modeling was used to analyze the correlation between the equivalent uniform doses (EUD) with an a value of 0.5, 1 (equivalent to mean dose), 3, 7, and 12 to the BM structures and the ANC. Results: Mean ± SD ANC nadir was 0.77 × 10 9 /L (±0.66 × 10 9 /L). Grades 3 and 4 ANC toxicity occurred in 26.7% and 44.4% of patients, respectively. The EUD a parameter of 0.5 was optimal for all BM models indicating high radiation sensitivity. EUD of TBM and ABM 50 and IBM 50 were all significantly associated with ANC nadir. However, model performance for ABM 50 was not superior to that of the TBM and IBM 50 models. Conclusions: Irradiation of pelvic BM was associated with HT. However, FDG-PET–defined ABM models failed to improve model performance compared to the TBM model.

  9. Locally Available Dietary Menus Promote Weight Gain among Acutely Malnourished Children Undergoing a Community-Based Nutrition Rehabilitation Program in Uganda

    International Nuclear Information System (INIS)

    Mugisha, Jennifer; Kakande, Celia

    2014-01-01

    Full text: Background: A significant proportion of Uganda’s children still suffer from acute malnutrition, despite decades of government, donor and agency investment in basic health services. The demand for the WHO recommended Ready to Use Therapeutic Foods (RUTF) for community based nutrition rehabilitation programs (CMAM) and costs involved have been overwhelming, thus prompting the need for alternative, sustainable, local solutions. Methods The Management Sciences for Health STRIDES for Family Health Project (MSH-STRIDES), funded by USAID, implemented a community-based nutritional rehabilitation intervention using the principles of Positive Deviance. The approach identified solutions (practices) already being used by community members with well-nourished children despite not having access to special resources (positive deviants). Community volunteers encouraged children to be assessed for nutrition during special growth monitoring sessions. Children found malnourished were enrolled into a nutrition rehabilitation program also known as a hearth cycle, in a volunteer’s home. Project staff and trained volunteers followed-up with malnourished children in their homes and invited the caregivers to bring them to participate in hearth cycles over 26 days. Caregivers were taught to recognize malnutrition and to treat it with supervised supplemental feedings of menu-mixtures of locally prepared, nutrient-dense foods. Weight gain was used as an outcome measure. Children were linked to health centers within the locality for curative services. MSH-STRIDES provided training to staff in the facilities and equipped them to serve as referral points for the children identified from the community. Results: Hearth cycles were conducted in 230 villages from 34 sub-counties in 11 out of 15 project districts. A total of 1336 health workers and 283 caregivers were trained and involved in the implementation of the community model. Overall, 2525 children with moderate and severe

  10. Comparing etoricoxib and celecoxib for preemptive analgesia for acute postoperative pain in patients undergoing arthroscopic anterior cruciate ligament reconstruction: a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    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

  11. Prospective evaluation of the development of contrast-induced nephropathy in patients with acute coronary syndrome undergoing rotational coronary angiography vs. conventional coronary angiography: CINERAMA study

    Directory of Open Access Journals (Sweden)

    Diego Fernández-Rodríguez

    2018-03-01

    Full Text Available Introduction and objectives: Rotational coronary angiography (RCA requires less contrast to be administered and can prevent the onset of contrast-induced nephropathy (CIN during invasive coronary procedures. The aim of the study is to evaluate the impact of RCA on CIN (increase in serum creatinine ≥0.5 mg/dL or ≥25% after an acute coronary syndrome. Methods: From April to September 2016, patients suffering acute coronary syndromes who underwent diagnostic coronary angiography, with the possibility of ad hoc coronary angioplasty, were prospectively enrolled. At the operator's discretion, patients underwent RCA or conventional coronary angiography (CCA. CIN (primary endpoint, as well as analytical, angiographic and clinical endpoints, were compared between groups. Results: Of the 235 patients enrolled, 116 patients received RCA and 119 patients received CCA. The RCA group was composed of older patients (64.0 ± 11.8 years vs. 59.7 ± 12.1 years; p = 0.006, a higher proportion of women (44.8 vs. 17.6%; p < 0.001, patients with a lower estimated glomerular filtration rate (76 ± 25 vs. 86 ± 27 ml/min/1.73 m2; p = 0.001, and patients who underwent fewer coronary angioplasties (p < 0.001 compared with the CCA group. Furthermore, the RCA group, received less contrast (113 ± 92 vs. 169 ± 103 ml; p < 0.001, including in diagnostic procedures (54 ± 24 vs. 85 ± 56 ml; p < 0.001 and diagnostic-therapeutic procedures (174 ± 64 vs. 205 ± 98 ml; p = 0.049 compared with the CCA group. The RCA group presented less CIN (4.3 vs. 22.7%; p < 0.001 compared to the CCA group, and this finding was maintained in the regression analysis (Adjusted relative risk: 0.868; 95% CI: 0.794–0.949; p = 0.002. There were no differences in clinical endpoints between the groups. Conclusions: RCA was associated

  12. Transradial versus transfemoral approach in patients undergoing primary percutaneous coronary intervention for ST-elevation acute myocardial infarction: insight from the CREDO-Kyoto AMI registry.

    Science.gov (United States)

    Yamashita, Yugo; Shiomi, Hiroki; Morimoto, Takeshi; Yaku, Hidenori; Kaji, Shuichiro; Furukawa, Yutaka; Nakagawa, Yoshihisa; Ando, Kenji; Kadota, Kazushige; Abe, Mitsuru; Akao, Masaharu; Nagao, Kazuya; Shizuta, Satoshi; Ono, Koh; Kimura, Takeshi

    2017-12-01

    Recent randomized clinical trials demonstrated that transradial approach was a preferred approach for primary percutaneous coronary intervention (PCI) in ST-elevation acute myocardial infarction (STEMI). However, clinical outcomes of transradial approach in STEMI have not been adequately evaluated yet in the real-world practice, which includes hemodynamically unstable high-risk patients. We identified 3662 STEMI patients who had primary PCI within 24 h after symptom onset and were treated by transradial (N = 471) or transfemoral (N = 3191) approach in the CREDO-Kyoto AMI registry. In the current analysis, we compared clinical characteristics and long-term outcomes between the 2 groups of patients treated by transradial approach and transfemoral approach. The prevalence of hemodynamically compromised patients (Killip II-IV) was significantly less in the transradial group than in the transfemoral group (19 vs. 25%, P = 0.002). Cumulative 5-year incidences of death/MI/stroke, and major bleeding were not significantly different between the transradial and transfemoral groups (26.7 vs. 25.9%, log-rank P = 0.91, and 11.3 vs. 11.5%, log-rank P = 0.71, respectively). After adjustment for confounders, the risks of the transradial group relative to the transfemoral group were not significant for both death/MI/stroke [Hazard ratio (HR) 1.15, 95% confidence interval (CI) 0.83-1.59, P = 0.41] and major bleeding (HR 1.29, 95% CI 0.77-2.15, P = 0.34). In the subgroup of hemodynamically compromised patients, there were also no significant differences in the risks for death/MI/stroke and major bleeding between the 2 groups. Clinical outcomes of transradial approach were not different from those of transfemoral approach in primary PCI for STEMI in the real-world practice.

  13. Selective inhibition of PED protein expression sensitizes B-cell chronic lymphocytic leukaemia cells to TRAIL-induced apoptosis.

    Science.gov (United States)

    Garofalo, Michela; Romano, Giulia; Quintavalle, Cristina; Romano, Maria Fiammetta; Chiurazzi, Federico; Zanca, Ciro; Condorelli, Gerolama

    2007-03-15

    B-cell chronic lymphocytic leukaemia (B-CLL) cells fail to undergo apoptosis. The mechanism underlying this resistance to cell death is still largely unknown. Tumour necrosis factor-related apoptosis-inducing ligand (TRAIL) effectively kills tumour cells but not normal cells, and thus represents an attractive tool for the treatment of cancer. Unfortunately, lymphocytes from B-CLL patients are resistant to TRAIL-mediated apoptosis. Thus, we aimed to study the involvement of PED, a DED-family member with a broad antiapoptotic action, in this resistance. We demonstrate that B lymphocytes obtained from patients with B-CLL express high levels of PED. Treatment of B-CLL cells with specific PED antisense oligonucleotides, a protein synthesis inhibitor or HDAC inhibitors, induced a significant downregulation of PED and sensitized these cells to TRAIL-induced cell death. These findings suggest a direct involvement of PED in resistance to TRAIL-induced apoptosis in B-CLL. It also identifies this DED-family member as a potential therapeutic target for this form of leukaemia. (c) 2006 Wiley-Liss, Inc.

  14. Short-Term High-Dose Vitamin E to Prevent Contrast Medium-Induced Acute Kidney Injury in Patients With Chronic Kidney Disease Undergoing Elective Coronary Angiography: A Randomized Placebo-Controlled Trial.

    Science.gov (United States)

    Rezaei, Yousef; Khademvatani, Kamal; Rahimi, Behzad; Khoshfetrat, Mehran; Arjmand, Nasim; Seyyed-Mohammadzad, Mir-Hossein

    2016-03-15

    Contrast medium-induced acute kidney injury (CIAKI) is a leading cause of acquired renal impairment. The effects of antioxidants have been conflicting regarding the prevention of CIAKI. We performed a study of vitamin E use to decrease CIAKI in patients undergoing elective coronary angiography. In a placebo-controlled randomized trial at 2 centers in Iran, 300 patients with chronic kidney disease-defined as estimated glomerular filtration rate vitamin E 12 hours before plus 400 mg vitamin E 2 hours before coronary angiography or to receive placebo. The primary end point was the development of CIAKI, defined as an increase ≥0.5 mg/dL or ≥25% in serum creatinine that peaked within 72 hours. Based on an intention-to-treat analysis, CIAKI developed in 10 (6.7%) and 21 (14.1%) patients in the vitamin E and placebo groups, respectively (P=0.037). Change in white blood cell count from baseline to peak value was greater in the vitamin E group compared with the placebo group (-500 [-1500 to 200] versus 100 [-900 to 600]×10(3)/mL, P=0.001). In multivariate analysis, vitamin E (odds ratio 0.408, 95% CI 0.170-0.982, P=0.045) and baseline Mehran score (odds ratio 1.257, 95% CI 1.007-1.569; P=0.043) predicted CIAKI. Prophylactic short-term high-dose vitamin E combined with 0.9% saline infusion is superior to placebo for prevention of CIAKI in patients undergoing elective coronary angiography. URL: https://www.clinicaltrials.gov/. Unique identifier: NCT02070679. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  15. Dissecting the role of aberrant DNA methylation in human leukaemia.

    Science.gov (United States)

    Amabile, Giovanni; Di Ruscio, Annalisa; Müller, Fabian; Welner, Robert S; Yang, Henry; Ebralidze, Alexander K; Zhang, Hong; Levantini, Elena; Qi, Lihua; Martinelli, Giovanni; Brummelkamp, Thijn; Le Beau, Michelle M; Figueroa, Maria E; Bock, Christoph; Tenen, Daniel G

    2015-05-22

    Chronic myeloid leukaemia (CML) is a myeloproliferative disorder characterized by the genetic translocation t(9;22)(q34;q11.2) encoding for the BCR-ABL fusion oncogene. However, many molecular mechanisms of the disease progression still remain poorly understood. A growing body of evidence suggests that the epigenetic abnormalities are involved in tyrosine kinase resistance in CML, leading to leukaemic clone escape and disease propagation. Here we show that, by applying cellular reprogramming to primary CML cells, aberrant DNA methylation contributes to the disease evolution. Importantly, using a BCR-ABL inducible murine model, we demonstrate that a single oncogenic lesion triggers DNA methylation changes, which in turn act as a precipitating event in leukaemia progression.

  16. Paternal Occupational Exposure to Endocrine-Disrupting Chemicals as a Risk Factor for Leukaemia in Children: A Case-Control Study from the North of England

    Directory of Open Access Journals (Sweden)

    Mark S. Pearce

    2014-01-01

    Full Text Available Occupations with exposures to a variety of chemicals, including those thought to be potential endocrine disruptors, have been associated with an increased risk of leukaemia in offspring. We investigated whether an association exists between paternal occupations at birth involving such exposures and risk of leukaemia in offspring. Cases (n=958 were matched, on sex and year of birth, to controls from two independent sources, one other cancers, one cancer-free live births. Paternal occupations at birth were classified, using an occupational exposure matrix, as having “very unlikely,” “possible,” or “likely” exposure to six groups of potential endocrine-disrupting chemicals. There was a significantly increased risk of acute nonlymphocytic leukaemia (ANLL for polychlorinated organic compounds (OR 1.95, 95% CI 1.08–3.54 only in comparison with cancer-free controls, and for phthalates (OR 1.61, 95% CI 1.00–2.61 only with registry controls. A number of other, including inverse, associations were seen, but limited to one control group only. No associations were seen with likely paternal exposure to heavy metals. The associations identified in this study require further investigation, with better exposure and potential confounding (for example maternal variables information, to evaluate the likelihood of true associations to assess whether they are real or due to chance.

  17. Granulopoiesis inhibition in acute inflammation: comparative studies in healthy and leukaemic mice

    Directory of Open Access Journals (Sweden)

    Mohamad Hamood

    1992-01-01

    Full Text Available It was demonstrated previously that mice undergoing an inflammatory reaction induced by subcutaneous (SC implantation of copper rods, produce humoral factors that initially enhance, but subsequently inhibit, diffusion chamber (DC granulopoiesis. This provided evidence that granulopoiesis is under the control of both humoral stimulators and inhibitors. In order to test the granulopoietic regulatory mechanism in leukaemic mice, we investigated the regulatory role of granulopoietic humoral inhibitors during in vivo granulopoiesis. We noticed that mice suffering from acute myeloid leukaemia (AML are unable to augment the production of these humoral inhibitory factors when acute inflammation is induced, since no change in DC cell content was observed with or without prior inflammation. Moreover, unlike healthy mice, the serum of leukaemic mice withdrawn during the inhibition phase of acute inflammation did not show any inhibitory activity toward granulocyte—monocyte (GM colony growth in vitro. Our results also show that increased levels of normal humoral inhibitors do not influence the proliferation and/or differentiation of leukaemic cells implanted in diffusion chamber cultures.

  18. Bivalent promoter marks and a latent enhancer may prime the leukaemia oncogene LMO1 for ectopic expression in T-cell leukaemia.

    Science.gov (United States)

    Oram, S H; Thoms, J; Sive, J I; Calero-Nieto, F J; Kinston, S J; Schütte, J; Knezevic, K; Lock, R B; Pimanda, J E; Göttgens, B

    2013-06-01

    LMO1 is a transcriptional regulator and a T-acute lymphoblastic leukaemia (T-ALL) oncogene. Although first identified in association with a chromosomal translocation in T-ALL, the ectopic expression of LMO1 occurs far more frequently in the absence of any known mutation involving its locus. Given that LMO1 is barely expressed in any haematopoietic lineage, and activation of transcriptional drivers in leukaemic cells is not well described, we investigated the regulation of this gene in normal haematopoietic and leukaemic cells. We show that LMO1 has two promoters that drive reporter gene expression in transgenic mice to neural tissues known to express endogenous LMO1. The LMO1 promoters display bivalent histone marks in multiple blood lineages including T-cells, and a 3' flanking region at LMO1 +57 contains a transcriptional enhancer that is active in developing blood cells in transgenic mouse embryos. The LMO1 promoters become activated in T-ALL together with the 3' enhancer, which is bound in primary T-ALL cells by SCL/TAL1 and GATA3. Taken together, our results show that LMO1 is poised for expression in normal progenitors, where activation of SCL/TAL1 together with a breakdown of epigenetic repression of LMO1 regulatory elements induces ectopic LMO1 expression that contributes to the development and maintenance of T-ALL.

  19. Local Experience in the Treatment of Acute Non-Lymphoblastic ...

    African Journals Online (AJOL)

    Seventy-six patients suffering from various forms of acute non-lymphoblastic leukaemia were seen at the Johannes- burg Hospital over an 8-year period. During this time various forms of therapy were used. Results with 6-mer- captopurine and prednisone were very poor, with less than. 10% of patients achieving complete ...

  20. Acute Leukemia Presenting with Gingival Bleeding. A Case Report ...

    African Journals Online (AJOL)

    This is a case report of a five year-old girl with acute lymphoblastic leukaemia who presented in our clinic with gingival bleeding. Sepcific highlights were focused on the management of the patient and current trends in the treatment of the disease with emphasis on early diagnosis of the disease in other to improve the ...

  1. A Study On The Acute Toxicological Effects Of Commercial Diesel

    African Journals Online (AJOL)

    (lPCS, 1982). Report furthermore, report indicate that benzene (aromatic hydrocarbon) content of gasoline as k known to induce acute non-lymphocytic leukaemia though occupational exposure (Austinetal,. 1988), the aromatic content of gasoline is about 10% of its hydrocarbon composition (Frankeriberger and .lohanson.

  2. Development of A model of B acute lymphoblastic leukemia for the investigation of the potential leukemogenic effects of 50 Hz magnetic fields

    Energy Technology Data Exchange (ETDEWEB)

    Bernard, N.; Alberdi, A.; Corona, A.; Guillosson, J.J.; Nafziger, J. [Universite Rene Descartes, Lab. d' Hematologie Cellulaire et Moleculaire, CNRS UMR 8147, Faculte de Pharmacie, 75 - Paris (France)

    2006-07-01

    Over the past 25 years, a possible association between exposure to extremely low frequency magnetic fields (50 Hz M.F.) and cancer has be en extensively studied. The most consistent data were found for B acute lymphoblastic leukaemia in children that represents the most common type of cancer encountered in childhood. However, controversial results were reported in epidemiologic studies about this potential adverse effect of 50 Hz M.F.. Therefore, we developed an animal model of B acute lymphoblastic leukaemia to investigate the possible co-initiating or promoting effects of 50 Hz M.F. on the incidence of leukaemia in children. In this model leukaemia was chemically induced in male W.K.A.H./H km rats by a nitrosourea derivative, N-butyl nitrosourea (B.N.U.) administered 5 days a week for 24 weeks. Development of leukaemia was monitored by clinical observation, follow-up of blood parameters and appearance of blasts cells in serially repeated peripheral blood samples. The phenotype of the leukaemia in the affected rats was determined by cytological examination and cytochemical reactions on blood and bone marrow cells and, by immuno phenotyping of bone marrow cells using various markers. Leukaemia occurred in 60% of B.N.U. treated rats. Among the leukemic rats, 65% developed B acute lymphoblastic leukaemia. The maximum of leukaemia development was observed between the 5. to the 8. month following the beginning of B.N.U. treatment. Using this model, we decided to investigate the potential co-initiating or promoting effects of 50 Hz M.F.. The possible effects of harmonics (150, 250 and 350 Hz) that pollute the electrical network are also studied. The total number of leukaemia and the phenotype of leukaemia obtained will be compared between the B.N.U. treated animals exposed to 50 Hz M.F. with or without harmonics and the animals treat ed with B.N.U. alone. We believe that the results of this experiment might be helpful to answer the question of whether or not 50 Hz M

  3. Targeted bone marrow irradiation in the conditioning of high-risk leukaemia prior to stem cell transplantation

    International Nuclear Information System (INIS)

    Reske, S.N.; Buchmann, I.; Seitz, U.; Glatting, G.; Neumaier, B.; Kotzerke, J.; Buck, A.; Martin, H.; Bergmann, L.

    2001-01-01

    Disease recurrence following stem cell transplantation (SCT) remains a major problem. Despite the sensitivity of leukaemias to chemotherapy and irradiation, conventional conditioning before SCT is limited by significant organ toxicity. Targeted irradiation of bone marrow and spleen by radioimmunotherapy may provide considerable dose escalation, with limited toxicity to non-target organs. In this study, 27 patients with high-risk or relapsing leukaemia were treated with rhenium-188-labelled CD66a,b,c,e radioimmunoconjugates ( 188 Re-mAb) specific for normal bone marrow in addition to conventional conditioning with high-dose chemotherapy and 12 Gy total body irradiation prior to SCT. A mean activity of 10.2±2.1 (range 6.9-15.8) GBq 188 Re-mAb was administered intravenously. Acute side-effects were assessed according to the CTC classification and patient outcome was determined. Mean radiation doses (Gy; range in parentheses) to relevant organs and whole body were as follows: 13.1 (6.5-22) to bone marrow, 11.6 (1.7-31.1) to spleen, 5.0 (2.0-11.7) to liver, 7.0 (2.3-11.6) to kidneys, 0.7 (0.3-1.3) to lungs and 1.4 (0.8-2.1) to the whole body. Stem cells engrafted in all patients within 9-18 days post SCT. Acute organ toxicity of grade II or less was observed. During follow-up for 25.4±5.3 (range 18-34) months, 4/27 (15%) patients died from relapse, and 9/27 (33%) from transplantation-related complications. Fourteen patients (52%) are still alive and in ongoing complete clinical remission. Radioimmunotherapy with the bone marrow-seeking 188 Re-labelled CD66 mAb can double the dose to bone marrow and spleen without undue extramedullary acute organ toxicity, when given in addition to high-dose chemotherapy and 12 Gy TBI before allogeneic SCT. This intensified conditioning regimen may reduce the relapse rate of high-risk leukaemia. (orig.)

  4. Ultraviolet B irradiation of human leukaemia HL-60 cells in vitro induces apoptosis

    International Nuclear Information System (INIS)

    Martin, S.J.; Cotter, T.G.

    1991-01-01

    UV radiation is known to be a potent agent for the induction of programmed cell death (apoptosis) in human skin. However, the mechanistic aspects of UV-induced apoptosis remain ill-defined. In this study the effects of varying periods of UV-irradiation on the human leukaemia HL-60 cell line and on five other human cell lines were investigated.HL-60 cells were found to rapidly undergo apoptosis en masse after short periods of UV-irradiation whereas prolonged exposure of these cells to this form of radiation induced a more rapid form of cell death which was suggestive of necrosis, the pathological mode of cell death. UV-induced apoptosis in cell lines was characterized by morphological changes as well as DNA fragmentation into unit multiples of ∼ 200 bp, which was indicative of endogenous endonuclease activation. This DNA fragmentation pattern was not detected in cells immediately after UV-irradiation, and was therefore not the result of direct UV-induced DNA damage. UV-induced apoptosis of the HL-60 cell line was found to require extracellular calcium and to be inhibited in a dose-dependent way by zinc added to the culture medium. (author)

  5. Early detection and intervention using neutrophil gelatinase-associated lipocalin (NGAL may improve renal outcome of acute contrast media induced nephropathy: A randomized controlled trial in patients undergoing intra-arterial angiography (ANTI-CIN Study

    Directory of Open Access Journals (Sweden)

    Stiegler Philipp

    2011-08-01

    Full Text Available Abstract Background Patients with pre-existing impaired renal function are prone to develop acute contrast media induced nephropathy (CIN. Neutrophil gelatinase-associated lipocalin (NGAL, a new biomarker predictive for acute kidney injury (AKI, has been shown to be useful for earlier diagnosis of CIN; however, urinary NGAL values may be markedly increased in chronic renal failure at baseline. Results from those studies suggested that urinary NGAL values may not be helpful for the clinician. An intravenous volume load is a widely accepted prophylactic measure and possibly a reasonable intervention to prevent deterioration of renal function. The aim of our study is to evaluate NGAL as an early predictor of CIN and to investigate the clinical benefit of early post-procedural i.v. hydration. Methods/Design The study will follow a prospective, open-label, randomized controlled design. Patients requiring intra-arterial contrast media (CM application will be included and receive standardized, weight-based, intravenous hydration before investigation. Subjects with markedly increased urinary NGAL values after CM application will be randomized into one of two study groups. Group A will receive 3-4 ml/kg BW/h 0.9% saline intravenously for 6 hours. Group B will undergo only standard treatment consisting of unrestricted oral fluid intake. The primary outcome measure will be CIN defined by an increase greater than 25% of baseline serum creatinine. Secondary outcomes will include urinary NGAL values, cystatin C values, contrast media associated changes in cardiac parameters such as NT-pro-BNP/troponin T, changes in urinary cytology, need for renal replacement treatment, length of stay in hospital and death. We assume that 20% of the included patients will show a definite rise in urinary NGAL. Prospective statistical power calculations indicate that the study will have 80% statistical power to detect a clinically significant decrease of CIN of 40% in the

  6. ATP concentration as possible marker of liver damage at leukaemia treatment: confocal microscopy-based experimental study and numerical simulations

    Science.gov (United States)

    Malashchenko, V.; Zyubin, A.; Babak, S.; Lavrova, A.

    2017-04-01

    We consider the method of confocal microscopy as a convenient instrument for determination of chemical compounds in biological tissues and cells. In particular, we study the dynamics of adenosine triphosphate (ATP) concentration that could be used as a bio-marker of energy metabolism pathologies at the treatment of acute lymphoblastic leukaemia (ALL). On the basis of data obtained by the confocal microscopy, the values of ATP concentration have been calculated for each case. Possible correlations with other characteristics of pathology processes obtained from plasma of leukemia patients show that ATP value could be a prognostic factor of the treatment success. The role of ATP in the drug metabolism switching is also discussed within the context of kinetic modelling of metabolism processes leading to the production of 6-Thioguanosine monophosphate, which is a principal acting agent in chemotherapy.

  7. Risk factors of childhood leukaemia with a focus on environmental hazards

    International Nuclear Information System (INIS)

    Schuez, J.

    2002-01-01

    Leukaemia is the most common malignancy in childhood. In Germany, there are annually about 620 new cases of childhood leukaemia among 13.2 million children. The causes of most leukaemias are still not known. Previous studies suggested a major role of environmental factors like low doses of ionizing radiation as well as electric and magnetic fields or pesticides. But recent studies contradict these assumptions. While weak associations between such factors and childhood leukaemia can not be ruled out, it can be estimated that they contribute at most to a minor fraction of leukaemias. Since leukaemia incidence is much higher in developed countries and since space-time clustering seems to be established for this disease, hypotheses involving a role of infectious agents have been put forward. Recent studies are suggestive that children with an appropriately modulated immune system have a lower risk of developing a leukaemia during childhood. As international collaborations emerge, it must be an aim that preventive actions are not only wishful thinking. (orig.) [de

  8. An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images

    Science.gov (United States)

    Chin Neoh, Siew; Srisukkham, Worawut; Zhang, Li; Todryk, Stephen; Greystoke, Brigit; Peng Lim, Chee; Alamgir Hossain, Mohammed; Aslam, Nauman

    2015-10-01

    This research proposes an intelligent decision support system for acute lymphoblastic leukaemia diagnosis from microscopic blood images. A novel clustering algorithm with stimulating discriminant measures (SDM) of both within- and between-cluster scatter variances is proposed to produce robust segmentation of nucleus and cytoplasm of lymphocytes/lymphoblasts. Specifically, the proposed between-cluster evaluation is formulated based on the trade-off of several between-cluster measures of well-known feature extraction methods. The SDM measures are used in conjuction with Genetic Algorithm for clustering nucleus, cytoplasm, and background regions. Subsequently, a total of eighty features consisting of shape, texture, and colour information of the nucleus and cytoplasm sub-images are extracted. A number of classifiers (multi-layer perceptron, Support Vector Machine (SVM) and Dempster-Shafer ensemble) are employed for lymphocyte/lymphoblast classification. Evaluated with the ALL-IDB2 database, the proposed SDM-based clustering overcomes the shortcomings of Fuzzy C-means which focuses purely on within-cluster scatter variance. It also outperforms Linear Discriminant Analysis and Fuzzy Compactness and Separation for nucleus-cytoplasm separation. The overall system achieves superior recognition rates of 96.72% and 96.67% accuracies using bootstrapping and 10-fold cross validation with Dempster-Shafer and SVM, respectively. The results also compare favourably with those reported in the literature, indicating the usefulness of the proposed SDM-based clustering method.

  9. Large granular lymphocytic leukaemia complicated with histiocytic sarcoma in a dog : clinical communication

    Directory of Open Access Journals (Sweden)

    T. Maruo

    2009-05-01

    Full Text Available A 10-year-old castrated male Golden retriever, weighing 36.3 kg was referred for evaluation owing to a decline in general condition. Findings from the complete blood count revealed a marked lymphocytosis (113 000/µℓ. Examination of Wright-Giemsa-stained films of peripheral blood revealed the presence of large granular lymphocytes (LGL. Seventy-two per cent (81 360/µℓ of the lymphocytes were found to be 12-17 µm in diameter, containing nuclei with mature clumped chromatin and abundant lightly basophilic cytoplasm with a variable number of fine azurophilic granules. Based on these findings this case was diagnosed as LGL leukaemia. As a result of multiple-agent chemotherapy, the markedly elevated levels of lymphocytes gradually decreased to 7500/µℓ on day 122 and the patient maintained a good quality of life for the following 3 months. However, on around day 237, a soft, raised, bosselated mass on the labial region was noted. The dog was diagnosed as having histiocytic sarcoma based on cytological and histological examination of the mass. Shortly after diagnosis, the dog developed sudden onset of central nervous system signs and died on day 270. A common outcome of canine LGL is the development of acute blast crisis or lymphoma. However, this case was notable for complication with histiocytic sarcoma from another origin.

  10. Site- and allele-specific polycomb dysregulation in T-cell leukaemia

    Science.gov (United States)

    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; Gut, Marta; Gut, Ivo G.; Dombret, Hervé; Macintyre, Elizabeth A.; Howe, Steven J.; Gaspar, H. Bobby; Thrasher, Adrian J.; Ifrah, Norbert; Payet-Bornet, Dominique; Duprez, Estelle; Andrau, Jean-Christophe; Asnafi, Vahid; Nadel, Bertrand

    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 reveals that >20% of monoallelic TAL1+ patients without previously known alterations display microinsertions or RAG1/2-mediated episomal reintegration in a single site 5′ to TAL1. Using ‘allelic-ChIP’ and CrispR assays, we demonstrate that such insertions induce a selective switch from H3K27me3 to H3K27ac at the inserted but not the germline allele. We also show that, despite a considerable mechanistic diversity, the mode of oncogenic TAL1 activation, rather than expression levels, impact on clinical outcome. Altogether, these studies establish site-specific epigenetic desilencing as a mechanism of oncogenic activation. PMID:25615415

  11. Childhood leukaemia close to high-voltage power lines--the Geocap study, 2002-2007.

    Science.gov (United States)

    Sermage-Faure, C; Demoury, C; Rudant, J; Goujon-Bellec, S; Guyot-Goubin, A; Deschamps, F; Hemon, D; Clavel, J

    2013-05-14

    High-voltage overhead power lines (HVOLs) are a source of extremely low-frequency magnetic fields (ELF-MFs), which are classified as possible risk factors for childhood acute leukaemia (AL). The study was carried out to test the hypothesis of an increased AL incidence in children living close to HVOL of 225-400 kV (VHV-HVOL) and 63-150 kV (HV-HVOL). The nationwide Geocap study included all the 2779 cases of childhood AL diagnosed in France over 2002-2007 and 30 000 contemporaneous population controls. The addresses at the time of inclusion were geocoded and precisely located around the whole HVOL network. Increased odds ratios (ORs) were observed for AL occurrence and living within 50 m of a VHV-HVOL (OR=1.7 (0.9-3.6)). In contrast, there was no association with living beyond that distance from a VHV-HVOL or within 50 m of a HV-HVOL. The present study, free from any participation bias, supports the previous international findings of an increase in AL incidence close to VHV-HVOL. In order to investigate for a potential role of ELF-MF in the results, ELF-MF at the residences close to HVOL are to be estimated, using models based on the annual current loads and local characteristics of the lines.

  12. An Intelligent Decision Support System for Leukaemia Diagnosis using Microscopic Blood Images

    Science.gov (United States)

    Chin Neoh, Siew; Srisukkham, Worawut; Zhang, Li; Todryk, Stephen; Greystoke, Brigit; Peng Lim, Chee; Alamgir Hossain, Mohammed; Aslam, Nauman

    2015-01-01

    This research proposes an intelligent decision support system for acute lymphoblastic leukaemia diagnosis from microscopic blood images. A novel clustering algorithm with stimulating discriminant measures (SDM) of both within- and between-cluster scatter variances is proposed to produce robust segmentation of nucleus and cytoplasm of lymphocytes/lymphoblasts. Specifically, the proposed between-cluster evaluation is formulated based on the trade-off of several between-cluster measures of well-known feature extraction methods. The SDM measures are used in conjuction with Genetic Algorithm for clustering nucleus, cytoplasm, and background regions. Subsequently, a total of eighty features consisting of shape, texture, and colour information of the nucleus and cytoplasm sub-images are extracted. A number of classifiers (multi-layer perceptron, Support Vector Machine (SVM) and Dempster-Shafer ensemble) are employed for lymphocyte/lymphoblast classification. Evaluated with the ALL-IDB2 database, the proposed SDM-based clustering overcomes the shortcomings of Fuzzy C-means which focuses purely on within-cluster scatter variance. It also outperforms Linear Discriminant Analysis and Fuzzy Compactness and Separation for nucleus-cytoplasm separation. The overall system achieves superior recognition rates of 96.72% and 96.67% accuracies using bootstrapping and 10-fold cross validation with Dempster-Shafer and SVM, respectively. The results also compare favourably with those reported in the literature, indicating the usefulness of the proposed SDM-based clustering method. PMID:26450665

  13. IRSN-ANCCLI partnership. Information day: Childhood leukaemia around French nuclear power plants - April 2012

    International Nuclear Information System (INIS)

    Clavel, Jacqueline; Laurier, Dominique; Sommelet, Daniele; Chantal Bardelay

    2012-04-01

    As an epidemiological study performed by the INSERM highlighted an excess of childhood leukaemia within 5 km around nuclear power plants during the 2002-2007 period, this meeting has been organised to discuss this issue. After a presentation of these results, a contribution discusses the context and research perspectives on the relationship between childhood leukaemia and nuclear sites. After the reported debate, a contribution presents the conclusion of a work-group on childhood leukaemia and ASN works, and a last one presents the activities of a work-group gathering the ANCCLI, IRSN and InVS on the health impact of nuclear installations. A debate on these issues is reported

  14. Using multistage models to describe radiation-induced leukaemia

    International Nuclear Information System (INIS)

    Little, M.P.; Muirhead, C.R.; Boice, J.D. Jr.; Kleinerman, R.A.

    1995-01-01

    The Armitage-Doll model of carcinogenesis is fitted to data on leukaemia mortality among the Japanese atomic bomb survivors with the DS86 dosimetry and on leukaemia incidence in the International Radiation Study of Cervical Cancer patients. Two different forms of model are fitted: the first postulates up to two radiation-affected stages and the second additionally allows for the presence at birth of a non-trivial population of cells which have already accumulated the first of the mutations leading to malignancy. Among models of the first form, a model with two adjacent radiation-affected stages appears to fit the data better than other models of the first form, including both models with two affected stages in any order and models with only one affected stage. The best fitting model predicts a linear-quadratic dose-response and reductions of relative risk with increasing time after exposure and age at exposure, in agreement with what has previously been observed in the Japanese and cervical cancer data. However, on the whole it does not provide an adequate fit to either dataset. The second form of model appears to provide a rather better fit, but the optimal models have biologically implausible parameters (the number of initiated cells at birth is negative) so that this model must also be regarded as providing an unsatisfactory description of the data. (author)

  15. Relation between thoracic aortic inflammation and features of plaque vulnerability in the coronary tree in patients with non-ST-segment elevation acute coronary syndrome undergoing percutaneous coronary intervention. An FDG-positron emission tomography and optical coherence tomography study

    Energy Technology Data Exchange (ETDEWEB)

    Taglieri, Nevio; Ghetti, Gabriele; Saia, Francesco; Bacchi Reggiani, Maria Letizia; Rapezzi, Claudio [Alma Mater Studiorum Universita di Bologna, Istituto di Cardiologia, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Bologna (Italy); Nanni, Cristina; Bonfiglioli, Rachele; Lima, Giacomo Maria; Fanti, Stefano [Alma Mater Studiorum Universita di Bologna, Istituto di Medicina Nucleare, Dipartimento di Medicina Specialistica, Diagnostica e Sperimentale, Bologna (Italy); Marco, Valeria [CLI Foundation, Rome (Italy); Prati, Francesco [CLI Foundation, Rome (Italy); Ettore Sansavini Health Science Foundation, GVM Care and Research, Cotignola (Italy)

    2017-10-15

    To evaluate the relationship between aortic inflammation as assessed by {sup 18}F-fluorodeoxyglucose-positron emission tomography ({sup 18}F-FDG-PET) and features of plaque vulnerability as assessed by frequency domain-optical coherence tomography (FD-OCT). We enrolled 30 consecutive non-ST-segment elevation acute coronary syndrome patients undergoing percutaneous coronary intervention. All patients underwent three-vessel OCT before intervention and {sup 18}F-FDG-PET before discharge. Univariable and C-reactive protein (CRP)-adjusted linear regression analyses were performed between features of vulnerability [namely:lipid-rich plaques with and without macrophages and thin cap fibroatheromas (TCFA)] and {sup 18}F-FDG uptake in both ascending (AA) and descending aorta (DA) [measured either as averaged mean and maximum target-to-blood ratio (TBR) or as active slices (TBR{sub max} ≥ 1.6)]. Mean age was 62 years, and 26 patients were male. On univariable linear regression analysis TBR{sub mean} and TBR{sub max} in DA was associated with the number of lipid-rich plaques (β = 4.22; 95%CI 0.05-8.39; p = 0.047 and β = 3.72; 95%CI 1.14-6.30; p = 0.006, respectively). TBR{sub max} in DA was also associated with the number of lipid-rich plaques containing macrophages (β = 2.40; 95%CI 0.07-4.72; p = 0.044). A significant CRP adjusted linear association between the TBR{sub max} in DA and the number of lipid-rich plaques was observed (CRP-adjusted β = 3.58; 95%CI -0.91-6.25; p = 0.01). TBR{sub max} in DA showed a trend towards significant CRP-adjusted association with number of lipid-rich plaques with macrophages (CRP-adjusted β = 2.30; 95%CI -0.11-4.71; p = 0.06). We also observed a CRP-adjusted (β = 2.34; 95%CI 0.22-4.47; p = 0.031) linear association between the number of active slices in DA and the number of lipid-rich plaques. No relation was found between FDG uptake in the aorta and the number of TCFAs. In patients with first NSTEACS{sup ,} {sup 18}F-FDG uptake in

  16. A phase II trial evaluating the efficacy and safety of perioperative pirfenidone for prevention of acute exacerbation of idiopathic pulmonary fibrosis in lung cancer patients undergoing pulmonary resection: West Japan Oncology Group 6711 L (PEOPLE Study).

    Science.gov (United States)

    Iwata, Takekazu; Yoshino, Ichiro; Yoshida, Shigetoshi; Ikeda, Norihiko; Tsuboi, Masahiro; Asato, Yuji; Katakami, Nobuyuki; Sakamoto, Kazuhiro; Yamashita, Yoshinori; Okami, Jiro; Mitsudomi, Tetsuya; Yamashita, Motohiro; Yokouchi, Hiroshi; Okubo, Kenichi; Okada, Morihito; Takenoyama, Mitsuhiro; Chida, Masayuki; Tomii, Keisuke; Matsuura, Motoki; Azuma, Arata; Iwasawa, Tae; Kuwano, Kazuyoshi; Sakai, Shuji; Hiroshima, Kenzo; Fukuoka, Junya; Yoshimura, Kenichi; Tada, Hirohito; Nakagawa, Kazuhiko; Nakanishi, Yoichi

    2016-07-22

    Idiopathic pulmonary fibrosis (IPF) often accompanies lung cancer, and life-threatening acute exacerbation (AE) of IPF (AE-IPF) is reported to occur in 20 % of IPF patients who undergo lung cancer surgery. Pirfenidone is an anti-fibrotic agent known to reduce disease progression in IPF patients. A phase II study was conducted to evaluate whether perioperative pirfenidone treatment could reduce the incidence of postoperative AE-IPF patients with lung cancer. Pirfenidone was orally administered to IPF patients who were candidates for lung cancer surgery; pirfenidone was dosed at 600 mg/day for the first 2 weeks, followed by 1200 mg/day. Surgery was performed after at least 2 weeks of 1200-mg/day administration. The primary endpoint was non-AE-IPF rate during postoperative days 0-30, compared to the null value of 80 %, and the secondary endpoint was safety. Radiologic and pathologic diagnoses of IPF and AE-IPF were confirmed by an independent review committee. From June 2012 to January 2014, 43 cases were enrolled, and 39 were eligible (full analysis set [FAS]). Both pirfenidone treatment and surgery were performed in 36 patients (per protocol set [PPS]). AE-IPF did not occur in 37/39 patients (94.9 % [95 % confidential interval: 82.7-99.4 %, p = 0.01]) in the FAS, and in 38/39 patients (97.2 % [95 % confidential interval: 85.5-99.9 %, p = 0.004] in the PPS. A grade 5 adverse event (death) occurred in 1 patient, after AE-IPF; no other grade 3-5 adverse events were observed. Perioperative pirfenidone treatment is safe, and is promising for reducing AE-IPF after lung cancer surgery in IPF patients. This clinical trial was registered with the University Hospital Medical Information Network (UMIN) on April 16th, 2012 (REGISTRATION NUMBER: UMIN000007774 ).

  17. Charcot-Marie-Tooth Disease in a Child with Acute Lymphoblastic ...

    African Journals Online (AJOL)

    Results: Facial nerve palsy, increasing lower extremities muscle weakness and abnormal gait were noticed 4 weeks into vincristine therapy in a ten year old male on treatment for acute lymphoblastic leukaemia (ALL). On a suspicion of vincristine neurotoxicity, vincristine was excluded from his chemotherapy regimen.

  18. Stringent or nonstringent complete remission and prognosis in acute myeloid leukemia

    DEFF Research Database (Denmark)

    Øvlisen, Andreas K; Oest, Anders; Bendtsen, Mette D

    2018-01-01

    transfusion dependency and were suggested to be of prognostic value. In the present report, we evaluated the prognostic impact of achieving sCR and non-sCR in the Danish National Acute Leukaemia Registry, including 769 patients registered with classical CR (ie, bone marrow...

  19. Leukaemia inhibitory factor--an exercise-induced myokine

    DEFF Research Database (Denmark)

    Broholm, Christa; Pedersen, Bente Klarlund

    2010-01-01

    During and following exercise skeletal muscle synthesises and releases a number of myokines that exert their effects either systemically or locally within the muscle. Several of these myokines influence metabolism, regeneration and/or hypertrophy and are therefore considered to be important...... to oscillations in intracellular Ca2+ concentrations. However, circulating levels of LIF are not increased with exercise suggesting that LIF exerts its effect locally. LIF stimulates muscle satellite cell proliferation and is involved in muscle hypertrophy and regeneration. Thus, LIF may be produced by skeletal...... contributing factors in muscle homeostasis and muscle adaptation to exercise training. Leukaemia inhibitory factor (LIF) is produced and released from muscle cells in vitro and from intact skeletal muscle in vivo. During exercise, skeletal muscle potently up-regulates LIF mRNA expression, likely due...

  20. Temporal trends in childhood leukaemia incidence following exposure to radioactive fallout from atmospheric nuclear weapons testing.

    Science.gov (United States)

    Wakeford, Richard; Darby, Sarah C; Murphy, Michael F G

    2010-05-01

    Notably raised rates of childhood leukaemia incidence have been found near some nuclear installations, in particular Sellafield and Dounreay in the United Kingdom, but risk assessments have concluded that the radiation doses estimated to have been received by children or in utero as a result of operations at these installations are much too small to account for the reported increases in incidence. This has led to speculation that the risk of childhood leukaemia arising from internal exposure to radiation following the intake of radioactive material released from nuclear facilities has been substantially underestimated. The radionuclides discharged from many nuclear installations are similar to those released into the global environment by atmospheric nuclear weapons testing, which was at its height in the late-1950s and early-1960s. Measurements of anthropogenic radionuclides in members of the general public resident in the vicinity of Sellafield and Dounreay have found levels that do not differ greatly from those in persons living remote from nuclear installations that are due to ubiquitous exposure to the radioactive debris of nuclear weapons testing. Therefore, if the leukaemia risk to children resulting from deposition within the body of radioactive material discharged from nuclear facilities has been grossly underestimated, then a pronounced excess of childhood leukaemia would have been expected as a consequence of the short period of intense atmospheric weapons testing. We have examined childhood leukaemia incidence in 11 large-scale cancer registries in three continents for which data were available at least as early as 1962. We found no evidence of a wave of excess cases corresponding to the peak of radioactive fallout from atmospheric weapons testing. The absence of a discernible increase in the incidence of childhood leukaemia following the period of maximum exposure to the radioactive debris of this testing weighs heavily against the suggestion that

  1. Phenotypically Dormant and Immature Leukaemia Cells Display Increased Ribosomal Protein S6 Phosphorylation.

    Directory of Open Access Journals (Sweden)

    Monica Pallis

    Full Text Available Mechanistic/mammalian target of rapamycin (mTOR activity drives a number of key metabolic processes including growth and protein synthesis. Inhibition of the mTOR pathway promotes cellular dormancy. Since cells from patients with acute myeloid leukaemia (AML can be phenotypically dormant (quiescent, we examined biomarkers of their mTOR pathway activity concurrently with Ki-67 and CD71 (indicators of cycling cells by quantitative flow cytometry. Using antibodies to phosphorylated epitopes of mTOR (S2448 and its downstream targets ribosomal protein S6 (rpS6, S235/236 and 4E-BP1 (T36/45, we documented that these phosphorylations were negligible in lymphocytes, but evident in dormant as well as proliferating subsets of both mobilised normal stem cell harvest CD34+ cells and AML blasts. Although mTOR phosphorylation in AML blasts was lower than that of the normal CD34+ cells, p-4E-BP1 was 2.6-fold higher and p-rpS6 was 22-fold higher. Moreover, in contrast to 4E-BP1, rpS6 phosphorylation was higher in dormant than proliferating AML blasts, and was also higher in the immature CD34+CD38- blast subset. Data from the Cancer Genome Atlas show that rpS6 expression is associated with that of respiratory chain enzymes in AML. We conclude that phenotypic quiescence markers do not necessarily predict metabolic dormancy and that elevated rpS6 ser235/236 phosphorylation is characteristic of AML.

  2. Epidemiological studies of leukaemia in children and young adults around nuclear facilities: a critical review

    International Nuclear Information System (INIS)

    2008-01-01

    An epidemiological study published in late 2007 described an increased risk of leukaemia in children under 5 living within 5 kilometres of German nuclear power plants. A great deal of research has been carried out on this subject since the early 1980's. The aim of this report was to provide a synthesis and critical analysis of results related to the risk of leukaemia in children and young adults aged under 25 living close to nuclear facilities. The report is structured in three sections: - a reminder of the main characteristics of childhood leukaemia and a description of the methods used to conduct epidemiological studies; - the most exhaustive review possible of epidemiological studies published in the international literature describing the frequency of leukaemia close to nuclear facilities in different countries around the world. A critical analysis is made of the published results. Some results from studies not focused on nuclear facilities are also presented. The methodological limitations associated with descriptive studies are explained and discussed; - the last section discusses the possible causes of childhood leukaemia and the main hypotheses explored to explain certain clusters of cases observed locally close to some nuclear sites. Appendices at the end of the document provide additional explanations of the concepts and methods used in epidemiology and statistics, and of the classification of malignant hemopathies. (authors)

  3. Risk of childhood leukaemia in the vicinity of nuclear installations: Findings and recent controversies

    International Nuclear Information System (INIS)

    Dominique Laurier; Bernd Grosche; Hall, Per

    2002-01-01

    The identification of a local excess of cancer cases, possibly associated with ionizing radiation, always receives substantial media coverage and communication about clusters is difficult. We reviewed studies that examined the risk of leukaemia among young people near nuclear installations. An excess of leukaemia exists near some nuclear installations, at least for the reprocessing plants at Sellafield and Dounreay and the nuclear power plant Kruemmel. Nonetheless, the results of multi-site studies invalidate the hypothesis of an increased risk of leukaemia related to nuclear discharge. Up until now, analytic studies have not found an explanation for the leukaemia clusters observed near certain nuclear installations. The hypothesis of an infectious aetiology associated with population mixing has been proposed, but needs to be investigated further. The review illustrates two recent examples in France (La Hague reprocessing plant) and in Germany (Kruemmel power plant), where controversies developed after reports of increased leukaemia risks. These examples show the importance of recalling the current epidemiological knowledge and of using systematic recording of cases to replace the alleged excesses in a more general framework. Some elements should also be suggested from the recent French and German experiences to reinforce credibility in the results

  4. Current approach to the treatment of chronic myeloid leukaemia.

    Science.gov (United States)

    Pasic, Ivan; Lipton, Jeffrey H

    2017-04-01

    Of all the cancers, chronic myeloid leukaemia (CML) has witnessed the most rapid evolution of the therapeutic milieu in recent decades. The introduction of tyrosine kinase inhibitors (TKIs) as a therapeutic option has profoundly changed patient experience and outcome. The availability of multiple new highly effective therapies has increasingly underscored the importance of a good understanding of the underlying pathophysiological basis in CML, as well as patient-specific factors in choosing the right treatment for every individual. The treatment of CML has migrated in many jurisdictions from the office of a highly specialized malignant hematologist to the general hematologist or even a general practitioner. The goal of this review is to offer an overview of the modern approach to the treatment of CML, with an emphasis on chronic phase (CP) CML, including both TKI-based therapies such as imatinib, dasatinib, nilotinib, bosutinib and ponatinib, and non-TKI medications, such as omacetaxine. We discuss evidence behind each drug, most common and material adverse reactions and outline how this information can be used in selecting the right drug for the right patient. We also discuss evidence as it relates to other therapies, including stem cell transplant (SCT), and patients in accelerated (AP) and blastic phase (BP). Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. The cribriform plate: a sanctuary site for meningeal leukaemia

    International Nuclear Information System (INIS)

    Williams, M.V.

    1987-01-01

    Cranial irradiation is an effective prophylactic treatment for subclinical meningeal infiltration in lymphoblastic leukaemia, but, central nervous system (CNS) relapse still occurs in 6-10% of cases overall and as many as 30% of cases with a poor prognosis in some series. These recurrences may be due in part to inadvertent underdosage of the cribriform plate, centrally situated between the orbits and projected over their upper third in a lateral view. The dose to the adjacent meninges may thus be reduced by shielding of the radiosensitive lenses. This problem is exacerbated if conventional lateral fields centred on the mid-skull are used, because the eyes will not then project over one another. If the field centre is moved to the edge of the orbit, this problem of beam divergence can be overcome. Central axis beam blocking of both lenses is possible, in some patients the cribriform plate can be adequately irradiated. In most children the geometry of the orbit is such that it is necessary to add an anterior electron beam to ensure homogeneous dosage. These refinements in technique might prevent meningeal relapse with a lower whole-brain dose and, hence, fewer neurophyschological sequelae. (author)

  6. Sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia: case report.

    Science.gov (United States)

    Diao, M; Tian, F; Sun, J

    2014-11-01

    Sudden sensorineural hearing loss rarely occurs in patients with chronic myeloid leukaemia. We present a case report of a patient who presented with sudden sensorineural hearing loss as the first manifestation of chronic myeloid leukaemia, and review the mechanisms responsible for sudden sensorineural hearing loss in leukaemic patients. A 31-year-old female presented to our clinic with unilateral sudden sensorineural hearing loss and tinnitus. Pure tone audiometry revealed profound sensorineural hearing loss in the left ear at all frequencies. During an investigation into her hearing loss, the patient was found to have chronic myeloid leukaemia. Every case of sudden sensorineural hearing loss must be carefully evaluated, and haematological disorders must be considered in the differential diagnosis of sudden hearing loss.

  7. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Science.gov (United States)

    2012-01-01

    Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines. PMID:22640463

  8. Childhood leukaemia following medical diagnostic exposure to ionizing radiation in utero or after birth

    International Nuclear Information System (INIS)

    Wakeford, R.

    2008-01-01

    A statistical association between childhood leukaemia and an abdominal X-ray examination of the pregnant mother was first reported in 1956 from a case-control study of childhood cancer mortality conducted in Great Britain. This study, later called the Oxford Survey of Childhood Cancers (OSCC), was continued and eventually showed a highly statistically significant ∼50% proportional increase in the risk of childhood leukaemia associated with antenatal diagnostic radiography. The association has been confirmed by many case-control studies carried out around the world, the appropriately combined results of which show a highly statistically significant increase in risk that is compatible with the OSCC finding. There is no doubt about the reality of the statistical association, but a causal interpretation has been questioned. On balance, however, the evidence points to low-level irradiation of the fetus increasing the risk of leukaemia in childhood, with an excess relative risk coefficient of around 50 Gy -1 (equivalent to an excess absolute risk coefficient of about 3% Gy -1 ), although the uncertainty associated with these coefficients is considerable and they are likely to be overestimates. In contrast to exposure in utero, the evidence from case-control studies for an association between childhood leukaemia and postnatal exposure to medical diagnostic irradiation is equivocal and sometimes conflicting. Since standard radiation risk models predict that low-level exposure in the early years of life should produce an increased risk of childhood leukaemia that is roughly similar to that arising from fetal exposure, this absence of persuasive evidence is likely to be due to various problems with the studies. This is unfortunate given the rise in relatively high dose diagnostic procedures (e.g. paediatric CT scans) that would be predicted to materially increase the relative risk of childhood leukaemia. (authors)

  9. Impact on learning of an e-learning module on leukaemia: a randomised controlled trial

    Directory of Open Access Journals (Sweden)

    Morgulis Yuri

    2012-05-01

    Full Text Available Abstract Background e-learning resources may be beneficial for complex or conceptually difficult topics. Leukaemia is one such topic, yet there are no reports on the efficacy of e-learning for leukaemia. This study compared the learning impact on senior medical students of a purpose-built e-learning module on leukaemia, compared with existing online resources. Methods A randomised controlled trial was performed utilising volunteer senior medical students. Participants were randomly allocated to Study and Control groups. Following a pre-test on leukaemia administered to both groups, the Study group was provided with access to the new e-learning module, while the Control group was directed to existing online resources. A post-test and an evaluation questionnaire were administered to both groups at the end of the trial period. Results Study and Control groups were equivalent in gender distribution, mean academic ability, pre-test performance and time studying leukaemia during the trial. The Study group performed significantly better than the Control group in the post-test, in which the group to which the students had been allocated was the only significant predictor of performance. The Study group’s evaluation of the module was overwhelmingly positive. Conclusions A targeted e-learning module on leukaemia had a significant effect on learning in this cohort, compared with existing online resources. We believe that the interactivity, dialogic feedback and integration with the curriculum offered by the e-learning module contributed to its impact. This has implications for e-learning design in medicine and other disciplines.

  10. Risk of therapy-related leukaemia and preleukaemia after Hodgkin's disease. Relation to age, cumulative dose of alkylating agents, and time from chemotherapy

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, J; Specht, L; Larsen, S O

    1987-01-01

    391 patients treated intensively for Hodgkin's disease were followed for up to 15 years to evaluate the risk of therapy-related acute non-lymphocytic leukaemia (t-ANLL) and preleukaemia. Only two independent factors, patient age and cumulative dose of alkylating agents, were related to the risk...... of t-ANLL. The hazard rate of t-ANLL was roughly proportional to the square of patient age and to the total cumulative dose of alkylating agents. In 320 patients treated with alkylating agents the cumulative risk of t-ANLL increased steadily from 1 year after the start of treatment and reached 13.......0% (SE 3.0) at 10 years after which time there were no further cases. Calculated from cessation of therapy with alkylating agents, however, the cumulative risk curve increased steeply during the first 1-2 years then gradually levelled out and no new cases were observed beyond 7 years. With a 15-year...

  11. An international prognostic index for patients with chronic lymphocytic leukaemia (CLL-IPI): a meta-analysis of individual patient data.

    Science.gov (United States)

    2016-06-01

    The management of patients with chronic lymphocytic leukaemia is currently undergoing improvements due to novel therapies and a plethora of biological and genetic variables that add prognostic information to the classic clinical staging systems. We established an international consortium with the aim to create an international prognostic index for chronic lymphocytic leukaemia (CLL-IPI) that integrates the major prognostic parameters. We used results from a systematic search of the Cochrane Haematological Malignancies Group of MEDLINE, Embase, and Central databases for prospective, clinical phase 2 and 3 trials of chronic lymphocytic leukaemia, published between Jan 1, 1950, and Dec 31, 2010, which identified 13 trials. We contacted the principal investigators of these 13 trials, of which eight agreed to include individual patient data. We used the individual patient data from these phase 3 trials from France, Germany, Poland, the UK, and the USA to create the full analysis dataset. The full analysis dataset was randomly divided, using a random sample procedure, into training and internal-validation datasets. We did a univariate analysis and multivariate analyses using 27 baseline factors and overall survival as an endpoint. We assigned weighted risk scores to each factor included in the final multivariable model. We assessed the discriminatory value using C-statistics and also the validity and reproducibility of the CLL-IPI by subgroup analysis. We used two additional datasets from the Mayo Clinic (Rochester, MN, USA; MAYO cohort) and the SCALE Scandinavian population-based case-control study (SCAN cohort) as the external-validation datasets. 3472 treatment-naive patients were included in the full analysis dataset; 2308 were randomly segregated into the training dataset and 1164 into the internal-validation dataset. 838 patients were included in the MAYO cohort and 416 in the SCAN cohort. Median age of patients in the full analysis dataset was 61 years (range 27

  12. Beta-escin, a natural triterpenoid saponin from Chinese horse chestnut seeds, depresses HL-60 human leukaemia cell proliferation and induces apoptosis.

    Science.gov (United States)

    Niu, Yang P; Wu, Li M; Jiang, Yan L; Wang, Wen X; Li, Lian D

    2008-09-01

    Beta-escin, a natural triterpenoid saponin isolated from the seed of the horse chestnut, is known to generate a wide variety of biochemical and pharmacological effects. The purpose of the present study was to examine the apoptotic and antiproliferative activity of beta-escin in HL-60 human acute myeloid leukaemia cells. Antiproliferative activity was examined by soft agar colony assay and the trypan blue exclusion method. Apoptotic activity was evaluated by morphological analysis, annexin V analysis, DNA fragmentation analysis and flow cytometry cell cycle analysis. The results showed that beta-escin caused a significant inhibition of HL-60 cell proliferation in a dose- and time-dependent manner. Morphological evidence of apoptosis, including vacuolization, apoptotic nuclei fragmentation and apoptotic body formation, was observed in cells treated with 30 microg mL(-1) of beta-escin for 24, 48 and 72 h. A significant increase in the population of annexin V+ and PI- cells (early apoptotic) among the total cells was observed in cells treated with beta-escin (30-50 microg mL(-1)) for 24 h (Pescin (30-50 microg mL(-1)) for 48 h by agarose gel electrophoresis. Flow cytometry cell cycle analysis revealed that beta-escin (30-50 microg mL(-1)) induced G1-S arrest and led to a significant accumulation of the sub-G1 population in HL-60 cells (Pescin is a potent natural inhibitor of cell proliferation and inducer of apoptosis in HL-60 acute myeloid leukaemia cells. The results indicate that beta-escin may be a useful candidate agent for exploring potential antileukaemic drugs.

  13. Preditores de injúria renal aguda em pacientes submetidos ao transplante ortotópico de fígado convencional sem desvio venovenoso Predictors of acute kidney injury in patients undergoing a conventional orthotopic liver transplant without veno-venous bypass

    Directory of Open Access Journals (Sweden)

    Olival Cirilo L. da Fonseca-Neto

    2011-06-01

    Full Text Available RADICAL: Injúria renal aguda é uma das complicações mais comuns do transplante ortotópico de fígado. A ausência de critério universal para sua definição nestas condições dificulta as comparações entre os estudos. A técnica convencional para o transplante consiste na excisão total da veia cava inferior retro-hepática durante a hepatectomia nativa. Controvérsias sobre o efeito da técnica convencional sem desvio venovenoso na função renal continuam. OBJETIVO: Estimar a incidência e os fatores de risco de injúria renal aguda entre os receptores de transplante ortotópico de fígado convencional sem desvio venovenoso. MÉTODOS: Foram avaliados 375 pacientes submetidos a transplante ortotópico de fígado. Foram analisadas as variáveis pré, intra e pós-operatórias em 153 pacientes submetidos a transplante ortotópico de fígado convencional sem desvio venovenoso. O critério para a injúria renal aguda foi valor da creatinina sérica > 1,5 mg/dl ou débito urinário BACKGROUND: Acute kidney injury is one of the most common complications of orthotopic liver transplantation. The absence of universal criteria for definition of these conditions make comparisons difficult between studies. The conventional technique for transplantation is the total excision of the inferior vena cava during liver retro-native hepatectomy. Controversies about the effect of the conventional technique without venovenous bypass on renal function remain. AIM: To estimate the incidence and risk of acute kidney injury factors among recipients of orthotopic liver transplantation without conventional venovenous bypass. METHODS: Was studied 375 patients undergoing orthotopic liver transplantation. Variables were analyzed in preoperative, intraoperative and postoperative complications in 153 patients undergoing orthotopic liver transplantation without conventional venovenous bypass. The criterion for acute kidney injury was serum creatinine > 1.5 mg/dl or

  14. Splenic irradiation before bone marrow transplantation for chronic myeloid leukaemia

    International Nuclear Information System (INIS)

    Gratwohl, A.; Hermans, J.; Biezen, A.V.

    1996-01-01

    A total of 229 patients with chronic myeloid leukaemia (CML) in chronic phase were randomized between 1986 and 1990 to receive or not receive additional splenic irradiation as part of their conditioning prior to bone marrow transplantation (BMT). Both groups, 115 patients with and 114 patients without splenic irradiation, were very similar regarding distribution of age, sex, donor/recipient sex combination, conditioning, graft-versus-host disease (GvHD) prevention method and blood counts at diagnosis or prior to transplant. 135 patients (59%) are alive as of October 1995 with a minimum follow-up of 5 years. 52 patients have relapsed (23%), 26 patients in the irradiated, 26 patients in the non-irradiated group (n.s.) with a relapse incident at 6 years of 28%. The main risk factor for relapse was T-cell depletion as the method for GvHD prevention, and an elevated basophil count in the peripheral blood prior to transplant. Relapse incidence between patients with or without splenic irradiation was no different in patients at high risk for relapse, e.g. patients transplanted with T-cell-depleted marrows (P = n.s.) and in patients with low risk for relapse, e.g. patients transplanted with non-T-cell-depleted transplants and basophil counts 3% basophils in peripheral blood). In this patient group, relapse incidence was 11% at 6 years with splenic irradiation but 32% in the non-irradiated group (P = 0.05). Transplant-related mortality was similar whether patients received splenic irradiation or not. This study suggests an advantage in splenic irradiation prior to transplantation for CML in this subgroup of patients and illustrates the need for tailored therapy. (Author)

  15. Studies on the role of RNA tumour viruses in human leukaemia

    International Nuclear Information System (INIS)

    Nooter, K.

    1979-01-01

    A search has been made for an etiological role of retroviruses in human leukemia and cocultivation studies have led to the isolation of a presumed human type C virus which appeared to be oncogenic for experimental animals. The experimental procedures and results are fully discussed. The parallels between irradiation induced lymphomas in mice and leukaemias in man are explored. (C.F.)

  16. Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

    NARCIS (Netherlands)

    Jethwa, Alexander; Hüllein, Jennifer; Stolz, Tatjana; Blume, Carolin; Sellner, Leopold; Jauch, Anna; Sill, Martin; Kater, Arnon P.; te Raa, G. Doreen; Geisler, Christian; van Oers, Marinus; Dietrich, Sascha; Dreger, Peter; Ho, Anthony D.; Paruzynski, Anna; Schmidt, Manfred; von Kalle, Christof; Glimm, Hanno; Zenz, Thorsten

    2013-01-01

    Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were

  17. Targeted resequencing for analysis of clonal composition of recurrent gene mutations in chronic lymphocytic leukaemia

    DEFF Research Database (Denmark)

    Jethwa, Alexander; Hüllein, Jennifer; Stolz, Tatjana

    2013-01-01

    Recurrent gene mutations contribute to the pathogenesis of chronic lymphocytic leukaemia (CLL). We developed a next-generation sequencing (NGS) platform to determine the genetic profile, intratumoural heterogeneity, and clonal structure of two independent CLL cohorts. TP53, SF3B1, and NOTCH1 were...

  18. Childhood leukaemia risks: from unexplained findings near nuclear installations to recommendations for future research.

    Science.gov (United States)

    Laurier, D; Grosche, B; Auvinen, A; Clavel, J; Cobaleda, C; Dehos, A; Hornhardt, S; Jacob, S; Kaatsch, P; Kosti, O; Kuehni, C; Lightfoot, T; Spycher, B; Van Nieuwenhuyse, A; Wakeford, R; Ziegelberger, G

    2014-09-01

    Recent findings related to childhood leukaemia incidence near nuclear installations have raised questions which can be answered neither by current knowledge on radiation risk nor by other established risk factors. In 2012, a workshop was organised on this topic with two objectives: (a) review of results and discussion of methodological limitations of studies near nuclear installations; (b) identification of directions for future research into the causes and pathogenesis of childhood leukaemia. The workshop gathered 42 participants from different disciplines, extending widely outside of the radiation protection field. Regarding the proximity of nuclear installations, the need for continuous surveillance of childhood leukaemia incidence was highlighted, including a better characterisation of the local population. The creation of collaborative working groups was recommended for consistency in methodologies and the possibility of combining data for future analyses. Regarding the causes of childhood leukaemia, major fields of research were discussed (environmental risk factors, genetics, infections, immunity, stem cells, experimental research). The need for multidisciplinary collaboration in developing research activities was underlined, including the prevalence of potential predisposition markers and investigating further the infectious aetiology hypothesis. Animal studies and genetic/epigenetic approaches appear of great interest. Routes for future research were pointed out.

  19. Cases of leukaemia in the Sellafield area: the ''Sir Douglas Black'' report

    International Nuclear Information System (INIS)

    Dousset, M.; Jammet, H.

    1984-01-01

    The report of this Advisory Group was published in the summer of 1984. Its conclusions can be summarised as follows: 1. Epidemiological surveys, although still incomplete, show that the incidence of cases of leukaemia and deaths caused by leukaemia in persons under 25 years of age is ''unusual'' in the village of Seascale and the Millom rural district. However, they are not unique and the same phenomenon can be found in comparable population groups located far away from any nuclear plants. 2. Taking all children born Seascale since 1950 who lived in the village up until 1980, their equivalent dose in the red marrow of the bone caused by Sellafield nuclear waste and the Windscale reactor fire of 1957 is only 13% of the equivalent dose due to background radiation. 3. The excessive leukaemia mortality rate at Seascale cannot be explained by radioactive waste. For this, a factor of 40 to 400 would be necessary. However, since doubts remain with respect to Sellafield nuclear waste, it must be temporarily concluded that the hypothesis of a connexion between the proximity of the nuclear plant and the excessive leukaemia rate cannot be fully eliminated. But neither can it be easily proven. The advisory Group recommendations are relating to: the surveys to be carried on; the inspection to be improved around the Sellafield plant; the incumbent regulations to be taken into consideration [fr

  20. Childhood leukaemia in Europe after Chernobyl: Five year follow-up of cancer registry populations

    International Nuclear Information System (INIS)

    Parkin, D.M.; Black, R.J.; Kramarova, E.; Clayton, D.

    1997-01-01

    The European Childhood Leukaemia-Lymphoma Incidence Study (ECLIS) aims to monitor trends in the incidence of these diseases in European populations in relation to estimated exposures to radioactive material released at the time of the Chernobyl accident. Thirty-six cancer registries in 23 countries are collaborating in ECLIS, coordinated by the International Agency for Research on Cancer (IARC). 3 figs, 3 tabs

  1. Experience with alemtuzumab in treatment of chronic lymphocytic leukaemia in the Netherlands.

    NARCIS (Netherlands)

    Laros, B.A.P. van; Huisman, C.A.; Wijermans, P.W.; Schipperus, M.R.

    2007-01-01

    BACKGROUND: Alemtuzumab (MabCampath) is a monoclonal antibody against CD52, indicated as third-line treatment of chronic lymphocytic leukaemia (CLL). As most important side effect opportunistic infections are mentioned. It is, however, unknown whether these complications often lead to problems in

  2. Genome-wide association analysis implicates dysregulation of immunity genes in chronic lymphocytic leukaemia

    NARCIS (Netherlands)

    Law, Philip J; Berndt, Sonja I.; Speedy, Helen E; Camp, Nicola J; Sava, Georgina P; Skibola, Christine F.; Holroyd, Amy; Joseph, Vijai; Sunter, Nicola J; Nieters, Alexandra; Bea, Silvia; Monnereau, Alain; Martin-Garcia, David; Goldin, Lynn R; Clot, Guillem; Teras, Lauren R.; Quintela, Inés; Birmann, Brenda M.; Jayne, Sandrine; Cozen, Wendy; Majid, Aneela; Smedby, Karin E; Lan, Qing; Dearden, Claire; Brooks-Wilson, Angela R.; Hall, Andrew G; Purdue, Mark P.; Mainou-Fowler, Tryfonia; Vajdic, Claire M.; Jackson, Graham H; Cocco, Pierluigi; Marr, Helen; Zhang, Yawei; Zheng, Tongzhang; Giles, Graham G.; Lawrence, Charles; Call, Timothy G.; Liebow, Mark; Melbye, Mads; Glimelius, Bengt; Mansouri, Larry; Glenn, Martha; Curtin, Karen; Diver, W. Ryan; Link, Brian K.; Conde, Lucia; Bracci, Paige M.; Holly, Elizabeth A.; Jackson, Rebecca D.; Tinker, Lesley F.; Benavente, Yolanda; Boffetta, Paolo; Brennan, Paul; Maynadie, Marc; McKay, James; Albanes, Demetrius; Weinstein, Stephanie; Wang, Zhaoming; Caporaso, Neil E; Morton, Lindsay M.; Severson, Richard K.; Riboli, Elio; Vineis, Paolo; Vermeulen, Roel C H; Southey, Melissa C.; Milne, Roger L; Clavel, Jacqueline; Topka, Sabine; Spinelli, John; Kraft, Peter; Ennas, Maria Grazia; Summerfield, Geoffrey; Ferri, Giovanni M; Harris, Robert J; Miligi, Lucia; Pettitt, Andrew R; North, Kari E.; Allsup, David J; Fraumeni, Joseph F.; Bailey, James R; Offit, Kenneth; Pratt, Guy; Hjalgrim, Henrik; Pepper, Chris; Chanock, Stephen J.; Fegan, Chris; Rosenquist, Richard; De Sanjose, Silvia; Carracedo, Angel; Dyer, Martin J S; Catovsky, Daniel; Campo, Elias; Cerhan, James R.; Allan, James M; Rothman, Nathanial; Houlston, Richard S; Slager, Susan L.

    2017-01-01

    Several chronic lymphocytic leukaemia (CLL) susceptibility loci have been reported; however, much of the heritable risk remains unidentified. Here we perform a meta-analysis of six genome-wide association studies, imputed using a merged reference panel of 1,000 Genomes and UK10K data, totalling

  3. Periodic acid Schiff reaction in childhood lymphoblastic leukaemia. The Medical Research Council Working Party on Childhood Leukaemia.

    Science.gov (United States)

    Lilleyman, J S; Britton, J A; Anderson, L M; Richards, S M; Bailey, C C; Chessells, J M

    1994-01-01

    AIMS--To assess the prevalence and degree of periodic acid Schiff (PAS) positivity in blast cells from children with lymphoblastic leukaemia (ALL); its association with other disease characteristics; and its clinical importance in predicting the outcome of treatment. METHODS--Marrow slides from entrants to a large United Kingdom multicentre ALL trial (UKALL X) were batch processed and assessed blind for PAS positivity by one morphologist. Patients were classified into groups A, B, and C, corresponding to less than 1% PAS positive cells, 1-10%, and over 10%, respectively. Their PAS pattern was then compared with other clinical and pathological features of ALL and with treatment outcome. RESULTS--Slides from 921 children were examined of which 371 (40%) were categorised as group A, 324 (35%) as group B, and 226 (25%) as group C. There was a clear association between the presence of blast cell vacuoles on Romanowsky staining and PAS positivity. Group A (PAS negative) patients included a disproportionate excess of those with L2 morphology, those under 2 or over 6 years of age, those with an initial white cell count over 50 x 10(9)/l, those with a T or null cell immunophenotype, and those with chromosomal abnormalities other than "high hyperdiploidy". Four years from diagnosis, group C patients had an 8% disease free survival advantage over those in group A (2p = 0.01). This was irrespective of initial white cell count, but not of immunophenotype or the presence of vacuoles. CONCLUSIONS--Strong PAS positivity is a feature of "common" ALL and is particularly associated with blast cell vacuoles. It does occasionally occur in other disease subtypes with or without vacuoles. It predicts a better response to current treatment, but not independently of other cell characteristics. Images PMID:7962616

  4. Occupational exposure of fathers to ionizing radiation and the risk of leukaemia in offspring

    International Nuclear Information System (INIS)

    McLaughlin, J.R.; Clarke, E.A.; Anderson, T.W.; King, W.

    1992-08-01

    An epidemiologic study was performed to determine whether there was an association between childhood leukaemia and the occupational exposure of fathers in the nuclear industry to ionizing radiation prior to the child's conception. The study employed a case-control design. Children with cancer ('cases') and children who did not develop cancer ('controls') were compared with respect to their exposure history. The cases, which occurred from 1950 to 1988, consisted of children aged 0 to 14 years who died from or were diagnosed with leukaemia and were born to mothers who lived near an operating nuclear facility in Ontario. Eight controls were matched to each case according to date of birth and mother's residence. There were 112 cases and 890 controls (six controls died before the development of the associated case's leukaemia). Data on the occupational exposure of the 1002 fathers were obtained from the Canadian National Dose Registry (NDR) and examination of employer records. Links to the NDR were found for 95 fathers. For each father doses were obtained regarding whole body external dose, tritium dose, and (for uranium miners) internal exposures to the lungs due to radon and radon daughters. Radiation exposures were estimated (a) over the father's lifetime before the child's conception; (b) during the six months prior to the child's conception; (c) during the three months prior to the child's conception; and (d) over the father's lifetime, ending in the month of the child's diagnosis. There was no evidence of an elevated leukaemia risk in relation to any exposure period or exposure type, and there was no apparent gradient of effect with increasing radiation dose. It is concluded that there was no association between childhood leukaemia and the occupational exposure of fathers to ionizing radiation prior to conception or diagnosis. Odds ratios were close to 1.0 for all radiation dose categories and occupations except for uranium mining, which had a larger but not

  5. Effect of solcoseryl on antitumour action and acute toxicity of some antineoplastic drugs.

    Science.gov (United States)

    Danysz, A; Sołtysiak-Pawluczuk, D; Czyzewska-Szafran, H; Jedrych, A; Jastrzebski, Z

    1991-01-01

    The in vivo effect of Solcoseryl on the antitumour activity and acute toxicity of some antineoplastic drugs was examined. It was found that Solcoseryl does not inhibit the antineoplastic effectiveness of the drugs against transplantable P 388 leukaemia in mice. Studies of the effect of Solcoseryl on acute toxicity of selected antineoplastic drugs in mice revealed that the biostimulator could exert a modifying influence. The prior administration of Solcoseryl significantly decreases the acute toxicity of methotrexate but has no effect on acute toxicity of 5-fluorouracil, increases the acute toxicity of bleomycin and vinblastine and has no effect on acute toxicity of methotrexate and mitoxantron. On the other hand, Solcoseryl administered simultaneously with the antineoplastic drugs increases acute toxicity of 5-fluorouracil, bleomycin and mitoxantron. The protective effect of the biostimulator noted exclusively against acute toxicity of 5-fluorouracil was also observed after multiple administration of this anticancer drug.

  6. 27. The impact of introduction of code-stemi program on clinical outcomes of acute st-elevation myocardial infarction (stemi patients undergoing primary pci: Single center study in Saudi Arabia

    Directory of Open Access Journals (Sweden)

    A. ALYAHYA

    2016-07-01

    Full Text Available This study was conducted to evaluate the effect of direct Emergency Department activation of the Catheterization Lab on door to balloon (D2B time and outcomes of acute ST-elevation myocardial infarction (STEMI patients in King Khalid University Hospital (KKUH. Establishing dedicated comprehensive STEMI programs aiming at reducing door to balloon time will impact favourably the outcomes of patients presenting with acute STEMI. This was a retrospective cohort study that involved 100 patients in KKUH who presented with acute STEMI and underwent primary percutaneous intervention (PPCI, between June 2010 and January 2015. The cohort was divided into two groups, the first group consisted of 50 patients who were treated before establishing the Code-STEMI protocol, whereas the second group were 50 patients who were treated according to the protocol, which was implemented in June 2013. Code-STEMI program is a comprehensive program that includes direct activation of the cath lab team using a single call system, data monitoring and feedback, and standardized order forms. The mean age in both groups was 54 ± 12 years and 86% (43 and 94% (47 of the patients in the two groups were males, respectively. 90% (90 of patients in both groups had one or more comorbidities.Code-STEMI group had a significantly lower D2BT with 70% of patients treated within the recommended 90 minutes (median = 76.5 min, IQR: 63–90 min compared to only 26% of pre code-STEMI patients (median = 107 min, IQR: 74–149 min In-hospital complications were lower in the Code-STEMI group; however, the only statistically significant reduction was in non-fatal re-infarction, (8% vs. 0%, p = 0.043. In addition, the number of patients with more than one in-hospital complications was also reduced by 20%.Implementation of direct ER-Catheterization lab activation protocol was associated with a significant reduction in D2B time, and an overall improvement of in-hospital outcomes.

  7. Carnitine prevents the early mitochondrial damage induced by methylglyoxal bis(guanylhydrazone) in L1210 leukaemia cells.

    OpenAIRE

    Nikula, P; Ruohola, H; Alhonen-Hongisto, L; Jänne, J

    1985-01-01

    We previously found that the anti-cancer drug methylglyoxal bis(guanylhydrazone) (mitoguazone) depresses carnitine-dependent oxidation of long-chain fatty acids in cultured mouse leukaemia cells [Nikula, Alhonen-Hongisto, Seppänen & Jänne (1984) Biochem. Biophys. Res. Commun. 120, 9-14]. We have now investigated whether carnitine also influences the development of the well-known mitochondrial damage produced by the drug in L1210 leukaemia cells. Palmitate oxidation was distinctly inhibited in...

  8. Measuring the impact of a restrictive transfusion guideline in patients with acute myeloid leukaemia

    DEFF Research Database (Denmark)

    Hoeg, R T; Leinoe, E B; Andersen, P

    2013-01-01

    Interventions to change physician transfusion behavior are often evaluated by examining the amount of red blood cell (RBC) units transfused or the proportion of patients transfused before and after the intervention. The pre-transfusion haemoglobin concentration is a sensitive measure of transfusi...... concentration fell significantly. Pre-transfusion haemoglobin determination is a sensitive measure of the effect of an intervention to change physician transfusion behaviour....

  9. Safe and feasible outpatient treatment following induction and consolidation chemotherapy for patients with acute leukaemia

    DEFF Research Database (Denmark)

    Møller, Tom; Nielsen, Ove Juul; Welinder, Pernille

    2010-01-01

    incorporating comprehensive patient education for self-care management at home during pancytopenia and involvement of patients in care of their tunnelled central venous catheter (CVC). During neutropenia, patients are treated with prophylactic ciprofloxacine, amoxicillin/clavulanic acid and fluconazole. Herein...... were identified in the entire patient cohort, the latter exclusively observed in patients receiving antibiotic prophylaxis. The majority of the patients were able to take care of their CVC including change in dressing and heparin flushing. There were 12 CVC-related infections. There were no treatment...

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

    DEFF Research Database (Denmark)

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

    2000-01-01

    to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma