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Sample records for acute lymphoblastic leukaemia

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

    NARCIS (Netherlands)

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

    2012-01-01

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

  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

    2000-01-01

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

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

    Directory of Open Access Journals (Sweden)

    P. Schneider

    2011-01-01

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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1997-02-01

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

  5. [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...

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

    International Nuclear Information System (INIS)

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

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

    Directory of Open Access Journals (Sweden)

    Stanković Tatjana

    2008-01-01

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

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  9. Orbital mass secondary to infantile acute lymphoblastic leukaemia.

    Science.gov (United States)

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

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2014-01-01

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

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

    OpenAIRE

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

    1987-01-01

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

  12. Is this acute lymphoblastic leukaemia or juvenile rheumatoid arthritis.

    Science.gov (United States)

    Kirubakaran, Chellam; Scott, Julius Xavier; Ebenezer, Sam

    2011-08-01

    Arthritis could be a presenting feature of acute lymphoblastic leukaemia (ALL) and could be wrongly diagnosed as juvenile rheumatoid arthritis (JRA). Clinical and laboratory parameters might differentiate ALL and JRA in children who present with arthritis. Out of a total of 250 children of ALL, 10 were referred to the department of child health and paediatric haemato-oncology of Christian Medical College, Vellore during 1990-2002. They were compared with 10 age-matched children who had systematic onset of JRA. The age groups in ALL and JRA were 6.05 +/- 2.45 years and 5.47 +/- 4.4 years respectively. Severe pain as evidenced by inability to walk was found in children but one child with JRA was unable to walk (p JRA group. ESR was elevated in all cases in both the groups. One case in each group had antinuclear antibody positivity. It can be concluded that ALL can masquerade as systematic onset of JRA. So paediatricians should be careful enough while diagnosing the disease process.

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

    Science.gov (United States)

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

    2016-04-01

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

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

    DEFF Research Database (Denmark)

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

    2016-01-01

    toxic effects, that no two protocols shared identical definitions of all toxic effects, and that no toxic effect definition was shared by all protocols. Using the Delphi method over three face-to-face plenary meetings, consensus definitions were obtained for all 14 toxic effects. In the overall......Although there are high survival rates for children with acute lymphoblastic leukaemia, their outcome is often counterbalanced by the burden of toxic effects. This is because reported frequencies vary widely across studies, partly because of diverse definitions of toxic effects. Using the Delphi...... method, 15 international childhood acute lymphoblastic leukaemia study groups assessed acute lymphoblastic leukaemia protocols to address toxic effects that were to be considered by the Ponte di Legno working group. 14 acute toxic effects (hypersensitivity to asparaginase, hyperlipidaemia, osteonecrosis...

  15. 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.

  16. 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 and...

  17. 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....

  18. Venous thromboembolism in adults treated for acute lymphoblastic leukaemia: Effect of fresh frozen plasma supplementation

    NARCIS (Netherlands)

    I. Lauw (Ivoune); B. van der Holt (Bronno); S. Middeldorp (Saskia); J.C.M. Meijers; J.J. Cornelissen (Jan); B.J. Biemond (Bart)

    2013-01-01

    textabstractTreatment of acute lymphoblastic leukaemia (ALL) is frequently complicated by venous thromboembolism (VTE). The efficacy and optimal approach of VTE prevention are unclear, particularly in adult patients. We assessed the effect of thromboprophylaxis on symptomatic VTE incidence in cycle

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

    NARCIS (Netherlands)

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

    2004-01-01

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

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    S Jain

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Gulhadiye Avcu

    2016-03-01

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

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

    OpenAIRE

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

    2016-01-01

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

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

    OpenAIRE

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

    1991-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

  6. 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...

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

    DEFF Research Database (Denmark)

    Schmiegelow, Kjeld

    2016-01-01

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

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

    DEFF Research Database (Denmark)

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

    2012-01-01

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

  9. Visuomotor function in children treated for acute lymphoblastic leukaemia with chemotherapy only.

    Science.gov (United States)

    Knight, Sarah; McCarthy, Maria; Anderson, Vicki; Hutchinson, Esther; De Luca, Cinzia

    2014-01-01

    This study aimed to evaluate visuomotor function in children treated for acute lymphoblastic leukaemia (ALL). The performance of 64 children, 1-7 years post-chemotherapy for ALL, was compared to that of their healthy peers (n = 56) on visuomotor integration (VMI) and motor coordination (MC) tasks. Children posttreatment for ALL displayed significantly reduced VMI, but not MC, performances as compared to controls. Children treated on chemotherapy-only ALL regimes are at heightened risk for visuomotor integration deficits. Monitoring of visuomotor skills and implementation of appropriate interventions targeting higher level visuomotor integration skills should form an important component of any ALL long-term effects program. PMID:24571929

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1996-04-01

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

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

    OpenAIRE

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

    2012-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

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

    NARCIS (Netherlands)

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

    2007-01-01

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

  14. 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 le

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  17. Inherited coding variants at the CDKN2A locus influence susceptibility to acute lymphoblastic leukaemia in children

    DEFF Research Database (Denmark)

    Xu, Heng; Zhang, Hui; Yang, Wenjian;

    2015-01-01

    There is increasing evidence from genome-wide association studies for a strong inherited genetic basis of susceptibility to acute lymphoblastic leukaemia (ALL) in children, yet the effects of protein-coding variants on ALL risk have not been systematically evaluated. Here we show a missense varia...

  18. 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.

  19. 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 stem-cel

  20. 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......), methylated metabolites (E-MeMP), Methotrexate polyglutamates (E-MTX), and to thiopurine methyltransferase activity (TPMT)....

  1. 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.)

  2. 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...... within an asparaginase-intensive protocol has been poorly reported. Children (1-17 years) on the ongoing Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL2008 protocol with asparaginase-associated pancreatitis (AAP) diagnosed between 2008 and 2012 were identified through the online NOPHO...... 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...

  3. 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

    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......A very precise and reproducible polymerase chain reaction (PCR) method was developed in order to quantify minimal residual disease (MRD) in children with acute lymphoblastic leukaemia (ALL). A clone-specific competitor was constructed by introducing a restriction site in a PCR product identical...... to parts of the highly specific rearranged T-cell receptor delta (TCR-delta), T-cell receptor gamma (TCR-gamma), or immunoglobulin heavy chain (IgH) genes of the malignant clone. Using primers located externally to the restriction site the competitor and the DNA from the malignant clone will be amplified...

  4. Arthroplasties of hips and knees ankylosis in an adolescent with acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Dipo Samuel OLABUMUYI

    2011-10-01

    Full Text Available Acute lymphoblastic leukaemia (ALL is the most common malignancy in children, representing one third of all paediatric malignancies. Patients are often at high risk for complications due aggressive chemotherapy regimes required for treatment. Musculoskeletal complications include septic arthritis, osteonecrosis, osteoporosis, avascular necrosis and bony ankylosis. We report the case of a 16-year-old boy with ALL who developed osteonecrosis of multiple bones on a background of septicaemia, resulting in bony ankylosis of both hips and knees. He was treated with bilateral conversion of ankylosed hips (one hip to total hip replacement, the second hip to Girdlestone arthroplasty and bilateral ankylosed knees to total knee replacements. He remained well in remission five years after the last surgery. Our case highlights he possible musculoskeletal complications of ALL. 

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

    Directory of Open Access Journals (Sweden)

    Yatiee Swany Lahuri

    2015-11-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  8. Long-term in vitro maintenance of clonal abundance and leukaemia-initiating potential in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Pal, D; Blair, H J; Elder, A; Dormon, K; Rennie, K J; Coleman, D J L; Weiland, J; Rankin, K S; Filby, A; Heidenreich, O; Vormoor, J

    2016-08-01

    Lack of suitable in vitro culture conditions for primary acute lymphoblastic leukaemia (ALL) cells severely impairs their experimental accessibility and the testing of new drugs on cell material reflecting clonal heterogeneity in patients. We show that Nestin-positive human mesenchymal stem cells (MSCs) support expansion of a range of biologically and clinically distinct patient-derived ALL samples. Adherent ALL cells showed an increased accumulation in the S phase of the cell cycle and diminished apoptosis when compared with cells in the suspension fraction. Moreover, surface expression of adhesion molecules CD34, CDH2 and CD10 increased several fold. Approximately 20% of the ALL cells were in G0 phase of the cell cycle, suggesting that MSCs may support quiescent ALL cells. Cellular barcoding demonstrated long-term preservation of clonal abundance. Expansion of ALL cells for >3 months compromised neither feeder dependence nor cancer initiating ability as judged by their engraftment potential in immunocompromised mice. Finally, we demonstrate the suitability of this co-culture approach for the investigation of drug combinations with luciferase-expressing primograft ALL cells. Taken together, we have developed a preclinical platform with patient-derived material that will facilitate the development of clinically effective combination therapies for ALL.

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    Institute of Scientific and Technical Information of China (English)

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

    2004-01-01

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

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

    OpenAIRE

    Chan, Shu-wing, Sophia; 陳舒穎

    2015-01-01

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

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

    OpenAIRE

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

    2013-01-01

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

  14. 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....

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

    Directory of Open Access Journals (Sweden)

    Robert J Weeks

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

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

    Directory of Open Access Journals (Sweden)

    Kostić Gordana

    2009-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Nóra Kutszegi

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

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

    Directory of Open Access Journals (Sweden)

    Daphne eChen

    2012-11-01

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

  19. Longitudinal assessment of nutritional status in children treated for acute lymphoblastic leukaemia in Cuba.

    Science.gov (United States)

    González, A; Cortina, L; González, P; González, C; García, T; de Svarch, E G

    2004-05-01

    Malnutrition has a deleterious effect on the results of therapy for malignant diseases in childhood. The impact of radiotherapy on growth is well known but the impact of cytotoxic drugs on nutritional status is more controversial. The purpose of this study was to determine the nutritional status of a cohort of children treated for acute lymphoblastic leukaemia (ALL) in Cuba. The study involved 49 children admitted to a single center and treated with a Berlin-Frankfurt-Munster-based protocol. Nutritional assessment included measurements of height, weight, body mass index and skin-fold thickness, made at diagnosis, after the intensive phase of treatment and at the end of therapy. Z-scores were used for height and comparison of percentiles for the rest of the variables. All the patients were above the third percentile in all the measurements. There were no statistically significant differences between the results at diagnosis, after intensive therapy and at the end of treatment. Although the sample was small, there was no demonstrable effect of chemotherapy on nutritional status in this Cuban paediatric population, in contrast to that reported in children with ALL in other developing countries.

  20. 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.

  1. The pre-B-cell receptor checkpoint in acute lymphoblastic leukaemia.

    Science.gov (United States)

    Eswaran, J; Sinclair, P; Heidenreich, O; Irving, J; Russell, L J; Hall, A; Calado, D P; Harrison, C J; Vormoor, J

    2015-08-01

    The B-cell receptor (BCR) and its immature form, the precursor-BCR (pre-BCR), have a central role in the control of B-cell development, which is dependent on a sequence of cell-fate decisions at specific antigen-independent checkpoints. Pre-BCR expression provides the first checkpoint, which controls differentiation of pre-B to immature B-cells in normal haemopoiesis. Pre-BCR signalling regulates and co-ordinates diverse processes within the pre-B cell, including clonal selection, proliferation and subsequent maturation. In B-cell precursor acute lymphoblastic leukaemia (BCP-ALL), B-cell development is arrested at this checkpoint. Moreover, malignant blasts avoid clonal extinction by hijacking pre-BCR signalling in favour of the development of BCP-ALL. Here, we discuss three mechanisms that occur in different subtypes of BCP-ALL: (i) blocking pre-BCR expression; (ii) activating pre-BCR-mediated pro-survival and pro-proliferative signalling, while inhibiting cell cycle arrest and maturation; and (iii) bypassing the pre-BCR checkpoint and activating pro-survival signalling through pre-BCR independent alternative mechanisms. A complete understanding of the BCP-ALL-specific signalling networks will highlight their application in BCP-ALL therapy.

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

    Science.gov (United States)

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

    2015-09-01

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

  3. Alternating hemiparesis and orolingual apraxia as manifestations of methotrexate neurotoxicity in a paediatric case of acute lymphoblastic leukaemia.

    Science.gov (United States)

    Yap, Siew Mei; MacEneaney, Peter; Ryan, Clodagh; O'Toole, Orna

    2016-01-01

    A 15-year-old girl with a recent diagnosis of acute lymphoblastic leukaemia was admitted to hospital with pancytopaenia after having received high-dose intrathecal methotrexate 1 day prior. During the next week she had intermittent episodes of alternating hemiparesis associated with speech arrest lasting minutes to hours at a time. The episodes were not associated with altered level of consciousness or headache. MRI of the brain showed features consistent with methotrexate encephalopathy. This report discusses the typical clinical and radiological features of methotrexate neurotoxicity in addition to differential diagnoses and the proposed pathophysiological mechanisms. PMID:27113788

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

    Science.gov (United States)

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

    2016-02-01

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

  5. 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.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

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

    NARCIS (Netherlands)

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

    2006-01-01

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

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

    NARCIS (Netherlands)

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

    1998-01-01

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

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

    DEFF Research Database (Denmark)

    Rosthøj, Susanne; Keiding, Niels; Schmiegelow, Kjeld

    2012-01-01

    Childhood acute lymphoblastic leukaemia is treated with long-term intensive chemotherapy. During the latter part of the treatment, the maintenance therapy, the patients receive oral doses of two cytostatics. The doses are tailored to blood counts measured on a weekly basis, and the treatment...... of the methods in relation to the formulation of alternative dosing strategies for the maintenance therapy....

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  11. 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...

  12. Myocardial 2D strain echocardiography and cardiac biomarkers in children during and shortly after anthracycline therapy for acute lymphoblastic leukaemia (ALL): a prospective study

    NARCIS (Netherlands)

    Mavinkurve-Groothuis, A.M.C.; Marcus, K.A.; Pourier, M.; Loonen, J.; Feuth, T.; Hoogerbrugge, P.M.; Korte, C.L. de; Kapusta, L.

    2013-01-01

    AIMS: The aim of this study was to investigate myocardial 2D strain echocardiography and cardiac biomarkers in the assessment of cardiac function in children with acute lymphoblastic leukaemia (ALL) during and shortly after treatment with anthracyclines. METHODS AND RESULTS: Cardiac function of 60 c

  13. 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

  14. Management of adult and paediatric acute lymphoblastic leukaemia in Asia: resource-stratified guidelines from the Asian Oncology Summit 2013

    Science.gov (United States)

    Yeoh, Allen EJ; Tan, Daryl; Li, Chi-Kong; Hori, Hiroki; Tse, Eric; Pui, Ching-Hon

    2014-01-01

    The survival rates for both adult and children with acute lymphoblastic leukaemia have improved substantially in recent years with wider use of improved risk-directed therapy and supportive care. In nearly all developed countries, clinical practice guidelines have been formulated by multidisciplinary panels of leukaemia experts, with the goal of providing recommendations on standard treatment approaches based on current evidence. However, those guidelines do not take into account resource limitations in low-income countries, including financial and technical challenges. In Asia, there are huge disparities in economy and infrastructure among the countries, and even among different regions in some large countries. This review summarizes the recommendations developed for Asian countries by a panel of adult and paediatric leukaemia therapists, based on the availability of financial, skill and logistical resources, at a consensus session held as part of the 2013 Asian Oncology Summit in Bangkok, Thailand. The management strategies described here are stratified by a four-tier system (basic, limited, enhanced and maximum) based on the resources available to a particular country or region. PMID:24176570

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

    Science.gov (United States)

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

    1993-01-01

    A total of 2192 children with acute lymphoblastic leukaemia who had reached cessation of therapy in complete remission were followed for a median time of 52 months after treatment suspension. Of the 485 relapses observed, 62.3% occurred in the first year off therapy and 68.9% involved the bone marrow. Eight relapses were reported more than 5 years (62-143 months) after treatment withdrawal. Males fared worse than females consistently, experiencing 1.5 times more relapses (P 20 years) were married and 16 have had 21 healthy children. Twenty-four per cent of patients experienced an unfavourable event. Relapses accounted for 93% of failures. Central nervous system late effects and second malignancies were the major causes of non-leukaemic morbidity and mortality.

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

    Science.gov (United States)

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

    2016-08-01

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

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

    OpenAIRE

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

    2010-01-01

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

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

    OpenAIRE

    Celena eScheede-Bergdahl; R Thomas Jagoe

    2013-01-01

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

  19. PKCζ and PKMζ are overexpressed in TCF3-rearranged paediatric acute lymphoblastic leukaemia and are associated with increased thiopurine sensitivity.

    Science.gov (United States)

    Hartsink-Segers, S A; Beaudoin, J J; Luijendijk, M W J; Exalto, C; Pieters, R; Den Boer, M L

    2015-02-01

    Both tumour suppressor and oncogenic functions have been ascribed to the atypical zeta isoform of protein kinase C (PKCζ), whereas its constitutively active form PKMζ is almost exclusively expressed in the brain where it has a role in long-term memory. Using primers unique for either isoform, we found that both PKCζ and PKMζ were expressed in a subset of paediatric acute lymphoblastic leukaemia (ALL) cases carrying a TCF3 (E2A) chromosomal rearrangement. Combined PKCζ and PKMζ (PKC/Mζ) protein as well as phosphorylation levels were elevated in ALL cases, especially TCF3-rearranged precursor B-ALL cases, compared with normal bone marrow (P<0.01). Furthermore, high PKC/Mζ expression in primary ALL cells was associated with increased sensitivity to 6-thioguanine and 6-mercaptopurine (P<0.01), thiopurines used in ALL treatment. PKCζ is believed to stabilize mismatch-repair protein MSH2, facilitating thiopurine responsiveness in T-ALL. However, PKC/Mζ knockdown in a TCF3-rearranged cell line model decreased MSH2 expression but did not induce thiopurine resistance, indicative that the link between high PKC/Mζ levels and thiopurine sensitivity in paediatric precursor B-ALL is not directly causal. Collectively, our data indicate that thiopurine treatment may be effective, especially in paediatric TCF3-rearranged ALL and other patients with a high expression of PKC/Mζ.

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

    Science.gov (United States)

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

    2016-01-01

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

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

    Science.gov (United States)

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

    2001-08-01

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

  2. Vitamin and mineral supplements in pregnancy and the risk of childhood acute lymphoblastic leukaemia: a case-control study

    Directory of Open Access Journals (Sweden)

    Skegg David CG

    2007-07-01

    Full Text Available Abstract Background An earlier case-control study from Western Australia reported a protective effect of maternal folic acid supplementation during pregnancy on the risk of childhood acute lymphoblastic leukaemia (ALL. The present study tested that association. Methods A national case-control study was conducted in New Zealand. The mothers of 97 children with ALL and of 303 controls were asked about vitamin and mineral supplements taken during pregnancy. Results There was no association between reported folate intake during pregnancy and childhood ALL (adjusted odds ratio (OR 1.1, 95% confidence interval (CI 0.5–2.7. Combining our results with the study from Western Australia and another study from Québec in a meta-analysis gave a summary OR of 0.9 (95% CI 0.8–1.1. Conclusion Our own study, of similar size to the Australian study, does not support the hypothesis of a protective effect of folate on childhood ALL. Neither do the findings of the meta-analysis.

  3. 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.

  4. 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

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

    Energy Technology Data Exchange (ETDEWEB)

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

    1991-09-01

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

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

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    Kaspers Gert Jan L

    2008-11-01

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

  7. Prospective molecular monitoring of BCR/ABL transcript in children with Ph+ acute lymphoblastic leukaemia unravels differences in treatment response.

    Science.gov (United States)

    Cazzaniga, Giovanni; Lanciotti, Marina; Rossi, Vincenzo; Di Martino, Daniela; Aricò, Maurizio; Valsecchi, Maria Grazia; Basso, Giuseppe; Masera, Giuseppe; Micalizzi, Concetta; Biondi, Andrea

    2002-11-01

    Children with Philadelphia-chromosome-positive (Ph+) acute lymphoblastic leukaemia (ALL) represent a subgroup at very high risk for treatment failure, despite intensive chemotherapy. However, recent retrospective studies showed that Ph+ childhood ALL is a heterogeneous disease with regard to treatment response. We have prospectively monitored, by reverse transcription polymerase chain reaction (RT-PCR) during follow-up, the presence of the BCR/ABL fusion transcript in Ph+ ALL children diagnosed in the Italian multicentre Associazione Italiana Ematologia Oncologia Pediatrica ALL-AIEOP-95 therapy protocol. To our knowledge, this is the first report on the evaluation of minimal residual disease (MRD) in childhood Ph+ ALL prospectively enrolled in an intensive, Berlin-Frankfurt-Munster (BFM)-type treatment protocol. Twenty-seven of 36 (75.0%) Ph+ patients consecutively enrolled into the high-risk group of the AIEOP-ALL protocol between May 1995 and October 1999 were successfully analysed. Twenty were good responders to the pre-phase of prednisone/intrathecal methotrexate treatment (PGR) and seven were poor responders (PPR). Within the PPR group, the RT-PCR monitoring constantly showed positivity for the BCR/ABL fusion transcript and all the patients died of disease progression. In contrast, highly sensitive qualitative RT-PCR monitoring revealed heterogeneity within the PGR group of Ph+ childhood ALL patients. Three different subgroups could be defined, according to the clearance of Ph+ cells within the first 5 months of treatment. This provides useful information on the capability of chemotherapy to reduce the leukaemic clone, with prognostic implications.

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

  9. 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.

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

    Directory of Open Access Journals (Sweden)

    Dokmanović Lidija

    2008-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Lohit Kumar Kalita

    2015-05-01

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

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

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    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.

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

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    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.

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

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    Mohammed Al Reesi

    2014-10-01

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

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

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

    2008-01-01

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

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

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    Elva Jiménez-Hernández

    2015-01-01

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

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

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    Vujić Dragana

    2010-01-01

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

  19. 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...

  20. 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.

  1. Deletion mapping indicates that MTS1 is the target of frequent deletions at chromosome 9p21 in paediatric acute lymphoblastic leukaemias.

    Science.gov (United States)

    Guidal-Giroux, C; Gérard, B; Cavé, H; Duval, M; Rohrlich, P; Elion, J; Vilmer, E; Grandchamp, B

    1996-02-01

    Recent reports have indicated a high frequency of deletions of MTS1 (CDKN2, p16ink4, CDKI4) in acute lymphoblastic leukaemias (ALLs). This gene is located at chromosome 9p21 and encodes an inhibitor of cyclin D-dependent kinases. In contrast with the observations in some other malignancies, no inactivation of MTS1 by intragenic mutation was demonstrated in leukaemias. A contribution of MTS1 alterations to leukaemogenesis therefore remains questionable. In order to test for the implication of MTS1 as a tumour suppressor gene in paediatric ALLs we have explored the 9p21 chromosomal region of 46 children with this disease. The copy number of the MTS1 gene in blasts from the patients was determined using a quantitative PCR assay enabling us to precisely detect mono- and bi-allelic deletions. Rearrangements of the gene were sought by Southern blot analysis. The extent of the deletions was studied using microsatellite markers spanning the 9p21 chromosomal region. Point mutations were sought in exon 1 and exon 2 of the MTS1 gene in patients with a mono-allelic deletion in addition, exon 2 of MTS1, which contains two-thirds of the coding region, was sequenced in all patients who had no deletion of the gene. Altogether, our data are consistent with the view that MTS1 is the target of 9p21 deletions. Either one or two alleles of the gene were deleted in 36% of non-selected children with B-lineage ALL and both alleles were deleted in all seven patients we studied with T-lineage ALL. The absence of any point mutation implies that the major mechanism of inactivation of MTS1 in ALLs is deletional.

  2. 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.)

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

    Directory of Open Access Journals (Sweden)

    Ashish Narayan Masurekar

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

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

    Science.gov (United States)

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

    2016-09-01

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

  5. Implications of delayed bone marrow aspirations at the end of treatment induction for risk stratification and outcome in children with acute lymphoblastic leukaemia.

    Science.gov (United States)

    Zuna, Jan; Moericke, Anja; Arens, Mari; Koehler, Rolf; Panzer-Grümayer, Renate; Bartram, Claus R; Fischer, Susanna; Fronkova, Eva; Zaliova, Marketa; Schrauder, André; Stanulla, Martin; Zimmermann, Martin; Trka, Jan; Stary, Jan; Attarbaschi, Andishe; Mann, Georg; Schrappe, Martin; Cario, Gunnar

    2016-06-01

    Minimal residual disease (MRD) at the end of induction therapy is important for risk stratification of acute lymphoblastic leukaemia (ALL), but bone marrow (BM) aspiration is often postponed or must be repeated to fulfil qualitative and quantitative criteria for morphological assessment of haematological remission and/or MRD analysis. The impact of BM aspiration delay on measured MRD levels and resulting risk stratification is currently unknown. We analysed paired MRD data of 289 paediatric ALL patients requiring a repeat BM aspiration. MRD levels differed in 108 patients (37%) with a decrease in the majority (85/108). This would have resulted in different risk group allocation in 64 of 289 patients (23%) when applying the ALL-Berlin-Frankfurt-Münster 2000 criteria. MRD change was associated with the duration of delay; 40% of patients with delay ≥7 days had a shift to lower MRD levels compared to only 18% after a shorter delay. Patients MRD-positive at the original but MRD-negative at the repeat BM aspiration (n = 50) had a worse 5-year event-free survival than those already negative at first aspiration (n = 115) (86 ± 5% vs. 94 ± 2%; P = 0·024). We conclude that BM aspirations should be pursued as scheduled in the protocol because delayed MRD sampling at end of induction may result in false-low MRD load and distort MRD-based risk assessment.

  6. 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.)

  7. CD38+ CD58- is an independent adverse prognostic factor in paediatric Philadelphia chromosome negative B cell acute lymphoblastic leukaemia patients.

    Science.gov (United States)

    Li, Xu-Mian; Zhang, Le-Ping; Wang, Ya-Zhe; Lu, Ai-Dong; Chang, Yan; Zhu, Hong-Hu; Qin, Ya-Zhen; Lai, Yue-Yun; Kong, Yuan; Huang, Xiao-Jun; Liu, Yan-Rong

    2016-04-01

    To explore new risk predictors for a high risk of relapse in Philadelphia chromosome negative (Ph-) B cell acute lymphoblastic leukaemia (B-ALL) patients, 196 paediatric Ph- B-ALL patients (≤ 18 years) were retrospectively analysed. We mainly focus on investigating the prognostic value of CD38 and CD58 expression in leukemic blasts in these patients by four colour flow cytometry. The CD38+ CD58- group (n=16) had a higher relapse rate, a shorter 3-year event-free survival (EFS) and overall survival (OS) than the CD38+ CD58+ group (n=157; 31.3% vs 10.2%, P=0.04; 52.4% vs 92.3%, P<0.01; 32.5% vs 91.0%, P=0.01); CD38+ CD58- was an independent adverse prognostic predictor for relapse (hazard ratio [HR], 0.203; 95%CI, 0.063-0.656; P=0.01), 3-year EFS (HR, 0.091; 95%CI, 0.023-0.355; P<0.01) and OS (HR, 0.102; 95%CI, 0.026-0.3971; P<0.01) in this cohort, as determined by Cox multivariate analysis. We identified, for the first time, a higher risk population of paediatric Ph- B-ALL patients with CD38+ CD58- who had a higher relapse risk and a shorter survival. Our results may allow better risk stratification and individualized treatment.

  8. L-Asparaginase as potent anti-leukemic agent and its significance of having reduced glutaminase side activity for better treatment of acute lymphoblastic leukaemia.

    Science.gov (United States)

    Ramya, L N; Doble, Mukesh; Rekha, V P B; Pulicherla, K K

    2012-08-01

    Acute lymphoblastic leukaemia (ALL) is one of the leading types of malignant disorder seen in children. Viral infections, genetic factors and exposure to chemical carcinogens are some of the factors responsible for causing ALL. Treatment strategies followed for curing ALL include chemotherapy or radiation therapy, wherein, chemotherapy involves the use of the enzymatic drug L-Asparaginase. The enzyme can be produced from various plants, animals, bacterial and fungal sources but, among them, bacterial sources are widely used for production of this enzyme. The enzyme is non-human in origin having certain bottle necks with L-Asparaginase therapy in the form of side effects such as pancreatitis, thrombosis which are mainly due to glutaminase side activity. Hence, present-day research is mainly focussed on minimizing or completely eliminating the glutaminase activity of the enzyme L-Asparaginase. This review is focussed on the complications associated with glutaminase side activity and use of glutaminase free enzymatic drug L-Asparaginase in treating ALL and the other developments related to the modification of the drug for quality treatment. PMID:22684410

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

    Directory of Open Access Journals (Sweden)

    Vargha-Khadem Faraneh

    2011-10-01

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

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

    Directory of Open Access Journals (Sweden)

    Celena eScheede-Bergdahl

    2013-04-01

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

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

    Science.gov (United States)

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

    2011-01-01

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

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

    OpenAIRE

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

    1998-01-01

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

  13. 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.

  14. 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.

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

    Institute of Scientific and Technical Information of China (English)

    王学文

    2011-01-01

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

  16. Etoposide, Prednisone, Vincristine Sulfate, Cyclophosphamide, and Doxorubicin Hydrochloride With Asparaginase in Treating Patients With Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    Science.gov (United States)

    2016-04-26

    B Acute Lymphoblastic Leukemia; B Lymphoblastic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent B Lymphoblastic Lymphoma; Recurrent T Lymphoblastic Leukemia/Lymphoma; Refractory B Lymphoblastic Lymphoma; Refractory T Lymphoblastic Lymphoma; T Acute Lymphoblastic Leukemia; T Lymphoblastic Lymphoma

  17. Childhood Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  18. Bortezomib and Combination Chemotherapy in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Lymphoblastic Lymphoma

    Science.gov (United States)

    2014-09-30

    B-cell Adult Acute Lymphoblastic Leukemia; B-cell Childhood Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Lymphoblastic Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma; T-cell Adult Acute Lymphoblastic Leukemia; T-cell Childhood Acute Lymphoblastic Leukemia

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

    OpenAIRE

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

    2006-01-01

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

  20. LONGITUDINAL ANTHROPOMETRIC STUDY IN CHILDREN WITH ACUTE LYMPHOBLASTIC-LEUKEMIA

    NARCIS (Netherlands)

    TAMMINGA, RYJ; KAMPS, WA; DRAYER, NM; HUMPHREY, GB

    1992-01-01

    In four groups of patients with acute lymphoblastic leukaemia, anthropometric variables were investigated every 3 months for 2 years. Group 1 (n = 7) was treated with a high-risk protocol, group 2 (n = 13) with a standard-risk protocol including cranial irradiation, group 3 (n = 13) with a standard-

  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.

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

    Science.gov (United States)

    2016-10-24

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

  3. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  4. General Information about Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  5. Stages of Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

  6. Treatment Options for Adult Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... Treatment Childhood AML Treatment Research Adult Acute Lymphoblastic Leukemia Treatment (PDQ®)–Patient Version General Information About Adult Acute Lymphoblastic Leukemia Go to Health Professional Version Key Points Adult ...

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  8. Gene expression profiling in acute myeloid leukaemia

    NARCIS (Netherlands)

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

    2011-01-01

    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 morpholog

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

    Science.gov (United States)

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

    1998-06-01

    From June 1990 to February 1996, 35 patients with B-cell acute lymphoblastic leukaemia (B-ALL) 13 of whom had CNS disease and 28 patients with stage IV B-cell non-Hodgkin's lymphoma (B-NHL) 22 of whom had CNS involvement were treated with a short, intensive multiagent chemotherapy regimen (UKCCSG 9003 protocol) based on the French LMB 86 regimen. Fifty-five were boys. The age range was 11 months to 16.5 years (median 8.4 years). Chemotherapy included cyclophosphamide, vincristine, daunorubicin, high-dose methotrexate (COPADM) and etoposide/high-dose cytarabine (CYVE) with frequent intrathecal (i.t.) triple therapy (methotrexate, cytarabine and hydrocortisone). Cranial irradiation (24 Gy in 15 fractions) was recommended in patients with overt CNS disease. One patient with Wiskott-Aldrich syndrome was withdrawn after entry and has been excluded from the analysis. Ten patients (16%) have relapsed (CNS, four; BM, two; combined CNS and BM, three; and jaw, one) 4-11 months after diagnosis and two patients never achieved complete remission (CR). All have died. In seven of the patients who relapsed, treatment had been modified or delayed because of poor clinical condition. Seven patients (11%) died of toxicity 11 days to 4 months after diagnosis. The cause of death was sepsis (n = 5) or sepsis with renal failure (n = 2). With a median follow-up of 3.1 years from diagnosis (range 9 months to 6.3 years), 43 patients (69%) survive in CR. This study confirms the effectiveness of this regimen with regard to the relapse rate (16%), although the rate of toxic death is of concern. PMID:9649146

  10. Combination Chemotherapy With or Without Donor Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-09-09

    Adult Acute Lymphoblastic Leukemia in Remission; Adult B Acute Lymphoblastic Leukemia; Adult B Acute Lymphoblastic Leukemia With t(9;22)(q34;q11.2); BCR-ABL1; Adult L1 Acute Lymphoblastic Leukemia; Adult L2 Acute Lymphoblastic Leukemia; Adult T Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

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

    Science.gov (United States)

    2013-10-07

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

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

    Science.gov (United States)

    2016-08-25

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

  13. Medical Research Council leukaemia trial--UKALL V: an attempt to reduce the immunosuppressive effects of therapy in childhood acute lymphoblastic leukemia. Report to the Council by the Working Party on Leukaemia in Childhood.

    Science.gov (United States)

    Chessells, J M; Durrant, J; Hardy, R M; Richards, S

    1986-12-01

    The Medical Research Council UKALL V trial for children with standard-risk acute lymphoblastic leukemia (ALL) (aged 1 to 14 years, leucocyte count less than 20 X 10(9)/L) was designed to determine whether the immunosuppressive effects of treatment could be reduced without sacrifice of antileukemic effect by alterations in the type of continuing therapy or in fractionation of cranial irradiation. Remission was achieved in 496 children on standard induction therapy, and 309 children received 24 Gy of cranial irradiation in ten to 16 fractions over 21 days, and 174 received 21 Gy in five to nine fractions over 21 days. The type of radiotherapy administered had no influence on relapse at any site or rate of death in remission. All 496 children were randomized to receive chemotherapy for 2 or 3 years with 6-mercaptopurine and methotrexate either as a continuous (group C) or a semicontinuous (group G) regimen or as a five-day pulse every 3 weeks (group I). All groups also received vincristine and prednisolone every 6 weeks. With a minimum follow-up of almost 7 years, patients in group I had significantly fewer remission deaths (P = .025) but a much higher rate of bone marrow relapse than those in group C or G (P = .002). There was an overall benefit for 3 years of chemotherapy compared with 2 years, which in contrast to previous studies, was more apparent in girls and in patients in groups C and G. Testicular relapse occurred in 37 boys, including 19 patients off therapy, with a previously negative biopsy. The overall results confirmed the prognostic significance of initial leucocyte count, even among these standard-risk patients, while girls had a superior rate of disease-free survival, but not of hematologic remission. It is concluded that, even among standard-risk patients, the prognosis is influenced by the height of the initial leukocyte count. While alterations in the fractionation of cranial irradiation do not appear to have influenced disease-free survival

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

    Science.gov (United States)

    2014-03-20

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

  15. Osteonecrosis in children treated for acute lymphoblastic leukemia: a magnetic resonance imaging study after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Ojala, A.; Lanning, F.; Paakko, E.; Lanning, B. [Oulu Univ. (Finland)

    1998-02-01

    The purpose of this study was to find out the prevalence of osteonecrosis in children with acute lymphoblastic leukaemia (ALL) in complete bone marrow remission at the end of the treatment. Finally, the study suggests that the intensification phase of the treatment protocols with intensive dexamethasone medication might be responsible for the development of osteonecrosis. (N.C.)

  16. 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.

  17. 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.

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

    Science.gov (United States)

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

    2002-01-01

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

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

    OpenAIRE

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

    1988-01-01

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

  20. Blinatumomab and Combination Chemotherapy or Dasatinib, Prednisone, and Blinatumomab in Treating Older Patients With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-10-05

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

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

    OpenAIRE

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

    2012-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Sunil Pazhayanur Venkateswaran

    2012-10-01

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

  3. Aberrant Gene Expression in Acute Myeloid Leukaemia

    DEFF Research Database (Denmark)

    Bagger, Frederik Otzen

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

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

    OpenAIRE

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

    1998-01-01

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

  5. Acute Lymphoblastic Leukemia (ALL) (For Parents)

    Science.gov (United States)

    ... of WBC) are produced, a child will develop acute lymphoblastic, or lymphoid, leukemia (ALL). This is the most common type of childhood leukemia, affecting about 75% of kids with this cancer of the blood cells. Kids ... (AML) Chronic Myelogenous Leukemia (CML) Cancer ...

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

    Science.gov (United States)

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

    2003-10-01

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

  7. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Sabina Chiaretti

    2014-10-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a disseminated malignancy of B- or T-lymphoblasts which imposes a rapid and accurate diagnostic process to support an optimal risk-oriented therapy and thus increase the curability rate. The need for a precise diagnostic algorithm is underlined by the awareness that both ALL therapy and related success rates may vary greatly in function of ALL subset, from standard chemotherapy in patients with standard-risk ALL, to allotransplantation (SCT and targeted therapy in high-risk patients and cases expressing suitable biological targets, respectively. This review offers a glimpse on how best identify ALL and the most relevant ALL subsets.

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

    OpenAIRE

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

    2014-01-01

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

  9. Acute lymphocytic leukaemia in children in the Netherlands

    International Nuclear Information System (INIS)

    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.)

  10. Brain Function in Young Patients Receiving Methotrexate for Acute Lymphoblastic Leukemia

    Science.gov (United States)

    2016-04-08

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Cognitive Side Effects of Cancer Therapy; Long-Term Effects Secondary to Cancer Therapy in Children; Neurotoxicity Syndrome; Psychological Impact of Cancer; Untreated Childhood Acute Lymphoblastic Leukemia

  11. 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.

  12. EBV-associated post-transplantation B-cell lymphoproliferative disorder following allogenic stem cell transplantation for acute lymphoblastic leukaemia: tumor regression after reduction of immunosuppression - a case report

    Directory of Open Access Journals (Sweden)

    Niedobitek Gerald

    2010-03-01

    Full Text Available Abstract Epstein-Barr virus (EBV-associated B-cell post-transplantation lymphoproliferative disorder (PTLD is a severe complication following stem cell transplantation. This is believed to occur as a result of iatrogenic immunosuppression leading to a relaxation of T-cell control of EBV infection and thus allowing viral reactivation and proliferation of EBV-infected B-lymphocytes. In support of this notion, reduction of immunosuppressive therapy may lead to regression of PTLD. We present a case of an 18-year-old male developing a monomorphic B-cell PTLD 2 months after receiving an allogenic stem cell transplant for acute lymphoblastic leukemia. Reduction of immunosuppressive therapy led to regression of lymphadenopathy. Nevertheless, the patient died 3 months afterwards due to extensive graft-vs.-host-disease and sepsis. As a diagnostic lymph node biopsy was performed only after reduction of immunosuppressive therapy, we are able to study the histopathological changes characterizing PTLD regression. We observed extensive apoptosis of blast cells, accompanied by an abundant infiltrate comprising predominantly CD8-positive, Granzyme B-positive T-cells. This observation supports the idea that regression of PTLD is mediated by cytotoxic T-cells and is in keeping with the observation that T-cell depletion, represents a major risk factor for the development of PTLD.

  13. Pathogenesis and prognostication in acute lymphoblastic leukemia

    OpenAIRE

    Zuckerman, Tsila; Rowe, Jacob M.

    2014-01-01

    The process of lymphoid maturation is tightly controlled by the hierarchical activation of transcription factors and selection through functional signal transduction. Acute lymphoblastic leukemia (ALL) represents a group of B/T-precursor-stage lymphoid cell malignancies arising from genetic alterations that block lymphoid differentiation and drive aberrant cell proliferation and survival. With recent advances in next-generation sequencing, we are discovering new mutations affecting normal lym...

  14. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    OpenAIRE

    Fullmer, Amber; O’Brien, Susan; Kantarjian, Hagop; Jabbour, Elias

    2009-01-01

    The outcome of salvage therapy for relapsed acute lymphoblastic leukemia (ALL) remains poor. Salvage therapy mimics regimens with activity in newly diagnosed ALL. Novel strategies under investigation as monotherapy or in combination with chemotherapy improve the treatment of relapsed disease. For some ALL subsets, specific therapies are indicated. The addition of targeted therapy in Philadelphia chromosome–positive ALL has improved responses in relapsed patients without resistance to availabl...

  15. Flow-cytometric monitoring of disease-associated expression of 9-O-acetylated sialoglycoproteins in combination with known CD antigens, as an index for MRD in children with acute lymphoblastic leukaemia: a two-year longitudinal follow-up study

    Directory of Open Access Journals (Sweden)

    Chandra Sarmila

    2008-02-01

    Full Text Available Abstract Background Over expression of 9-O-acetylated sialoglycoproteins (Neu5,9Ac2-GPs, abbreviated as OAcSGP has been demonstrated as a disease-associated antigen on the lymphoblasts of childhood acute lymphoblastic leukaemia (ALL. Achatinin-H, a lectin, has selective affinity towards terminal 9-O-acetylated sialic acids-α2-6-Nacetylated galactosamine. Exploring this affinity, enhanced expression of OAcSGP was observed, at the onset of disease, followed by its decrease with chemotherapy and reappearance with relapse. In spite of treatment, patients retain the diseased cells referred to as minimal residual disease (MRD responsible for relapse. Our aim was to select a suitable template by using the differential expression of OAcSGP along with other known CD antigens to monitor MRD in peripheral blood (PB and bone marrow (BM of Indian patients with B- or T-ALL during treatment and correlate it with the disease status. Methods A two-year longitudinal follow-up study was done with 109 patients from the onset of the disease till the end of chemotherapy, treated under MCP841protocol. Paired samples of PB (n = 1667 and BM (n = 999 were monitored by flow cytometry. Three templates selected for this investigation were OAcSGP+CD10+CD19+ or OAcSGP+CD34+CD19+ for B-ALL and OAcSGP+CD7+CD3+ for T-ALL. Results Using each template the level of MRD detection reached 0.01% for a patient in clinical remission (CR. 81.65% of the patients were in CR during these two years while the remaining relapsed. Failure in early clearance of lymphoblasts, as indicated by higher MRD, implied an elevated risk of relapse. Soaring MRD during the chemotherapeutic regimen predicted clinical relapse, at least a month before medical manifestation. Irrespective of B- or T-lineage ALL, the MRD in PB and BM correlated well. Conclusion A range of MRD values can be predicted for the patients in CR, irrespective of their lineage, being 0.03 ± 0.01% (PB and 0.05 ± 0.015% (BM. These

  16. Combination Chemotherapy in Treating Young Patients With Newly Diagnosed T-Cell Acute Lymphoblastic Leukemia or T-cell Lymphoblastic Lymphoma

    Science.gov (United States)

    2016-09-26

    Adult T Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Stage II Adult T-Cell Leukemia/Lymphoma; Stage II Childhood Lymphoblastic Lymphoma; Stage II Contiguous Adult Lymphoblastic Lymphoma; Stage II Non-Contiguous Adult Lymphoblastic Lymphoma; Stage III Adult Lymphoblastic Lymphoma; Stage III Adult T-Cell Leukemia/Lymphoma; Stage III Childhood Lymphoblastic Lymphoma; Stage IV Adult Lymphoblastic Lymphoma; Stage IV Adult T-Cell Leukemia/Lymphoma; Stage IV Childhood Lymphoblastic Lymphoma; Untreated Adult Acute Lymphoblastic Leukemia; Untreated Childhood Acute Lymphoblastic Leukemia

  17. High functional P-glycoprotein activity is more often present in T-cell acute lymphoblastic leukaemic cells in adults than in children

    NARCIS (Netherlands)

    Plasschaert, SLA; Vellenga, E; De Bont, ESJM; van der Kolk, D.M.; Veerman, AJP; Sluiter, WJ; Daenen, SMG; De Vries, EGE; Kamps, WA

    2003-01-01

    There is a distinct difference in prognosis between childhood versus adult acute lymphoblastic leukaemia (ALL). To define whether multidrug resistance (MDR) genes might contribute to this distinction, the expression and functional activity of P-glycoprotein (P-gp) and MDR associated proteins (MRP) w

  18. Entinostat and Clofarabine in Treating Patients With Newly Diagnosed, Relapsed, or Refractory Poor-Risk Acute Lymphoblastic Leukemia or Bilineage/Biphenotypic Leukemia

    Science.gov (United States)

    2014-07-16

    Acute Leukemias of Ambiguous Lineage; Philadelphia Chromosome Negative Adult Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  19. Development of A model of B acute lymphoblastic leukemia for the investigation of the potential leukemogenic effects of 50 Hz magnetic fields

    International Nuclear Information System (INIS)

    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

  20. 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

  1. Effective re-induction therapy with dasatinib and clofarabine in relapsed Philadelphia chromosome positive acute lymphoblastic leukemia

    OpenAIRE

    Anne Loes van den Boom; H Berna Beverloo; van der Velden, Vincent H.J.; Arjan Lankester; Rob Pieters; C. Michel Zwaan

    2012-01-01

    This case discusses a 10 year old female patient with a late relapse of Ph-chromosome positive B-cell precursor acute lymphoblastic leukaemias (ALL) who had previously been treated with chemotherapy and allogeneic stem-cell transplantation. Treatment for relapse consisted of single-agent dasatinib, followed by 2 blocks of a combination of dasatinib and clofarabine as consolidation therapy. Using this schedule both morphological and cytogenetic complete remission were obtained. This regimen wa...

  2. [Nephrotoxicity evaluation of cytostatic agents in children with acute lymphoblastic leukemia].

    Science.gov (United States)

    Tomaszewska, B; Zoch-Zwierz, W M

    1995-11-01

    Urinary excretion of the markers of tubular nephrotoxicity, total NAG and isoenzymes A and B and B-2-M, were evaluated in urine of 21 children with acute lymphoblastic leukaemia after the first injection of cytostatic administrated according to the BFM scheme: VCR + Rub, L-aspa, CY, Ara-C. Every administrated drug caused temporary elevation in urinary excretion of total NAG and isoenzyme B and B-2-M. GFR was unchanged. These results point to nephrotoxicity of cytostatics. Peak total NAG, isoenzyme B and B-2-M excretion was observed on the third day after L-aspa and Ara-C injection.

  3. Experiencia y resultados en el tratamiento de la leucemia linfoblástica aguda en la edad pediátrica en el periodo comprendido entre 1989 y 2005 en la Comunidad de Navarra Experience and results of acute lymphoblastic leukaemia treatment in children between 1989-2005 in Navarre

    Directory of Open Access Journals (Sweden)

    J. Molina

    2007-12-01

    Full Text Available Fundamento. El conocimiento de factores que se comportan como pronósticos en la leucemia linfoblástica aguda (LLA es cada vez más importante para establecer una estrategia de tratamiento correcta. Se analiza la supervivencia global (SG, supervivencia libre de eventos (SLE y los factores pronósticos en 16 años de experiencia en nuestra comunidad. Material y métodos. Estudio descriptivo retrospectivo en el que se incluyen los pacientes diagnosticados de leucemia aguda (LA en ese periodo de tiempo. Análisis uni y multivariante de aquellos factores que hemos considerado relevantes en nuestra serie aplicando el paquete estadístico SPSS para Windows versión 12. Resultados. En el periodo comprendido entre enero de 1989 y diciembre de 2005 se diagnosticaron 58 pacientes de LA, 50 de ellos tipo linfoblástica aguda (LLA. Se analiza un subgrupo de 41 pacientes de forma más exhaustiva por ser el tipo de leucemia más frecuente y por haber estado incluidos en protocolos bien establecidos. En este grupo la SLE fue del 78% y la SG del 87,8%. Las variables multivariante predictoras en nuestra serie fueron: el inmunofenotipo (B-Común/Otras con un HR de 13,82 (IC95%: 1.019-166.008 pBackground. The determination of prognostic factors in acute lymphoblastic leukaemia (ALL is increasingly important in establishing a correct treatment. We analyse the overall survival (OS, event free survival (EFS and prognostic factors in our 16 years experience of treating acute lymphoblastic leukaemia. Methods. We performed univariate and multivariate analyses of the prognostic factors we considered most significant in our serie of patients Results. From January 1989 to December 2005, 50 cases of ALL were reported in 58 patients with LA. We analysed a subgroup of 41 patients with LLA as they were included in standard protocols. In this group the EFS was 78% and OS 87.8%. Inmunophenotype is a predictor of prognosis when we compare Common with Others, with a HR of 13

  4. New genetics and diagnosis of childhood B-cell precursor acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Christine Harrison

    2011-06-01

    Full Text Available Over the last 50 years, while significant advances have been made in the successful treatment of childhood leukaemia, similar progress has been made in understanding the genetics of the disease. In childhood B-cell precursor acute lymphoblastic leukaemia (BCP-ALL, the incidences of individual chromosomal abnormalities are well established and cytogenetics provides a reliable tool for risk stratification for treatment. In spite of this role, a number of patients will relapse. Increasing numbers of additional genetic changes, including deletions and mutations, are being discovered. Their associations with established cytogenetic subgroups and with each other remain unclear. Whether they have a link to outcome is the most important factor in terms of refinement of risk factors in relation to clinical trials. For a number of newly identified abnormalities, appropriately modified therapy has significantly improved outcome. Alternatively, some of these aberrations are providing novel molecular markers for targeted therapy.

  5. GOOD OUTCOME FOR VERY HIGH RISK ADULT B-CELL ACUTE LYMPHOBLASTIC LEUKAEMIA CARRYING GENETIC ABNORMALITIES t(4;11(q21;q23 or t(9;22(q34;q11, IF PROMPTLY SUBMITTED TO ALLOGENEIC TRANSPLANTATION, AFTER OBTAINING A GOOD MOLECULAR REMISSION.

    Directory of Open Access Journals (Sweden)

    Matteo Parma

    2015-05-01

    Full Text Available Background and Objectives: Acute lymphoblastic leukaemia (ALL carrying t(9;22 or t(4;11 genetic abnormalities represents a very high risk subtype of disease (VHR-ALL. Hematopoietic stem cell transplantation (HSCT still remains the only curative option also in the Imatinib era. In the last years low molecular level of minimal residual disease (MRD before HSCT was reported as one of the best favourable indexes for survival in ALL. Here we observed that even these patients can show a favourable outcome, if submitted to HSCT with very low MRD. Methods: We considered 18 consecutive VHR-ALL patients eligible to HSCT. 16 of them were transplanted upon first remission, as soon as possible, employing myelo-ablative conditioning regimens. Molecular MRD has been evaluated before and after HSCT.Results: Immediately before HSCT MRD revealed: complete molecular remission (MRDneg for 5 patients and a level <1x10-3 for 7 patients; 100 days after HSCT we had: MRDneg for 7 patients and a decrease for all the others after HSCT. After tapering of immunosuppressive drugs, 13 patients reached the MRDneg in a median time of 8 months (range 3-16; Based on intention to treat analysis: 14/18 patients are alive and disease free at the time of analysis, overall survival and event free survival is of 78% and 66% respectively, with an average follow-up of 45 months (range 6-84 since HSCT. Conclusion: Early transplantation with low MRD level seems to be correlated with a favourable outcome also in VHR-ALL

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

    Science.gov (United States)

    2016-09-08

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

  7. Epidemiology of acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Although the etiology of acute leukemia is largely unknown, some facets of the puzzle are becoming clarified. Recognition of important patterns in age-specific mortality rates has suggested that events early in life, perhaps even prenatally, may have an influence on developing leukemia in childhood. The racial differences evident in mortality, incidence, and immunologic subtype of ALL suggest either differences in exposures to certain factors or differences in responses to those factors by white children. Hereditary factors appear to play a role. Familial and hereditary conditions exist that have high incidences of acute leukemia. Chromosomal anomalies are common in these conditions. Viral infections may play a role by contributing to alteration in genetic material through incorporation of the viral genome. How that virus is dealt with after primary infection seems important. The presence of immunodeficiency may allow wider dissemination or enhanced replication of such viruses, thereby increasing the likelihood of cellular transformation to an abnormal cell. Proliferation of that malignant cell to a clone may depend on other cofactors. Perhaps prolonged exposure to substances like benzene or alkylating agents may enhance these interactions between virus and genetic material. Does this change DNA repair mechanisms. Are viral infections handled differently. Is viral genomic information more easily integrated into host cells. Ionizing radiation has multiple effects. Alteration in genetic material occurs both at the molecular and chromosomal levels. DNA may be altered, lost, or added in the cell's attempt to recover from the injury

  8. Nanomedicine approaches in acute lymphoblastic leukemia.

    Science.gov (United States)

    Tatar, Andra-Sorina; Nagy-Simon, Timea; Tomuleasa, Ciprian; Boca, Sanda; Astilean, Simion

    2016-09-28

    Acute lymphoblastic leukemia (ALL) is the malignancy with the highest incidence amongst children (26% of all cancer cases), being surpassed only by the cancers of the brain and of the nervous system. The most recent research on ALL is focusing on new molecular therapies, like targeting specific biological structures in key points in the cell cycle, or using selective inhibitors for transmembranary proteins involved in cell signalling, and even aiming cell surface receptors with specifically designed antibodies for active targeting. Nanomedicine approaches, especially by the use of nanoparticle-based compounds for the delivery of drugs, cancer diagnosis or therapeutics may represent new and modern ways in the near future anti-cancer therapies. This review offers an overview on the recent role of nanomedicine in the detection and treatment of acute lymphoblastic leukemia as resulting from a thorough literature survey. A short introduction on the basics of ALL is presented followed by the description of the conventional methods used in the ALL detection and treatment. We follow our discussion by introducing some of the general nano-strategies used for cancer detection and treatment. The detailed role of organic and inorganic nanoparticles in ALL applications is further presented, with a special focus on gold nanoparticle-based nanocarriers of antileukemic drugs. PMID:27460684

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

    NARCIS (Netherlands)

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

    2000-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  11. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    DEFF Research Database (Denmark)

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

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic...... approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia....... leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were...

  12. Hematopoietic Stem Cell Transplantation in Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Ibrahim Bayram

    2014-01-01

    In children patients with acute lymphoblastic leukemia, according to the European bone marrow transplant handbook, the indications for stem cell transplantation, conditioning regimen, donor selection and information about sources of stem cells will be evaluated.

  13. 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

    International Nuclear Information System (INIS)

    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)

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

    Institute of Scientific and Technical Information of China (English)

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

    2008-01-01

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

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

    Science.gov (United States)

    2014-01-23

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

  16. 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.)

  17. Acute Myeloid Leukaemia: Optimal Management and Recent Developments

    OpenAIRE

    Villela, Luis; Bolaños-Meade, Javier

    2011-01-01

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

  18. The effect of dietary intake changes on nutritional status in acute leukaemia patients after first induction chemotherapy.

    Science.gov (United States)

    Malihi, Z; Kandiah, M; Chan, Y M; Esfandbod, M; Vakili, M; Hosseinzadeh, M; Zarif Yeganeh, M

    2015-07-01

    This study aimed to evaluate how changes in dietary intake among acute lymphoblastic and acute myeloid leukaemia (ALL and AML) patients affect nutritional status after the first induction chemotherapy. Dietary intake was assessed using 24-h recall and a 136-item food frequency questionnaire. Nutritional status was assessed by Patients Subjective Global Assessment questionnaire before starting induction therapy and again after 1 month. All newly diagnosed acute leukaemia patients aged 15 years old and older who attended three referral hospitals for initiation of their induction chemotherapy were included in the sample selection provided that they gave informed consent. A total of 30 AML and 33 ALL patients participated in the study. Dietary intake and nutritional status worsened after the chemotherapy treatment. Dietary intake in terms of macronutrients, micronutrients, food variety and diet diversity score changed significantly after the induction chemotherapy. No significant relationship was found between the changes in dietary indices and nutritional status. Chemotherapy-related side effects as an additional factor to cancer itself could affect dietary intake of leukaemia patients. The effectiveness of an early assessment of nutritional status and dietary intake should be further investigated in order to deter further deterioration.

  19. Temsirolimus, Dexamethasone, Mitoxantrone Hydrochloride, Vincristine Sulfate, and Pegaspargase in Treating Young Patients With Relapsed Acute Lymphoblastic Leukemia or Non-Hodgkin Lymphoma

    Science.gov (United States)

    2015-07-09

    Childhood B Acute Lymphoblastic Leukemia; Childhood T Acute Lymphoblastic Leukemia; Mature T-Cell and NK-Cell Non-Hodgkin Lymphoma; Recurrent Childhood Acute Lymphoblastic Leukemia; Recurrent Childhood Lymphoblastic Lymphoma

  20. Genetic abnormalities associated with acute lymphoblastic leukemia.

    Science.gov (United States)

    Yokota, Takafumi; Kanakura, Yuzuru

    2016-06-01

    Acute lymphoblastic leukemia (ALL) occurs with high frequency in childhood and is associated with high mortality in adults. Recent technical advances in next-generation sequencing have shed light on genetic abnormalities in hematopoietic stem/progenitor cells as the precursor to ALL pathogenesis. Based on these genetic abnormalities, ALL is now being reclassified into newly identified subtypes. Philadelphia chromosome-like B-lineage ALL is one of the new high-risk subtypes characterized by genetic alterations that activate various signaling pathways, including those involving cytokine receptors, tyrosine kinases, and epigenetic modifiers. Philadelphia chromosome-like ALL is essentially heterogeneous; however, deletion mutations in the IKZF1 gene encoding the transcription factor IKAROS underlie many cases as a key factor inducing aggressive phenotypes and poor treatment responses. Whole-genome sequencing studies of ALL patients and ethnically matched controls also identified inherited genetic variations in lymphoid neoplasm-related genes, which are likely to increase ALL susceptibility. These findings are directly relevant to clinical hematology, and further studies on this aspect could contribute to accurate diagnosis, effective monitoring of residual disease, and patient-oriented therapies. PMID:26991355

  1. High-Risk Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2009-01-01

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

  2. High-risk childhood acute lymphoblastic leukemia.

    Science.gov (United States)

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

    2009-01-01

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

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

    Science.gov (United States)

    Timonen, T T; Palva, I P

    1980-01-01

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

  4. GLUCOCORTICOID RECEPTOR IN CHILDHOOD ACUTE LYMPHOBLASTIC LEUKEMIA

    Institute of Scientific and Technical Information of China (English)

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

    1999-01-01

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

  5. Effect of doxorubicin and daunorubicin on the activity of acetylcholinesterase in acute lymphoblastic leukamia

    International Nuclear Information System (INIS)

    Background: Our study was based on the alteration in the Michaelis Mentin parameters Apparent Michaelis Constant (aKm) and Apparent Maximum Velocity (aVm), which reflects activity of actyl cholinesterase (AChE). This activity decreases in Acute Lymphoblastic Leukaemia (ALL). This decrease in aKm and aVm values shows bad prognosis. Similarly the anticancer drugs like Daunorubicin and Doxorubicin further decreases the aKm and aVm values which worsen the prognosis. The objective of this study was to determine and compare the extent of inhibition of Acetylcholine Esterase by Daunorubicin and Doxorubicin in ALL. Methods: Study of 100 patients including both male and female children who's age ranged from 4 to 8 years and were advised doxorubicin and daunorubicin separately were tested by Ellman's method using acetylcholine iodide as substrate and 5,5-dithiobis 2-nitrobenzine as a colour reagent regardless of dose regimen i.e. (once in 3 week, small dose per week or a continuous infusion for 72 to 96 hours. Results: In this study the Michaelis Mentin parameters Apparent Michaelis Constant (aKm) and Apparent Maximum Velocity (aVm) of the enzyme were estimated both in normal individuals and in the patients and also during treatment with daunorubicin and doxorubicin. The value of Michaelis Mentin parameters, aKm, aVm and percentage activity of the enzyme in normal individual are 23, 70, and 100 respectively. The values of aKm, aVm and percentage activity of the enzyme were also estimated in the patients before and after treatment. The values of aKm and aVm in patients of acute lymphoblastic leukaemia and percentage activity of enzyme is decreased. After the treatment with daunorubicin and doxorubicin the values and activity is further decreased. Conclusion: We conclude that the drugs under study both decrease the enzyme activity but daunorubicin inhibits the enzyme more than doxorubicin. (author)

  6. 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.

  7. JAK kinase inhibitors for the treatment of acute lymphoblastic leukemia

    OpenAIRE

    Degryse, Sandrine; Cools, Jan

    2015-01-01

    Recent studies of acute lymphoblastic leukemia have identified activating mutations in components of the interleukin-7 receptor complex (IL7R, JAK1, and JAK3). It will be of interest to investigate both JAK1 and JAK3 kinase inhibitors as targeted agents for these leukemias.

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

    DEFF Research Database (Denmark)

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

    2013-01-01

    PURPOSE: Second malignant neoplasms (SMNs) after diagnosis of childhood acute lymphoblastic leukemia (ALL) are rare events. PATIENTS AND METHODS: We analyzed data on risk factors and outcomes of 642 children with SMNs occurring after treatment for ALL from 18 collaborative study groups between 19...

  9. L-asparaginase treatment in acute lymphoblastic leukemia

    NARCIS (Netherlands)

    R. Pieters (Rob); S.P. Hunger (Stephen); J. Boos (Joachim); C. Rizzari (Carmelo); L.B. Silverman (Lewis); A. Baruchel (André); N. Goekbuget (Nicola); M. Schrappe (Martin); C.H. Pui (Ching-Hon)

    2011-01-01

    textabstractAsparaginases are a cornerstone of treatment protocols for acute lymphoblastic leukemia (ALL) and are used for remission induction and intensification treatment in all pediatric regimens and in the majority of adult treatment protocols. Extensive clinical data have shown that intensive a

  10. Acute lymphoblastic leukemia in children with Down syndrome

    DEFF Research Database (Denmark)

    Buitenkamp, Trudy D; Izraeli, Shai; Zimmermann, Martin;

    2014-01-01

    Children with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials from 1995...

  11. Pharmacokineties of vincristine monotherapy in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Groninger, E; Meeuwsen-de Boer, T; Koopmans, P; UGes, D; Sluiter, W; Veerman, A; Kamps, W

    2002-01-01

    We studied vincristine pharmacokinetics in 70 children newly diagnosed with acute lymphoblastic leukemia, after a single dose of vincristine as monotherapy. Vincristine plasma concentrations were measured by HPLC analysis. A two-compartment, first-order pharmacokinetic model was fitted to the data b

  12. Molecular mechanisms of glucocorticoid resistance in childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    W.J.E. Tissing (Wim)

    2006-01-01

    textabstractAcute lymphoblastic leukemia (ALL) is the most common form of cancer in children, with 110 – 120 newly diagnosed children in the Netherlands each year. ALL is a haematological malignancy of lymphoid precursor cells and can be divided into two sub-groups: B-cell precursor ALL and T-cell p

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

    DEFF Research Database (Denmark)

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

    2008-01-01

    The pattern of infections in the first years of life modulates our immune system, and a low incidence of infections has been linked to an increased risk of common childhood acute lymphoblastic leukemia (ALL). We here present a new interpretation of these observations--the adrenal hypothesis...

  14. Neurodevelopmental Sequelae of Pediatric Acute Lymphoblastic Leukemia and Its Treatment

    Science.gov (United States)

    Janzen, Laura A.; Spiegler, Brenda J.

    2008-01-01

    This review will describe the neurocognitive outcomes associated with pediatric acute lymphoblastic leukemia (ALL) and its treatment. The literature is reviewed with the aim of addressing methodological issues, treatment factors, risks and moderators, special populations, relationship to neuroimaging findings, and directions for future research.…

  15. Obesity in patients with acute lymphoblastic leukemia in childhood

    Directory of Open Access Journals (Sweden)

    Iughetti Lorenzo

    2012-01-01

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

  16. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  17. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    Science.gov (United States)

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  18. General Information about Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

  19. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

    ... leukemia may come back in the blood and bone marrow , brain, spinal cord , testicles , or other parts of the body. ... lymphoblastic leukemia (ALL) that comes back outside the bone marrow may include the ... to the brain and/or spinal cord for cancer that comes back in the ...

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

    NARCIS (Netherlands)

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

    2012-01-01

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

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

    Science.gov (United States)

    2013-10-07

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

  2. Aleukemic Leukemia Cutis Presenting as a Sole Sign of Relapsed Paediatric Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Joshi, Kshitij; Panchal, Harsha; Parikh, Sonia; Modi, Gaurang; Talele, Avinash; Anand, Asha; Uparkar, Urmila; Joshi, Nitin; Khatawani, Itesh

    2016-06-01

    The author describes paediatric case of relapsed acute lymphoblastic leukaemia (ALL) presented as aleukemic leukaemia cutis (ALC). A 2 year old child was admitted in tertiary oncology centre. He suffered from pre B cell ALL with absent Philadelphia chromosome. This patient received multiagent induction chemotherapy as per Berlin-Frankfurt-Munster (BFM) protocol for ALL. He achieved remission after 28 days of treatment. Subsequently he presented with multiple skin lesions in the form of multiple small erythematous violaceous macules, papules, plaques and nodules on face, chest and back regions. Histopathological examination of biopsy of skin revealed diffuse infiltration of tumor cells with prominent nucleoli, scant eosinophilic cytoplasm and numerous mitotic figures consistent with LC. Immunohistochemistry was positive for CD 10, CD 19, CD 22, CD 24, CD 79-a and TdT while negative for surface immunoglobulin. At the time of presentation his peripheral blood smear and bone marrow examination was negative for malignant cells. Sanctuary sites including central nervous system and testicles were not involved. So patient was diagnosed as ALC. He was managed as per BFM relapse protocol for ALL. Skin lesions disappeared completely after 2 weeks of treatment. Unfortunately patient developed bone marrow and testicular relapse after 2 months. He was given testicular radiotherapy and systemic chemotherapy for relapsed ALL. But his marrow was showing persistent activity and he expired after 4 months.

  3. Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

    OpenAIRE

    Bernt, Kathrin M.; Armstrong, Scott A.

    2009-01-01

    Leukemias and other cancers have been proposed to contain a subpopulation of cells that display characteristics of stem cells, and which maintain tumor growth. That most anti-cancer therapy is directed against the bulk of the tumor, and possibly spares the cancer stem cells, may lie at the heart of treatment failures with conventional modalities. Leukemia stem cells are fairly well described for acute myeloid leukemia (AML), but their existence and relevance for acute lymphoblastic leukemia (...

  4. Antibodies: Immunoconjugates and autologous cellular therapy in acute lymphoblastic leukemia.

    Science.gov (United States)

    Advani, Anjali

    2015-01-01

    Using a case study of a 57-year-old man with relapsed/refractory precursor-B (pre-B) acute lymphoblastic leukemia (ALL), this review discusses treatment with immunoconjugates and autologous therapy in acute ALL. Three therapies--blinatumomab, inotuzumab, and CAR T cells--are considered here, each with advantages in specific clinical situations. These therapies represent some of the exciting advances that have been made in the treatment of ALL over the last several years.

  5. Treatment on leukaemia in children

    Energy Technology Data Exchange (ETDEWEB)

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

    1984-06-01

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

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

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2016-01-06

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

  8. 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

    2014-05-01

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

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

    OpenAIRE

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

    1998-01-01

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

  10. Nilotinib and Combination Chemotherapy in Treating Patients With Newly Diagnosed Philadelphia Chromosome-Positive Acute Lymphoblastic Leukemia or Blastic Phase Chronic Myelogenous Leukemia

    Science.gov (United States)

    2015-10-29

    B-cell Adult Acute Lymphoblastic Leukemia; Blastic Phase Chronic Myelogenous Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Untreated Adult Acute Lymphoblastic Leukemia

  11. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    Directory of Open Access Journals (Sweden)

    Stephen E. Langabeer

    2016-01-01

    Full Text Available The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to be associated with a distinct phenotype and a lower risk of thrombosis yet their impact on disease progression is less well defined. The as yet undescribed scenario of pro-B cell acute lymphoblastic leukemia arising in CALR mutated essential thrombocythemia is presented. Intensive treatment for the leukemia allowed for expansion of the original CALR mutated clone. Whether CALR mutations in myeloproliferative neoplasms predispose to the acquisition of additional malignancies, particularly lymphoproliferative disorders, is not yet known.

  12. New decision support tool for acute lymphoblastic leukemia classification

    Science.gov (United States)

    Madhukar, Monica; Agaian, Sos; Chronopoulos, Anthony T.

    2012-03-01

    In this paper, we build up a new decision support tool to improve treatment intensity choice in childhood ALL. The developed system includes different methods to accurately measure furthermore cell properties in microscope blood film images. The blood images are exposed to series of pre-processing steps which include color correlation, and contrast enhancement. By performing K-means clustering on the resultant images, the nuclei of the cells under consideration are obtained. Shape features and texture features are then extracted for classification. The system is further tested on the classification of spectra measured from the cell nuclei in blood samples in order to distinguish normal cells from those affected by Acute Lymphoblastic Leukemia. The results show that the proposed system robustly segments and classifies acute lymphoblastic leukemia based on complete microscopic blood images.

  13. Role of Ikaros in T-cell acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    Philippe; Kastner; Susan; Chan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene.Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia.In particular,Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia.Its role in T-cell leukemia,however,has been more controversial.While Ikaros deficiency appears to be very frequent in murine T-cell leukemias,loss of Ikaros appears to be rare in human T-cell acute lymphoblastic leukemia (T-ALL).We review here the evidence linking Ikaros to T-ALL in mouse and human systems.

  14. Pancytopenic Prodrome (pre-ALL) of Acute Lymphoblastic Leukemia in Adults: Possible Pathogenesis

    OpenAIRE

    Sohn, Sang Kyun; Suh, Jang Soo; Lee, Jaetae; Lee, Kyu Bo

    1998-01-01

    We report two cases of adult acute lymphoblastic leukemia presenting with preleukemic phase of pancytopenia with a few abnormal lymphoid cells in bone marrow aspirates. The initial diagnosis of each case was suspicious aplastic anemia and hypoplastic anemia. Both cases progressed to overt acute lymphoblastic leukemia within 1 year. We suggest that initial pancytopenic phase (pre-ALL) may precede the diagnosis of acute lymphoblastic leukemia in adults and differential diagnosis from myelodyspl...

  15. Distribution of common acute lymphoblastic leukemia antigen in nonhematopoietic tissues

    OpenAIRE

    1981-01-01

    The common acute lymphoblastic leukemia antigen (CALLA), as defined by J-5 murine monoclonal antibodies, was detected on renal tubular and glomerular cells from fetal and adult donors by an indirect immunoperoxidase technique. CALLA could also be detected on epithelial cells of the fetal small intestine and on myoepithelial cells of adult breast but not on myoepithelial cells of the salivary gland. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis analysis of immunoprecipitated 125I-l...

  16. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    OpenAIRE

    Langabeer, Stephen E.; Karl Haslam; David O’Brien; Johanna Kelly; Claire Andrews; Ciara Ryan; Richard Flavin; Hayden, Patrick J.; Bacon, Christopher L.

    2016-01-01

    The development of acute lymphoblastic leukemia in an existing myeloproliferative neoplasm is rare with historical cases unable to differentiate between concomitant malignancies or leukemic transformation. Molecular studies of coexisting JAK2 V617F-positive myeloproliferative neoplasms and mature B cell malignancies indicate distinct disease entities arising in myeloid and lymphoid committed hematopoietic progenitor cells, respectively. Mutations of CALR in essential thrombocythemia appear to...

  17. Optic nerve infiltration by acute lymphoblastic leukemia: MRI contribution

    Energy Technology Data Exchange (ETDEWEB)

    Soares, Maria de Fatima; Braga, Flavio Tulio [Federal University of Sao Paulo, Department of Diagnostic Imaging, Paulista School of Medicine, Sao Paulo (Brazil); Rocha, Antonio Jose da [Santa Casa de Misericordia de Sao Paulo, Servico de Diagnostico por Imagem, Sao Paulo (Brazil); Lederman, Henrique Manoel [Federal University of Sao Paulo, Division of Diagnostic Imaging in Pediatrics, Department of Diagnostic Imaging, Sao Paulo (Brazil)

    2005-08-01

    We describe the clinical presentation and imaging features of a patient with acute lymphoblastic leukemia (ALL) that was complicated by optic nerve infiltration. The clinical and diagnostic characteristics of this complication must be recognized so that optimal therapy can be started to prevent blindness. MR imaging is useful in early detection and should be performed in any leukemic patient with ocular complaints, even during remission. (orig.)

  18. Acute lymphoblastic leukemia: Are Egyptian children adherent to maintenance therapy?

    OpenAIRE

    Elhamy Rifky Abdel Khalek; Laila M Sherif; Naglaa Mohamed Kamal; Gharib, Amal F.; H M Shawky

    2015-01-01

    Background, Aims, Settings and Design: Poor adherence to oral maintenance chemotherapy can cause relapse of acute lymphoblastic leukemia (ALL). A multicenter study for the evaluation of adherence to oral 6-mercaptopurine (6-MP) maintenance chemotherapy for childhood ALL in Egypt to identify contributing factors and possible steps to promote adherence. Materials and Methods: The study included 129 children with ALL in complete remission receiving 6-MP single daily oral dose in the evening....

  19. Vitamin D Protects Acute Lymphoblastic Leukemia Cells from Dexamethasone

    OpenAIRE

    Antony, Reuben; Sheng, Xia; Ehsanipour, Ehsan A.; Ng, Emily; Pramanik, Rocky; Klemm, Lars; Ichihara, Brian; Mittelman, Steven D.

    2012-01-01

    Vitamin D deficiency has been linked with increased cancer risk, and vitamin D has been shown to be cytotoxic to some cancer cells in vitro. In the present study we evaluated whether vitamin D would have antiproliferative or cytotoxic effects on human pre-B acute lymphoblastic leukemia cells. Contrary to our hypotheses, calcitriol, the active form of vitamin D, had no effect on leukemia cell proliferation. Calcitriol actually had a modest effect to impair dexamethasone cytotoxicity and induct...

  20. Effect of Taurine on Febrile Episodes in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Mina Islambulchilar

    2015-03-01

    Full Text Available Purpose: The purpose of our study was to evaluate the effect of oral taurine on the incidence of febrile episodes during chemotherapy in young adults with acute lymphoblastic leukemia. Methods: Forty young adults with acute lymphoblastic leukemia, at the beginning of maintenance course of their chemotherapy, were eligible for this study. The study population was randomized in a double blind manner to receive either taurine or placebo (2 gram per day orally. Life quality and side effects including febrile episodes were assessed using questionnaire. Data were analyzed using Pearson’s Chi square test. Results: Of total forty participants, 43.8% were female and 56.3 % were male. The mean age was 19.16±1.95 years (ranges: 16-23 years. The results indicated that the levels of white blood cells are significantly (P<0.05 increased in taurine treated group. There was no elevation in blasts count. A total of 70 febrile episodes were observed during study, febrile episodes were significantly (P<0.05 lower in taurine patients in comparison to the control ones. Conclusion: The overall incidence of febrile episodes and infectious complications in acute lymphoblastic leukemia patients receiving taurine was lower than placebo group. Taurine’s ability to increase leukocyte count may result in lower febrile episodes.

  1. Acute Lymphoblastic Leukemia Presented as Multiple Breast Masses

    Energy Technology Data Exchange (ETDEWEB)

    Bayrak, Ilkay Koray; Yalin, Turkay; Ozmen, Zafer; Aksoz, Tolga; Doughanji, Roula [Ondokuz Mayis University, Samsun (Turkmenistan)

    2009-10-15

    Breast metastases in cases leukemia are very rare and occur primarily in patients with acute myeloid leukemia. We report the involvement of breast metastases in a 30-year-old woman with acute T cell lymphoblastic leukemia. The patient's mammograms revealed an extremely dense pattern with ill-defined, denser mass-like lesions in both breasts. A bilateral breast ultrasonographic evaluation revealed lobular-shaped and partly ill-defined hypoechoic masses with a multi-septated nodular (mottled) appearance.

  2. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    LENUS (Irish Health Repository)

    Kelly, Kevin

    2012-02-01

    Esophageal stricture is a rare complication of paediatric cancer treatment that usually occurs after esophageal exposure to radiotherapy. We describe 4 cases of esophageal stricture during chemotherapy for acute lymphoblastic leukemia. All patients presented with refractory vomiting and were diagnosed with radiologic contrast studies. None of the patients had received radiotherapy. Esophageal candidiasis was seen in 2 patients but the remaining 2 patients had earlier systemic candidiasis. High-dose dexamethasone may predispose these children to both esophageal candidiasis and peptic esophagitis. The etiology of esophageal strictures during treatment for acute leukemia is likely to be multifactorial but systemic candidiasis may play a significant role.

  3. Acute Hepatitis A Induction of Precursor B-Cell Acute Lymphoblastic Leukemia: A Causal Relationship?

    OpenAIRE

    Senadhi, V.; Emuron, D.; R. Gupta

    2010-01-01

    Background Precursor B-cell acute lymphoblastic leukemia accounts for 2% of all lymphoid neoplasms in the United States and occurs most frequently in childhood, but can also occur in adults with a median age of 39 years. It is more commonly seen in males and in Caucasians. Case Report We present a case of a 51-year-old Caucasian female with the development of precursor B-cell acute lymphoblastic leukemia after suffering acute hepatitis A 4 weeks prior to her diagnosis. She presented with mala...

  4. Leukemia cutis with lymphoglandular bodies: a clue to acute lymphoblastic leukemia cutis

    OpenAIRE

    Obiozor, Cynthia; Ganguly, Siddhartha; Fraga, Garth R.

    2015-01-01

    Leukemia cutis describes cutaneous lesions produced by infiltrates of leukemic cells. It usually manifests contemporaneously with the initial diagnosis of systemic leukemia, but may also precede or follow systemic leukemia. Most cases are associated with acute myeloid leukemia. Adult B-cell lymphoblastic leukemia cutis is very rare. We report a 59-year-old woman with a history of B-cell acute lymphoblastic leukemia who relapsed with aleukemic lymphoblastic leukemia cutis. Lymphoglandular bodi...

  5. Acute myelogenous leukemia switch lineage upon relapse to acute lymphoblastic leukemia: a case report

    OpenAIRE

    Dorantes-Acosta, Elisa; Arreguin-Gonzalez, Farina; Rodriguez-Osorio, Carlos A; Sadowinski, Stanislaw; Pelayo, Rosana; Medina-Sanson, Aurora

    2009-01-01

    Acute leukemia, the most common form of cancer in children, accounts for approximately 30% of all childhood malignancies, with acute lymphoblastic leukemia being five times more frequent than acute myeloid leukemia. Lineage switch is the term that has been used to describe the phenomenon of acute leukemias that meet the standard French-American-British system criteria for a particular lineage (either lymphoid or myeloid) upon initial diagnosis, but meet the criteria for the opposite lineage a...

  6. [Necrotizing tonsillitis and renal vein thrombosis due to acute myeloid leukaemia].

    Science.gov (United States)

    Akram, Javed; Josefsson, Pernilla; Rømeling, Frans

    2012-09-01

    A 37-year-old woman was admitted to hospital with severe tonsillitis with unilateral necrotizing tonsillitis. She suddenly got fever, malaise, difficulties swallowing, pain in the throat and deterioration despite four days of penicillin treatment. During hospitalisation, she experienced abdominal pain, and blood tests showed pancytopenia. She was transferred to a haematological department, where a bone marrow biopsy showed acute myeloid leukaemia. Subsequently, an abdominal computed tomography with intravenous contrast revealed bilateral renal vein thrombosis, probably because of coagulopathy due to leukaemia.

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

    Directory of Open Access Journals (Sweden)

    Andrei Cucuianu

    2010-01-01

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

  8. Somatic PTPN11 mutations in childhood acute myeloid leukaemia.

    Science.gov (United States)

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

    2005-05-01

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

  9. 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.

  10. Antileukemic Efficacy of Continuous vs Discontinuous Dexamethasone in Murine Models of Acute Lymphoblastic Leukemia.

    Directory of Open Access Journals (Sweden)

    Laura B Ramsey

    Full Text Available Osteonecrosis is one of the most common, serious, toxicities resulting from the treatment of acute lymphoblastic leukemia. In recent years, pediatric acute lymphoblastic leukemia clinical trials have used discontinuous rather than continuous dosing of dexamethasone in an effort to reduce the incidence of osteonecrosis. However, it is not known whether discontinuous dosing would compromise antileukemic efficacy of glucocorticoids. Therefore, we tested the efficacy of discontinuous dexamethasone against continuous dexamethasone in murine models bearing human acute lymphoblastic leukemia xenografts (n = 8 patient samples or murine BCR-ABL+ acute lymphoblastic leukemia. Plasma dexamethasone concentrations (7.9 to 212 nM were similar to those achieved in children with acute lymphoblastic leukemia using conventional dosages. The median leukemia-free survival ranged from 16 to 59 days; dexamethasone prolonged survival from a median of 4 to 129 days in all seven dexamethasone-sensitive acute lymphoblastic leukemias. In the majority of cases (7 of 8 xenografts and the murine BCR-ABL model we demonstrated equal efficacy of the two dexamethasone dosing regimens; whereas for one acute lymphoblastic leukemia sample, the discontinuous regimen yielded inferior antileukemic efficacy (log-rank p = 0.002. Our results support the clinical practice of using discontinuous rather than continuous dexamethasone dosing in patients with acute lymphoblastic leukemia.

  11. A Rare Case of Adult Acute Lymphoblastic Leukemia Presenting with Paraparesis and Multiple Osteolytic Lesions

    OpenAIRE

    Verma, S P; Dubashi, B.; Basu, D; Dutta, T. K.; Kar, R.

    2013-01-01

    Acute lymphoblastic leukemia presenting with bone involvement and multiple osteolytic lesions has been commonly reported in pediatric population. Various myeloid and lymphoid malignancies can rarely present with bony lesions. We are reporting an adult female patient with acute lymphoblastic leukemia who presented with paraparesis and multiple osteolytic lesions in skull initially giving false impression of multiple myeloma.

  12. CD20 expression characteristic and prognosis in childhood acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    夏敏

    2014-01-01

    Objective To analyzed the expression and clinical characteristics of CD20 marker in children with B-lineage acute lymphoblastic leukemia(B-ALL)and evaluated its medical significance in assessing the prognosis of disease.Methods From November 2008 to July 2012,125cases of children with B-lineage acute lymphoblastic leukemia were collected from Shanghai Children’s Hospital,

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

    Institute of Scientific and Technical Information of China (English)

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

    2014-01-01

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

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

    Science.gov (United States)

    2013-10-29

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

  15. 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...

  16. Role of Ikaros in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Kastner, Philippe; Chan, Susan

    2011-01-01

    Ikaros is a zinc finger transcriptional regulator encoded by the Ikzf1 gene. Ikaros displays crucial functions in the hematopoietic system and its loss of function has been linked to the development of lymphoid leukemia. In particular, Ikaros has been found in recent years to be a major tumor suppressor involved in human B-cell acute lymphoblastic leukemia. Its role in T-cell leukemia, however, has been more controversial. While Ikaros deficiency appears to be very frequent in murine T-cell l...

  17. Transplantations in adult acute lymphoblastic leukemia--grounds for optimism?

    Science.gov (United States)

    Goldstone, Anthony H

    2009-01-01

    The large MRC/ECOG Adult Acute Lymphoblastic Leukemia Study establishes the value of sibling donor allogeneic transplantation in patients with standard risk, demonstrating superior outcome to conventional chemotherapy. The small but significant number of patients having matched unrelated donor transplantations on this study protocol appear to do well and might establish the value of such an approach for those without a sibling. Reduced-intensity conditioning might begin to address the transplantation-related mortality problems of the older patients. The youngest adults might not need to undergo transplantation at all. If they are now treated on pediatric chemotherapy protocols, their outcome appears to improve significantly. PMID:19778843

  18. Oral health of children with acute lymphoblastic leukemia: A review

    Directory of Open Access Journals (Sweden)

    Kadalagere Lakshmana Girish Babu

    2016-01-01

    Full Text Available Leukemia is a malignancy of the bone marrow and blood. It is the most common childhood cancer in India. Advances in the treatment regimens have greatly increased the chances of survival. Both the disease and its treatment change the oral environment. In some cases, oral manifestations are the presenting feature of the disease and it will be the dentist′s responsibility to identify the underlying disorder and guide the diagnosis of the patient. Hence, the aim of present article is to review the literature concerning the oral health of children with acute lymphoblastic leukemia (ALL.

  19. Effective re-induction therapy with dasatinib and clofarabine in relapsed Philadelphia chromosome positive acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Anne Loes van den Boom

    2012-12-01

    Full Text Available This case discusses a 10 year old female patient with a late relapse of Ph-chromosome positive B-cell precursor acute lymphoblastic leukaemias (ALL who had previously been treated with chemotherapy and allogeneic stem-cell transplantation. Treatment for relapse consisted of single-agent dasatinib, followed by 2 blocks of a combination of dasatinib and clofarabine as consolidation therapy. Using this schedule both morphological and cytogenetic complete remission were obtained. This regimen was well tolerated, and no major toxicity concerns occurred. Subsequently, the patient received a 2nd stem cell transplantation from a matched unrelated donor. Unfortunately, the child died after complete molecular remission at day +104 post-transplantation, due to a disseminated adenoviral infection. We conclude that dasatinib and clofarabine combination therapy was safe and effective in this patient, and should be further explored as a salvage regimen in relapsed/refractory Philadelphia chromosome positive ALL patients.

  20. 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)

    2013-07-03

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

  1. Vitamin E and N-Acetylcysteine as Antioxidant Adjuvant Therapy in Children with Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Youssef Al-Tonbary

    2009-01-01

    Full Text Available Although cancer therapies have experienced great success nowadays, yet the associated toxic response and free radicals formation have resulted in significant number of treatment-induced deaths rather than disease-induced fatalities. Complications of chemotherapy have forced physicians to study antioxidant use as adjunctive treatment in cancer. This study aimed to evaluate the antioxidant role of vitamin E and N-acetyl cysteine (NAC in overcoming treatment-induced toxicity in acute lymphoblastic leukaemia (ALL during the intensive period of chemo-/radiotherapy, almost the first two months of treatment. Forty children newly diagnosed with ALL were enrolled in this study. Twenty children (group I have taken vitamin E and NAC supplementations with chemotherapy and the other twenty children (group II have not taken any adjuvant antioxidant therapy. They were evaluated clinically for the occurrence of complications and by the laboratory parameters (blood levels of glutathione peroxidase (Glu.PX antioxidant enzyme, malondialdehyde (MDA, tumor necrosis factor- (TNF-, liver enzymes, and bone marrow picture. Results revealed reduced chemotherapy and radiotherapy toxicity as evidenced by decreasing level of MDA, increasing level of Glu.Px and decreased occurrence of toxic hepatitis, haematological complications, and need for blood and platelet transfusions in group I compared to group II. We can conclude that vitamin E and NAC have been shown to be effective as antioxidant adjuvant therapy in children with ALL to reduce chemo-/radiotherapy-related toxicities during the initial period of treatment.

  2. Radiation-induced acute myeloid leukaemia in mice

    International Nuclear Information System (INIS)

    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)

  3. Fanconi Syndrome: A Rare Initial Presentation of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Sahu, Kamal Kant; Law, Arjun Datt; Jain, Nidhi; Khadwal, Alka; Suri, Vikas; Malhotra, Pankaj; Varma, Subhash Chander

    2016-06-01

    A-14-year old boy, presented with a short history of excessive thirst and increased urine output. Clinical examination showed pallor, generalized lymphadenopathy and hepatosplenomegaly. For evaluation of his polyuric state he underwent routine laboratory investigations, including renal function test, acid-base studies, urine analysis. Blood tests suggested hypokalemia, hypouricemia, hypocalcemia and hyperchloremia with normal liver and kidney function tests. The arterial blood gas analysis was suggestive of normal anion gap metabolic acidosis. Urine analysis was suggestive of hyperuricosuria, hypercalciuria and glycosuria with a positive urine anion gap. His hemogram showed pancytopenia with differential count showing 88% blasts. Bone marrow examination and flowcytometry confirmed the diagnosis of B cell acute lymphoblastic leukemia. Hence this case was atypical and very interesting in the sense that the Fanconi syndrome is very rare to be an initial presenting feature of acute lymphoblastic leukemia. The patient was started on oral as well intravenous supplementation with potassium, bicarbonate, calcium and phosphorus. Simultaneously, as per the modified BFM -90 protocol (four drug based regimen-Prednisolone, vincristine, daunorubicin, cyclophosphamide along with l-asparaginase), he was started on induction protocol. By the end of 3rd week of induction therapy, his urine output started normalizing and finally settled at the end of induction therapy. At present he is in the maintenance phase of chemotherapy. PMID:27408343

  4. Treatment of Acute Lymphoblastic Leukemia from Traditional Chinese Medicine

    Directory of Open Access Journals (Sweden)

    Ya-Li Hsiao

    2014-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a cancer that immature white blood cells continuously overproduce in the bone marrow. These cells crowd out normal cells in the bone marrow bringing damage and death. Methotrexate (MTX is a drug used in the treatment of various cancer and autoimmune diseases. In particular, for the treatment of childhood acute lymphoblastic leukemia, it had significant effect. MTX competitively inhibits dihydrofolate reductase (DHFR, an enzyme that participates in the tetrahydrofolate synthesis so as to inhibit purine synthesis. In addition, its downstream metabolite methotrexate polyglutamates (MTX-PGs inhibit the thymidylate synthase (TS. Therefore, MTX can inhibit the synthesis of DNA. However, MTX has cytotoxicity and neurotoxin may cause multiple organ injury and is potentially lethal. Thus, the lower toxicity drugs are necessary to be developed. Recently, diseases treatments with Traditional Chinese Medicine (TCM as complements are getting more and more attention. In this study, we attempted to discover the compounds with drug-like potential for ALL treatment from the components in TCM. We applied virtual screen and QSAR models based on structure-based and ligand-based studies to identify the potential TCM component compounds. Our results show that the TCM compounds adenosine triphosphate, manninotriose, raffinose, and stachyose could have potential to improve the side effects of MTX for ALL treatment.

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

    Directory of Open Access Journals (Sweden)

    Čolović Milica

    2011-01-01

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

  6. CDX2 gene expression in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Hanaa H. Arnaoaut

    2014-06-01

    Full Text Available CDX genes are classically known as regulators of axial elongation during early embryogenesis. An unsuspected role for CDX genes has been revealed during hematopoietic development. The CDX gene family member CDX2 belongs to the most frequent aberrantly expressed proto-oncogenes in human acute leukemias and is highly leukemogenic in experimental models. We used reversed transcriptase polymerase chain reaction (RT-PCR to determine the expression level of CDX2 gene in 30 pediatric patients with acute lymphoblastic leukemia (ALL at diagnosis and 30 healthy volunteers. ALL patients were followed up to detect minimal residual disease (MRD on days 15 and 42 of induction. We found that CDX2 gene was expressed in 50% of patients and not expressed in controls. Associations between gene expression and different clinical and laboratory data of patients revealed no impact on different findings. With follow up, we could not confirm that CDX2 expression had a prognostic significance.

  7. [Tumor lysis syndrome in a pregnancy complicated with acute lymphoblastic leukemia].

    Science.gov (United States)

    Álvarez-Goris, M P; Sánchez-Zamora, R; Torres-Aguilar, A A; Briones Garduño, J C

    2016-04-01

    Acute leukemia is rare during pregnancy, affects about 1 in 75,000 pregnancies, of all leukemias diagnosed only 28% are acute lymphoblastic leukemia, this is a risk factor to develop spontaneous tumor lysis syndrome, it's a oncologic complication potentially deadly if the prophylactic treatment its avoided. Cases of acute lymphoblastic leukemia associated with pregnancy has been poorly documented in the literature the association of these two entities to pregnancy is the first report published worldwide, so the information is limited. PMID:27443101

  8. Acute Pancreatitis and Diabetic Ketoacidosis following L-Asparaginase/Prednisone Therapy in Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Dania Lizet Quintanilla-Flores

    2014-01-01

    Full Text Available Acute pancreatitis and diabetic ketoacidosis are unusual adverse events following chemotherapy based on L-asparaginase and prednisone as support treatment for acute lymphoblastic leukemia. We present the case of a 16-year-old Hispanic male patient, in remission induction therapy for acute lymphoblastic leukemia on treatment with mitoxantrone, vincristine, prednisone, and L-asparaginase. He was hospitalized complaining of abdominal pain, nausea, and vomiting. Hyperglycemia, acidosis, ketonuria, low bicarbonate levels, hyperamylasemia, and hyperlipasemia were documented, and the diagnosis of diabetic ketoacidosis was made. Because of uncertainty of the additional diagnosis of acute pancreatitis as the cause of abdominal pain, a contrast-enhanced computed tomography was performed resulting in a Balthazar C pancreatitis classification.

  9. Prognostic relevance of RUNX1 mutations in T-cell acute lymphoblastic leukemia

    OpenAIRE

    Grossmann, Vera; Kern, Wolfgang; Harbich, Stefan; Alpermann, Tamara; Jeromin, Sabine; Schnittger, Susanne; Haferlach, Claudia; Haferlach, Torsten; Kohlmann, Alexander

    2011-01-01

    The runt-related transcription factor 1, RUNX1, is crucial in the development of myeloid and lymphoid cell lineages and has been reported to be mutated in myeloid malignancies in approximately 30% of cases. In this study, the mutational status of RUNX1 was investigated in 128 acute lymphoblastic leukemia patients. We detected a mutation rate of 18.3% (13 of 71) in patients with T-cell acute lymphoblastic leukemia, 3.8% (2 of 52) in patients with B-cell acute lymphoblastic leukemia and no muta...

  10. Acute Lymphoblastic Leukemia in a Man Treated With Fingolimod for Relapsing Multiple Sclerosis

    Directory of Open Access Journals (Sweden)

    Stanley Cohan MD, PhD

    2015-03-01

    Full Text Available A man with relapsing multiple sclerosis, treated with fingolimod 0.5 mg/d for 15 months, developed acute lymphoblastic leukemia and died 4 months after immune ablation and bone marrow allograft, from graft versus host disease. To our knowledge, this is the first case of acute lymphoblastic leukemia reported in a patient treated with fingolimod. Although no causal relationship can be established between fingolimod use and acute lymphoblastic leukemia risk in this single case, future surveillance for lymphatic cell malignancies in patients treated with fingolimod appears justified.

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

    DEFF Research Database (Denmark)

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

    2002-01-01

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

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

    NARCIS (Netherlands)

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

    2014-01-01

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

  14. The acute lymphoblastic leukemia of Down Syndrome - Genetics and pathogenesis.

    Science.gov (United States)

    Izraeli, Shai

    2016-03-01

    Children with Down Syndrome (DS) are at markedly increased risk for acute lymphoblastic leukemia (ALL). The ALL is of B cell precursor (BCP) phenotype. T-ALL is only rarely diagnosed as well as infant leukemia. Gene expression profiling and cytogenetics suggest that DS-ALL is an heterogeneous disease. More than half of the leukemias are characterized by aberrant expression of the thymic stromal lymphopoietin (TSLP) receptor CRLF2 caused by genomic rearrangements. These rearrangements are often associated with somatic activating mutations in the receptors or in the downstream components of the JAK-STAT pathway. The activation of JAK-STAT pathway suggests that targeted therapy with JAK or downstream inhibitors may be effective for children with DS-ALL. The basis of the increased risk of BCP-ALL and in particular of the CRLF2 aberrations is presently unknown. Neither is it known which genes on the trisomic chromosome 21 are involved. PMID:26631987

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

    Science.gov (United States)

    Takagi, Masatoshi; Urayama, Kevin

    2016-07-01

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

  16. Prediction of intellectual deficits in children with acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Possible predictors of reported lower cognitive functioning in irradiated children with acute lymphoblastic leukemia (ALL) were investigated. Thirty-four subjects, 5-14 years old, with ALL in continuous complete remission and without evidence of current or past central nervous system disease, were examined 9-110 months after diagnosis, using standard measures of intelligence and academic achievement. Subjects with a history of post-irradiation somnolence syndrome were significantly older at diagnosis than nonsomnolent subjects. Intelligence (IQ) was found to be unrelated to history of somnolence syndrome. IQ and achievement were unrelated to age at irradiation, irradiation-examination interval, and radiation dosages. The strongest predictor of IQ by far is parental social class. The importance of controlling for social class differences when searching for treatment effects on IQ and achievement is stressed

  17. Cerebral aspergillus infection in pediatric acute lymphoblastic leukemia induction therapy

    Directory of Open Access Journals (Sweden)

    Gaurav Prakash

    2012-01-01

    Full Text Available Angioinvasive pulmonary infection from filamentous fungi is not an uncommon occurrence in immunocompromised patients like acute lymphoblastic leukemia (ALL. Rarely, these lesions can spread via the hematogenous route and involve multiple visceral organs. We report a case of a 14-year-old boy with ALL who developed angioinvasive pulmonary aspergillosis early in the course of induction therapy, which was followed by hematogenous dissemination and formation of multiple brain abscesses. The patient was treated with intravenous amphotericin B. There was no response to the therapy and the patient succumbed to disseminated infection. Postmortem lung biopsy confirmed angioinvasive pulmonary aspergillosis. Poor penetration of amphotericin B across the blood-brain barrier could be one of the contributory factors for poor response to antifungal therapy. We discuss the various antifungal agents with respect to their penetration in brain.

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

    Science.gov (United States)

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

    2009-01-01

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

  19. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    NARCIS (Netherlands)

    Hulleman, Esther; Kazemier, Karin M.; Holleman, Amy; VanderWeele, David J.; Rudin, Charles M.; Broekhuis, Mathilde J. C.; Evans, William E.; Pieters, Rob; Den Boer, Monique L.

    2009-01-01

    Treatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant pr

  20. The controversy of varicella vaccination in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Caniza, Miguela A; Hunger, Stephen P; Schrauder, Andre;

    2012-01-01

    The available guidelines for varicella vaccination of susceptible children with acute lymphoblastic leukemia (ALL) have become increasingly conservative. However, vaccination of those who have remained in continuous complete remission for 1 year and are receiving chemotherapy is still considered ...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    BACKGROUND: Methotrexate (MTX) eradicates leukemic cells by disrupting de novo nucleotide biosynthesis and DNA replication, resulting in cell death. Since its introduction in 1947, MTX-containing chemotherapeutic regimens have proven instrumental in achieving curative effects in acute lymphoblastic...

  2. 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....... Here we have investigated how the development and progression of this leukaemia affect oxygenation, pH and proliferation of normal and leukaemic cells in vivo. Bone marrow pH was measured by a needle electrode. Nitroimidazol-theophylline (NITP) was used to identify hypoxic cells, and we applied...... bromodeoxyuridine (BrdUrd) to identify DNA replicating cells. The leukaemia progressed slowly until day 27 after which a rapid deterioration could be observed leading to severe changes over the following 5 d. In whole blood there was evidence of progressing metabolic acidosis. In bone marrow the fraction...

  3. Osteoporosis resulting from acute lymphoblastic leukemia in a 7-year-old boy: a case report

    OpenAIRE

    Salim, Hendra; Ariawati, Ketut; Suryawan, Wayan Bikin; Arimbawa, Made

    2014-01-01

    Introduction Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. Etiological factors responsible for osteoporosis secondary to chronic illness include immobility, pubertal delay and other hormonal disturbances. Rarely, it can be a manifestation of acute lymphoblastic leukemia. Most of the reported bone fracture incidences associated with acute lymphoblastic leukemia occur during the course of the chemotherapy, not...

  4. Environment-mediated drug resistance in Bcr/Abl-positive acute lymphoblastic leukemia

    OpenAIRE

    Feldhahn, Niklas; Arutyunyan, Anna; Stoddart, Sonia; ZHANG Bin; Schmidhuber, Sabine; Yi, Sun-ju; Kim, Yong-Mi; Groffen, John; Heisterkamp, Nora

    2012-01-01

    Although cure rates for acute lymphoblastic leukemia (ALL) have increased, development of resistance to drugs and patient relapse are common. The environment in which the leukemia cells are present during the drug treatment is known to provide significant survival benefit. Here, we have modeled this process by culturing murine Bcr/Abl-positive acute lymphoblastic leukemia cells in the presence of stroma while treating them with a moderate dose of two unrelated drugs, the farnesyltransferase i...

  5. Outcome of Adult Acute Lymphoblastic Leukemia in South East of Iran (Zahedan)

    OpenAIRE

    Mashhadi, Mohammad Ali; Koushyar, Mohhamad Mahdi; Mohammadi, Mehdi

    2012-01-01

    Background Acute lymphoblastic leukemia is a lymphoid malignancy, resulting from autonomous proliferation of monoclonal abnormal stem cell. The aim of this study was to evaluate the response rate and prognostic factor of adult patients suffering from acute lymphoblastic leukemia, who were treated with chemotherapy in south east of Iran and demographic methods were used for this study. Methods This study was conducted in Ali Ebne Abitaleb Hospital in south east of Iran (Zahedan) from 2003-2010...

  6. Central nervous system involvement in acute lymphoblastic leukemia: diagnosis by immunophenotyping

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2013-08-01

    Full Text Available The central nervous system is the most commonly affected extramedullary site in acute lymphoblastic leukemia. Although morphologic evaluation of the cerebrospinal fluid has been traditionally used for diagnosing central nervous system involvement, it is a method of low sensitivity. The present study aimed at evaluating the use of immunophenotyping in the detection of blasts in the cerebrospinal fluid from children and adolescents with acute lymphoblastic leukemia.

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

    Institute of Scientific and Technical Information of China (English)

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

    2016-01-01

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

  8. Conservative Management of Pancreatic Pseudocysts in Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Spraker, Holly L.; Spyridis, Georgios P.; Pui, Ching-Hon; Howard, Scott C.

    2009-01-01

    Treatment with asparaginase for acute lymphoblastic leukemia (ALL) can cause acute pancreatitis. Complication of pancreatitis by pancreatic pseudocyst formation can prolong the hospital stay, delay chemotherapy, and necessitate long-term parenteral nutrition. We report five children with ALL who developed acute pancreatitis complicated by pancreatic pseudocysts. They required modifications to their chemotherapy regimen and prolonged parenteral nutrition but no surgical intervention. All five ...

  9. Vincristine in childhood leukaemia : no pharmacokinetic rationale for dose reduction in adolescents

    NARCIS (Netherlands)

    Frost, BM; Lonnerholm, G; Koopmans, P; Abrahamsson, J; Behrendtz, M; Castor, A; Forestier, E; Uges, DRA

    2003-01-01

    Aim: To investigate whether there is any pharmacokinetic rationale for the common practice of administering vincristine to adolescents at relatively lower doses than those to younger children. Methods: A total of 98 children, aged 1.3-17.3 y, with acute lymphoblastic leukaemia (ALL) were studied on

  10. 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

    2005-01-01

    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 y

  11. Neurofibromatosis and childhood leukaemia/lymphoma: a population-based UKCCSG study.

    OpenAIRE

    Stiller, C A; Chessells, J M; Fitchett, M

    1994-01-01

    There is a well-known raised risk of leukaemia in children with neurofibromatosis type 1 (NF-1). We carried out the first detailed population-based study of leukaemia and non-Hodgkin lymphoma (NHL) associated with NF-1 in order to estimate the risk and elucidate the relationship between these conditions. Over the 17 year study period there were five cases of chronic myelomonocytic leukaemia (CMML) in patients with NF-1 (relative risk 221; 95% CI 71-514), 12 cases of acute lymphoblastic leukae...

  12. 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. PMID:27130539

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

    OpenAIRE

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

    1981-01-01

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

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

    OpenAIRE

    Frech, Miriam

    2014-01-01

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

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

    OpenAIRE

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

    2009-01-01

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

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

    OpenAIRE

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

    2014-01-01

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

  17. Hereditary and acquired p53 gene mutations in childhood acute lymphoblastic leukemia.

    OpenAIRE

    Felix, C A; Nau, M M; Takahashi, T.; Mitsudomi, T.; Chiba, I.; Poplack, D G; Reaman, G H; Cole, D E; Letterio, J J; Whang-Peng, J

    1992-01-01

    The p53 gene was examined in primary lymphoblasts of 25 pediatric patients with acute lymphoblastic leukemia by the RNase protection assay and by single strand conformation polymorphism analysis in 23 of 25 cases. p53 mutations were found to occur, but at a low frequency (4 of 25). While all four mutations were identified by single strand conformation polymorphism, the comparative sensitivity of RNase protection was 50% (2 of 4). Heterozygosity was retained at mutated codons in 3 of 4 cases. ...

  18. Acute Lymphoblastic Leukemia with Eosinophilia and Strongyloides Stercoralis Hyperinfection

    Directory of Open Access Journals (Sweden)

    Yadollah Zahedpasha

    2011-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in children. Bone pain is an important symptom that can be severe. Eosinophilia without any other abnormal laboratory findings is rare in ALL. Strongyloides stercoralis in ALL causes disseminated fatal disease.Case Presentation: This 9-year-old girl presented with bone pain in lumbar region. Bone pain was the only symptom. The patient didnt have organomegaly. The BM samples were studied by flow cytometry, which showed pre-B cell ALL. Larva of Strongyloides stercoralis was found in fecal examination. Plain chest x ray showed bilateral para-cardiac infiltration. Strongyloidiasis was treated before starting chemotherapy. After two days treatment with Mebendazol the patient developed cough, dyspnea, respiratory distress and fever. The treatment changed to Ivermectin for 2 days. Chemotherapy started five days after diagnosis of leukemia.Conclusion: The patient complained merely of bone pain in lumbar region without any other signs and symptoms. Peripheral blood smear showed eosinophilia without any other abnormality. Stool examination showed Strongyloides stercoralis larvae. We suggest that all patients diagnosed as ALL in tropical and subtropical regions should be evaluated for parasitic infection especially with Strongyloides stercoralis.

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

    Science.gov (United States)

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

    1998-06-01

    Ninety-two Israeli children with acute lymphoblastic leukemia (ALL) (67 B-lineage and 25 T-lineage) were analyzed for the immunological antigen receptor gene configuration. Thirty-nine of the patients (27 B-lineage and 12 T-lineage) relapsed. The incidence of the identified rearrangements within the immunoglobulin heavy chain (IgH) and T-cell receptor (TCR)beta, gamma and delta genes, at diagnosis, was in accordance with previous studies from other countries. Furthermore, the clinical relevance of bi/oligoclonal status, at diagnosis, and clonal selection was determined in this long-term follow-up study (median 112 months). A similar relapse rate was observed among the B-lineage patients with bi/oligoclonal and monoclonal patterns indicated by IgH gene rearrangement. Based on our results, we suggest that bi/oligoclonality has no prognostic significance (P=0.8533). Clonal variations between diagnosis and subsequent relapses were detected in 60% (12/20) of the patients; 64% (7/11) B-lineage and 55% (5/9) T-lineage. Clonal selection significantly correlated with shorter duration of remission and earlier recurrence (P=0.0025). PMID:9678715

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

    Science.gov (United States)

    Pui, Ching-Hon; Evans, William E.

    2013-01-01

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

  1. Radiation-induced hypopituitarism in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mehrdad Mirouliaei

    2013-01-01

    Full Text Available Background: Acute Lymphoblastic Leukemia (ALL is the most common malignancy among children for whom radiotherapy and chemotherapy are used for treatment. When hypothalamus-pituitary axis is exposed to radiotherapy, children′s hormone level and quality of life are influenced. The aim of this study is to determine late effects of radiotherapy on hormonal level in these patients. Materials and Methods: In this study 27 children with ALL, who have been referred to Shahid Ramezanzadeh Radiation Oncology Center in Yazd-Iran and received 18-24 Gy whole brain radiation with Cobalt 60 or 9 MV linear accelerator, were assessed. These patient′s basic weight, height and hormonal levels were measured before radiotherapy and also after different periods of time. Results: GHD (growth hormone deficiency after clonidine stimulation test was observed in 44% ( n=12 and that in 50% of them ( n=6, less than 1 year, had been passed from their radiation therapy. None of these patients demonstrated hormone deficiency in other axes. Conclusions: This study showed that even application of a 18-24 Gy radiation dose might influence growth hormone levels; therefore, we recommend reduction of radiotherapy dose in such patients whenever possible.

  2. Microenvironmental cues for T-cell acute lymphoblastic leukemia development.

    Science.gov (United States)

    Passaro, Diana; Quang, Christine Tran; Ghysdael, Jacques

    2016-05-01

    Intensive chemotherapy regimens have led to a substantial improvement in the cure rate of patients suffering from T-cell acute lymphoblastic leukemia (T-ALL). Despite this progress, about 15% and 50% of pediatric and adult cases, respectively, show resistance to treatment or relapse with dismal prognosis, calling for further therapeutic investigations. T-ALL is an heterogeneous disease, which presents intrinsic alterations leading to aberrant expression of transcription factors normally involved in hematopoietic stem/progenitor cell development and mutations in genes implicated in the regulation of cell cycle progression, apoptosis, and T-cell development. Gene expression profiling allowed the classification of T-ALL into defined molecular subgroups that mostly reflects the stage of their differentiation arrest. So far this knowledge has not translated into novel, targeted therapy. Recent evidence points to the importance of extrinsic signaling cues in controlling the ability of T-ALL to home, survive, and proliferate, thus offering the perspective of new therapeutic options. This review summarizes the present understanding of the interactions between hematopoietic cells and bone marrow/thymic niches during normal hematopoiesis, describes the main signaling pathways implicated in this dialog, and finally highlights how malignant T cells rely on specific niches to maintain their ability to sustain and propagate leukemia. PMID:27088913

  3. TREATMENT OF ADOLESCENT AND YOUNG ADULTS WITH ACUTE LYMPHOBLASTIC LEUKEMIA

    Directory of Open Access Journals (Sweden)

    Josep-Maria Ribera

    2014-07-01

    Full Text Available The primary objective of this review was to update and discuss the current concepts andthe results of the treatment of acute lymphoblastic leukemia (ALL in adolescents and young adults(AYA. After a brief consideration of the epidemiologic and clinicobiologic characteristics of ALLin the AYA population, the main retrospective comparative studies stating the superiority ofpediatric over adult-based protocols were reviewed. The most important prospective studies inyoung adults using pediatric inspired or pediatric unmodified protocols were also reviewedemphasizing their feasibility at least up to the age of 40 yr and their promising results, with eventfreesurvival rates of 60-65% or greater. Results of trials from pediatric groups have shown that theunfavourable prognosis of adolescents is no more adequate. The majority of the older adolescentswith ALL can be cured with risk-adjusted and minimal residual disease-guided intensivechemotherapy, without stem cell transplantation. However, some specific subgroups, which aremore frequent in adolescents than in children (e.g., early pre-T, iAMP21, and BCR-ABL-like,deserve particular attention. In summary, the advances in treatment of ALL in adolescents havebeen translated to young adults, and that explains the significant improvement in survival of thesepatients in recent years.

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

    International Nuclear Information System (INIS)

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

  5. The molecular genetic makeup of acute lymphoblastic leukemia.

    Science.gov (United States)

    Mullighan, Charles G

    2012-01-01

    Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention. Mutations in genes regulating lymphoid development are a hallmark of ALL, and alterations of the lymphoid transcription factor gene IKZF1 (IKAROS) are associated with a high risk of treatment failure in B-ALL. Approximately 20% of B-ALL cases harbor genetic alterations that activate kinase signaling that may be amenable to treatment with tyrosine kinase inhibitors, including rearrangements of the cytokine receptor gene CRLF2; rearrangements of ABL1, JAK2, and PDGFRB; and mutations of JAK1 and JAK2. Whole-genome sequencing has also identified novel targets of mutation in aggressive T-lineage ALL, including hematopoietic regulators (ETV6 and RUNX1), tyrosine kinases, and epigenetic regulators. Challenges for the future are to comprehensively identify and experimentally validate all genetic alterations driving leukemogenesis and treatment failure in childhood and adult ALL and to implement genomic profiling into the clinical setting to guide risk stratification and targeted therapy.

  6. Acute Lymphoblastic Leukemia Transformation in Polycythemia Vera: A Rare Phenomenon.

    Science.gov (United States)

    Gaweł, Władysław B; Helbig, Grzegorz; Boral, Kinga; Kyrcz-Krzemień, Sławomira

    2016-06-01

    Leukemic transformation in patients diagnosed with polycythemia vera (PV) is associated with poor prognosis and median survival not exceeding 3 months. To date only a few cases of post-PV acute lymphoblastic leukemia (ALL) have been reported. A 64-year-old female patient developed ALL 4 years after she had met PV criteria. At PV diagnosis a molecular study was positive for the JAK2V617F mutation. Due to high risk features (history of deep vein thrombosis) she was treated with hydroxyurea (HU) with moderate efficacy. She became anemic and thrombocytopenic with mild leukocytosis while still on HU. Blood and bone marrow smears revealed 40 and 100 % of blast cells, respectively. The immunophenotyping of blasts was consistent with a diagnosis of early precursor B cell ALL. She was found to be positive for the JAK2V617F mutation. Patient received an ALL induction regimen and achieved complete remission with negative minimal residual disease by flow cytometry. The post-chemotherapy study for the JAK2V617F mutation was positive. Patient has remained in remission for 4 months. A suitable donor searching was initiated. Post-PV ALL is an extremely rare phenomenon. Due to poor prognosis, an allogeneic stem cell transplantation should be considered in fit patients who achieved remission. PMID:27408357

  7. BCL6 modulation of acute lymphoblastic leukemia response to chemotherapy.

    Science.gov (United States)

    Slone, William L; Moses, Blake S; Hare, Ian; Evans, Rebecca; Piktel, Debbie; Gibson, Laura F

    2016-04-26

    The bone marrow niche has a significant impact on acute lymphoblastic leukemia (ALL) cell phenotype. Of clinical relevance is the frequency with which quiescent leukemic cells, in this niche, survive treatment and contribute to relapse. This study suggests that marrow microenvironment regulation of BCL6 in ALL is one factor that may be involved in the transition between proliferative and quiescent states of ALL cells. Utilizing ALL cell lines, and primary patient tumor cells we observed that tumor cell BCL6 protein abundance is decreased in the presence of primary human bone marrow stromal cells (BMSC) and osteoblasts (HOB). Chemical inhibition, or shRNA knockdown, of BCL6 in ALL cells resulted in diminished ALL proliferation. As many chemotherapy regimens require tumor cell proliferation for optimal efficacy, we investigated the consequences of constitutive BCL6 expression in leukemic cells during co-culture with BMSC or HOB. Forced chronic expression of BCL6 during co-culture with BMSC or HOB sensitized the tumor to chemotherapy induced cell death. Combination treatment of caffeine, which increases BCL6 expression in ALL cells, with chemotherapy extended the event free survival of mice. These data suggest that BCL6 is one factor, modulated by microenvironment derived cues that may contribute to regulation of ALL therapeutic response. PMID:27015556

  8. Acute respiratory distress syndrome associated with tumor lysis syndrome in a child with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Alessandra Macaluso

    2015-03-01

    Full Text Available Tumor lysis syndrome is a serious and dangerous complication usually associated with antiblastic treatment in some malignancies characterized by high cell turn-over. Mild or severe electrolyte abnormalities including high serum levels of uric acid, potassium, phosphorus, creatinine, bun and reduction of calcium can be responsible for multi-organ failure, involving mostly kidneys, heart and central nervous system. Renal damage can be followed by acute renal failure, weight gain, progressive liver impairment, overproduction of cytokines, and subsequent maintenance of multi-organ damage. Life-threatening acute respiratory failure associated with tumor lysis syndrome is rare. We describe a child with T-cell acute lymphoblastic leukemia, who developed an unusually dramatic tumor lysis syndrome, after administration of the first low doses of steroid, that was rapidly associated with severe acute respiratory distress syndrome. Subsequent clinical course and treatment modalities that resulted in the gradual and full recovery of the child are also described.

  9. Acute respiratory distress syndrome associated with tumor lysis syndrome in a child with acute lymphoblastic leukemia.

    Science.gov (United States)

    Macaluso, Alessandra; Genova, Selene; Maringhini, Silvio; Coffaro, Giancarlo; Ziino, Ottavio; D'Angelo, Paolo

    2015-02-24

    Tumor lysis syndrome is a serious and dangerous complication usually associated with antiblastic treatment in some malignancies characterized by high cell turn-over. Mild or severe electrolyte abnormalities including high serum levels of uric acid, potassium, phosphorus, creatinine, bun and reduction of calcium can be responsible for multi-organ failure, involving mostly kidneys, heart and central nervous system. Renal damage can be followed by acute renal failure, weight gain, progressive liver impairment, overproduction of cytokines, and subsequent maintenance of multi-organ damage. Life-threatening acute respiratory failure associated with tumor lysis syndrome is rare. We describe a child with T-cell acute lymphoblastic leukemia, who developed an unusually dramatic tumor lysis syndrome, after administration of the first low doses of steroid, that was rapidly associated with severe acute respiratory distress syndrome. Subsequent clinical course and treatment modalities that resulted in the gradual and full recovery of the child are also described. PMID:25918625

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  11. High frequency of BTG1 deletions in acute lymphoblastic leukemia in children with down syndrome

    DEFF Research Database (Denmark)

    Lundin, Catarina; Hjorth, Lars; Behrendtz, Mikael;

    2012-01-01

    Previous cytogenetic studies of myeloid and acute lymphoblastic leukemias in children with Down syndrome (ML-DS and DS-ALL) have revealed significant differences in abnormality patterns between such cases and acute leukemias in general. Also, certain molecular genetic aberrations characterize DS...

  12. Targeted Resequencing of 9p in Acute Lymphoblastic Leukemia Yields Concordant Results with Array CGH and Reveals Novel Genomic Alterations

    NARCIS (Netherlands)

    Sarhadi, V.K.; Lahti, L.M.; Scheinin, I.; Tyybäkinoja, A.; Savola, S.; Usvasalo, A.; Räty, R.; Elonen, E.; Saarinen-Pihkala, U.M.; Knuutila, S.

    2013-01-01

    Genetic alterations of the short arm of chromosome 9 are frequent in acute lymphoblastic leukemia. We performed targeted sequencing of 9p region in 35 adolescent and adult acute lymphoblastic leukemia patients and sought to investigate the sensitivity of detecting copy number alterations in comparis

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  14. Assessing Compliance With Mercaptopurine Treatment in Younger Patients With Acute Lymphoblastic Leukemia in First Remission | Division of Cancer Prevention

    Science.gov (United States)

    This randomized phase III trial studies compliance to a mercaptopurine treatment intervention compared to standard of care in younger patients with acute lymphoblastic leukemia in remission. Assessing ways to help patients who have acute lymphoblastic leukemia to take their medications as prescribed may help them in taking their medications more consistently and may improve treatment outcomes. |

  15. 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.; Kooy, Marinus van Marwijk; 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.; Boer, Fransien Croon-de; Eefting, Matthijs; Jie, Kon-Siong G.; de Loosdrecht, Arjan A. van; 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

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

    Directory of Open Access Journals (Sweden)

    Amanda Dixon-McIver

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

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

    Science.gov (United States)

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

    2015-07-01

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

  18. Acute Lymphoblastic Leukemia in a Young Adult Presenting as Hepatitis and Acute Kidney Injury

    Science.gov (United States)

    Heincelman, Marc; Karakala, Nithin; Rockey, Don C.

    2016-01-01

    Acute lymphoblastic leukemia (ALL) in adults is a relatively rare malignancy. The typical presentation includes signs and symptoms associated with bone marrow failure, including fevers, infections, fatigue, and excessive bruising. In this article, we report an unusual systemic presentation of ALL in a previously healthy 18-year-old man. He initially presented with several-day history of nausea and vomiting, 10-pound weight loss, and right upper quadrant abdominal pain with evidence of acute hepatocellular liver injury (elevations in aspartate aminotransferase/alanine aminotransferase) and elevation in serum creatinine. Further history revealed that he just joined the Marine Corp; in preparation, he had been lifting weights and taking protein and creatine supplements. A complete serological evaluation for liver disease was negative and creatine phosphokinase was normal. His aspartate aminotransferase and alanine aminotransferase declined, and he was discharged with expected improvement. However, he returned one week later with continued symptoms and greater elevation of aminotransferases. Liver biopsy was nondiagnostic, revealing scattered portal and lobular inflammatory cells (primarily lymphocytes) felt to be consistent with drug-induced liver injury or viral hepatitis. Given his elevated creatinine, unresponsive to aggressive volume expansion, a kidney biopsy was performed, revealing normal histology. He subsequently developed an extensive left lower extremity deep venous thrombosis. Given his deep venous thrombosis, his peripheral blood was sent for flow cytometry, which revealed lymphoblasts. Bone marrow biopsy revealed 78% blasts with markers consistent with acute B-cell lymphoblastic leukemia. This report emphasizes that right upper quadrant abdominal pain with liver test abnormalities may be the initial presentation of a systemic illness such as ALL.

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Pictorial essay: Acute neurological complications in children with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Seema A Kembhavi

    2012-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the commonest childhood malignancy with high cure rates due to recent advances in central nervous system (CNS prophylaxis. The disease per se, as well as the prophylactic therapy, predisposes the child to complications such as cerebrovascular events, infections, drug toxicities, etc. The purpose of this study is to highlight the pathophysiology and the imaging features (with appropriate examples of these complications and to propose a diagnostic algorithm based on MRI. Interpreting these scans in the light of clinical inputs very often helps the radiologist reach an appropriate diagnosis and help treatment and management.

  1. Cytologic Phenotypes of B-Cell Acute Lymphoblastic Leukemia-

    Directory of Open Access Journals (Sweden)

    Ramyar Asghar

    2009-06-01

    Full Text Available Acute lymphoblastic leukemia (ALL is a malignant disorder of lymphoid precursor cells, which could be classified according to morphological and cytochemical methods as well as immunophenotyping. Twenty patients with ALL, who had been referred to the Children's Medical Center Hospital, during the year 2007, were enrolled in this study in order to evaluate the morphologic and immunophenotypic profile of these patients. Cytologic analysis of blood and bone marrow samples revealed that the frequency of ALL-L1 was 70%, followed by ALL-L2 and ALL-L3. The onset age of the patients with ALL-L1 was significantly lower than the patients with L2/L3. Severe anemia was significantly detected more in L1 group. Flow cytometic study of bone marrow showed that 10 cases had Pre-B1 ALL and 7 cases had Pre-B2 ALL, while three cases had Pro-B ALL. Comparisons of the characteristics and clinical manifestations among these groups did not show any appreciable difference. There were an increase percentage of CD20+ cells and a decrease CD10+ cells in pre-B2 group in comparison with pre-B1 group. Fifteen patients were in standard risk and five were in high risk. Although standard risk patients were more common in the group of pre-B1, this was not significant. Our results confirm the previous reports indicating heterogeneity of ALL. Immunophenotyping is not the only diagnostic test of importance, while morphological assessment still can be used in the diagnosis and classification of the disease.

  2. Improved Prognosis for Older Adolescents With Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Pui, Ching-Hon; Pei, Deqing; Campana, Dario; Bowman, W. Paul; Sandlund, John T.; Kaste, Sue C.; Ribeiro, Raul C.; Rubnitz, Jeffrey E.; Coustan-Smith, Elaine; Jeha, Sima; Cheng, Cheng; Metzger, Monika L.; Bhojwani, Deepa; Inaba, Hiroto; Raimondi, Susana C.; Onciu, Mihaela; Howard, Scott C.; Leung, Wing; Downing, James R.; Evans, William E.; Relling, Mary V.

    2011-01-01

    Purpose The prognosis for older adolescents and young adults with acute lymphoblastic leukemia (ALL) has been historically much worse than that for younger patients. We reviewed the outcome of older adolescents (age 15 to 18 years) treated in four consecutive Total Therapy studies to determine if recent improved treatment extended to this high-risk group. Patients and Methods Between 1991 and 2007, 963 pediatric patients, including 89 older adolescents, were enrolled on Total Therapy studies XIIIA, XIIIB, XIV, and XV. In the first three studies, treatment selection was based on presenting clinical features and leukemic cell genetics. In study XV, the level of residual disease was used to guide treatment, which featured intensive methotrexate, glucocorticoid, vincristine, and asparaginase, as well as early triple intrathecal therapy for higher-risk ALL. Results The 89 older adolescents were significantly more likely to have T-cell ALL, the t(4;11)(MLL-AF4), and detectable minimal residual disease during or at the end of remission induction; they were less likely to have the t(12;21)(ETV6-RUNX1) compared with younger patients. In the first three studies, the 44 older adolescents had significantly poorer event-free survival and overall survival than the 403 younger patients. This gap in prognosis was abolished in study XV: event-free survival rates at 5 years were 86.4% ± 5.2% (standard error) for the 45 older adolescents and 87.4% ± 1.7% for the 453 younger patients; overall survival rates were 87.9% ± 5.1% versus 94.1% ± 1.2%, respectively. Conclusion Most older adolescents with ALL can be cured with risk-adjusted intensive chemotherapy without stem-cell transplantation. PMID:21172890

  3. Cholinergic Machinery as Relevant Target in Acute Lymphoblastic T Leukemia

    Science.gov (United States)

    Dobrovinskaya, Oxana; Valencia-Cruz, Georgina; Castro-Sánchez, Luis; Bonales-Alatorre, Edgar O.; Liñan-Rico, Liliana; Pottosin, Igor

    2016-01-01

    Various types of non-neuronal cells, including tumors, are able to produce acetylcholine (ACh), which acts as an autocrine/paracrine growth factor. T lymphocytes represent a key component of the non-neuronal cholinergic system. T cells-derived ACh is involved in a stimulation of their activation and proliferation, and acts as a regulator of immune response. The aim of the present work was to summarize the data about components of cholinergic machinery in T lymphocytes, with an emphasis on the comparison of healthy and leukemic T cells. Cell lines derived from acute lymphoblastic leukemias of T lineage (T-ALL) were found to produce a considerably higher amount of ACh than healthy T lymphocytes. Additionally, ACh produced by T-ALL is not efficiently hydrolyzed, because acetylcholinesterase (AChE) activity is drastically decreased in these cells. Up-regulation of muscarinic ACh receptors was also demonstrated at expression and functional level, whereas nicotinic ACh receptors seem to play a less important role and not form functional channels in cells derived from T-ALL. We hypothesized that ACh over-produced in T-ALL may act as an autocrine growth factor and play an important role in leukemic clonal expansion through shaping of intracellular Ca2+ signals. We suggest that cholinergic machinery may be attractive targets for new drugs against T-ALL. Specifically, testing of high affinity antagonists of muscarinic ACh receptors as well as antagomiRs, which interfere with miRNAs involved in the suppression of AChE expression, may be the first choice options. PMID:27630569

  4. Nanoparticle targeted therapy against childhood acute lymphoblastic leukemia

    Science.gov (United States)

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

    2011-06-01

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

  5. Anticancer activity of cryptotanshinone on acute lymphoblastic leukemia cells.

    Science.gov (United States)

    Wu, Ching-Fen; Klauck, Sabine M; Efferth, Thomas

    2016-09-01

    Cryptotanshinone, a well-known diterpene quinone from a widely used traditional Chinese herb named Salvia miltiorrhiza, has been reported for its therapeutical potentials on diverse activities. In this study, pharmacological effects of cryptotanshinone on acute lymphoblastic leukemia cells were investigated. IC50 values of 5.0 and 4.8 were obtained in CEM/ADR5000 and CCRF-CEM. Microarray-based mRNA expression revealed that cryptotanshinone regulated genes associated with cell cycle, DNA damage, reactive oxygen species (ROS), NFκB signaling and cellular movement. The involvement of these pathways in the mode of action of cryptotanshinone was subsequently validated by additional independent in vitro studies. Cryptotanshinone stimulated ROS generation and induced DNA damage. It arrested cells in G2/M phase of the cell cycle and induced apoptosis as measured by annexin V-FITC-conjugating fluorescence. The induction of the intrinsic apoptotic pathway by cryptotanshinone was proved by loss of mitochondrial membrane potential and increased cleavage of caspase 3/7, caspase 9 and poly ADP ribose polymerase (PARP). DNA-binding motif analysis of the microarray-retrieved deregulated genes in the promoter region revealed NFκB as potential transcription factor involved in cryptotanshinone's mode of action. Molecular docking and Western blotting provided supportive evidence, suggesting that cryptotanshinone binds to IKK-β and inhibits the translocation of p65 from the cytosol to the nucleus. In addition, cryptotanshinone inhibited cellular movement as shown by a fibronectin-based cellular adhesion assay, indicating that this compound exerts anti-invasive features. In conclusion, cryptotanshinone exerts profound cytotoxicity, which is caused by multispecific modes of actions, including G2/M arrest, apoptosis and inhibition of cellular movement. The inhibitory activities of this compound may be explained by inhibition of NFκB, which orchestrates all these mechanisms. PMID

  6. Advances in the Genetics and Therapy of Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Chiaretti, Sabina; Gianfelici, Valentina; O'Brien, Susan M; Mullighan, Charles G

    2016-01-01

    Acute lymphoblastic leukemia (ALL) remains an important cause of morbidity in children and adults. In this article, we highlight advances in the genetics and therapy of three key subtypes of ALL: T-cell ALL, BCR-ABL1 (Philadelphia [Ph] chromosone-positive), and Ph-like ALL. T-ALL is an aggressive disease that accounts for about 15% and 25% of ALL among pediatric and adult cohorts, respectively, and exhibits a multistep nature of cancer initiation and progression. The integration of cytogenetics, molecular biology, and immunophenotype analyses has led to the identification of defined T-ALL subgroups, such as early T-cell precursor ALL and novel lesions with a prognostic role, for which specific inhibitors are being developed. Ph-positive ALL was historically regarded as a subtype of ALL with a poor prognosis, and allogeneic stem cell transplant was recommended for all patients who could undergo this procedure. The deep complete responses seen with combination tyrosine kinase inhibitors (TKIs) and chemotherapy in Ph-positive ALL, and the reports of long-term survival among some patients not undergoing allogeneic stem cell transplant, has raised the question of whether there is a subset of patients who could be cured without this intervention. Ph-like ALL is a subtype of B-progenitor ALL common among older children and adults and associated with a diverse range of genetic alterations that activate kinase signaling. Ph-like ALL is also associated with poor outcome, for which precision medicine trials identifying kinase alterations and testing TKI therapy are being developed. PMID:27249738

  7. Rituximab in B-Lineage Adult Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Maury, Sébastien; Chevret, Sylvie; Thomas, Xavier; Heim, Dominik; Leguay, Thibaut; Huguet, Françoise; Chevallier, Patrice; Hunault, Mathilde; Boissel, Nicolas; Escoffre-Barbe, Martine; Hess, Urs; Vey, Norbert; Pignon, Jean-Michel; Braun, Thorsten; Marolleau, Jean-Pierre; Cahn, Jean-Yves; Chalandon, Yves; Lhéritier, Véronique; Beldjord, Kheira; Béné, Marie C; Ifrah, Norbert; Dombret, Hervé

    2016-09-15

    Background Treatment with rituximab has improved the outcome for patients with non-Hodgkin's lymphoma. Patients with B-lineage acute lymphoblastic leukemia (ALL) may also have the CD20 antigen, which is targeted by rituximab. Although single-group studies suggest that adding rituximab to chemotherapy could improve the outcome in such patients, this hypothesis has not been tested in a randomized trial. Methods We randomly assigned adults (18 to 59 years of age) with CD20-positive, Philadelphia chromosome (Ph)-negative ALL to receive chemotherapy with or without rituximab, with event-free survival as the primary end point. Rituximab was given during all treatment phases, for a total of 16 to 18 infusions. Results From May 2006 through April 2014, a total of 209 patients were enrolled: 105 in the rituximab group and 104 in the control group. After a median follow-up of 30 months, event-free survival was longer in the rituximab group than in the control group (hazard ratio, 0.66; 95% confidence interval [CI], 0.45 to 0.98; P=0.04); the estimated 2-year event-free survival rates were 65% (95% CI, 56 to 75) and 52% (95% CI, 43 to 63), respectively. Treatment with rituximab remained associated with longer event-free survival in a multivariate analysis. The overall incidence rate of severe adverse events did not differ significantly between the two groups, but fewer allergic reactions to asparaginase were observed in the rituximab group. Conclusions Adding rituximab to the ALL chemotherapy protocol improved the outcome for younger adults with CD20-positive, Ph-negative ALL. (Funded by the Regional Clinical Research Office, Paris, and others; ClinicalTrials.gov number, NCT00327678 .). PMID:27626518

  8. Acute lymphoblastic leukemia: Are Egyptian children adherent to maintenance therapy?

    Directory of Open Access Journals (Sweden)

    Elhamy Rifky Abdel Khalek

    2015-01-01

    Full Text Available Background, Aims, Settings and Design: Poor adherence to oral maintenance chemotherapy can cause relapse of acute lymphoblastic leukemia (ALL. A multicenter study for the evaluation of adherence to oral 6-mercaptopurine (6-MP maintenance chemotherapy for childhood ALL in Egypt to identify contributing factors and possible steps to promote adherence. Materials and Methods: The study included 129 children with ALL in complete remission receiving 6-MP single daily oral dose in the evening. Evaluation was done through specific questionnaires for the patients as well as serum 6-MP measurements. Results: Nonadherence was detected in around 56% by questionnaires and around 50% by serum 6-MP level measurement. There was a highly significant correlation between nonadherence as found by the questionnaire and 6-MP level (P - 0.001. Nonadherence was significantly associated with low socioeconomic standard, noneducation and low educational level and large family size by both methods. High cost to come for follow-up visits was significant by questionnaire but not by 6-MP measurement. Adolescent age, the higher number of siblings, lack of written instructions, long time spent per visit, were all associated with higher rates of nonadherence, although none reached statistical significance. Conclusions: Nonadherence is a real problem in pediatric patients. Specific questionnaires can be an excellent reliable method for the routine follow-up of these children, and drug level assay can be requested only for confirmation. This protocol is especially effective in developing countries where financial resources may be limited. Every effort should be made to uncover its true incidence, contributing factors, and best methods of intervention.

  9. Measures of 6-mercaptopurine and methotrexate maintenance therapy intensity in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

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

    2016-01-01

    PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree of myelosuppress......PURPOSE: Normal white blood cell counts (WBC) are unknown in children with acute lymphoblastic leukemia (ALL). Accordingly, 6-mercaptopurine (6MP) and methotrexate (MTX) maintenance therapy is adjusted by a common WBC target of 1.5-3.0 × 10(9)/L. Consequently, the absolute degree...

  10. Causes of childhood leukaemia and lymphoma

    International Nuclear Information System (INIS)

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

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

    Science.gov (United States)

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

    2013-01-01

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

  12. Prevention of infection in children with acute leukaemia - No major difference between total and selective bowel decontamination

    NARCIS (Netherlands)

    Muis, N; Kamps, WA

    1996-01-01

    To evaluate the effect of total bowel decontamination (TD) and selective bowel decontamination (SD) in a non-protective environment clinical and laboratory data of children treated for acute leukaemia between 1983 and 1991 were analysed retrospectively. From 1983 until 1989 34 patients [18 acute non

  13. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries: prognostic factors, treatment and outcome.

    Science.gov (United States)

    Oskarsson, Trausti; Söderhäll, Stefan; Arvidson, Johan; Forestier, Erik; Montgomery, Scott; Bottai, Matteo; Lausen, Birgitte; Carlsen, Niels; Hellebostad, Marit; Lähteenmäki, Päivi; Saarinen-Pihkala, Ulla M; Jónsson, Ólafur G; Heyman, Mats

    2016-01-01

    Relapse is the main reason for treatment failure in childhood acute lymphoblastic leukemia. Despite improvements in the up-front therapy, survival after relapse is still relatively poor, especially for high-risk relapses. The aims of this study were to assess outcomes following acute lymphoblastic leukemia relapse after common initial Nordic Society of Paediatric Haematology and Oncology protocol treatment; to validate currently used risk stratifications, and identify additional prognostic factors for overall survival. Altogether, 516 of 2735 patients (18.9%) relapsed between 1992 and 2011 and were included in the study. There were no statistically significant differences in outcome between the up-front protocols or between the relapse protocols used, but an improvement over time was observed. The 5-year overall survival for patients relapsing in the period 2002-2011 was 57.5±3.4%, but 44.7±3.2% (Pacute lymphoblastic leukemia.

  14. Role of CXCR4-mediated bone marrow colonization in CNS infiltration by T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Jost, Tanja Rezzonico; Borga, Chiara; Radaelli, Enrico; Romagnani, Andrea; Perruzza, Lisa; Omodho, Lorna; Cazzaniga, Giovanni; Biondi, Andrea; Indraccolo, Stefano; Thelen, Marcus; Te Kronnie, Geertruy; Grassi, Fabio

    2016-06-01

    Infiltration of the central nervous system is a severe trait of T cell acute lymphoblastic leukemia. Inhibition of CXC chemokine receptor 4 significantly ameliorates T cell acute lymphoblastic leukemia in murine models of the disease; however, signaling by CXC chemokine receptor 4 is important in limiting the divagation of peripheral blood mononuclear cells out of the perivascular space into the central nervous system parenchyma. Therefore, Inhibition of CXC chemokine receptor 4 potentially may untangle T cell acute lymphoblastic leukemia cells from retention outside the brain. Here, we show that leukemic lymphoblasts massively infiltrate cranial bone marrow, with diffusion to the meninges without invasion of the brain parenchyma, in mice that underwent xenotransplantation with human T cell acute lymphoblastic leukemia cells or that developed leukemia from transformed hematopoietic progenitors. We tested the hypothesis that T cell acute lymphoblastic leukemia neuropathology results from meningeal infiltration through CXC chemokine receptor 4-mediated bone marrow colonization. Inhibition of leukemia engraftment in the bone marrow by pharmacologic CXC chemokine receptor 4 antagonism significantly ameliorated neuropathologic aspects of the disease. Genetic deletion of CXCR4 in murine hematopoietic progenitors abrogated leukemogenesis induced by constitutively active Notch1, whereas lack of CCR6 and CCR7, which have been shown to be involved in T cell and leukemia extravasation into the central nervous system, respectively, did not influence T cell acute lymphoblastic leukemia development. We hypothesize that lymphoblastic meningeal infiltration as a result of bone marrow colonization is responsible for the degenerative alterations of the neuroparenchyma as well as the alteration of cerebrospinal fluid drainage in T cell acute lymphoblastic leukemia xenografts. Therefore, CXC chemokine receptor 4 may constitute a pharmacologic target for T cell acute lymphoblastic

  15. Inter-Platform comparability of microarrays in acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Mintz Michelle

    2004-09-01

    Full Text Available Abstract Background Acute lymphoblastic leukemia (ALL is the most common pediatric malignancy and has been the poster-child for improved therapeutics in cancer, with life time disease-free survival (LTDFS rates improving from 80% today. There are numerous known genetic prognostic variables in ALL, which include T cell ALL, the hyperdiploid karyotype and the translocations: t(12;21[TEL-AML1], t(4;11[MLL-AF4], t(9;22[BCR-ABL], and t(1;19[E2A-PBX]. ALL has been studied at the molecular level through expression profiling resulting in un-validated expression correlates of these prognostic indices. To date, the great wealth of expression data, which has been generated in disparate institutions, representing an extremely large cohort of samples has not been combined to validate any of these analyses. The majority of this data has been generated on the Affymetrix platform, potentially making data integration and validation on independent sample sets a possibility. Unfortunately, because the array platform has been evolving over the past several years the arrays themselves have different probe sets, making direct comparisons difficult. To test the comparability between different array platforms, we have accumulated all Affymetrix ALL array data that is available in the public domain, as well as two sets of cDNA array data. In addition, we have supplemented this data pool by profiling additional diagnostic pediatric ALL samples in our lab. Lists of genes that are differentially expressed in the six major subclasses of ALL have previously been reported in the literature as possible predictors of the subclass. Results We validated the predictability of these gene lists on all of the independent datasets accumulated from various labs and generated on various array platforms, by blindly distinguishing the prognostic genetic variables of ALL. Cross-generation array validation was used successfully with high sensitivity and high specificity of gene predictors

  16. Outcomes after Induction Failure in Childhood Acute Lymphoblastic Leukemia

    Science.gov (United States)

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

    2012-01-01

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

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

    DEFF Research Database (Denmark)

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

    2007-01-01

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

  18. MicroRNA characterize genetic diversity and drug resistance in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    D. Schotte (Diana); R.X. de Menezes (Renee); F. Akbari Moqadam (Farhad); L.M. Khankahdani (Leila Mohammadi); E.A.M. Lange-Turenhout (Ellen); C. Chen (Caifu); R. Pieters (Rob); M.L. den Boer (Monique)

    2011-01-01

    textabstractBackground MicroRNA regulate the activity of protein-coding genes including those involved in hematopoietic cancers. The aim of the current study was to explore which microRNA are unique for seven different subtypes of pediatric acute lymphoblastic leukemia. Design and Methods Expression

  19. Physicians compliance during maintenance therapy in children with Down syndrome and acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Bohnstedt, C; Levinsen, M; Rosthøj, S;

    2013-01-01

    Children with Down syndrome (DS) and acute lymphoblastic leukemia (ALL) have an inferior prognosis compared with non-DS ALL patients. We reviewed methotrexate (MTX)/mercaptopurine (6MP) maintenance therapy data for children with DS treated according to the Nordic Society of Pediatric Hematology...

  20. Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries

    DEFF Research Database (Denmark)

    Lundin, Catarina; Forestier, Erik; Klarskov Andersen, Mette;

    2014-01-01

    BACKGROUND: Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. METHODS...

  1. Inhibition of glycolysis modulates prednisolone resistance in acute lymphoblastic leukemia cells

    OpenAIRE

    Hulleman, Esther; Kazemier, Karin; Holleman, Amy; VanderWeele, David; Rudin, Charles; Broekhuis, Mathilde; Evans, William; Pieters, Rob; Boer, M.L.D.

    2009-01-01

    textabstractTreatment failure in pediatric acute lymphoblastic leukemia (ALL) is related to cellular resistance to glucocorticoids (eg, prednisolone). Recently, we demonstrated that genes associated with glucose metabolism are differentially expressed between prednisolone-sensitive and prednisolone-resistant precursor B-lineage leukemic patients. Here, we show that prednisolone resistance is associated with increased glucose consumption and that inhibition of glycolysis sensitizes prednisolon...

  2. The landscape of somatic mutations in infant MLL-rearranged acute lymphoblastic leukemias

    DEFF Research Database (Denmark)

    Andersson, Anna K; Ma, Jing; Wang, Jianmin;

    2015-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL rearrangements (MLL-R) represents a distinct leukemia with a poor prognosis. To define its mutational landscape, we performed whole-genome, exome, RNA and targeted DNA sequencing on 65 infants (47 MLL-R and 18 non-MLL-R cases) and 20 older childr...

  3. Gene-expression patterns in drug-resistant acute lymphoblastic leukemia cells and response to treatment

    NARCIS (Netherlands)

    A. Holleman (Amy); C. Cheng (Cheng); C.H. Pui (Ching-Hon); W.E. Evans (William); M.V. Relling (Mary); R. Pieters (Rob); G.E. Janka-Schaub (Gritta); M.H. Cheok (Meyling); M.L. den Boer (Monique); W. Yang; A.J. Veerman; K.M. Kazemier (Karin); D. Pei (Deqing)

    2004-01-01

    textabstractBACKGROUND: Childhood acute lymphoblastic leukemia (ALL) is curable with chemotherapy in approximately 80 percent of patients. However, the cause of treatment failure in the remaining 20 percent of patients is largely unknown. METHODS: We tested leukemia cells from 173

  4. Vincristine pharmacokinetics is related to clinical outcome in children with standard risk acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Loennerholm, Gudmar; Frost, Britt-Marie; Abrahamsson, Jonas; Behrendtz, Mikael; Castor, Anders; Forestier, Erik; Heyman, Mats; Uges, Donald R. A.; de Graaf, Siebold S. N.

    2008-01-01

    Vincristine is a key drug in the treatment of childhood and adult acute lymphoblastic leukemia (ALL), and many other childhood malignancies. Despite decades of wide clinical use, no data on the correlation between vincristine pharmacokinetics and long-term clinical outcome have been published. We he

  5. Glioblastoma multiforme in a child with acute lymphoblastic leukemia: Case report and review of literature

    Directory of Open Access Journals (Sweden)

    Shah Kirit

    2004-07-01

    Full Text Available An 11-year-old boy with acute lymphoblastic leukemia had received prophylactic cranial irradiation (1800 cGy /10 fractions and intrathecal methotrexate. Five years later, he developed a glioblastoma multiforme in the right frontal region while the leukemia was in remission. It is possible that the glioma may have been induced by radiation and /or chemotherapy.

  6. The role of ABC-transporters in childhood and adult acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Plasschaert, Sabine Louise Anne

    2005-01-01

    Acute lymphoblastic leukemia is a disease characterized by an uncontrolled proliferation and maturation arest of lymphoid progenitor cells in the bone marrow, resulting in an excesso f malignant cells. The disease has a peak incidence between the age of 2-5 years, and a low and steady rise from the

  7. The role of ABC-transporters in childhood and adult acute lymphoblastic leukemia

    OpenAIRE

    Plasschaert, Sabine Louise Anne

    2005-01-01

    Acute lymphoblastic leukemia is a disease characterized by an uncontrolled proliferation and maturation arest of lymphoid progenitor cells in the bone marrow, resulting in an excesso f malignant cells. The disease has a peak incidence between the age of 2-5 years, and a low and steady rise from the age of 40 ... Zie: Summary

  8. An Initial Reintegration Treatment of Children with Acute Lymphoblastic Leukemia (ALL).

    Science.gov (United States)

    Lurie, Michelle; Kaufman, Nadeen

    2001-01-01

    Evaluated the cognitive, psychological, and social adjustment of pediatric acute lymphoblastic leukemia (ALL) patients and assessed how their needs could best be met through reintegration programs focusing on learning/ educational needs. Findings from three case studies highlight the need for ALL patients to be provided with comprehensive programs…

  9. Prediction of immunophenotype, treatment response, and relapse in childhood acute lymphoblastic leukemia using DNA microarrays

    DEFF Research Database (Denmark)

    Willenbrock, Hanni; Juncker, Agnieszka; Schmiegelow, K.;

    2004-01-01

    Gene expression profiling is a promising tool for classification of pediatric acute lymphoblastic leukemia ( ALL). We analyzed the gene expression at the time of diagnosis for 45 Danish children with ALL. The prediction of 5-year event-free survival or relapse after treatment by NOPHO-ALL92 or 2000...

  10. Analysis of relapse factors and risk assessment of adult acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    陈培翠

    2014-01-01

    Objective To explore the risk factors of acute lymphoblastic leukemia(ALL)recurrence in adult patients and establish a prognosis index(PI)calculation model in order to improve the prevention strategy of ALL in adults.Methods 104 adult ALL patients from Blood Diseases Hospital&Chinese Academy of Medical Sciences between August 2008 and November 2011

  11. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kang, Si Won [Daejeon St. Mary' s Hospital, College of Medicine, Catholic University, Daejeon (Korea, Republic of)

    2006-04-15

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  12. DNA methylation-based subtype prediction for pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Zachariadis, Vasilios;

    2015-01-01

    BACKGROUND: We present a method that utilizes DNA methylation profiling for prediction of the cytogenetic subtypes of acute lymphoblastic leukemia (ALL) cells from pediatric ALL patients. The primary aim of our study was to improve risk stratification of ALL patients into treatment groups using DNA...

  13. Delayed Neurotoxicity Associated with Therapy for Children with Acute Lymphoblastic Leukemia

    Science.gov (United States)

    Cole, Peter D.; Kamen, Barton A.

    2006-01-01

    Most children diagnosed today with acute lymphoblastic leukemia (ALL) will be cured. However, treatment entails risk of neurotoxicity, causing deficits in neurocognitive function that can persist in the years after treatment is completed. Many of the components of leukemia therapy can contribute to adverse neurologic sequelae, including…

  14. Genome-wide signatures of differential DNA methylation in pediatric acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Nordlund, Jessica; Bäcklin, Christofer L; Wahlberg, Per;

    2013-01-01

    BACKGROUND: Although aberrant DNA methylation has been observed previously in acute lymphoblastic leukemia (ALL), the patterns of differential methylation have not been comprehensively determined in all subtypes of ALL on a genome-wide scale. The relationship between DNA methylation, cytogenetic...

  15. High concordance of subtypes of childhood acute lymphoblastic leukemia within families

    DEFF Research Database (Denmark)

    Schmiegelow, K.; Thomsen, U Lautsen; Baruchel, A;

    2012-01-01

    Polymorphic genes have been linked to the risk of acute lymphoblastic leukemia (ALL). Surrogate markers for a low burden of early childhood infections are also related to increased risk for developing childhood ALL. It remains uncertain, whether siblings of children with ALL have an increased risk...

  16. Genetic and metabolic determinants of methotrexate-induced mucositis in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    den Hoed, M. A. H.; Lopez-Lopez, E.; te Winkel, M. L.; Tissing, W.; de Rooij, J. D. E.; Gutierrez-Camino, A.; Garcia-Orad, A.; den Boer, E.; Pieters, R.; Pluijm, S. M. F.; de Jonge, R.; van den Heuvel-Eibrink, M. M.

    2015-01-01

    Methotrexate (MTX) is an effective and toxic chemotherapeutic drug in the treatment of pediatric acute lymphoblastic leukemia (ALL). In this prospective study, we aimed to identify metabolic and genetic determinants of MTX toxicity. One hundred and thirty-four Dutch pediatric ALL patients were treat

  17. Tracheoesophageal fistula resulting from invasive aspergillosis in acute lymphoblastic leukemia: a case report

    International Nuclear Information System (INIS)

    Tracheoesophageal fistula (TEF) in adult patients is an uncommon complication in leukemia. We present here on a case of TEF in a 46-year-old woman with ALL. The patient was asymptomatic and TEF is resulted from aspergillus bronchitis during the chemotherapy for acute lymphoblastic leukemia (ALL)

  18. Clonal origins of ETV6-RUNX1+ acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Alpar, D.; Wren, D.; Ermini, Luca;

    2015-01-01

    Studies on twins with concordant acute lymphoblastic leukemia (ALL) have revealed that ETV6-RUNX1 gene fusion is a common, prenatal genetic event with other driver aberrations occurring subclonally and probably postnatally. The fetal cell type that is transformed by ETV6-RUNX1 is not identified b...

  19. LAF4, an AF4-related gene, is fused to MLL in infant acute lymphoblastic leukemia

    NARCIS (Netherlands)

    von Bergh, ARM; Beverloo, HB; Rombout, P; van Wering, ER; van Weel, MH; Beverstock, GC; Kluin, PM; Slater, RM; Schuuring, E

    2002-01-01

    Infant acute lymphoblastic leukemia (ALL) with MLL gene rearrangements is characterized by a proB phenotype and a poor clinical outcome. We analyzed an infant proB ALL with t(2; 11)(p 15;p 14) and an MLL rearrangement on Southern blot analysis, Rapid amplification of cDNA ends-polymerase chain react

  20. Acute lymphoblastic leukemia and obesity : increased energy intake or decreased physical activity?

    NARCIS (Netherlands)

    Jansen, H.; Postma, A.; Stolk, R. P.; Kamps, W. A.

    2009-01-01

    Background Obesity is a well-known problem in children with acute lymphoblastic leukemia ( ALL), and it might be the result of an excess in energy intake, reduced energy expenditure, or both. The aim of this study is to describe energy intake and physical activity during treatment for ALL with inter

  1. The significance of change of Th22 cells in patients with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    刘立民

    2013-01-01

    Objective To investigate the proportion of Th22 cells in peripheral blood of patients with acute lympho-blastic leukemia(ALL) and evaluate its significance.Methods The proportions of Th22 cells in peripheral blood of B-ALL and T-ALL patients before therapy(group 1),

  2. Pharmacogenetic risk factors for altered bone mineral density and body composition in pediatric acute lymphoblastic leukemia

    NARCIS (Netherlands)

    M.L. te Winkel (Mariël Lizet); R.D. van Beek (Robert Diederik); S.M.P.F. de Muinck Keizer-Schrama (Sabine); A.G. Uitterlinden (André); W.C.J. Hop (Wim); R. Pieters (Rob); M.M. van den Heuvel-Eibrink (Marry)

    2010-01-01

    textabstractBackground This study investigates pharmacogenetic risk factors for bone mineral (apparent) density (BM(A)D) and body composition in pediatric acute lymphoblastic leukemia Design and Methods We determined the influence of SNPs in 4 genes (vitamin-D receptor (VDR: BsmI/ApaI/TaqI and Cdx-2

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

    NARCIS (Netherlands)

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

    2005-01-01

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

  4. Neuropsychological outcome in chemotherapy-only-treated children with acute lymphoblastic leukemia

    NARCIS (Netherlands)

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

    2008-01-01

    Purpose To evaluate neuropsychological functioning over time in children treated for acute lymphoblastic leukemia (ALL) with chemotherapy only. Patients and Methods Forty-nine consecutive patients (median age at first assessment, 6.8 years; range, 4.0 to 11.8 years) treated with intrathecal and syst

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

    NARCIS (Netherlands)

    Pui, CH; Chessells, JM; Camitta, B; Baruchel, A; Biondi, A; Boyett, JM; Carroll, A; Eden, OB; Evans, WE; Gadner, H; Harbott, J; Harms, DO; Harrison, CJ; Harrison, PL; Heerema, N; Janka-Schaub, G; Kamps, W; Masera, G; Pullen, J; Raimondi, SC; Richards, S; Riehm, H; Sallan, S; Sather, H; Shuster, J; Silverman, LB; Valsecchi, MG; Vilmer, E; Zhou, Y; Gaynon, PS; Schrappe, M

    2003-01-01

    To assess the clinical heterogeneity among patients with acute lymphoblastic leukemia (ALL) and various 11q23 abnormalities, we analyzed data on 497 infants, children and young adults treated between 1983 and 1995 by 11 cooperative groups and single institutions. The substantial sample size allowed

  6. Handwriting and fine motor problems after treatment for acute lymphoblastic leukemia

    NARCIS (Netherlands)

    Reinders-Messelink, H.A.; Schoemaker, M.M.; Goeken, L.N H; van den Briel, M.M.; Kamps, W.A; Simner, M L; Leedham, C G; Thomassen, A J W M

    1996-01-01

    Fine motor skills and handwriting performance were investigated in 17 children at least two years after treatment for acute lymphoblastic leukemia. It was hypothesized that as a late effect of vincristine neuropathy, children would still have fine motor and/or handwriting problems. Gross and fine mo

  7. Fine motor and handwriting problems after treatment for childhood acute lymphoblastic leukemia

    NARCIS (Netherlands)

    ReindersMesselink, HA; Schoemaker, MM; Hofte, M; Goeken, LNH; Kingma, A; vandenBriel, MM; Kamps, WA

    1996-01-01

    Motor skills were investigated in 18 children 2 years after treatment for acute lymphoblastic leukemia (ALL). Cross and fine motor functioning were examined with the Movement Assessment Battery for Children. Handwriting as a specific fine motor skill was studied with a computerized writing task. We

  8. Prognostic Impact of WT-1 Gene Expression in Egyptian Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Hagag, Adel A; Badraia, Ibrahim M; Hassan, Samir M; Abd El-Lateef, Amal E

    2016-01-01

    Background Acute lymphoblastic leukemia (ALL) is the most common childhood cancer representing 23% of pediatric cancers. Wilms’ tumor -1 gene is a novel prognostic factor, minimal residual disease marker and therapeutic target in acute leukemia. Aim of the work The aim of this work was to study the impact of WT-1 gene expression in the prognosis of ALL. Patients and methods This study was conducted on 40 Egyptian children with newly diagnosed ALL who were subjected to full history taking, tho...

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

    Directory of Open Access Journals (Sweden)

    Nicolas Bonadies

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

  10. Aggravated bone density decline following symptomatic osteonecrosis in children with acute lymphoblastic leukemia.

    Science.gov (United States)

    den Hoed, Marissa A H; Pluijm, Saskia M F; te Winkel, Mariël L; de Groot-Kruseman, Hester A; Fiocco, Martha; Hoogerbrugge, Peter; Leeuw, Jan A; Bruin, Marrie C A; van der Sluis, Inge M; Bresters, Dorien; Lequin, Maarten H; Roos, Jan C; Veerman, Anjo J P; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2015-12-01

    Osteonecrosis and decline of bone density are serious side effects during and after treatment of childhood acute lymphoblastic leukemia. It is unknown whether osteonecrosis and low bone density occur together in the same patients, or whether these two osteogenic side-effects can mutually influence each other's development. Bone density and the incidence of symptomatic osteonecrosis were prospectively assessed in a national cohort of 466 patients with acute lymphoblastic leukemia (4-18 years of age) who were treated according to the dexamethasone-based Dutch Child Oncology Group-ALL9 protocol. Bone mineral density of the lumbar spine (BMDLS) (n=466) and of the total body (BMDTB) (n=106) was measured by dual X-ray absorptiometry. Bone density was expressed as age- and gender-matched standard deviation scores. Thirty patients (6.4%) suffered from symptomatic osteonecrosis. At baseline, BMDLS and BMDTB did not differ between patients who did or did not develop osteonecrosis. At cessation of treatment, patients with osteonecrosis had lower mean BMDLS and BMDTB than patients without osteonecrosis (respectively, with osteonecrosis: -2.16 versus without osteonecrosis: -1.21, Pacute lymphoblastic leukemia does not seem to influence the occurrence of symptomatic osteonecrosis. Bone density declines from the time that osteonecrosis is diagnosed; this suggests that the already existing decrease in bone density during acute lymphoblastic leukemia therapy is further aggravated by factors such as restriction of weight-bearing activities and destruction of bone architecture due to osteonecrosis. Osteonecrosis can, therefore, be considered a risk factor for low bone density in children with acute lymphoblastic leukemia.

  11. Monoclonal Antibody Therapy in Treating Patients With Chronic Lymphocytic Leukemia, Lymphocytic Lymphoma, Acute Lymphoblastic Leukemia, or Acute Myeloid Leukemia

    Science.gov (United States)

    2013-06-03

    Extranodal Marginal Zone B-cell Lymphoma of Mucosa-associated Lymphoid Tissue; Nodal Marginal Zone B-cell Lymphoma; Noncontiguous Stage II Marginal Zone Lymphoma; Noncontiguous Stage II Small Lymphocytic Lymphoma; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Adult Acute Myeloid Leukemia; Recurrent Marginal Zone Lymphoma; Recurrent Small Lymphocytic Lymphoma; Refractory Chronic Lymphocytic Leukemia; Splenic Marginal Zone Lymphoma; Stage III Marginal Zone Lymphoma; Stage III Small Lymphocytic Lymphoma; Stage IV Marginal Zone Lymphoma; Stage IV Small Lymphocytic Lymphoma

  12. 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...

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

    DEFF Research Database (Denmark)

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

    2012-01-01

    Children with acute lymphoblastic leukemia (ALL) react very differently to chemotherapy. One explanation for this is inherited genetic variation. The glutathione S-transferase (GST) enzymes inactivate a number of chemotherapeutic drugs administered in childhood ALL therapy. Two multiplexing metho...

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

    NARCIS (Netherlands)

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

    2002-01-01

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

  15. Low frequency of MLL-partial tandem duplications in paediatric acute myeloid leukaemia using MLPA as a novel DNA screenings technique.

    NARCIS (Netherlands)

    Balgobind, B.V.; Hollink, I.H.; Reinhardt, D.; Wering, E.R. van; Graaf, S.S.N. de; Baruchel, A.; Stary, J.; Beverloo, H.B.; Greef, G.E. de; Pieters, R.; Zwaan, C.M.; Heuvel-Eibrink, M.M. van den

    2010-01-01

    Mixed-lineage leukaemia (MLL)-partial tandem duplications (PTDs) are found in 3-5% of adult acute myeloid leukaemia (AML), and are associated with poor prognosis. In adult AML, MLL-PTD is only detected in patients with trisomy 11 or internal tandem duplications of FLT3 (FLT3-ITD). To date, studies i

  16. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG)

    NARCIS (Netherlands)

    Groninger, E; Meeuwsen-de Boer, T; Koopmans, P; Uges, D; Sluiter, W; Veerman, A; Kamps, W

    2005-01-01

    The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Ther

  17. Vincristine pharmacokinetics and response to vincristine monotherapy in an up-front window study of the Dutch Childhood Leukaemia Study Group (DCLSG).

    NARCIS (Netherlands)

    Groninger, E.; Boer, T. de; Koopmans, P.P.; Uges, D.R.A.; Sluiter, W.J.; Veerman, A.; Kamps, W.; Graaf, S.S.N. de

    2005-01-01

    The relationship between vincristine pharmacokinetics and its antileukaemic effect in children is unknown. Since vincristine plays a key role in the treatment of childhood acute lymphoblastic leukaemia (ALL), it is worthwhile to explore if efficacy can be improved by individual dose adjustment. Ther

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

    Directory of Open Access Journals (Sweden)

    Carolyn S. Grove

    2014-08-01

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

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

    Science.gov (United States)

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

    2016-01-01

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

  20. Evidence that continued remission in patients treated for acute leukaemia is dependent upon autologous natural killer cells.

    Science.gov (United States)

    Lowdell, Mark W; Craston, Rose; Samuel, David; Wood, Marion E; O'Neill, Elena; Saha, Vaskar; Prentice, H Grant

    2002-06-01

    Although it has been known for more than 40 years that allogeneic immune responses cure leukaemias after bone marrow transplantation, autologous leukaemia-specific immunity remains controversial and its impact upon survival has not been established. Here we have tested 25 patients with de novo acute leukaemias, while in remission at completion of their anti-leukaemia therapy, for evidence of autologous cytolytic immunity to their leukaemic cells taken and cryopreserved at disease presentation. We have measured this degree of cell-mediated cytotoxicity in vitro and termed it "leukaemia cytolytic activity" (LCA). Patients whose disease ultimately relapsed had significantly lower LCA than those who remained in remission beyond 2 years (P LCA when in remission predicted subsequent relapse within 2 years with a sensitivity of 100% and specificity of 77%. LCA was mediated in vitro by CD56+/CD8alpha+/CD3- natural killer cells. We propose that it is this immune response, rather than the chemotherapy per se, which is responsible for continued remission and that measurement of LCA in patients at completion of therapy may be used as an indicator of risk of subsequent relapse. Patients lacking this response will require further treatment, either with an allogeneic donor transplant or an alternative immunotherapeutic strategy. PMID:12060116

  1. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    Science.gov (United States)

    Lustosa de Sousa, Daniel Willian; de Almeida Ferreira, Francisco Valdeci; Cavalcante Félix, Francisco Helder; de Oliveira Lopes, Marcos Vinicios

    2015-01-01

    Objective To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment. Methods Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância – acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan–Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors. Results The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%). The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5%) than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/μL and white blood cell counts <5.0 × 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%. Conclusion The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age and baseline white

  2. Acute lymphoblastic leukemia in children and adolescents: prognostic factors and analysis of survival

    Directory of Open Access Journals (Sweden)

    Daniel Willian Lustosa de Sousa

    2015-08-01

    Full Text Available OBJECTIVE: To describe the clinical and laboratory features of children and adolescents with acute lymphoblastic leukemia treated at three referral centers in Ceará and evaluate prognostic factors for survival, including age, gender, presenting white blood cell count, immunophenotype, DNA index and early response to treatment.METHODS: Seventy-six under 19-year-old patients with newly diagnosed acute lymphoblastic leukemia treated with the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia-93 and -99 protocols between September 2007 and December 2009 were analyzed. The diagnosis was based on cytological, immunophenotypic and cytogenetic criteria. Associations between variables, prognostic factors and response to treatment were analyzed using the chi-square test and Fisher's exact test. Overall and event-free survival were estimated by Kaplan-Meier analysis and compared using the log-rank test. A Cox proportional hazards model was used to identify independent prognostic factors.RESULTS: The average age at diagnosis was 6.3 ± 0.5 years and males were predominant (65%. The most frequently observed clinical features were hepatomegaly, splenomegaly and lymphadenopathy. Central nervous system involvement and mediastinal enlargement occurred in 6.6% and 11.8%, respectively. B-acute lymphoblastic leukemia was more common (89.5% than T-acute lymphoblastic leukemia. A DNA index >1.16 was found in 19% of patients and was associated with favorable prognosis. On Day 8 of induction therapy, 95% of the patients had lymphoblast counts <1000/µL and white blood cell counts <5.0 Ã- 109/L. The remission induction rate was 95%, the induction mortality rate was 2.6% and overall survival was 72%.CONCLUSION: The prognostic factors identified are compatible with the literature. The 5-year overall and event-free survival rates were lower than those reported for developed countries. As shown by the multivariate analysis, age

  3. Treatment of refractory/relapsed adult acute lymphoblastic leukemia with bortezomib- based chemotherapy

    Directory of Open Access Journals (Sweden)

    Zhao J

    2015-06-01

    Full Text Available Junmei Zhao,* Chao Wang,* Yongping Song, Yuzhang Liu, Baijun FangHenan Key Lab of Experimental Haematology, Henan Institute of Haematology, Henan Tumor Hospital, Zhengzhou University, Zhengzhou, People’s Republic of China  *These authors contributed equally to this work Abstract: Nine pretreated patients aged >19 years with relapsed/refractory acute lymphoblastic leukemia (ALL were treated with a combination of bortezomib plus chemotherapy before allogeneic hematopoietic stem cell transplantation (allo-HSCT. Eight (88.9% patients, including two Philadelphia chromosome-positive ALL patients, achieved a complete remission. Furthermore, the evaluable patients have benefited from allo-HSCT after response to this reinduction treatment. We conclude that bortezomib-based chemotherapy was highly effective for adults with refractory/relapsed ALL before allo-HSCT. Therefore, this regimen deserves a larger series within prospective trials to confirm these results. Keywords: acute lymphoblastic leukemia, refractory, relapsed, bortezomib

  4. Supportive medical care for children with acute lymphoblastic leukemia in low- and middle-income countries.

    Science.gov (United States)

    Ceppi, Francesco; Antillon, Federico; Pacheco, Carlos; Sullivan, Courtney E; Lam, Catherine G; Howard, Scott C; Conter, Valentino

    2015-10-01

    In the last two decades, remarkable progress in the treatment of children with acute lymphoblastic leukemia has been achieved in many low- and middle-income countries (LMIC), but survival rates remain significantly lower than those in high-income countries. Inadequate supportive care and consequent excess mortality from toxicity are important causes of treatment failure for children with acute lymphoblastic leukemia in LMIC. This article summarizes practical supportive care recommendations for healthcare providers practicing in LMIC, starting with core approaches in oncology nursing care, management of tumor lysis syndrome and mediastinal masses, nutritional support, use of blood products for anemia and thrombocytopenia, and palliative care. Prevention and treatment of infectious diseases are described in a parallel paper. PMID:26013005

  5. Sweet′s Syndrome in Acute Lymphoblastic Leukemia with t (9:22

    Directory of Open Access Journals (Sweden)

    Khushboo Dewan

    2015-01-01

    Full Text Available Sweet′s syndrome (SS is a rare disease diagnosed in children and is characterized by fever, erythematous skin lesions, and dense infiltration of neutrophils in the upper dermis without evidence of leukocytoclastic vasculitis on histopathology. It may occur secondary to infection, malignancy or drug intake. A case of a 9-year-old boy diagnosed as acute precursor B-cell lymphoblastic leukemia with BCR-ABL1 mutation and treated with induction chemotherapy and imatinib mesylate (IM therapy is presented. After 8 weeks of consolidation chemotherapy, the patient developed painful and erythematous nodules where a biopsy showed dense neutrophilic infiltrate and edema in the papillary dermis consistent with SS. Whether SS is caused clinically by acute lymphoblastic leukemia, the presence of BCR-ABL1 mutation or due to IM therapy is discussed.

  6. Hypoglycemia associated with L-asparaginase in acute lymphoblastic leukemia treatment: a case report

    OpenAIRE

    Tanaka Ryuma; Osumi Tomoo; Miharu Masashi; Ishii Tomohiro; Hasegawa Tomonobu; Takahashi Takao; Shimada Hiroyuki

    2012-01-01

    Abstract A patient with acute lymphoblastic leukemia repeatedly developed hypoglycemia during chemotherapy. Comparison of serum glucose trends between chemotherapy with and without L-asparaginase (L-Asp) demonstrated a strong association between L-Asp and hypoglycemia. Critical blood sampling during hypoglycemia indicated hyperinsulinism, suggesting that L-Asp induced hypoglycemia in the patient through inappropriate insulin secretion. Identification of hypoglycemia as an adverse effect will ...

  7. Successful outcome of mucormycosis in two children on induction therapy for acute lymphoblastic leukemia

    OpenAIRE

    Anshul Gupta; Sandeep Jain; Charu Agrawal; Gauri Kapoor

    2013-01-01

    Zygomycetes are one of the less common causes of invasive fungal infections in patients with the hematological malignancies. We report two cases of acute lymphoblastic leukemia in the pediatric age group, complicated by disseminated cutaneous mucormycosis during induction chemotherapy. In one of our cases, cutaneous mucormycosis progressed to osteomyelitis of the proximal ulna while in the other it disseminated to lungs and distant cutaneous site. Aggressive treatment, which included intraven...

  8. Acute lymphoblastic leukemia cells that survive combination chemotherapy in vivo remain sensitive to allogeneic immune effects

    OpenAIRE

    Jansson, Johan; Hsu, Yu-Chiao; Kuzin, Igor I.; Campbell, Andrew; Mullen, Craig A.

    2010-01-01

    Allogeneic hematopoietic stem cell transplantation is often performed for patients with acute lymphoblastic leukemia (ALL) whose disease has relapsed after chemotherapy treatment. However, graft versus leukemia (GVL) effects in ALL are generally weak and the mechanisms of this weakness are unknown. These studies tested the hypothesis that ALL cells that have survived conventional chemotherapy in vivo acquire relative resistance to the allogeneic GVL effect. C57BL/6 mice were injected with mur...

  9. Imaging findings of recurrent acute lymphoblastic leukemia in children and young adults, with emphasis on MRI

    Energy Technology Data Exchange (ETDEWEB)

    Porter, Rosalyn P. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Kaste, Sue C. [Department of Diagnostic Imaging, St. Jude Children' s Research Hospital, 332 N. Lauderdale, Memphis, TN 38105-2794 (United States); Department of Radiology, University of Tennessee, College of Medicine, Memphis, Tennessee (United States)

    2004-05-01

    Acute lymphoblastic leukemia (ALL) is the most common of all childhood malignancies. Current remission rates approach 80%. Recurrent disease can present in a wide variety of ways. MR imaging plays a crucial role in the detection of disease relapse. Because other disorders can mimic recurrence of leukemia, it is important for the radiologist to judge recurrence from non-recurrence accurately in order to avoid unnecessary testing and emotional stress on the patient and family. (orig.)

  10. The molecular genetic makeup of acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Abstract: Genomic profiling has transformed our understanding of the genetic basis of acute lymphoblastic leukemia (ALL). Recent years have seen a shift from microarray analysis and candidate gene sequencing to next-generation sequencing. Together, these approaches have shown that many ALL subtypes are characterized by constellations of structural rearrangements, submicroscopic DNA copy number alterations, and sequence mutations, several of which have clear implications for risk stratification and targeted therapeutic intervention.

  11. Clinical features and early treatment response of central nervous system involvement in childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Levinsen, Mette; Taskinen, Mervi; Abrahamsson, Jonas;

    2014-01-01

    BACKGROUND: Central nervous system (CNS) involvement in childhood acute lymphoblastic leukemia (ALL) remains a therapeutic challenge. PROCEDURE: To explore leukemia characteristics of patients with CNS involvement at ALL diagnosis, we analyzed clinical features and early treatment response of 744....... Symptoms or clinical findings were present among 27 of 54 patients with CNS3 versus only 7 of 39 patients with CNS2 and 15 of 75 patients with TLP+ (P bone marrow residual disease level did...

  12. Duplication of the MYB oncogene in T cell acute lymphoblastic leukemia.

    Science.gov (United States)

    Lahortiga, Idoya; De Keersmaecker, Kim; Van Vlierberghe, Pieter; Graux, Carlos; Cauwelier, Barbara; Lambert, Frederic; Mentens, Nicole; Beverloo, H Berna; Pieters, Rob; Speleman, Frank; Odero, Maria D; Bauters, Marijke; Froyen, Guy; Marynen, Peter; Vandenberghe, Peter; Wlodarska, Iwona; Meijerink, Jules P P; Cools, Jan

    2007-05-01

    We identified a duplication of the MYB oncogene in 8.4% of individuals with T cell acute lymphoblastic leukemia (T-ALL) and in five T-ALL cell lines. The duplication is associated with a threefold increase in MYB expression, and knockdown of MYB expression initiates T cell differentiation. Our results identify duplication of MYB as an oncogenic event and suggest that MYB could be a therapeutic target in human T-ALL.

  13. Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia

    OpenAIRE

    Emine Guven Maiorov; Ozlem Keskin; Ozden Hatirnaz Ng; Ugur Ozbek; Attila Gursoy

    2013-01-01

    Hindawi Publishing Corporation BioMed Research International Volume 2013, Article ID 210253, 20 pages http://dx.doi.org/10.1155/2013/210253 Research Article Identification of Interconnected Markers for T-Cell Acute Lymphoblastic Leukemia Emine Guven Maiorov,1 Ozlem Keskin,1 Ozden Hatirnaz Ng,2 Ugur Ozbek,2 and Attila Gursoy1 1 Center for Computational Biology and Bioinformatics and College of Engineering, Koc¸ University, Rumelifeneri Yolu, Sariyer, 34450 Istanbu...

  14. Childhood Acute Lymphoblastic Leukemia : Genetic and Epigenetic Analysis of Archived Samples

    OpenAIRE

    Najmi, Laeya Abdoli

    2012-01-01

    Acute lymphoblastic leukemia (ALL) is recognized as a fast-developing cancer originated from blood-progenitor cells. Blasts cells are immature cells which generate white blood cells (leukocytes), and it is the malignancy of the blast cells which lead to leukemias. The bone marrow is gradually filled up with these blasts and as a result, the production of healthy blood cells will be damaged. Malignant cells might also find their way to the blood circulation and have the ability to infiltrate v...

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

    OpenAIRE

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

    2009-01-01

    Ambient exposure from residential proximity to applications of agricultural pesticides may contribute to the risk of childhood acute lymphoblastic leukemia (ALL). Using residential histories collected from the families of 213 ALL cases and 268 matched controls enrolled in the Northern California Childhood Leukemia Study, the authors assessed residential proximity within a half-mile (804.5 meters) of pesticide applications by linking address histories with reports of agricultural pesticide use...

  16. Glucocorticoid use in acute lymphoblastic leukemia: comparison of prednisone and dexamethasone

    OpenAIRE

    Inaba, Hiroto; Pui, Ching-Hon

    2010-01-01

    Glucocorticoids (prednisone and dexamethasone) play an essential role in the treatment of acute lymphoblastic leukemia (ALL) but their optimal doses and bioequivalence have not been established. Pre-clinical studies showed that dexamethasone has a longer half-life and better central nervous system (CNS) penetration. In prospective randomized trials, dexamethasone yielded better control of CNS leukemia. At a prednisone (mg)/dexamethasone (mg) dose ratio less than 7, dexamethasone treatment (6–...

  17. Filariasis in an infant with B-cell acute lymphoblastic leukemia: a rare enigma

    OpenAIRE

    Yadav, Yogesh Kumar; Sipayya, Varuna; KHANNA, Geetika; Gupta, Oneal

    2011-01-01

    Filariasis, a tropical parasitic infection, is a common public health problem in the Indian sub-continent. Occurrence of filariasis with acute lymphoblastic leukemia (ALL) is unusual, particularly in infants, since filariasis has a long incubation period of about 1 year. Though, there are case reports of leishmaniasis, malaria and other vector borne diseases seen in association with leukemias, filariasis co-existing with ALL has not been documented to the best of our knowledge. We report an i...

  18. Management of Ontario children with acute lymphoblastic leukemia by the Dana-Farber Cancer Institute protocols.

    OpenAIRE

    Desai, S J; Barr, R D; Andrew, M.; deVeber, L L; Pai, M K

    1989-01-01

    There is ample evidence of the value of intensive therapeutic strategies in the management of acute lymphoblastic leukemia (ALL), the commonest form of malignant disease in children. Such a program, devised at the Dana-Farber Cancer Institute (DFCI), Boston, and incorporating high-dose L-asparaginase, was adopted in 1984 by the Children's Hospital at Chedoke-McMaster, Hamilton, Ont., and the Children's Hospital of Western Ontario, London. We describe the experience of these institutions in th...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

  20. Fetal liver transplantation in 2 patients with acute leukaemia after total body irradiation

    Energy Technology Data Exchange (ETDEWEB)

    Lucarelli, G.; Izzi, T.; Porcellini, A.; Delfini, C.; Galimberti, M.; Moretti, L.; Polchi, P.; Agostinelli, F.; Andreani, M.; Manna, M. (Haematological Department, Pesaro Hospital, Pesaro, Italy)

    1982-01-01

    2 patients with acute leukaemia in relapse were transplanted with fetal liver cells following a conditioning regimen of cyclophosphamide (120 mg/kg) and total body irradiation (1000 r). Each patient achieved a remission with haematopoietic recovery that was rapid in one case and delayed in the other. In one case there was evidence of chimerism as demonstrated by the presence of the XYY karyotype of the donor fetus in 20 % of marrow metaphases, by the presence of double Y bodies in the peripheral blood, by the appearance of new HLA-antigens, and by red cell isoenzyme phenotypes of donor origin. In the second case there was prompt haemotopoietic recovery and the appearance of red cell isoenzyme phenotypes of donor origin. Survival was 153 and 30 d, respectively, and both patients died of interstitial pneumonia without evidence of graft versus host disease.

  1. Auricular Oedema and Dyshidrotic Eczema in a Patient with Acute Myeloid Leukaemia Treated with Cytarabine

    Directory of Open Access Journals (Sweden)

    K. Brandt

    2010-10-01

    Full Text Available Cytarabine is an effective drug in the treatment of haematological malignancies. The therapy is associated with various complications. Frequencies of dermatological side-effects range from 2–72% and occur most commonly after high-dose regimens. Although most cutaneous reactions are mild and resolve spontaneously within several days, they may result in an increased risk of infection and alterations in comfort. In some cases, severe life-threatening reactions have been reported. Here we describe the case of a patient with acute myeloid leukaemia, who developed severe exceptional skin toxicity in terms of auricular oedema and palmar dyshidrotic eczema after the application of low-dose cytarabine. Re-administration of the drug resulted in reduced skin toxicity during further cycles of chemotherapy. Negative epicutaneous patch-testing supported the existence of cytarabine-provoked toxicity.

  2. Myeloid Sarcoma Presenting with Leukemoid Reaction in a Child Treated for Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Aylin Canbolat Ayhan

    2014-01-01

    Full Text Available Background. Myeloid sarcoma is an extramedullary neoplasm of immature myeloid cells. Our study reports a presentation of myeloid sarcoma which presented with severe leukemoid reaction as a secondary malignancy in a patient who was treated for acute lymphoblastic leukemia previously. The case emphasizes the difficulties in diagnosis of patients who do not have concomitant leukemia. Case Presentation. A 6-year-old girl who was treated for acute lymphoblastic leukemia previously presented with fatigue, paleness, and hepatosplenomegaly. Peripheral blood smear and bone marrow aspirate examination did not demonstrate any blasts in spite of severe leukemoid reaction with a white cell count 158000/mm3. FDG/PET CT revealed slight uptake in cervical and supraclavicular lymph nodes. Excisional lymph node biopsy was performed from these lymph nodes and it showed myeloid sarcoma. Conclusion. Myeloid sarcoma can develop as a secondary malignancy in children who are treated for acute lymphoblastic leukemia. It can be associated with severe leukemoid reaction and diagnosis may be difficult if there is not concomitant leukemia. PET/CT is helpful in such cases.

  3. Frequency of chromosomally-integrated human herpesvirus 6 in children with acute lymphoblastic leukemia.

    Directory of Open Access Journals (Sweden)

    Annie Gravel

    Full Text Available INTRODUCTION: Human herpesvirus 6 (HHV-6 is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6. The biological consequences of chromosomal integration by HHV-6 remain unknown. OBJECTIVE: To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. METHODOLOGY: A total of 293 DNA samples from children with pre-B (n=255, pre-pre-B (n=4, pre-T (n=26 and undetermined (n=8 leukemia were analyzed for ciHHV-6 by quantitative TaqMan PCR (QPCR using HHV-6 specific primers and probe. As control, DNA samples from 288 healthy individuals were used. Primers and probe specific to the cellular GAPDH gene were used to estimate integrity and DNA content. RESULTS: Out of 293 DNA samples from the leukemic cohort, 287 contained amplifiable DNA. Of these, only 1 (0.35% contained ciHHV-6. Variant typing indicates that the ci-HHV-6 corresponds to variant A. None of the 288 DNA samples from healthy individuals contained ciHHV-6. CONCLUSION: The frequency of ciHHV-6 in children with acute lymphoblastic leukemia is similar (p=0.5 to that of healthy individuals. These results suggest that acute lymphoblastic leukemia does not originate as a consequence to integration of HHV-6 within the chromosomes.

  4. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults.

    Science.gov (United States)

    Lee, Kum Ja; Chow, Vivian; Weissman, Ashley; Tulpule, Sunil; Aldoss, Ibrahim; Akhtari, Mojtaba

    2016-01-01

    Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug warnings and toxicity management. PMID:27601914

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

    OpenAIRE

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

    2015-01-01

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

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

    Science.gov (United States)

    2016-09-29

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

  7. Thyroiditis mimicking relapse of acute lymphoblastic leukemia: Gallium-67 scan suggested the diagnosis

    Directory of Open Access Journals (Sweden)

    Othman Saleh

    2010-01-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common form of leukemia in childhood and accounts for 85% of cases. ALL frequently presents as an infectious process with an abrupt onset of high fever. Thyroid disease has been reported to have a strong association with acute leukemia. Gallium (Ga-67 citrate has been used in the investigation of patients labeled as having pyrexia of unknown origin. We report a case of a 13-year-old female patient who presented with fever and suspected disease relapse after a period of disease remission; however, gallium-67 citrate whole body scan suggested the diagnosis of thyroiditis.

  8. Tumefactive intracranial presentation of precursor B-cell acute lymphoblastic leukemia

    Energy Technology Data Exchange (ETDEWEB)

    Forester, Craig M. [University of Utah, Salt Lake City, UT (United States); Braunreiter, Chi L. [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Helen DeVos Children' s Hospital, Department of Pediatric Hematology Oncology, Grand Rapids, MI (United States); Yaish, Hasan; Afify, Zeinab [University of Utah, Division of Pediatric Hematology Oncology, Primary Children' s Medical Center, Salt Lake City, UT (United States); Hedlund, Gary L. [Primary Children' s Medical Center, Department of Pediatric Radiology, Salt Lake City, UT (United States)

    2009-11-15

    In children, leukemia is the most common malignancy, and approximately 75% of leukemias are acute lymphoblastic leukemia (ALL). Central nervous system leukemia is found at diagnosis in fewer than 5% of children with ALL. Leukemic intracranial masses have been described with acute myeloid leukemia, but ALL presenting as a mass lesion is rare. We describe a unique case of an intracranial confirmed precursor B cell (pre-B) ALL mass in a 13-year-old girl that was diagnosed by brain CT, MRI and cerebral angiography, and confirmed by biopsy. This report details pertinent history and distinguishing imaging features of an intracranial ALL tumefaction. (orig.)

  9. Two cases of aspergillus endocarditis in non neutropenic children on chemotherapy for acute lymphoblastic leukaemia.

    Directory of Open Access Journals (Sweden)

    Emmanouil Nikolousis

    2011-06-01

    Full Text Available Fungal endocarditis (FE is a rare complication in immunocompromised patients which is difficult to diagnose and has been characterized by excessive mortality (> 50% and morbidity, regardless of treatment. The lack of clinical trials due to the small number of cases contributes further to a poor outcome. In our two cases of aspergilllus endocarditis we reviewed the clinical features, echocardiographic findings, microbiologic data, treatment, and outcome of these 2 cases and provide a current characterization of the syndrome. In this paper we have demonstrated the diversity of presentation of a critical fungal infection in immunocompromised but non neutropenic paediatric patients. The prompt diagnosis and initiation of treatment is crucial for a favourable outcome along with the use of double antifungal treatment with liposomal amphotericin and voriconazole initially which could be later switched to oral voriconazole with a good tissue penetration. Histological samples as well as radiological evidence and echocardiograms should be reviewed by experienced clinicians in order to aid diagnosis and promptly initiate treatment for these patients in order to achieve a favourable outcome

  10. Haploidentical hematopoietic stem cell transplantation for paediatric high-risk T-cell acute lymphoblastic leukaemia.

    Science.gov (United States)

    Xu, Zheng-Li; Huang, Xiao-Jun; Liu, Kai-Yan; Chen, Huan; Zhang, Xiao-Hui; Han, Wei; Chen, Yu-Hong; Wang, Feng-Rong; Wang, Jing-Zhi; Wang, Yu; Chen, Yao; Yan, Chen-Hua; Xu, Lan-Ping

    2016-06-01

    Paediatric HR T-cell ALL demonstrates dismal prognosis with chemotherapy, and poor outcomes could be improved with allo-SCT. HID-SCT is an almost immediately available choice; however, few studies have focused on the outcomes of HID-SCT for paediatric HR T-ALL. Forty-eight consecutive HR T-ALL children who underwent HID-SCT were included. Survival outcomes and factors predictive of outcomes were retrospectively analysed. Of the 48 patients, 35 were in CR1, 10 in CR2, and three in relapse. The cumulative incidence of grade 3/4 aGVHD was 10.4% and that of extensive cGVHD was 28.4%. The CIR at three yr was 30.8% and that of NRM at three yr was 14.7%. At a median follow-up of 20.0 (range 2.5-124.2) months, the three-yr LFS was 54.4%. Children who received transplants during CR1 had a better LFS (65.7% vs. 26.0%, p = 0.008) and a lower relapse rate (19.8% vs. 56.7%, p = 0.014) compared to those during non-CR1. HID-SCT is feasible for HR T-ALL children, and survival outcomes are better when performed in CR1 compared to non-CR1. Prospective clinical trials would be needed to confirm that. PMID:26996140

  11. 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

    .01). Classification and regression tree analysis demonstrated rs11033797 (OR51F1), rs2835265 (CBR1), rs28627172 (POLDIP3) and rs1129844 (CCL11) to be predictive of outcome. Among 61 patients for whom read-outs were available for all four SNPs, 40 of 41 patients with the worst SNP profile experienced at least one...... infectious event compared with five of the remaining 20 patients (Hazard ratio 9.0, 95% CI 3.4–23.5, which was unchanged after adjustments for neutrophil counts). Pathway analysis identified variations in ‘G-protein-coupled receptor (GPCR) downstream signalling’, ‘Bile acid and bile salt metabolism...

  12. Oral manifestations leading to the diagnosis of acute lymphoblastic leukemia in a young girl

    Directory of Open Access Journals (Sweden)

    B A Silva

    2012-01-01

    Full Text Available Background: oral complications may be leukemia′s first presentation. Aim: to present a case of a young girl with a swelling on the face that led to the diagnosis of acute lymphoblastic leukemia is reported. Results: a 10-year old anemic girl was referred for evaluation and treatment of a swelling at the left-nasolabial region. Symptoms reported (tiredness, poor appetite, fever, lethargy, and musculoskeletal pain and clinical findings (enlargement at the presternal region and brownish stain in the lumbar region led to the suspicion of a hematopoietic malignancy. The diagnosis of lymphoblastic leukemia was attained after specific examination conducted by the pediatric oncologist and hematologist. Conclusion: dentists must be able to clearly recognize oral physiological characteristics, and, when identifying changes of normalcy, to fully investigate it requesting additional tests or referring the patient to specialized professionals.

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

    Science.gov (United States)

    2016-03-01

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

  14. Incidence and risk factors for central nervous system relapse in children and adolescents with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Camila Silva Peres Cancela

    2012-01-01

    Full Text Available BACKGROUND: Despite all the advances in the treatment of childhood acute lymphoblastic leukemia, central nervous system relapse remains an important obstacle to curing these patients. This study analyzed the incidence of central nervous system relapse and the risk factors for its occurrence in children and adolescents with acute lymphoblastic leukemia. METHODS: This study has a retrospective cohort design. The studied population comprised 199 children and adolescents with a diagnosis of acute lymphoblastic leukemia followed up at Hospital das Clinicas, Universidade Federal de Minas Gerais (HC-UFMG between March 2001 and August 2009 and submitted to the Grupo Brasileiro de Tratamento de Leucemia da Infância - acute lymphoblastic leukemia (GBTLI-LLA-99 treatment protocol. RESULTS: The estimated probabilities of overall survival and event free survival at 5 years were 69.5% ( 3.6% and 58.8% ( 4.0%, respectively. The cumulative incidence of central nervous system (isolated or combined relapse was 11.0% at 8 years. The estimated rate of isolated central nervous system relapse at 8 years was 6.8%. In patients with a blood leukocyte count at diagnosis > 50 x 10(9/L, the estimated rate of isolated or combined central nervous system relapse was higher than in the group with a count 50 x 10(9/L at diagnosis seems to be a significant prognostic factor for a higher incidence of central nervous system relapse in childhood acute lymphoblastic leukemia.

  15. 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

  16. ZEB2 drives immature T-cell lymphoblastic leukaemia development via enhanced tumour-initiating potential and IL-7 receptor signalling

    NARCIS (Netherlands)

    S. Goossens (Steven); E. Radaelli (Enrico); O. Blanchet (Odile); K. Durinck (Kaat); J. van der Meulen (Joni); S. Peirs (Sofie); T. Taghon (Tom); C.S. Tremblay (Cedric S.); M. Costa (Magdaline); M.F. Ghahremani; J. De Medts (Jelle); S. Bartunkova (Sonia); K. Haigh (Katharina); C. Schwab (Claire); N. Farla (Natalie); T. Pieters (Tim); F. Matthijssens (Filip); N. van Roy (Nadine); J.A. Best (J. Adam); K. Deswarte (Kim); P. Bogaert (Pieter); C. Carmichael (Catherine); A. Rickard (Adam); S. Suryani (Santi); L.S. Bracken (Lauryn S.); R. Alserihi (Raed); K. Canté-Barrett (Kirsten); L. Haenebalcke (Lieven); E. Clappier; P. Rondou (Pieter); K. Slowicka (Karolina); D. Huylebroeck (Danny); A.W. Goldrath (Ananda W.); V. Janzen (Viktor); M.P. McCormack (Matthew P.); R.B. Lock (Richard B.); D.J. Curtis (David J.); C.J. Harrison (Christine); G. Berx (Geert); F. Speleman (Franki); J.P.P. Meijerink (Jules); J. Soulier (Jean); P. van Vlierberghe (Pieter); K. Haigh (Katharina)

    2015-01-01

    textabstractEarly T-cell precursor leukaemia (ETP-ALL) is a high-risk subtype of human leukaemia that is poorly understood at the molecular level. Here we report translocations targeting the zinc finger E-box-binding transcription factor ZEB2 as a recurrent genetic lesion in immature/ETP-ALL. Using

  17. Genetic variegation of clonal architecture and propagating cells in leukaemia.

    Science.gov (United States)

    Anderson, Kristina; Lutz, Christoph; van Delft, Frederik W; Bateman, Caroline M; Guo, Yanping; Colman, Susan M; Kempski, Helena; Moorman, Anthony V; Titley, Ian; Swansbury, John; Kearney, Lyndal; Enver, Tariq; Greaves, Mel

    2011-01-20

    Little is known of the genetic architecture of cancer at the subclonal and single-cell level or in the cells responsible for cancer clone maintenance and propagation. Here we have examined this issue in childhood acute lymphoblastic leukaemia in which the ETV6-RUNX1 gene fusion is an early or initiating genetic lesion followed by a modest number of recurrent or 'driver' copy number alterations. By multiplexing fluorescence in situ hybridization probes for these mutations, up to eight genetic abnormalities can be detected in single cells, a genetic signature of subclones identified and a composite picture of subclonal architecture and putative ancestral trees assembled. Subclones in acute lymphoblastic leukaemia have variegated genetics and complex, nonlinear or branching evolutionary histories. Copy number alterations are independently and reiteratively acquired in subclones of individual patients, and in no preferential order. Clonal architecture is dynamic and is subject to change in the lead-up to a diagnosis and in relapse. Leukaemia propagating cells, assayed by serial transplantation in NOD/SCID IL2Rγ(null) mice, are also genetically variegated, mirroring subclonal patterns, and vary in competitive regenerative capacity in vivo. These data have implications for cancer genomics and for the targeted therapy of cancer. PMID:21160474

  18. Serial Ultrasound Monitoring for Early Recognition of Asparaginase Associated Pancreatitis in Children With Acute Lymphoblastic Leukemia

    DEFF Research Database (Denmark)

    Raja, Raheel Altaf; Schmiegelow, K.; Henriksen, Birthe Merete;

    2015-01-01

    BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L-asparagina......BACKGROUND: Acute lymphoblastic leukemia (ALL) is the most common cancer in children and L-asparaginase is an essential component of the treatment. Cessation of L-asparaginase decreases event free survival. Acute pancreatitis is the toxicity that most commonly results in cessation of L...... protocol, with PEG-asparaginase of 2 or 6 week intervals, for 30 weeks had their pancreas monitored using serial ultrasound in order to detect early signs of inflammation. RESULTS: Nineteen of 31 eligible patients were included. Three of the included patients developed AAP. None of the patients, including...... the three patients that developed AAP, had signs of inflammatory edema or pancreas enzymes above three times the upper normal limit prior to AAP. CONCLUSION: We found no signs of inflammatory edema within the pancreas on ultrasound during treatment with PEG-asparginase in our cohort prior to development...

  19. Segmentation of White Blood Cell from Acute Lymphoblastic Leukemia Images Using Dual-Threshold Method

    Directory of Open Access Journals (Sweden)

    Yan Li

    2016-01-01

    Full Text Available We propose a dual-threshold method based on a strategic combination of RGB and HSV color space for white blood cell (WBC segmentation. The proposed method consists of three main parts: preprocessing, threshold segmentation, and postprocessing. In the preprocessing part, we get two images for further processing: one contrast-stretched gray image and one H component image from transformed HSV color space. In the threshold segmentation part, a dual-threshold method is proposed for improving the conventional single-threshold approaches and a golden section search method is used for determining the optimal thresholds. For the postprocessing part, mathematical morphology and median filtering are utilized to denoise and remove incomplete WBCs. The proposed method was tested in segmenting the lymphoblasts on a public Acute Lymphoblastic Leukemia (ALL image dataset. The results show that the performance of the proposed method is better than single-threshold approach independently performed in RGB and HSV color space and the overall single WBC segmentation accuracy reaches 97.85%, showing a good prospect in subsequent lymphoblast classification and ALL diagnosis.

  20. Disseminated fusariosis and endogenous fungal endophthalmitis in acute lymphoblastic leukemia following platelet transfusion possibly due to transfusion-related immunomodulation

    Directory of Open Access Journals (Sweden)

    Yong Ku

    2011-11-01

    Full Text Available Abstract Background To report a case of disseminated fusariosis with endogenous endophthalmitis in a patient with acute lymphoblastic leukemia. Transfusion-associated immune modulation secondary to platelet transfusion could play an important role in the pathophysiology of this case. Case Presentation A 9 year-old male with acute lymphoblastic leukemia complicated by pancytopenia and disseminated Intravascular coagulation was given platelet transfusion. He developed disseminated fusariosis and was referred to the ophthalmology team for right endogenous endophthalmitis. The infection was controlled with aggressive systemic and intravitreal antifungals. Conclusion Patients with acute lymphoblastic leukemia are predisposed to endogenous fungal endophthalmitis. Transfusion-associated immune modulation may further increase host susceptibility to such opportunistic infections.

  1. Imaging findings of the brain abnormalities in acute lymphoblastic leukemia of children during and after treatment

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Kyung Joo; Lee, Seung Rho; Park, Dong Woo; Joo, Kyung Bin; Kim, Jang Wook; Hahm, Chang Kok; Kim, Ki Joong; Lee, Hahng [College of Medicine, Hanyang Univ., Seoul (Korea, Republic of)

    2001-09-01

    We evaluated the imaging abnormalities of the brain observed during and after treatment of acute childhood lymphoblastic leukemia. The study group consisted of 30 patients (male : female=19 : 11 ; mean age, 64 months) with acute childhood lymphoblastic leukemia during the previous ten-year period who had undergone prophylaxis of the central nervous system. Irrespective of the CNS symptoms, base-line study of the brain involving CT and follow-up CT or MRI was undertaken more than once. We retrospectively evaluated the imaging findings, methods of treatment, associated CNS symptoms, and the interval between diagnosis and the time at which brain abnormalities were revealed by imaging studies. In 15 (50% ; male : female=9 : 6 ; mean age, 77 months) of 30 patients, brain abnormalities that included brain atrophy (n=9), cerebral infarctions (n=4), intracranial hemorrhage (n=1), mineralizing microangiopathy (n=2), and periventricular leukomalacia (n=3) were seen on follow-up CT or MR images. In four of nine patients with brain atrophy, imaging abnormalities such as periventricular leukomalacia (n=2), infarction (n=1) and microangiopathy (n=1) were demonstrated. Fourteen of the 15 patients underwent similar treatment ; the one excluded had leukemic cells in the CSF. Six patients had CNS symptoms. In the 15 patients with abnormal brain imaging findings, the interval between diagnosis and the demonstration of brain abnormalities was between one month and four years. After the cessation of treatment, imaging abnormalities remained in all patients except one with brain atrophy. Various imaging abnormalities of the brain may be seen during and after the treatment of acute childhood lymphoblastic leukemia and persist for a long time. In children with this condition, the assessment of brain abnormalities requires follow-up study of the brain.

  2. Clinical use of blinatumomab for B-cell acute lymphoblastic leukemia in adults

    Directory of Open Access Journals (Sweden)

    Lee KJ

    2016-08-01

    Full Text Available Kum Ja Lee,1 Vivian Chow,1 Ashley Weissman,2 Sunil Tulpule,3 Ibrahim Aldoss,4 Mojtaba Akhtari5 1Department of Clinical Pharmacy and Pharmaceutical Economics and Policy, University of Southern California, 2Department of Pharmacy, University of Southern California Norris Cancer Hospital, Los Angeles, CA, 3Department of Medicine, Raritan Bay Medical Center, Perth Amboy, NJ, 4Department of Hematology and Hematopoietic Cell Transplantation, City of Hope, Duarte, CA, 5Jane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California Norris Comprehensive Cancer Center, Los Angeles, CA, USA Abstract: Adults with relapsed or refractory B-cell acute lymphoblastic leukemia have a dismal prognosis with a short median overall survival that can be measured in months. Because most patients will have chemotherapy-resistant disease, allogeneic hematopoietic stem cell transplantation remains the only potentially curative treatment. Despite advances in current management, patients continue to have poor outcomes and lack of durable responses. Thus, new therapies with alternative modes of actions are currently being investigated. Blinatumomab is a novel bispecific T-cell engager that simultaneously binds CD3-positive cytotoxic T-cells and CD19-positive B-cells, resulting in selective lysis of tumor cells. It has shown promising results in patients with relapsed or refractory acute lymphoblastic leukemia or those achieving hematologic response with persistent minimum residual disease. Future clinical trials will answer questions regarding its optimal place in the treatment paradigm. Dose-limiting toxicities include immunological toxicities and cytokine release syndrome. However, most patients tolerate the therapy relatively well. This review will focus on the pharmacology, clinical efficacy, and safety of blinatumomab in the treatment of adult B-cell acute lymphoblastic leukemia while highlighting its unique drug

  3. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J.; Mecucci, Cristina

    2016-01-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia. PMID:27151989

  4. Deletions of the long arm of chromosome 5 define subgroups of T-cell acute lymphoblastic leukemia.

    Science.gov (United States)

    La Starza, Roberta; Barba, Gianluca; Demeyer, Sofie; Pierini, Valentina; Di Giacomo, Danika; Gianfelici, Valentina; Schwab, Claire; Matteucci, Caterina; Vicente, Carmen; Cools, Jan; Messina, Monica; Crescenzi, Barbara; Chiaretti, Sabina; Foà, Robin; Basso, Giuseppe; Harrison, Christine J; Mecucci, Cristina

    2016-08-01

    Recurrent deletions of the long arm of chromosome 5 were detected in 23/200 cases of T-cell acute lymphoblastic leukemia. Genomic studies identified two types of deletions: interstitial and terminal. Interstitial 5q deletions, found in five cases, were present in both adults and children with a female predominance (chi-square, P=0.012). Interestingly, these cases resembled immature/early T-cell precursor acute lymphoblastic leukemia showing significant down-regulation of five out of the ten top differentially expressed genes in this leukemia group, including TCF7 which maps within the 5q31 common deleted region. Mutations of genes known to be associated with immature/early T-cell precursor acute lymphoblastic leukemia, i.e. WT1, ETV6, JAK1, JAK3, and RUNX1, were present, while CDKN2A/B deletions/mutations were never detected. All patients had relapsed/resistant disease and blasts showed an early differentiation arrest with expression of myeloid markers. Terminal 5q deletions, found in 18 of patients, were more prevalent in adults (chi-square, P=0.010) and defined a subgroup of HOXA-positive T-cell acute lymphoblastic leukemia characterized by 130 up- and 197 down-regulated genes. Down-regulated genes included TRIM41, ZFP62, MAPK9, MGAT1, and CNOT6, all mapping within the 1.4 Mb common deleted region at 5q35.3. Of interest, besides CNOT6 down-regulation, these cases also showed low BTG1 expression and a high incidence of CNOT3 mutations, suggesting that the CCR4-NOT complex plays a crucial role in the pathogenesis of HOXA-positive T-cell acute lymphoblastic leukemia with terminal 5q deletions. In conclusion, interstitial and terminal 5q deletions are recurrent genomic losses identifying distinct subtypes of T-cell acute lymphoblastic leukemia.

  5. Frequency of Chromosomally-Integrated Human Herpesvirus 6 in Children with Acute Lymphoblastic Leukemia

    OpenAIRE

    Annie Gravel; Daniel Sinnett; Louis Flamand

    2013-01-01

    Introduction Human herpesvirus 6 (HHV-6) is a ubiquitous pathogen infecting nearly 100% of the human population. Of these individuals, between 0.2% and 1% of them carry chromosomally-integrated HHV-6 (ciHHV-6). The biological consequences of chromosomal integration by HHV-6 remain unknown. Objective To determine and compare the frequency of ciHHV-6 in children with acute lymphoblastic leukemia to healthy blood donors. Methodology A total of 293 DNA samples from children with pre-B (n = 255), ...

  6. T-lineage acute lymphoblastic leukemia and parvovirus infection in a child with neurofibromastosis-1

    Directory of Open Access Journals (Sweden)

    Pallavi Agarwal

    2013-01-01

    Full Text Available Neurofibromatosis (NF-1 patients have an increased risk of developing malignancies most commonly rhabdomyosarcomas, optic gliomas, brain tumors and non-lymphocytic leukemias. Acute lymphoblastic leukemia (ALL has been infrequently reported in association with NF-1. We describe a rare association of NF-1, T-lineage ALL and parvovirus infection in a 12-year-old child. In addition, it is also to emphasize that a high index of suspicion should be kept for parvovirus B19 infection as a cause of bicytopenia/pancytopenia in ALL patients following induction chemotherapy.

  7. FACIAL PALSY AS FIRST PRESENTATION OF ACUTE LYMPHOBLASTIC LEUKEMIA: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    S. Inaloo

    2008-11-01

    Full Text Available ObjectiveFacial paralysis in children is very often idiopathic and isolated facial nerve palsy, resulting from leukemic infiltration is a rare occurrence. Here we present the case of a 14 year-old boy with acute lymphobastic leukemia, who first presented with isolated right side peripheral facial nerve paralysis and was initially diagnosed with Bell's palsy.ConclusionThe presence of Bell's palsy in young children requires a complete evaluation, keeping in mind the possibility of leptomeningeal disease.Key words: Lymphoblastic Leukemia, Facial nerve palsy, Children.

  8. Successful Treatment of Fanconi Anemia and T-Cell Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    Terrie Flatt

    2012-01-01

    Full Text Available Fanconi anemia is associated with an increased risk of malignancy. Patients are sensitive to the toxic effects of chemotherapy. We report the case of a patient with Fanconi anemia who developed T-cell acute lymphoblastic leukemia. He experienced chemotherapy-related complications including prolonged neutropenia, grade IV vincristine neuropathy, and disseminated aspergillosis. He was successfully treated with modified dosing of cytarabine and intrathecal methotrexate followed by allogeneic bone marrow transplant. The aspergillosis was treated with systemic antifungal treatment and surgical resection. Now 30 months after bone marrow transplant the patient is without evidence of aspergillosis or leukemia.

  9. TEL-AML1 transgenic zebrafish model of precursor B cell acute lymphoblastic leukemia

    OpenAIRE

    Sabaawy, Hatem E.; Azuma, Mizuki; Embree, Lisa J.; Tsai, Huai-Jen; Matthew F Starost; Dennis D Hickstein

    2006-01-01

    Acute lymphoblastic leukemia (ALL) is a clonal disease that evolves through the accrual of genetic rearrangements and/or mutations within the dominant clone. The TEL-AML1 (ETV6-RUNX1) fusion in precursor-B (pre-B) ALL is the most common genetic rearrangement in childhood cancer; however, the cellular origin and the molecular pathogenesis of TEL-AML1-induced leukemia have not been identified. To study the origin of TEL-AML1-induced ALL, we generated transgenic zebrafish expressing TEL-AML1 eit...

  10. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    OpenAIRE

    Xian-Ming Mo; Hong Xu; Ting-Ting Zeng; Neng-Gang Jiang; Yong-Qian Jia; Jing-Tao Dong; Jian-Hua Yu; Wen-Tong Meng

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease. We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development, including IL-7R alpha (CD127), cytoplasmic CD79a (cCD79a), CD19, VpreB (CD179a), and sIgM, which are successive and essential for progression of B cells along their developmental pathway. Anal...

  11. Philadelphia Chromosome-positive Acute Lymphoblastic Leukemia or Chronic Myeloid Leukemia in Lymphoid Blast Crisis.

    Science.gov (United States)

    Kolenova, Alexandra; Maloney, Kelly W; Hunger, Stephen P

    2016-08-01

    The clinical characteristics of chronic myeloid leukemia (CML) in lymphoid blast crisis (BC) can resemble those of Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph ALL). Because of this, there can be concern as to whether a patient with newly diagnosed Ph leukemia has Ph ALL or CML in lymphoid BC. This distinction has significant potential therapeutic implications because most children with Ph ALL are now treated with chemotherapy plus a tyrosine kinase inhibitor, whereas allogeneic stem cell transplant is usually recommended for any patient with CML that presents in or later develops BC. PMID:27164534

  12. Targetable kinase-activating lesions in Ph-like acute lymphoblastic leukemia | Office of Cancer Genomics

    Science.gov (United States)

    Publication Abstract:  Philadelphia chromosome-like acute lymphoblastic leukemia (Ph-like ALL) is characterized by a gene-expression profile similar to that of BCR-ABL1-positive ALL, alterations of lymphoid transcription factor genes, and a poor outcome. The frequency and spectrum of genetic alterations in Ph-like ALL and its responsiveness to tyrosine kinase inhibition are undefined, especially in adolescents and adults. We performed genomic profiling of 1725 patients with precursor B-cell ALL and detailed genomic analysis of 154 patients with Ph-like ALL.

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

    Science.gov (United States)

    Vrooman, Lynda M; Silverman, Lewis B

    2016-10-01

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

  14. Testicular involvement in acute lymphoblastic leukemia. Consequences of radiotherapy and chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Brauner, R.; Czernichow, P.; Rappaport, R.; Schaison, G.

    1986-06-05

    Acute lymphoblastic leukemia has a higher mortality rate in boys as a result of possible testicular involvement; indeed, the testicle is the site of initial relapse in 6% of cases and is involved in 15% of all cases. Clinical diagnosis of testicular involvement is usually readily established. Treatment is delivery of 24 grays to both testicles and intensification of chemotherapy. In children who recover from their leukemia, this irradiation produces not only destruction of germ cells but also endocrine impairment which should be looked for and treated; replacement therapy with slow-action testosterone will be combined with the other hormonal treatments which pituitary deficiencies secondary to cranial irradiation may require.

  15. Trigeminal nerve involvement in T-cell acute lymphoblastic leukemia: value of MR imaging

    Energy Technology Data Exchange (ETDEWEB)

    Karadag, Demet; Karaguelle, Ayse Tuba; Erden, Ilhan; Erden, Ayse E-mail: erden@ada.net.tr

    2002-10-01

    A 30-year-old male with T-cell acute lymphoblastic leukemia presented with facial numbness. Neurological examination revealed paresthesia of the left trigeminal nerve. Cerebrospinal fluid (CSF) cytology showed no atypical cells. Gadolinium-enhanced magnetic resonance (MR) imaging demonstrated enlargement and enhancement of intracranial portions of the left trigeminal nerve. The abnormal MR imaging findings almost completely resolved after the chemotherapy. Gadolinium-enhanced MR imaging is not only a useful procedure for the early diagnosis of cranial nerve invasion by leukemia but it might be helpful to follow the changes after the treatment.

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

    Science.gov (United States)

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

    2014-11-01

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

  17. VARIATIONS OF THE LEUKOCYTES AND LYMPHOCYTES IN THE CASE OF ACUTE LYMPHOBLASTIC LEUKEMIA

    OpenAIRE

    Mirela Cozma; Marioara Nicoleta Filimon

    2005-01-01

    The purpose of this study is to approximate the surviving period in patients with acute lymphoblastic leukemia. For this study we took in to consideration 10 patients 0 to 20 years old, coming from rural or urban environments and their evolution has been studied for a period of 60 days from the primary presentation to the hospital. The diagnosis was made after a careful history and physical examination and was completed after a blood count insisting on the number of leukocytes and on the peri...

  18. OSTEOPOROSIS IN A SEVENTH YEAR OLD BOY WITH ACUTE LYMPHOBLASTIC LEUKEMIA (Case Report)

    OpenAIRE

    Salim, H.; I Ariawati; W Bikin-Suryawan; I Arimbawa

    2013-01-01

    Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. It can be a manifestation of acute lymphoblastic leukemia (ALL). About a-quarters of children with ALL will have signs and symptoms of osteoporosis. We report the case of a seventh-year-old boy with back pain. His antero-posterior pelvic radiograph showed the osteoporotic bone. The bone age study revealed six-year-old bone. Review of peripheral blood smear showed...

  19. Precursor T-Cell acute lymphoblastic leukemia/lymphoma with rare presentation in the urinary bladder

    Directory of Open Access Journals (Sweden)

    Alexander Pham

    2011-10-01

    Full Text Available We present the 16th reported case of Acute Lymphoblastic Leukemia (ALL with involvement in the bladder. Our patient was a 22 yearold man with T-cell ALL with a mediastinal mass. He received hyperfractionated cyclophosphamide, vincristine, doxorubicin, dexamethasone (HyperCVAD with mediastinal radiation. Prior to starting maintenance, he relapsed in the bladder and marrow. He received a nelarabine- based induction regimen and achieved remission. This was followed by an unrelated 11/12 HLA-matched myeloablative allogeneic stem cell transplant. He is in complete remission for the past 409 days.

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

    Energy Technology Data Exchange (ETDEWEB)

    Castillo, L.A.; Craft, A.W.; Kernahan, J.; Evans, R.G.; Aynsley-Green, A. (Royal Victoria Infirmary, Newcastle upon Tyne (England))

    1990-01-01

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

  1. Spectral karyotyping reveals a comprehensive karyotype in an adult acute lymphoblastic leukemia

    OpenAIRE

    Da, Wan Ming; Fan, Hui; Guo, Bo; Li, Su Xia; Lu, Xue Chun; Zhu, Hong Li

    2012-01-01

    Cytogenetic abnormalities are frequently detected in patients with acute lymphoblastic leu-kemia (ALL). Comprehensive karyotype was related to poor prognosis frequently in ALL. We present a comprehensive karyotype in an adult ALL by spectral karyotyping (SKY) and R-banding. SKY not only confirmed the abnormalities previously seen by R-banding but also improved comprehensive karyotype analysis with the following result 47,XY,+9, ins(1;5)(q23;q23q34) t(6;7)(q23;p13). Our report demonstrated tha...

  2. Ophthalmic evaluation of long-term survivors of childhood acute lymphoblastic leukemia

    International Nuclear Information System (INIS)

    Thirty-four long-term survivors of childhood acute lymphoblastic leukemia (ALL) underwent comprehensive ophthalmic examinations to detect retinopathy or other ocular sequelae. Sixteen of the 34 patients received whole brain radiation (greater than or equal to 2400 rad). All 18 patients in the non-radiated group had normal eye examinations, while 4 of 16 in the radiated group had ocular abnormalities. None of the ocular abnormalities could be definitely attributed to radiation and all patients had normal visual acuity. No radiation retinopathy was found in either group

  3. [Ribonuclease binase induces death in T-cell acute lymphoblastic leukemia cells by apoptosis].

    Science.gov (United States)

    Burnysheva, K M; Petrushanko, I Yu; Spirin, P V; Prassolov, V S; Makarov, A A; Mitkevich, V A

    2016-01-01

    Bacterial ribonuclease binase is a potential anticancer agent. In the present study, we have determined the toxic effect of binase towards cell lines of T-cell acute lymphoblastic leukemia Jurkat and CEMss. We have shown that binase induces apoptosis in these cells. At the same time, binase does not cause toxic effects in leukocytes of healthy donors, which suggests that binase activity towards leukemic cells is selective. We have found that the treatment of cancer cells with binase leads to a reduction in reactive oxygen species and transcription factor NFκB levels, and demonstrated that these effects are a common feature of the action of RNases on cancer cells.

  4. Secondary acute lymphoblastic leukemia is an independent predictor of poor prognosis.

    Science.gov (United States)

    Giri, Smith; Chi, Michelle; Johnson, Benny; McCormick, David; Jamy, Omer; Bhatt, Vijaya Raj; Martin, Mike G

    2015-12-01

    Compared to secondary acute myeloid leukemia, secondary acute lymphoblastic leukemia (sALL) is poorly characterized. We utilized data from the Surveillance, Epidemiology, and End Results (SEER) 13 database to further elucidate patient characteristics and prognostic factors in sALL. Cases of adult de novo acute lymphoblastic leukemia (ALL) and sALL in patients with primary breast, rectum, cervix, or ovarian cancers or lymphoma with a latency period of at least 12 months were identified within the SEER 13 database. Survival in sALL and de novo ALL were compared after propensity matching based on age, gender, race, ALL subtype, and year of diagnosis. 4124 cases of de novo ALL and 79 cases of sALL were identified. sALL patients were older at diagnosis (median 62 years vs. 44 years; p<0.01). Overall survival (OS) in sALL was lower than de novo ALL (median 8 months vs. 11 months), 1 year OS: 35% vs. 47% (p=0.05), 2 year OS: 16% vs. 31% (p<0.01), and 5 year OS: 7% vs. 21% (p<0.01). Multivariate analysis revealed sALL as an independent predictor of worsened survival (adjusted HR 1.54; 95% CI 1.16-2.04, p<0.01) after propensity matching.

  5. Renal Calculi: An Unusual Presentation of T-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Daly, Gemma F; Barnard, Edward B G; Thoreson, Lynn

    2016-01-01

    Spontaneous tumor lysis syndrome is a rare initial presentation of hematologic malignancy in children that typically presents with complications of electrolyte derangement, specifically hyperkalemia, hyperphosphatemia, and hyperuricemia. We report a case of a 5-year-old boy who presented to the emergency department with gross hematuria, abdominal pain, and vomiting and was ultimately diagnosed with uric acid nephrolithiasis and acute renal failure secondary to spontaneous tumor lysis syndrome in the setting of T-cell acute lymphoblastic leukemia. Tumor lysis syndrome is considered an oncologic emergency, and in this case, the child required urgent treatment with potassium-binding agents, rasburicase, and hemodialysis. This case demonstrates that occult hematologic malignancy should be suspected in cases of nephrolithiasis and acute renal failure when found in conjunction with hyperuricemia despite a normal complete blood count at the time of presentation. PMID:26644483

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

    Science.gov (United States)

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

    2016-03-01

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

  7. Higher frequencies of chromosomal aberrations in lymphocytes of children with acute lymphoblastic leukemia after in vitro gamma irradiation

    Directory of Open Access Journals (Sweden)

    A Ramyar

    2012-12-01

    Full Text Available Background: Acute lymphoblastic leukemia (ALL is the most common malignancy in childhood, characterized by excess lymphoblasts, and immature white blood cells that are continuously multiplying and overproducing in the bone marrow. The aim of this investigation was to measure the sensitivity of lymphocytes against gamma irradiation in patients with acute lymphoblastic leukemia, and also find out the effect of such irradiations in causing chromosomal abnormalities.Methods: In this investigation performed between April 2010 and July 2011, at the Department of Genetics, Cancer Institute of Iran, we studied the effects of gamma irradiation on the lymphocytes of 20 children with acute lymphoblastic leukemia. The lymphocytes of 30 healthy donors were used to establish as a normal response to gamma irradiation and seven age-matched ataxia telangiectasia patients were recruited as positive control. The chromosomal radiosensitivity was assessed with the G2- and the G0-assay. We compared the mean number of chromosomal abnormalities such as chromosome and chromatid breakages, chromosome and chromatid gaps, and chromatid exchanges in one-hundred metaphases of patients and control groups.Results: The frequency of chromosomal aberrations was statistically higher among patients with acute lymphoblastic leukemia than the normal controls (P<0.01. In total, 65% of the patients were sensitive to gamma irradiation, but the remaining 35% were similar to the normal controls. Patients with ataxia telangiectasia showed the highest sensitivity to gamma irradiation (P=0.001.Conclusion: Our results showed that a high percentage of patients with acute lymphoblastic leukemia were sensitive to irradiation, meaning that maximum care should be taken during their treatment to avoid unnecessary X-rays or radiotherapies.

  8. Clinical and pharmacologic aspects of blinatumomab in the treatment of B-cell acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Portell CA

    2013-04-01

    Full Text Available Craig A Portell, Candice M Wenzell, Anjali S Advani Leukemia Program, Taussig Cancer Institute, Cleveland Clinic, Cleveland, OH, USA Abstract: Acute lymphoblastic leukemia (ALL in adults remains a challenging disease to treat, and novel therapies are needed. Precursor-B ALL comprises 80% of cases, and the CD19 antigen is expressed in nearly all precursor-B ALL patients. Bispecific T-cell-engaging antibodies are novel bioengineered proteins. The bispecific T-cell-engaging antibody blinatumomab engages polyclonal T cells to CD19-expressing B cells. By binding to both CD3 and CD19, blinatumomab physically brings these T cells in close proximity to malignant B cells and potentiates T-cell-induced cytotoxic cell kill. Blinatumomab requires continuous intravenous infusion due to its short half-life, the need for continuous exposure for the drug to exert sufficient efficacy, and lessened toxicity. A phase II trial of B-cell ALL patients with persistent or relapsed minimal residual disease demonstrated an 80% rate of complete molecular remission. Cytokine-release syndrome and central nervous system events, such as seizures and encephalopathy, are reversible toxicities. Promising results in B-cell ALL with minimal residual disease have led to further evaluation of this drug in newly diagnosed and relapsed B-cell ALL. Keywords: blinatumomab, B-cell acute lymphoblastic leukemia, CD19, BiTE antibodies

  9. Hardware Segmentation on Digital Microscope Images for Acute Lymphoblastic Leukemia Diagnosis Using Xilinx System Generator

    Directory of Open Access Journals (Sweden)

    Prof. Kamal A. ElDahshan

    2014-09-01

    Full Text Available Image segmentation is considered the most critical step in image processing and helps to analyze, infer and make decisions especially in the medical field. Analyzing digital microscope images for earlier acute lymphoblastic leukemia diagnosis and treatment require sophisticated software and hardware systems. These systems must provide both highly accurate and extremely fast processing of large amounts of image data. In this work, the hardware segmentation framework for Acute Lymphoblastic Leukemia (ALL images based color histogram of Hue channel of HSV color space is proposed to segment each leukemia image into blasts and background using Field Programmable Gate Array (FPGA. The main purpose of this work is to implement image segmentation framework in a FPGA with minimum hardware resources and low execution time to be suitable enough for medical applications. Hardware framework of segmentation is designed using Xilinx System Generator (XSG as DSP design tool that enables the use of Simulink models, implemented in VHDL and synthesized for Xilinx SPARTAN-3E Starter kit (XC3S500E-FG320 FPGA.

  10. Blinatumomab: Bridging the Gap in Adult Relapsed/Refractory B-Cell Acute Lymphoblastic Leukemia.

    Science.gov (United States)

    Folan, Stephanie A; Rexwinkle, Amber; Autry, Jane; Bryan, Jeffrey C

    2016-08-01

    Adult patients with acute lymphoblastic leukemia who relapse after frontline therapy have extremely poor outcomes despite advances in chemotherapy and hematopoietic stem cell transplantation. Blinatumomab is a first-in-class bispecific T-cell engager that links T cells to tumor cells leading to T-cell activation and tumor cell lysis. In December 2014, the Food and Drug Administration approved blinatumomab for treatment of relapsed or refractory Philadelphia chromosome-negative precursor B-cell acute lymphoblastic leukemia. In a phase II trial, blinatumomab produced response rates of 43%, and 40% of patients achieving a complete remission proceeded to hematopoietic stem cell transplantation. Early use of blinatumomab was complicated with adverse effects, including cytokine release syndrome and neurotoxicity. Management strategies, including dexamethasone premedication and 2-step dose escalation during the first cycle of blinatumomab, have decreased the incidence and severity of these adverse effects. Blinatumomab currently is being studied for other B-cell malignancies and has the potential to benefit many patients with CD19+ malignancies in the future. PMID:27521320

  11. Purification and characterization of fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA)

    DEFF Research Database (Denmark)

    Hokland, P; Rosenthal, P; Griffin, J D;

    1983-01-01

    Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual fluore...... that these cells are relatively immature lymphoid cells, CALLA+ cells do not appear to contain either myeloid precursor cells (CFU-G/M) or the earliest lymphoid stem cells. Udgivelsesdato: 1983-Jan-1......Fetal hematopoietic cells that express the common acute lymphoblastic leukemia antigen (CALLA) were purified from both fetal liver and fetal bone marrow by immune rosetting with sheep erythrocytes coated with rabbit anti-mouse immunoglobulin and by fluorescence-activated cell sorting. Dual...... fluorescence techniques disclosed that these cells were heterogenous with respect to the expression of a series of differentiation and activation antigens defined by monoclonal antibodies. Thus, whereas all CALLA+ cells were Ia+ and expressed two activation antigens, J2 and T10, only 30-50% expressed B1...

  12. Predicting the neurobehavioral side effects of dexamethasone in pediatric acute lymphoblastic leukemia.

    Science.gov (United States)

    Warris, Lidewij T; van den Akker, Erica L T; Aarsen, Femke K; Bierings, Marc B; van den Bos, Cor; Tissing, Wim J E; Sassen, Sebastiaan D T; Veening, Margreet A; Zwaan, Christian M; Pieters, Rob; van den Heuvel-Eibrink, Marry M

    2016-10-01

    Although dexamethasone is an effective treatment for acute lymphoblastic leukemia (ALL), it can induce a variety of serious neurobehavioral side effects. We hypothesized that these side effects are influenced by glucocorticoid sensitivity at the tissue level. We therefore prospectively studied whether we could predict the occurrence of these side effects using the very low-dose dexamethasone suppression test (DST) or by measuring trough levels of dexamethasone. Fifty pediatric patients (3-16 years of age) with acute lymphoblastic leukemia (ALL) were initially included during the maintenance phase (with dexamethasone) of the Dutch ALL treatment protocol. As a marker of glucocorticoid sensitivity, the salivary very low-dose DST was used. A post-dexamethasone cortisol level predictive values of the DST for psychosocial problems and sleeping problems were 50% and 30%, respectively. Dexamethasone levels were not associated with neurobehavioral side effects. We conclude that neither the very low-dose DST nor measuring dexamethasone trough levels can accurately predict dexamethasone-induced neurobehavioral side effects. However, patients with glucocorticoid hypersensitivity experienced significantly more symptoms associated with dexamethasone-induced depression. Future studies should elucidate further the mechanisms by which neurobehavioral side effects are influenced by glucocorticoid sensitivity. PMID:27448086

  13. Second malignancies in children treated for non-Hodgkin's lymphoma and T-cell leukaemia with the UKCCSG regimens.

    OpenAIRE

    Ingram, L; Mott, M G; Mann, J R; Raafat, F; Darbyshire, P J; Morris Jones, P. H.

    1987-01-01

    Eight children treated between 1977 and 1983 with the UK Children's Cancer Study Group's non-Hodgkin lymphoma (NHL) and T-cell protocols have developed second malignancies within 7 years of commencing treatment. Five developed acute non-lymphoblastic leukaemia and a sixth died from infection while pancytopenic with a pre-leukaemic marrow. The other malignancies were cerebral astrocytoma and an undifferentiated low grade sarcoma. These eight children were included among 261 children studied in...

  14. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Sabine Topka

    2015-06-01

    Full Text Available Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL, the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  15. Relapse of acute lymphoblastic leukemia in the pancreas after bone marrow transplant

    Institute of Scientific and Technical Information of China (English)

    Guang-Xian Wang; Jun-Lin Liao; Dong Zhang; Li Wen

    2015-01-01

    Background: Relapse of acute lymphoblastic leukemia (ALL) in the pancreas is rare. We report a case of a 12-year-old boy who experienced a relapse of ALL in the pancreas after a bone marrow transplant. Methods: Clinical data, including course of illness, laboratory results, and imaging studies are included. The patient presented with acute pancreatitis, suspected to be secondary to gallstones, with ampullary obstruction. Ultrasound and magnetic resonance imaging demonstrated a distended gallbladder and intra- and extra-hepatic biliary dilatation with a cutoff at the pancreatic head, but with no evidence of gallstones. Results: Ultrasound-guided biopsy of the pancreas revealed ALL in the pancreas. Systematic chemotherapy was recommended, but was declined by the parents. The patient died one week later. Conclusion: Relapse of ALL in the pancreas is rare, but when a history of ALL is present, it should be considered in patients with pancreatic enlargement, obstructive jaundice, and pancreatitis.

  16. BCR-ABL Translocation in Pediatric Acute Lymphoblastic Leukemia in Southern India.

    Science.gov (United States)

    Sugapriya, D; Preethi, S; Shanthi, P; Chandra, N; Jeyaraman, G; Sachdanandam, P; Thilagavathy, S; Venkatadesilalu, S

    2012-03-01

    Cytogenetics and polymerase chain reaction (PCR) based assays provide important information regarding biologically defined and prognostically relevant subgroups in acute leukemias. We utilized karyotyping and molecular analysis by reverse transcriptase PCR for the BCR-ABL translocation, in addition to morphological study, cytochemistry and immunophenotyping, to study 24 cases of pediatric acute lymphoblastic leukemia (ALL). Our objective was to determine the frequency of the BCRABL translocation in childhood ALL from southern India. Karyotyping showed one case of hyperdiploidy, one case of t (12; 21) translocation and one case of 46, XY-21+mar. The BCR-ABL translocation was found in 8.3% of these cases. One of these was a cryptic translocation, the karyotype being normal. BCR-ABL positivity in ALL is associated with aggressive disease and has been shown to be a poor prognostic factor, especially in children. PMID:23449388

  17. Human parvovirus B19 DNA is not detected in Guthrie cards from children who have developed acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Isa, Adiba; Priftakis, Peter; Broliden, Kristina;

    2004-01-01

    BACKGROUND: There has been much speculation about the cause of childhood acute lymphoblastic leukemia (ALL). It has been suggested, on the basis of findings in epidemiological studies, that ALL may be initiated by an in utero infection of the fetus. The human parvovirus B19 (B19) is etiologically...

  18. Acute lymphoblastic leukemia in children with Down syndrome: A retrospective analysis from the Ponte di Legno study group

    NARCIS (Netherlands)

    T.D. Buitenkamp (Trudy); S. Izraeli (Shai); M. Zimmermann (Martin); E. Forestier (Erik); N.A. Heerema (Nyla); M.M. van den Heuvel-Eibrink (Marry); R. Pieters (Rob); C.M. Korbijn (Carin); L.B. Silverman (Lewis); K. Schmiegelow (Kjeld); D.-C. Liang (Der-Cheng); K. Horibe (Keizo); M. Aricò (Maurizio); A. Biondi (Andrea); G. Basso (Giuseppe); K.R. Rabin (Karin); M. Schrappe (Martin); G. Cario (Gunnar); G. Mann (Georg); M. Morak (Maria); R. Panzer-Grümayer (Renate); V. Mondelaers (Veerle); T. Lammens (Tim); H. Cavé (Hèléne); B. Stark (Batia); I. Ganmore (Ithamar); A.V. Moorman (Anthony); A. Vora (Ajay); S.P. Hunger (Stephen); C.H. Pui (Ching-Hon); C.G. Mullighan (Charles); A. Manabe (Atsushi); G. Escherich (Gabriele); J.R. Kowalczyk (Jerzy R.); J.A. Whitlock (James); C.M. Zwaan (Michel)

    2014-01-01

    textabstractChildren with Down syndrome (DS) have an increased risk of B-cell precursor (BCP) acute lymphoblastic leukemia (ALL). The prognostic factors and outcome of DS-ALL patients treated in contemporary protocols are uncertain. We studied 653 DS-ALL patients enrolled in 16 international trials

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

    DEFF Research Database (Denmark)

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

    2015-01-01

    The membrane transporter P-glycoprotein, encoded by the ABCB1 gene, influences the pharmacokinetics of anti-cancer drugs. We hypothesized that variants of ABCB1 affect outcome and toxicity in childhood acute lymphoblastic leukemia (ALL). We studied 522 Danish children with ALL, 93% of all those e...

  20. Palonosetron for the prevention of nausea and vomiting in children with acute lymphoblastic leukemia treated with high dose methotrexate

    DEFF Research Database (Denmark)

    Nadaraja, Sambavy; Mamoudou, Aissata Diop; Thomassen, Harald;

    2012-01-01

    High dose methotrexate (HD-MTX), used in the treatment of children with acute lymphoblastic leukemia (ALL), is moderately emetogenic. First generation 5-HT(3) receptor antagonists are effective prophylactic agents but require multiple administrations. Palonosetron has a half life of 36-42 hours...

  1. Long-term results of NOPHO ALL-92 and ALL-2000 studies of childhood acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Schmiegelow, K; Forestier, E; Hellebostad, M;

    2010-01-01

    Analysis of 2668 children with acute lymphoblastic leukemia (ALL) treated in two successive Nordic clinical trials (Nordic Society of Paediatric Haematology and Oncology (NOPHO) ALL-92 and ALL-2000) showed that 75% of all patients are cured by first-line therapy, and 83% are long-term survivors...

  2. Comparison of clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    肖小珍

    2013-01-01

    Objective To investigate and compare the clinical implications of p16 deletion in childhood and adult B-lineage acute lymphoblastic leukemia (B-ALL) .Methods A total of 129 cases of de novo childhood (73 cases) and adult (56 cases) B-ALL were examined genetically and immunologically using G-banding techniqhe,interphase

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  4. The Eleventh International Childhood Acute Lymphoblastic Leukemia Workshop Report: Ponte di Legno, Italy, 6-7 May 2009

    DEFF Research Database (Denmark)

    Biondi, A; Baruchel, A; Hunger, S;

    2009-01-01

    An international childhood acute lymphoblastic leukemia (ALL)working group was formed during the 27th annual meeting of the International Society of Pediatric Oncology in 1995. Since then, 10 workshops have been held to address many issues that help advance treatment outcome of childhood ALL...

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  6. Hickman to central venous catheter: A case of difficult venous access in a child suffering from acute lymphoblastic leukemia

    Science.gov (United States)

    Chakraborty, Arunangshu; Agrawal, Sanjit; Datta, Taniya; Mitra, Suparna; Khemka, Rakhi

    2016-01-01

    Chemotherapy in children suffering from cancer usually requires placement of an indwelling central venous catheter (CVC). A child may need to undergo repeated procedures because of infection and occlusion of previous access devices. We present a case of CVC insertion in a child suffering from acute lymphoblastic leukemia where an innovative technique was employed. PMID:27695218

  7. Protracted and variable latency of acute lymphoblastic leukemia after TEL-AML1 gene fusion in utero

    NARCIS (Netherlands)

    Wiemels, JL; Ford, AM; Van Wering, ER; Postma, A; Greaves, M

    1999-01-01

    We report a pair of identical twins with concordant acute lymphoblastic leukemia (ALL). Unusually, their diagnoses were spaced 9 years apart at ages 5 and 14, Leukemic cells in both twins had a TEL-AML1 rearrangement, which was characterized at the DNA level by an adaptation of a long distance polym

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

    NARCIS (Netherlands)

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

    2004-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Rana Baraz

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

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

    DEFF Research Database (Denmark)

    Vaitkevičienė, Goda; Matuzevičienė, Rėda; Stoškus, Mindaugas;

    2014-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

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

    NARCIS (Netherlands)

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

    2013-01-01

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

  13. Precursor T-cell acute lymphoblastic leukemia presenting with bone marrow necrosis: a case report

    Directory of Open Access Journals (Sweden)

    Khoshnaw Najmaddin SH

    2012-10-01

    Full Text Available Abstract Introduction Bone marrow necrosis is a clinicopathological condition diagnosed most often at postmortem examination, but it is also seen during the course of malignancy and is not always associated with a poor prognosis. The morphological features of bone marrow necrosis are disruption of the normal marrow architecture and necrosis of myeloid tissue and medullary stroma. Non-malignant conditions associated with bone marrow necrosis are sickle cell anemia, infections, drugs (sulfasalazine, interferon α, all-trans retinoic acid, granulocyte colony-stimulating factor and fludarabine, disseminated intravascular coagulation, antiphospholipid antibody syndrome and acute graft versus host diseases. The malignant causes are leukemia, lymphoma and metastatic carcinomas. Herein we report the case of a patient with precursor T-cell acute lymphoblastic leukemia and bone marrow necrosis at initial presentation. Case presentation A 10-year-old Kurdish boy was presented with generalized bone pain and fever of 1 month’s duration which was associated with sweating, easy fatigability, nose bleeding, breathlessness and severe weight loss. On examination, we observed pallor, tachypnea, tachycardia, low blood pressure, fever, petechial hemorrhage, ecchymoses, tortuous dilated veins over the chest and upper part of abdomen, multiple small cervical lymph node enlargements, mildly enlarged spleen, palpable liver and gross abdominal distention. Blood analysis revealed pancytopenia and elevated lactate dehydrogenase and erythrocyte sedimentation rate. Imaging results showed mediastinal widening on a planar chest X-ray and diffuse focal infiltration of the axial bone marrow on magnetic resonance imaging of the lumbosacral vertebrae. Bone marrow aspiration and biopsy examination showed extensive bone marrow necrosis. Immunophenotyping analysis of the bone marrow biopsy confirmed T-cell acute lymphoblastic leukemia, as CD3 and terminal deoxynucleotidyl

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

    Institute of Scientific and Technical Information of China (English)

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

    2005-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Farhat L Khanim

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

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

    Directory of Open Access Journals (Sweden)

    Stefano Tiziani

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

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

    Science.gov (United States)

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

    2012-10-01

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

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

    OpenAIRE

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

    2011-01-01

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

  19. A novel chromosomal abnormality t (9;14)(p24;q13) in B-acute lymphoblastic leukemia

    OpenAIRE

    Sureshkumar Raveendran; Santhi Sarojam; Geetha Narayanan; Hariharan Sreedharan

    2014-01-01

    Acute lymphoblastic leukemia is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. We describe the clinical, morphologic, immunophenotypic and cytogenetic findings in the case of a 26-year-old man with B-lymphoblastic leukemia. Surface marker analysis revealed that they are positive for CD markers CD10, CD19, CD13, CD34, CD45 and HLA-DR, but negative for CD20, CD33, CD117 and CD11C markers. Cytogeneti...

  20. Acute myeloid leukaemia as a cause of acute ischaemic heart disease

    NARCIS (Netherlands)

    van Haelst, P.L.; Schot, Bart; Hoendermis, E.S.; van den Berg, M.P.

    2006-01-01

    Ischaemic heart disease is almost invariably the result of atherosclerotic degeneration of the coronary arteries. However, other causes of ischaemic heart disease should always be considered. Here we describe two patients with a classic presentation of ischaemic heart disease resulting from acute le

  1. The use of novel monoclonal antibodies in the treatment of acute lymphoblastic leukemia.

    Science.gov (United States)

    DeAngelo, Daniel J

    2015-01-01

    Regardless of age, patients with relapsed or refractory acute lymphoblastic leukemia (ALL) have extremely poor outcomes. The success of reinduction chemotherapy remains dismal, because complete remission rates are low and seldom durable. Clearly, new and novel strategies are needed to improve the outcome of patients with relapsed or refractory ALL. Patients with early relapse, especially those still receiving chemotherapy, tend to have a much poorer outcome and are often chemotherapy resistant. Although high-dose approaches may overcome chemotherapy resistance, long-term disease-free and overall survival remains limited. Several approaches have been used to target antigens, including cluster of differentiation (CD) 19, CD20, CD22, and CD52, on the surface of the malignant lymphoblast with striking efficacy. This review will focus on the clinical application of the major classes of antibodies, including naked antibodies, drug-antibody conjugates, immunotoxins, and T cell-engaging bispecific antibodies. Hopefully, these novel monoclonal antibodies will result in a significant improvement in the outcome of patients with relapsed or refractory ALL.

  2. Acute lymphoblastic leukemia presenting as a breast lump: A report of two cases

    Directory of Open Access Journals (Sweden)

    Syed Besina

    2013-01-01

    Full Text Available Extra-medullary leukemic infiltration of the breast by acute lymphoblastic leukemia (ALL is very rare. We report two cases of ALL presenting as breast masses and diagnosed on fine-needle aspiration (FNA. Our first patient, a post-partum 30-year-old female, developed bilateral breast lumps in her last trimester of pregnancy and complained of easy fatigability. Our second patient, a 14-year-old girl, presented with a right-breast lump of 1-week duration. She had received treatment for ALL 1 year back and had been in complete remission for the last 1 year. FNA of the breast nodules done in both the cases revealed diffuse infiltration by lymphoblasts. Subsequent hematological investigations confirmed bone marrow involvement by ALL in the first case and extra-medullary relapse in the second case. Fine-needle aspiration cytology (FNAC is an easy and cost effective method for the early diagnosis of metastatic leukemic infiltration, avoiding unnecessary excisional biopsies in such cases.

  3. Association of cytogenetics and immunophenotype in prognosis of children with acute lymphoblastic leukemia: Literature Review

    Directory of Open Access Journals (Sweden)

    Abdollah Banihashem

    2014-02-01

    Full Text Available Acute lymphoblastic leukemia (ALL is the most common type of neoplastic disorder diagnosed in childhood. It is the cause of one third of all pediatric malignancies. ALL is characterized by the abnormal production and proliferation of immature lymphoblasts in bone marrow (BM. It seems that ALL occurs due to a genetic mutation in DNA structure producing white blood cell (WBC stem cells. Because ALL is a systemic disease, its primary management is based on chemotherapy. There are important risk factors responsible for the poor prognosis of  ALL in children less than 1 year old and greater than 10 years old, such as: high WBC, mature T cell ,mature B cell, central nervous system (CNS involvement, DNA index 10 at diagnosis, no remission at the end of induction therapy and Minimal residual disease at the end of consolidation therapy. Complications might appear during the treatment including tumor lysis syndrome, bleeding, renal failure, sepsis, seizure, thrombosis, etc. Some consequences might identify after a long-term follow-up such as learning impairment, growth retardation, and secondary malignancies. It is estimated that up to 90% of pediatric ALL cases are curable.

  4. The BCL2 rheostat in glucocorticoid-induced apoptosis of acute lymphoblastic leukemia

    Science.gov (United States)

    Ploner, C; Rainer, J; Niederegger, H; Eduardoff, M; Villunger, A; Geley, S; Kofler, R

    2016-01-01

    Glucocorticoid (GC)-induced apoptosis is essential in the treatment of acute lymphoblastic leukemia (ALL) and related malignancies. Pro- and anti-apoptotic members of the BCL2 family control many forms of apoptotic cell death, but the extent to which this survival ‘rheostat’ is involved in the beneficial effects of GC therapy is not understood. We performed systematic analyses of expression, GC regulation and function of BCL2 molecules in primary ALL lymphoblasts and a corresponding in vitro model. Affymetrix-based expression profiling revealed that the response included regulations of pro-apoptotic and, surprisingly, anti-apoptotic BCL2 family members, and varied among patients, but was dominated by induction of the BH3-only molecules BMF and BCL2L11/Bim and repression of PMAIP1/Noxa. Conditional lentiviral gene overexpression and knock-down by RNA interference in the CCRF-CEM model revealed that induction of Bim, and to a lesser extent that of BMF, was required and sufficient for apoptosis. Although anti-apoptotic BCL2 members were not regulated consistently by GC in the various systems, their overexpression delayed, whereas their knock-down accelerated, GC-induced cell death. Thus, the combined clinical and experimental data suggest that GCs induce both pro- and anti-apoptotic BCL2 family member-dependent pathways, with the outcome depending on cellular context and additional signals feeding into the BCL2 rheostat. PMID:18046449

  5. Donor Umbilical Cord Blood Transplant With or Without Ex-vivo Expanded Cord Blood Progenitor Cells in Treating Patients With Acute Myeloid Leukemia, Acute Lymphoblastic Leukemia, Chronic Myelogenous Leukemia, or Myelodysplastic Syndromes

    Science.gov (United States)

    2016-09-09

    Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia in Remission; Acute Myeloid Leukemia Arising From Previous Myelodysplastic Syndrome; Acute Myeloid Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Mixed Phenotype Acute Leukemia; Myelodysplastic Syndrome; Pancytopenia; Refractory Anemia; Refractory Anemia With Excess Blasts; Refractory Anemia With Excess Blasts in Transformation; Secondary Acute Myeloid Leukemia

  6. A novel chromosomal abnormality t (9;14(p24;q13 in B-acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Sureshkumar Raveendran

    2014-01-01

    Full Text Available Acute lymphoblastic leukemia is a malignant disease of the bone marrow in which early lymphoid precursors proliferate and replace the normal hematopoietic cells of the marrow. We describe the clinical, morphologic, immunophenotypic and cytogenetic findings in the case of a 26-year-old man with B-lymphoblastic leukemia. Surface marker analysis revealed that they are positive for CD markers CD10, CD19, CD13, CD34, CD45 and HLA-DR, but negative for CD20, CD33, CD117 and CD11C markers. Cytogenetic analysis established a novel translocation, t (9;14(p24;q13. Apart from this, spectral karyotyping revealed an additional translocation, t (6p; 14q. This is the first documented case of B-lymphoblastic leukemia with concurrent occurrence of both abnormalities. Further studies are needed to understand the role of this abnormality in carcinogenesis.

  7. Thyroid-Like Follicular Carcinoma of the Kidney in a Young Patient with History of Pediatric Acute Lymphoblastic Leukemia

    Directory of Open Access Journals (Sweden)

    William W. Wu

    2014-01-01

    Full Text Available Thyroid-like follicular carcinoma of the kidney (TLFCK is a rare histological variant of renal cell carcinoma not currently included in the World Health Organization classification of renal tumors. Only 24 previous cases of TLFCK have been reported to date. We report a case of TLFCK in a 19-year-old woman with history of pediatric acute lymphoblastic leukemia. This patient is the youngest with TLFCK to be reported to date and the first with history of lymphoblastic leukemia. The development of TLFCK in a young patient with history of lymphoblastic leukemia is interesting and suggests that genes involved in leukemogenesis may also be important for TLFCK pathogenesis. Recognition of TLFCK is important to distinguish it from other conditions that show thyroid-like features, as a misdiagnosis can result in adverse patient care.

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

    Directory of Open Access Journals (Sweden)

    Walter Oleschko Arruda

    2005-06-01

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

  9. OSTEOPOROSIS IN A SEVENTH YEAR OLD BOY WITH ACUTE LYMPHOBLASTIC LEUKEMIA (Case Report

    Directory of Open Access Journals (Sweden)

    H Salim

    2013-09-01

    Full Text Available Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. It can be a manifestation of acute lymphoblastic leukemia (ALL. About a-quarters of children with ALL will have signs and symptoms of osteoporosis. We report the case of a seventh-year-old boy with back pain. His antero-posterior pelvic radiograph showed the osteoporotic bone. The bone age study revealed six-year-old bone. Review of peripheral blood smear showed normochromic anemia with thrombocytopenia. Immunophenotyping of peripheral blood revealed no dominant marker was seen, but the bone marrow aspiration confirms the diagnosis of ALL (L2.

  10. Chemotherapeutic treatment reduces circulating levels of surfactant protein-D in children with acute lymphoblastic leukemia

    DEFF Research Database (Denmark)

    Rathe, Mathias; Sorensen, Grith L; Wehner, Peder S;

    2016-01-01

    BACKGROUND: Surfactant protein D (SP-D) is a host defense molecule of the innate immune system that enhances pathogen clearance and modulates inflammatory responses. We hypothesized that circulating SP-D levels are associated with chemotherapy-induced mucositis and infectious morbidity in children...... with acute lymphoblastic leukemia (ALL). PROCEDURE: In a prospective study, 43 children receiving treatment for ALL were monitored for mucosal toxicity from diagnosis through the induction phase of treatment. Serial blood draws were taken to determine the levels of SP-D, interleukin-6 (IL-6), C......-reactive protein, and white blood cells. Data on fever, antibiotics, and bacteremia were collected. Baseline levels of circulating SP-D were compared with healthy controls. RESULTS: Baseline values of circulating SP-D were similar to levels in healthy controls (median: 829 ng/ml vs. 657 ng/ml, respectively, P > 0...

  11. CYLD Regulates Noscapine Activity in Acute Lymphoblastic Leukemia via a Microtubule-Dependent Mechanism

    Science.gov (United States)

    Yang, Yunfan; Ran, Jie; Sun, Lei; Sun, Xiaodong; Luo, Youguang; Yan, Bing; Tala; Liu, Min; Li, Dengwen; Zhang, Lei; Bao, Gang; Zhou, Jun

    2015-01-01

    Noscapine is an orally administrable drug used worldwide for cough suppression and has recently been demonstrated to disrupt microtubule dynamics and possess anticancer activity. However, the molecular mechanisms regulating noscapine activity remain poorly defined. Here we demonstrate that cylindromatosis (CYLD), a microtubule-associated tumor suppressor protein, modulates the activity of noscapine both in cell lines and in primary cells of acute lymphoblastic leukemia (ALL). Flow cytometry and immunofluorescence microscopy reveal that CYLD increases the ability of noscapine to induce mitotic arrest and apoptosis. Examination of cellular microtubules as well as in vitro assembled microtubules shows that CYLD enhances the effect of noscapine on microtubule polymerization. Microtubule cosedimentation and fluorescence titration assays further reveal that CYLD interacts with microtubule outer surface and promotes noscapine binding to microtubules. These findings thus demonstrate CYLD as a critical regulator of noscapine activity and have important implications for ALL treatment. PMID:25897332

  12. Successful outcome of mucormycosis in two children on induction therapy for acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Anshul Gupta

    2013-01-01

    Full Text Available Zygomycetes are one of the less common causes of invasive fungal infections in patients with the hematological malignancies. We report two cases of acute lymphoblastic leukemia in the pediatric age group, complicated by disseminated cutaneous mucormycosis during induction chemotherapy. In one of our cases, cutaneous mucormycosis progressed to osteomyelitis of the proximal ulna while in the other it disseminated to lungs and distant cutaneous site. Aggressive treatment, which included intravenous administration of amphotericin B; radical surgical intervention in the form of serial wound debridement in the former and wedge pulmonary resection in the later, allowed successful salvage, and administration of planned anti-leukemia treatment in both of our cases. High index of suspicion, timely diagnosis, and appropriate treatment are key components of a successful outcome.

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

    Science.gov (United States)

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

    2010-01-01

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

  14. Role of L-asparaginase in acute lymphoblastic leukemia: focus on adult patients

    Directory of Open Access Journals (Sweden)

    Rytting ME

    2012-06-01

    Full Text Available Michael E RyttingDepartment of Pediatrics and Leukemia, University of Texas MD Anderson Cancer Center, Houston, TX, USAAbstract: Asparaginase preparations deplete asparagine in acute lymphoblastic leukemia (ALL blasts. Asparaginase in its various forms is an important component of treatment regimens for pediatric ALL. Recently, interest and use of asparaginase in adult patients with ALL has increased, particularly in young adults. There is much less information on asparaginase use and toxicity in adult compared with pediatric populations. This review surveys prior published studies of the three most commonly used asparagine preparations as used in adult patients, and discusses important toxicities encountered in adult patients who receive asparaginase preparations.Keywords: asparaginase, leukemia, adults, children

  15. Characterization of xenoantiserum produced against B cell acute lymphoblastic leukemia cell line

    Directory of Open Access Journals (Sweden)

    Akagi,Tadaatsu

    1982-10-01

    Full Text Available Antiserum was produced in white rabbit by intravenously injecting living cells of a B cell acute lymphoblastic leukemia (ALL line (BALL-1. The reactivity of the antiserum against various lymphoid cell lines was examined by membrane immunofluorescence after appropriate absorption. Serum absorbed with non-T, non-B (NALL-1 and T-ALL (TALL-1 cells recognized B cell antigens distinct from Ia-like antigens on both normal and neoplastic B cells. After further absorption with tonsillar cells or normal B cell line (KO-HL-3, it reacted only with BALL-1 cells and did not react with other leukemia/lymphoma and normal B cell lines. The serum absorbed with tonsillar cells reacted only with BALL-1 and some B cell lines. Thus we were able to obtain antisera with specificity to B cell antigen, B-ALL antigen, and B cell line antigen.

  16. Body composition and phase angle in Russian children in remission from acute lymphoblastic leukemia

    Science.gov (United States)

    Tseytlin, G. Ja; Khomyakova, I. A.; Nikolaev, D. V.; Konovalova, M. V.; Vashura, A. Yu; Tretyak, A. V.; Godina, E. Z.; Rudnev, S. G.

    2010-04-01

    Elevated degree of body fatness and changes in other body composition parameters are known to be common effects of treatment for acute lymphoblastic leukemia (ALL) in children. In order to study peculiarities of somatic growth and development in ALL survivors, we describe the results of BIA body composition analysis of 112 boys and 108 girls aged 5-18 years in remission from ALL (remission time range 1-13 years) compared to data from the same number of age- and sex-matched healthy controls (n=220). Detrimental effect on height in ALL boys was observed, whereas girls experienced additional weight gain compared to healthy subjects. In ALL patients, resistance, body fat, and percent body fat were significantly increased. The reactance, phase angle, absolute and relative values of skeletal muscle and body cell mass were significantly decreased. Principal component analysis revealed an early prevalence of adiposity traits in the somatic growth and development of ALL girls compared to healthy controls.

  17. Individualized leukemia cell-population profiles in common B-cell acute lymphoblastic leukemia patients

    Institute of Scientific and Technical Information of China (English)

    Jian-Hua Yu; Jing-Tao Dong; Yong-Qian Jia; Neng-Gang Jiang; Ting-Ting Zeng; Hong Xu; Xian-Ming Mo

    2013-01-01

    Immunophenotype is critical for diagnosing common B-cell acute lymphoblastic leukemia (common ALL) and detecting minimal residual disease.We developed a protocol to explore the immunophenotypic profiles of common ALL based on the expression levels of the antigens associated with B lymphoid development,including IL-7Rα (CD127),cytoplasmic CD79a (cCD79a),CD19,VpreB (CD179a),and slgM,which are successive and essential for progression of B cells along their developmental pathway.Analysis of the immunophenotypes of 48 common ALL cases showed that the immunophenotypic patterns were highly heterogeneous,with the leukemic cell population differing from case to case.Through the comprehensive analysis of immunophenotypic patterns,the profiles of patient-specific composite leukemia cell populations could provide detailed information helpful for the diagnosis,therapeutic monitoring,and individualized therapies for common ALL.

  18. Case report of acute lymphoblastic leukemia with multiple soft tissue mass

    Energy Technology Data Exchange (ETDEWEB)

    Jang, Jung Yong; Huh, Kyung Hoe; Yi, Won Jin; Heo, Min Suk; Lee, Sam Sun; Choi, Soon Chul [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-06-15

    A 15-year-old patient, who had been diagnosed and treated as Burkitt cell type acute lymphoblastic leukemia (ALL-L3) already, visited our department. He complained of gingival enlargement and loosening teeth 1 month ago. The clinical examination revealed anterior open bite, gingival enlargement, and non tender swelling particularly in molar regions of both jaws. Deep periodontal pockets and severe mobility was shown on most of the teeth. The panoramic radiographs showed severe bone destruction and extrusion of the molars. The contrast enhanced CT showed multiple enhanced mass and bone marrow obliteration in both jaws. Chemotherapy was done the swelling was subsided at 1 month later. In conclusion, radiologic findings of leukemia with soft tissue mass, known as chloroma or granulocytic sarcoma, mimic those of lymphoma, so blood test may be needed for the final diagnosis.

  19. Acute lymphoblastic leukemia as second primary tumor in a patient with retinoblastoma.

    Science.gov (United States)

    Ganguly, Anasua; Kaliki, Swathi; Mohammad, Faraz Ali; Mishra, Dilip K; Vanajakshi, S; Reddy, Vijay Anand

    2016-01-01

    Second primary tumor (SPT) is defined as a second tumor that presents either simultaneously or after the diagnosis of an index tumor. Second primary malignancies are the leading cause of death in patients with heritable retinoblastoma (RB). Acute lymphoblastic leukemia (ALL), as SPT in RB patients, is extremely rare. To the best of our knowledge, only five cases of ALL as SPT in patients with RB has been documented in the literature. Herein, we report a case of a 6-year-old girl with bilateral RB, who developed ALL during the course of treatment of RB. This case highlights the importance of reviewing blood investigations regularly to diagnose leukemia as SPT in RB and also the necessity for proper counseling and lifelong follow-up in these patients. PMID:27433042

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

    DEFF Research Database (Denmark)

    Nersting, Jacob; Borst, Louise; Schmiegelow, Kjeld

    2011-01-01

    of acceptable toxicity, an individualized therapeutic approach is indicated. The mapping of the human genome and technological developments in DNA sequencing, gene expression profiling, and proteomics have raised the expectations for implementing genotype-phenotype data into the clinical decision process......, but also multiplied the complex interaction of genetic and other laboratory parameters that can be used for therapy adjustments. Thus, with the advances in the laboratory techniques, post laboratory issues have become major obstacles for treatment individualization. Many of these challenges have been...... illustrated by studies involving childhood acute lymphoblastic leukemia (ALL), where each patient may receive up to 13 different anticancer agents over a period of 2-3 years. The challenges include i) addressing important, but low-frequency outcomes, ii) difficulties in interpreting the impact of single drug...

  1. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2

    Science.gov (United States)

    Wang, Xiaoming; Zhou, Minran; Fu, Yue; Sun, Ting; Chen, Jin; Qin, Xuemei; Yu, Yuan; Jia, Jihui; Chen, Chunyan

    2016-01-01

    Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL), adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2) was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression. PMID:27008505

  2. RBP2 Promotes Adult Acute Lymphoblastic Leukemia by Upregulating BCL2.

    Directory of Open Access Journals (Sweden)

    Xiaoming Wang

    Full Text Available Despite recent increases in the cure rate of acute lymphoblastic leukemia (ALL, adult ALL remains a high-risk disease that exhibits a high relapse rate. In this study, we found that the histone demethylase retinoblastoma binding protein-2 (RBP2 was overexpressed in both on-going and relapse cases of adult ALL, which revealed that RBP2 overexpression was not only involved in the pathogenesis of ALL but that its overexpression might also be related to relapse of the disease. RBP2 knockdown induced apoptosis and attenuated leukemic cell viability. Our results demonstrated that BCL2 is a novel target of RBP2 and supported the notion of RBP2 being a regulator of BCL2 expression via directly binding to its promoter. As the role of RBP2 in regulating apoptosis was confirmed, RBP2 overexpression and activation of BCL2 might play important roles in ALL development and progression.

  3. Immunology of infusion reactions in the treatment of patients with acute lymphoblastic leukemia.

    Science.gov (United States)

    Asselin, Barbara

    2016-07-01

    Infusion reactions are potentially dose-limiting adverse events associated with intravenous administration of several common agents used to treat patients with acute lymphoblastic leukemia. True clinical hypersensitivity reactions are antibody-mediated and can occur only after repeated exposure to an antigen. Conversely, anaphylactoid infusion reactions are nonantibody-mediated and often occur on the initial exposure to a drug. Cytokine-release syndrome comprises a subset of nonantibody-mediated infusion reactions associated with the use of monoclonal antibodies and immune therapies. Clinical symptoms of hypersensitivity reactions and nonantibody-mediated infusion reactions heavily overlap and can be difficult to distinguish in practice. Regardless of the underlying mechanism, any infusion reaction can negatively affect treatment efficacy and patient safety. These events require prompt response, and potentially, modification of subsequent therapy. PMID:27086555

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

    Science.gov (United States)

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

    2001-03-01

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

  5. Population Analysis of Pharmacogenetic Polymorphisms Related to Acute Lymphoblastic Leukemia Drug Treatment

    Directory of Open Access Journals (Sweden)

    Marcela A. Chiabai

    2012-01-01

    Full Text Available This study aimed to evaluate in the Brazilian population, the genotypes and population frequencies of pharmacogenetic polymorphisms involved in the response to drugs used in treatment of acute lymphoblastic leukemia (ALL, and to compare the data with data from the HapMap populations. There was significant differentiation between most population pairs, but few associations between genetic ancestry and SNPs in the Brazilian population were observed. AMOVA analysis comparing the Brazilian population to all other populations retrieved from HapMap pointed to a genetic proximity with the European population. These associations point to preclusion of the use of genetic ancestry as a proxy for predicting drug response. In this way, any study aiming to correlate genotype with drug response in the Brazilian population should be based on pharmacogenetic SNP genotypes.

  6. The biology, pathogenesis and clinical aspects of acute lymphoblastic leukemia in children with Down syndrome.

    Science.gov (United States)

    Lee, P; Bhansali, R; Izraeli, S; Hijiya, N; Crispino, J D

    2016-09-01

    Children with Down syndrome (DS) are at a 20-fold increased risk for acute lymphoblastic leukemia (DS-ALL). Although the etiology of this higher risk of developing leukemia remains largely unclear, the recent identification of CRLF2 (cytokine receptor like factor 2) and JAK2 mutations and study of the effect of trisomy of Hmgn1 and Dyrk1a (dual-specificity tyrosine phosphorylation-regulated kinase 1A) on B-cell development have shed significant new light on the disease process. Here we focus on the clinical features, biology and genetics of ALL in children with DS. We review the unique characteristics of DS-ALL on both the clinical and molecular levels and discuss the differences in treatments and outcomes in ALL in children with DS compared with those without DS. The identification of new biological insights is expected to pave the way for novel targeted therapies. PMID:27285583

  7. Bone Marrow Cells in Acute Lymphoblastic Leukemia Create a Proinflammatory Microenvironment Influencing Normal Hematopoietic Differentiation Fates

    Directory of Open Access Journals (Sweden)

    Armando Vilchis-Ordoñez

    2015-01-01

    Full Text Available B-cell acute lymphoblastic leukemia (B-ALL is a serious public health problem in the pediatric population worldwide, contributing to 85% of deaths from childhood cancers. Understanding the biology of the disease is crucial for its clinical management and the development of therapeutic strategies. In line with that observed in other malignancies, chronic inflammation may contribute to a tumor microenvironment resulting in the damage of normal processes, concomitant to development and maintenance of neoplastic cells. We report here that hematopoietic cells from bone marrow B-ALL have the ability to produce proinflammatory and growth factors, including TNFα, IL-1β, IL-12, and GM-CSF that stimulate proliferation and differentiation of normal stem and progenitor cells. Our findings suggest an apparently distinct CD13+CD33+ population of leukemic cells contributing to a proinflammatory microenvironment that may be detrimental to long-term normal hematopoiesis within B-ALL bone marrow.

  8. Treatment and long-term results in children with acute myeloid leukaemia treated according to the AIEOP AML protocols.

    Science.gov (United States)

    Pession, A; Rondelli, R; Basso, G; Rizzari, C; Testi, A M; Fagioli, F; De Stefano, P; Locatelli, F

    2005-12-01

    Since 1982, four consecutive studies on childhood acute myeloid leukaemia (AML) (namely LAM-82, -87, -87M and -92) have been conducted in Italy by the Associazione Italiana di Ematologia e Oncologia Pediatrica (AIEOP) group. The induction therapy of the first three studies consisted of daunorubicin and cytarabine structured in a 3+7 backbone. In the most recent protocol (LAM92), patients received two induction courses including idarubicin, cytarabine and etoposide. Patients with acute promyelocytic leukaemia (20% of diagnoses) were included in LAM-87 and 87M studies. Postremissional therapy significantly changed over time, with an ever-increasing role given to stem cell transplantation (SCT). The long-term outcome of patients enrolled in the LAM-82, 87 and 87M studies was comparable, whereas that of children treated according to LAM-92 study was significantly better (P<0.005). Either allogeneic or autologous SCT was employed as consolidation therapy in more than 75% of cases enrolled in this latter study. Patients enrolled in the LAM-92 study were stratified in standard and high-risk groups with different outcome (67 vs 47%, respectively, P=0.04). Altogether, the results obtained in these four studies have permitted a progressive refinement of treatment, contributing to the structure of the ongoing LAM-2002 protocol that stratifies patients according to the presence of definite genetic anomalies and response to induction therapy.

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

    Science.gov (United States)

    Jiménez-Hernández, Elva; Dueñas-González, María Teresa; Arellano-Galindo, José; Medrano-Ortíz-De-Zárate, María Elena; Bekker-Méndez, Vilma Carolina; Berges-García, Adolfina; Solís-Labastida, Karina; Sánchez-Jara, Berenice; Tiznado-García, Héctor Manuel; Jaimes-Reyes, Ethel Zulie; García-Jiménez, Xochiketzalli; Espinoza-Hernández, Laura; Núñez-Villegas, Nora Nancy; Franco-Ornelas, Sergio; Pérez-Casillas, Ruy Xavier; Martínez Villegas, Octavio; Palomares, Teresa Marin; Mejía-Aranguré, Juan Manuel

    2015-01-01

    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. PMID:25821830

  10. 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.

  11. Analysis on the treatment of adult acute lymphoblastic leukemia%浅谈成人急性淋巴细胞白血病治疗分析

    Institute of Scientific and Technical Information of China (English)

    王文娟

    2015-01-01

    this paper summarizes the treatment of acute lymphoblastic leukemia negative pH, pH-positive acute lymphoblastic leukemia treatment, the treatment of relapsed acute lymphocytic leukemia, acute lymphoblastic leukemia, targeted therapies and new drugs, analyse the treatment progress of adult acute lymphoblastic leukemia,summarizes the main treatment strategies of adult acute lymphoblastic leukemia,proposed the treatment prospects of acute lymphoblastic leukemia,in order to provide a reference.%急性淋巴细胞白血病(all)是一组生物学和预后不同的异质性疾病。本文从 pH 阴性急性淋巴细胞白血病的治疗、pH 阳性急性淋巴细胞白血病的治疗、复发急性淋巴细胞白血病的治疗、急性淋巴细胞白血病的靶向治疗及新药这几方面分析了成人急性淋巴细胞白血病治疗进展,总结了成人急性淋巴细胞白血病治疗的主要策略,提出了对急性淋巴细胞白血病治疗的展望,以供参考。

  12. Discrimination of acute lymphoblastic leukemia from systemic-onset juvenile idiopathic arthritis at disease onset

    Directory of Open Access Journals (Sweden)

    Mirian S. Tamashiro

    2011-01-01

    Full Text Available OBJECTIVE: To assess clinical and laboratory features that differentiate acute lymphoblastic leukemia from systemic juvenile idiopathic arthritis at disease onset. METHODS: Fifty-seven leukemia patients with musculoskeletal involvement, without blasts on peripheral blood and without glucocorticoid therapy at disease onset and 102 systemic juvenile idiopathic arthritis patients (International League of Associations for Rheumatology criteria were retrospectively evaluated. The following features were examined: fever, rheumatoid rash, arthritis, limb pain, hepatomegaly, splenomegaly, pericarditis, myocarditis, pleuritis, weight loss, bleeding, anemia, leukopenia, neutropenia, thrombocytopenia, erythrocyte sedimentation rate, and lactic dehydrogenase levels. RESULTS: The median age at disease onset was significantly higher in leukemia patients than in those with systemic-onset juvenile idiopathic arthritis (5.8 vs. 3.8 years. In addition, the frequencies of limb pain, hepatomegaly, weight loss and hemorrhagic manifestations were significantly higher in leukemia patients than in systemic-onset juvenile idiopathic arthritis patients (70% vs. 1%, 54% vs. 32%, 30% vs. 8%, and 9% vs. 0%, respectively. Likewise, the frequencies of anemia, leukopenia, neutropenia, thrombocytopenia and high lactic dehydrogenase levels were statistically higher in leukemia patients than in patients with systemic-onset juvenile idiopathic arthritis (88% vs. 57%, 39% vs. 1%, 60% vs. 1%, 77% vs. 1%, and 56% vs. 14%, respectively. Remarkably, multivariate analysis revealed that limb pain (OR = 553; 95% CI =46.48-6580.42 and thrombocytopenia (OR = 754.13; 95% CI =64.57-8806.72 were significant independent variables that differentiated leukemia from systemic-onset juvenile idiopathic arthritis. The R2 of the Nagelkerke test was 0.91, and the Kaplan-Meier survival curves were similar for acute lymphoblastic leukemia patients with and without limb pain. CONCLUSION: Our study

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

    Science.gov (United States)

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

    2011-01-01

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

  14. Febrile neutropenia in children with acute lymphoblastic leukemia: single center experience

    Science.gov (United States)

    Özdemir, Nihal; Tüysüz, Gülen; Çelik, Nigar; Yantri, Leman; Erginöz, Ethem; Apak, Hilmi; Özkan, Alp; Yıldız, İnci; Celkan, Tiraje

    2016-01-01

    Aim: An important life-threatening complication of intensive chemotherapy administered in children with leukemia is febrile neutropenia. The objective of this study was to evaluate the clinical features and consequences of febrile neutropenia attacks in children who were treated for acute lymphoblastic leukemia. Material and Methods: Nighty-six children who received chemotherapy for acute lymphoblastic leukemia in our center between January 1995 and December 2010 were included in the study. The data related to demographic characteristics, treatment features, relapse and febrile neutropenia incidences, risk factors, culture results and prognosis were retrospectively evaluated from the patients’ files. Results: A total of two hundred-ninety nine febrile neutropenia attacks observed in the patients during initial treatment and relapse treatment were evaluated. When the incidence of febrile neutropenia was evaluated by years, it was observed that the patients treated after year 2000 had statistically significantly more febrile neutopenia attacks compared to the patients treated before year 2000. When the incidences of febrile neutropenia during initial treatment and during relapse treatment were compared, it was observed that more febrile neutropenia attacks occured during relapse treatment. Fifty-nine percent of all febrile neutropenia attacks were fever of unknown origin. Eighty microorganisms grew in cultures during febrile neutropenia throughout treatment in 75 patients; 86% were bacterial infections (50% gram positive and 50% gram negative), 8% were viral infections and 6% were fungal infections. Coagulase negative staphylococcus (n=17) was the most frequent gram positive pathogen; E. Coli (n=17) was the most commonly grown gram negative pathogen. Conclusions: In this study, it was found that an increase in the incidence of febrile neutropenia occured in years. Increments in treatment intensities increase the incidence of febrile neutropenia while improving

  15. Risk group assignment differs for children and adults 1-45 yr with acute lymphoblastic leukemia treated by the NOPHO ALL-2008 protocol

    DEFF Research Database (Denmark)

    Toft, Nina; Birgens, Henrik; Abrahamsson, Jonas;

    2013-01-01

    The prognosis of acute lymphoblastic leukemia is poorer in adults than in children. Studies have indicated that young adults benefit from pediatric treatment, although no upper age limit has been defined....

  16. Intrachromosomal amplification of chromosome 21 (iAMP21) detected by ETV6/RUNX1 FISH screening in childhood acute lymphoblastic leukemia: a case report

    OpenAIRE

    Daniela Ribeiro Ney Garcia; Alejandro Mauricio Arancibia; Ribeiro, Raul C.; Marcelo Gerardin Poirot Land; Maria Luiza Macedo Silva

    2013-01-01

    Chromosome abnormalities that usually define high-risk acute lymphoblastic leukemia are the t(9;22)/ breakpoint cluster region protein-Abelson murine leukemia viral oncogene homolog 1, hypodiploid with < 44 chromosomes and 11q23/ myeloid/lymphoid leukemia gene rearrangements. The spectrum of acute lymphoblastic leukemia genetic abnormalities is nevertheless rapidly expanding. Therefore, newly described chromosomal aberrations are likely to have an impact on clinical care in the near future. R...

  17. Common acute lymphoblastic leukemia antigen (CALLA) is active neutral endopeptidase 24.11 ("enkephalinase"): direct evidence by cDNA transfection analysis.

    OpenAIRE

    Shipp, M A; Vijayaraghavan, J.; Schmidt, E V; Masteller, E L; D'Adamio, L; Hersh, L.B.; Reinherz, E L

    1989-01-01

    The common acute lymphoblastic leukemia antigen (CALLA) is a 749-amino acid type II integral membrane protein expressed by most acute lymphoblastic leukemias, certain other lymphoid malignancies with an immature phenotype, and normal lymphoid progenitors. A computer search against the most recent GenBank release (no. 56) indicates that human CALLA cDNA encodes a protein nearly identical to the rat and rabbit neutral endopeptidase 24.11 ("enkephalinase;" EC 3.4.24.11). This zinc metalloendopep...

  18. ZFX Controls Propagation and Prevents Differentiation of Acute T-Lymphoblastic and Myeloid Leukemia

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    Stuart P. Weisberg

    2014-02-01

    Full Text Available Tumor-propagating cells in acute leukemia maintain a stem/progenitor-like immature phenotype and proliferative capacity. Acute myeloid leukemia (AML and acute T-lymphoblastic leukemia (T-ALL originate from different lineages through distinct oncogenic events such as MLL fusions and Notch signaling, respectively. We found that Zfx, a transcription factor that controls hematopoietic stem cell self-renewal, controls the initiation and maintenance of AML caused by MLL-AF9 fusion and of T-ALL caused by Notch1 activation. In both leukemia types, Zfx prevents differentiation and activates gene sets characteristic of immature cells of the respective lineages. In addition, endogenous Zfx contributes to gene induction and transformation by Myc overexpression in myeloid progenitors. Key Zfx target genes include the mitochondrial enzymes Ptpmt1 and Idh2, whose overexpression partially rescues the propagation of Zfx-deficient AML. These results show that distinct leukemia types maintain their undifferentiated phenotype and self-renewal by exploiting a common stem-cell-related genetic regulator.

  19. 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

    2007-01-01

    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 progn

  20. Trends in management of acute lymphoblastic leukemia: Influence of insurance based healthcare and treatment compliance on the outcome of adolescents and adults with acute lymphoblastic leukemia

    Directory of Open Access Journals (Sweden)

    Ravi Sankar Arigela

    2016-01-01

    Full Text Available Aim: In this study, we attempted to analyze the impact of insurance based health care system and treatment compliance on the outcome of adolescent and adults with acute lymphoblastic leukemia (ALL. Materials and Methods: Patients who underwent treatment for ALL during the period 2003-2011 were enrolled into this retrospective study. Patients on supportive or palliative care only and patients with age <10 years were excluded. The hospital records and tumor registry records were studied. Patients were stratified into two groups, Group A (prior to the introduction of state health insurance [SHI], 2003-2007 and Group B (after the introduction of SHI, 2008-2011. Overall survival (OS was calculated using Kaplan-Meier method. Results: A total of 420 patients with suspected or confirmed ALL visited our center during the study period and 179 patients (87 in Group A and 92 in Group B were considered for inclusion. The median age in years (range was 18 (10-57 and 18 (10-58 respectively in Groups A and B with males more than females. Median OS (95% CI was 9 (6.7-11.2 and 12 (7.3-16.7 months in the Groups A and B respectively (P = 0.265. Poor treatment compliance in both groups was high (36% in Group A and 41% in Group B, [P = 0.107] with lower default rates in Group B (P = 0.019. Patients with good compliance in the total study population and the individual study groups had significantly better OS. Conclusions: Insurance based health care has improved outcomes in the present study but not compliance to treatment. Significantly better OS was observed in patients with good compliance.