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Sample records for acute lymphoblastic leukaemia

  1. Giant Molluscum Contagiosum In Acute Lymphoblastic Leukaemia

    Venkatesan Sivaraman

    2001-01-01

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

  2. Rhinocerebral zygomycosis in acute lymphoblastic leukaemia.

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

    1993-01-01

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

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

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

    2012-01-01

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

  4. Academic career after treatment for acute lymphoblastic leukaemia

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

    2000-01-01

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

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

    Hjalmars, U; G. Gustafsson; . .

    1999-01-01

    A population-based sample of acute childhood leukaemia cases in Sweden 1973–94 was analysed by a geographical information system (GIS) for spatial leukaemia distribution in relation to population density. The annual incidence rate for acute lymphoblastic leukaemia (ALL) was 3.6, and for acute non-lymphoblastic leukaemia (ANLL) 0.7, cases per 100 000 children. Incidence rates in population centres, constituting 1.3% of Sweden's land area and approximately 80% of the population, compared with t...

  6. Oral mucositis in children suffering from acute lymphoblastic leukaemia

    Pels, Elżbieta

    2012-01-01

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

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

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

    1994-01-01

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

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

    P. Schneider

    2011-01-01

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

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

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

    1997-02-01

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

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

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

    2008-01-01

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

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

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

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

    Stanković Tatjana

    2008-01-01

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

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

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

    2011-01-01

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

  14. Orbital mass secondary to infantile acute lymphoblastic leukaemia.

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

    2016-01-01

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

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

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

    1999-01-01

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

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

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

    2014-01-01

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

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

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

    1987-01-01

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

  18. L-asparaginase induced hyperlipidaemia in acute lymphoblastic leukaemia

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

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

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

    2016-04-01

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

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

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

    2016-01-01

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

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

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

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

    Kelly, Kevin

    2008-12-01

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

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

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

    2016-06-01

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

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

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

    2011-01-01

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

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

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

    2004-01-01

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

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

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

    2011-01-01

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

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

    John Biju

    2009-12-01

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

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

    S Jain

    2015-01-01

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

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

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

    2000-01-01

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

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

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

    2016-01-01

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

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

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

    2014-01-01

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

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

    Gulhadiye Avcu

    2016-03-01

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

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

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

    1991-01-01

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

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

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

    2009-01-01

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

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

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

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

    Lorentzen, C L; thor Straten, Per

    2015-01-01

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

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

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

    2014-01-01

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

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

    Schmiegelow, Kjeld

    2016-01-01

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

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

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

    2012-01-01

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

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

    Sudin Varghese Daniel

    2010-01-01

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

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

    Birkebak, N; Clausen, N

    1998-01-01

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

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

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

    1996-04-01

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

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

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

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

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

    2012-01-01

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

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

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

    2007-01-01

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

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

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

    2007-01-01

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

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

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

    2002-01-01

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

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

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

    2002-01-01

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

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

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

    2000-01-01

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

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

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

    2015-01-01

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

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

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

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

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

    2008-03-15

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

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

    Yatiee Swany Lahuri

    2015-11-01

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

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

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

    2011-01-01

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

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

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

    2016-01-01

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

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

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

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

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

    2013-01-01

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

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

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

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

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

    2004-01-01

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

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

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

    2010-01-01

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

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

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

    2010-01-01

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

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

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

    2009-01-01

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

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

    Berrou, Ilhem

    2012-01-01

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

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

    Chan, Shu-wing, Sophia; 陳舒穎

    2015-01-01

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

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

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

    2000-01-01

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

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

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

    2013-01-01

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

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

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

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

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

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

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

    2014-04-01

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

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

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

    2014-01-01

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

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

    Robert J Weeks

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

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

    Kostić Gordana

    2009-01-01

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

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

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

    2016-04-01

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

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

    Nóra Kutszegi

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

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

    Daphne eChen

    2012-11-01

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

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

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

    2015-09-01

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

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

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

    2015-05-01

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

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

    Lazić Jelena

    2009-01-01

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

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

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

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

    Francis Richard W

    2010-04-01

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

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

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

    2016-06-01

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

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

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

    2016-02-01

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

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

    W. Y. Lim

    2015-01-01

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

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

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

    2008-01-01

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

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

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

    2001-01-01

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

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

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

    2006-01-01

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

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

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

    2014-01-01

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

  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

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

    Konstantinidis Georgios

    2011-01-01

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

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

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

    2011-08-01

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

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

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

    2001-01-01

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

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

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

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

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

    2016-08-01

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

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

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

    2010-01-01

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

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

    Celena eScheede-Bergdahl; R Thomas Jagoe

    2013-01-01

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

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

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

    2004-01-01

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

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

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

    2013-03-01

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

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

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

    2016-01-01

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

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

    Kaspers Gert Jan L

    2008-11-01

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

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

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

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

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

    1991-09-01

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

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

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

    2014-01-01

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

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

    Meenaghan, Teresa

    2012-01-01

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

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

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

    2011-01-01

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

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

    Dokmanović Lidija

    2008-01-01

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

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

    Lohit Kumar Kalita

    2015-05-01

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

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

    Bassem Y. Sheikh

    2013-09-01

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

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

    R. Simone

    2011-01-01

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

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

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

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

    Mohammed Al Reesi

    2014-10-01

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

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

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

    2011-01-01

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

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

    Rosthøj, Susanne; Keiding, Niels; Schmiegelow, Kjeld

    2012-01-01

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

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

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

    2008-01-01

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

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

    Elva Jiménez-Hernández

    2015-01-01

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

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

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

    2011-01-01

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

  16. 9-O-acetylated sialic acids differentiating normal haematopoietic precursors from leukemic stem cells with high aldehyde dehydrogenase activity in children with acute lymphoblastic leukaemia.

    Chowdhury, Suchandra; Chandra, Sarmila; Mandal, Chitra

    2014-10-01

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

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

    Vujić Dragana

    2010-01-01

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

  18. Analysis of images of acute human and animal leukaemia

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

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

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

    2000-01-01

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

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

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

    2015-04-03

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

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

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

  2. Acute lymphoblastic leukemia (ALL)

    Jeha S, Pui CH. Clinical manifestations and treatment of acute lymphoblastic leukemia in children. In: Hoffman R, Benz EJ Jr, Silberstein LE, Weitz JI, Anastasi J, eds. Hematology: Basic Principles and Practice. 6th ed. ...

  3. Significance of Phi bodies in acute leukaemia.

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

    1981-01-01

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

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

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

    2006-03-15

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

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

    Ashish Narayan Masurekar

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

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

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

    2016-04-15

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

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

    Vargha-Khadem Faraneh

    2011-10-01

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

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

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

    2011-02-01

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

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

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

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

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

    2011-04-01

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

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

    Celena eScheede-Bergdahl

    2013-04-01

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

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

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

    2016-09-01

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

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

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

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

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

    2011-01-01

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

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

    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

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

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

    1998-01-01

    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...

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

    Francesca Lanfranconi

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

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

    Mohr Brigitte

    2003-01-01

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

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

    王学文

    2011-01-01

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

  20. Childhood Acute Lymphoblastic Leukemia

    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...

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

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

    1990-01-01

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

  2. Oral manifestations of acute leukaemia

    Ivanović Mirjana

    2011-01-01

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

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

    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-

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

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

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

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

    2007-01-01

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

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

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

    2006-01-01

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

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

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

    2011-01-01

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

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

    2016-04-07

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

  9. Treatment Option Overview (Adult Acute Lymphoblastic Leukemia)

    ... 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 ...

  10. General Information about Adult Acute Lymphoblastic Leukemia

    ... 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 ...

  11. Stages of Adult Acute Lymphoblastic Leukemia

    ... 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 ...

  12. Treatment Options for Adult Acute Lymphoblastic Leukemia

    ... 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 ...

  13. The eye in acute leukaemia. 1

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

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

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

    2001-01-01

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

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

    Andersen, Mette K; Autio, Kirsi; Barbany, Gisela; Borgström, Georg; Cavelier, Lucia; Golovleva, Irina; Heim, Sverre; Heinonen, Kristina; Hovland, Randi; Johannsson, Johann H; Johansson, Bertil; Kjeldsen, Eigil; Nordgren, Ann; Palmqvist, Lars; Forestier, Erik

    2011-10-01

    The translocation t(1;19)(q23;p13)/der(19)t(1;19) is a risk stratifying aberration in childhood B-cell precursor acute lymphoblastic leukaemia (BCP ALL) in the Nordic countries. We have identified 47 children/adolescents with t(1;19)/der(19)t(1;19)-positive BCP ALL treated on two successive Nordic Society of Paediatric Haematology and Oncology (NOPHO) protocols between 1992 and 2007 and have reviewed the clinical and cytogenetic characteristics of these cases, comprising 1·8% of all cases. The translocation was balanced in 15 cases (32%) and unbalanced in 29 cases (62%). The most common additional chromosome abnormalities were del(9p), i(9q), del(6q), and del(13q). The median age was 7 years, the median white blood cell (WBC) count was 16 × 10(9)/l, and the female/male ratio was 1·2. The predicted event-free survival (EFS) at 5 and 10 years was 0·79, whereas the predicted overall survival (OS) at 5 and 10 years was 0·85 and 0·82, respectively. Nine patients had a bone marrow relapse after a median of 23 months; no patient had a central nervous system relapse. Additional cytogenetic abnormalities, age, gender, WBC count or whether the t(1;19) was balanced or unbalanced did not influence EFS or OS. Compared to cases with t(12,21) and high hyperdiploidy, EFS was similar, but overall survival was worse in patients with t(1;19)/der(19)t(1;19) (P = 0·004). PMID:21902680

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

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

    1998-06-01

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

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

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

    2003-01-01

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

  18. Immunological and ultrastructural studies in acute biphenotypic leukaemia.

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

    1993-01-01

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

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

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

    1986-12-01

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

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

    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.)

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

    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.)

  2. Cytochemical studies in leukaemias

    Batra Neelam

    1978-01-01

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

  3. Aberrant Gene Expression in Acute Myeloid Leukaemia

    Bagger, Frederik Otzen

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

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

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

    2012-01-01

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

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

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

    1988-01-01

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

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

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

    2012-01-01

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

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

    Sunil Pazhayanur Venkateswaran

    2012-10-01

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

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

    ... 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 ...

  9. DIAGNOSIS AND SUBCLASSIFICATION OF ACUTE LYMPHOBLASTIC LEUKEMIA

    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.

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

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

    2000-01-01

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

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

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

    1998-01-01

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

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

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

    2014-01-01

    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...

  13. MINIMAL RESIDUAL DISEASE IN ACUTE LYMPHOBLASTIC LEUKEMIA

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well established; studies in...

  14. Novel Therapies for Relapsed Acute Lymphoblastic Leukemia

    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. Pathogenesis and prognostication in acute lymphoblastic leukemia

    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...

  16. Acute lymphocytic leukaemia in children in the Netherlands

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

  17. Exit of pediatric pre-B acute lymphoblastic leukaemia cells from the bone marrow to the peripheral blood is not associated with cell maturation or alterations in gene expression

    Wiebe Thomas

    2008-08-01

    Full Text Available Abstract Background Childhood pre-B acute lymphoblastic leukemia (ALL is a bone marrow (BM derived disease, which often disseminates out of the BM cavity, where malignant cells to a variable degree can be found circulating in the peripheral blood (PB. Normal pre-B cells are absolutely dependent on BM stroma for survival and differentiation. It is not known whether transformed pre-B ALL cells retain any of this dependence, which possibly could impact on drug sensitivity or MRD measurements. Results Pre-B ALL cells, highly purified by a novel method using surface expression of CD19 and immunoglobulin light chains, from BM and PB show a very high degree of similarity in gene expression patterns, with differential expression of vascular endothelial growth factor (VEGF as a notable exception. In addition, the cell sorting procedure revealed that in 2 out of five investigated patients, a significant fraction of the malignant cells had matured beyond the pre-B cell stage. Conclusion The transition of ALL cells from the BM into the circulation does not demand, or result in, major changes of gene expression pattern. This might indicate an independence of BM stroma on the part of transformed pre-B cells, which contrasts with that of their normal counterparts.

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

    Niedobitek Gerald

    2010-03-01

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

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

    Chandra Sarmila

    2008-02-01

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

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

    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

  1. Molecular therapy for acute myeloid leukaemia.

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

    2016-05-01

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

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

    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...

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

    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

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

    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

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

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

  6. Epidemiology of acute lymphoblastic leukemia

    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

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

    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.

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

    J. Molina

    2007-12-01

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

  9. Myeloid sarcoma in a child with acute myeloblastic leukaemia

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

  10. Relapsed childhood acute lymphoblastic leukemia in the Nordic countries

    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...... 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...... development of novel approaches is urgently needed to increase survival in relapsed childhood acute lymphoblastic leukemia....

  11. [The dysplasia of myelopoiesis in patients with acute lymphoblastic leucosis].

    Frenkel', M A; Kupryshkina, N A; Lebedeva, N B; Zharova, Z D; Baranova, O Iu; Tupitsyn, N N

    2012-12-01

    Nowadays, the analysis of hematopoiesis in patients with acute lymphoblastic leucosis includes only quantitative characteristics of residue myeloid process of bone marrow. The evaluation of myelodysplasia is unexplored still. The analysis of myelopoiesis was carried on sampling of 108 patients with primary acute lymphoblastic leucosis (27 - T-acute lymphohlastic leucosis, 81 - B-acute Iymphoblastic leucosis). The characteristics of dysplasia of granulocytes, erythroid cells and megakaryocytes were based on the parameters of WHO classification of acute myeloid leucosis (2001). The monolinear dysplasia was established in 35 patients (32.4%). multilinear dysplasia--in 9 patients (8.3%). Under T- acute lymphoblastic leucosis the bilinear dysplasia was detected reliably more often and absence of dysplasia more rare than under B-acute lymphoblastic leucosis. The signs of dysplasia of various myeloid lines had no inter-correlation and had no dependencies from indicators of expression of early antigens (CCD34 and TdT) and myeloid antigens (CD13, CD33). The comparison of factual data with indicators of dysplasia under acute mteloid leucosis (181 patients) demonstrated that rates of uni- and multilinear dysplasia under T-acute Iymphoblastic leucosis and acute myeloid leucosis have no significant difference. The myelodysplasia is detected reliably (more often under B-acute lymphoblastic leucosis as compared with acute myeloid leucosis. PMID:23479968

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

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

    2007-01-01

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

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

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

    2000-01-01

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

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

    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.

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

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

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

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

    2008-01-01

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

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

    2015-07-09

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

  18. Prognostic significance of cell surface phenotype in acute lymphoblastic leukemia

    Shiek Aejaz Aziz; Susheel Kumar Sharma; Iram Sabah; M Aleem Jan

    2015-01-01

    Context: To find out the phenotypic character of lymphoblasts of acute lymphoblastic leukemia (ALL) patients in our study cohort and their possible effect on the prognosis. Aims: To investigate the phenotype in ALL in our demographic population and to prognosticate various upfront current protocols employed in our hospital. Settings and Design: The study spanned over a period of 4 years with retrospective and prospective data of January 2008 through December 2011. Materials and Methods: 159 p...

  19. High-flow priapism in acute lymphatic leukaemia

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

    2004-07-01

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

  20. Minimal residual disease in acute lymphoblastic leukemia.

    Campana, Dario

    2009-01-01

    In patients with acute lymphoblastic leukemia (ALL), monitoring of minimal residual disease (MRD) offers a way to precisely assess early treatment response and detect relapse. Established methods to study MRD are flow cytometric detection of abnormal immunophenotypes, polymerase chain reaction (PCR) amplification of antigen-receptor genes, and PCR amplification of fusion transcripts. The strong correlation between MRD levels and risk of relapse in childhood ALL is well demonstrated; studies in adult patients also support its prognostic value. Hence, results of MRD studies can be used to select treatment intensity and duration, and to estimate the optimal timing for hematopoietic stem cell transplantation. Practical issues in the implementation of MRD assays in clinical studies include determining the most informative time point to study MRD and the levels of MRD that will trigger changes in treatment intensity, as well as the relative cost and informative power of different methodologies. The identification of new markers of leukemia and the use of increasingly refined assays should further facilitate routine monitoring of MRD and help to clarify the cellular and biologic features of leukemic cells that resist chemotherapy in vivo. PMID:19100372

  1. Genetic abnormalities associated with acute lymphoblastic leukemia.

    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

  2. Acute Myeloid Leukaemia: Optimal Management and Recent Developments

    Villela, Luis; Bolaños-Meade, Javier

    2011-01-01

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

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

    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)

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

    Timonen, T T; Palva, I P

    1980-01-01

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

  5. Attentional ability among survivors of leukaemia

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

    1999-01-01

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

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

    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.…

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

    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...

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

    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.

  9. Pharmacokineties of vincristine monotherapy in childhood acute lymphoblastic leukemia

    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

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

    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

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

    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 1980...

  12. Risk Groups for Childhood Acute Lymphoblastic Leukemia

    ... 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 ...

  13. Treatment Option Overview (Childhood Acute Lymphoblastic Leukemia)

    ... 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 ...

  14. General Information about Childhood Acute Lymphoblastic Leukemia

    ... 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 ...

  15. Treatment Options for Childhood Acute Lymphoblastic Leukemia

    ... 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 ...

  16. Leukemia Stem Cells and Human Acute Lymphoblastic Leukemia

    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 (...

  17. Childhood leukaemia in Wessex

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

  18. MicroRNAs as Potential Biomarkers in Acute Promyelocytic Leukaemia

    Imilia Ismail

    2014-01-01

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

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

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

    2012-01-01

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

  20. Current standard treatment of adult acute promyelocytic leukaemia.

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

    2016-03-01

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

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

    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.

  2. New decision support tool for acute lymphoblastic leukemia classification

    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.

  3. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    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.

  4. Treatment on leukaemia in children

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

    1984-06-01

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

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

    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...

  6. Minimal Residual Disease Assessment in Childhood Acute Lymphoblastic Leukemia

    Thörn, Ingrid

    2009-01-01

    Traditionally, response to treatment in hematological malignancies is evaluated by light microscopy of bone marrow (BM) smears, but due to more effective therapies more sensitive methods are needed. Today, detection of minimal residual disease (MRD) using immunological and molecular techniques can be 100 times more sensitive than morphology. The main aim of this thesis was to compare and evaluate three currently available MRD methods in childhood acute lymphoblastic leukemia (ALL): (i) real-t...

  7. Estimation of physical development of children at acute lymphoblastic leukemia

    The problem of the work is data of 124 children with acute lymphoblastic leukemia and Hodgkin's disease after combination treatment.The objective of the work is to detect physical stature of children after cancer therapy in children and comparison of their antropometrical data before and after therapy.The possibility of detection of combination therapy's influence on physical stature of children in remission was shown. (authors)

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

    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...

  9. Acute Lymphoblastic Leukemia Arising in CALR Mutated Essential Thrombocythemia

    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...

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

    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....

  11. Vitamin D Protects Acute Lymphoblastic Leukemia Cells from Dexamethasone

    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...

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

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

  13. Fludarabine Phosphate and Total-Body Irradiation Followed by Donor Peripheral Blood Stem Cell Transplant in Treating Patients With Acute Lymphoblastic Leukemia or Chronic Myelogenous Leukemia That Has Responded to Treatment With Imatinib Mesylate, Dasatinib, or Nilotinib

    2015-07-20

    Adult Acute Lymphoblastic Leukemia in Remission; Blastic Phase Chronic Myelogenous Leukemia; Childhood Acute Lymphoblastic Leukemia in Remission; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Chronic Phase Chronic Myelogenous Leukemia; Philadelphia Chromosome Positive Adult Precursor Acute Lymphoblastic Leukemia; Philadelphia Chromosome Positive Childhood Precursor Acute Lymphoblastic Leukemia; Recurrent Adult Acute Lymphoblastic Leukemia; Recurrent Childhood Acute Lymphoblastic Leukemia; Relapsing Chronic Myelogenous Leukemia

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

    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.

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

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

    2016-01-01

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

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

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

    2014-05-01

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

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

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

    2014-01-01

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

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

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

    1998-01-01

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

  19. Harnessing the immune system in acute myeloid leukaemia.

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

    2016-07-01

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

  20. Esophageal strictures during treatment for acute lymphoblastic leukemia.

    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.

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

    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...

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

    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...

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

    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...

  4. Acute lymphoblastic leukemia of childhood presenting as aplastic anemia: report of two cases

    Laura Villarreal-Martínez; José Carlos Jaime-Pérez; Marisol Rodríguez-Martínez; Oscar González-Llano; David Gómez-Almaguer

    2012-01-01

    Acute lymphoblastic leukemia is the most common malignancy in pediatric patients; its diagnosis is usually easy to establish as malignant lymphoblasts invade the bone marrow and peripheral blood. Some acute lymphoblastic leukemia patients may initially present with pancytopenia and a hypoplastic bone marrow leading to the initial diagnosis of aplastic anemia. In most of these patients clinical improvement occurs, with normalization of the complete blood count within six months, although recov...

  5. Caffeine-hydrazones as anticancer agents with pronounced selectivity toward T-lymphoblastic leukaemia cells

    Kaplánek, R.; Jakubek, M.; Rak, J.; Kejik, Z.; Havlík, M.; Dolenský, B.; Frydrych, I.; Hajduch, M.; Kolář, M.; Bogdanová, K.; Králová, Jarmila; Dzubak, P.; Král, V.

    2015-01-01

    Roč. 60, Jun (2015), s. 19-29. ISSN 0045-2068 Grant ostatní: GA MŠk(CZ) EE2.3.30.0060; GA MŠk CZ.1.07/2.3.00/30.0041; GA MŠk(CZ) LO1304 Institutional support: RVO:68378050 Keywords : Anticancer agents * Cancer treatment * Caffeine-hydrazones * Leukaemia * Selectivity Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 2.152, year: 2014

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

    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.

  7. Acute parotitis during induction therapy including L-asparaginase in acute lymphoblastic leukemia.

    Sica, S; Pagano, L; Salutari, P; Di Mario, A; Rutella, S; Leone, G

    1994-02-01

    In a patient affected by acute lymphoblastic leukemia (ALL) and subjected to therapy with Erwinia L-asparaginase, acute parotitis was observed. Microbiological studies excluded any infectious etiology. Regression of parotitis was spontaneous. This complication has not been previously reported and could be due to the same mechanism of pancreatic injury. The occurrence of acute parotitis needs to be promptly recognized in order to avoid the continuation of L-asparaginase. PMID:8148421

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

    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

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

    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.

  10. Radiation treatment of testicular relapse in acute lymphoblastic leukemia

    Ten patients with testicular relapse among 128 cases of acute lymphoblastic leukemia are reported. At the time of the initial diagnosis of leukemia all patients with later testicular relapse showed one or more risk factors as predictive for leukemic infiltration of the testicles. All patients except one, who underwent orchiectomy and died 11 weeks after surgical intervention, received radiation therapy with doses ranging from 12 to 20 Gy and chemotherapy. The local control was excellent. Average survival time from testicular relapse to death was 68 weeks in 8 of 9 patients treated by irradiation and chemotherapy. One patient is still alive without signs of disease after 6 years. (orig.)